Notices. Notice and request for comments

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BILLING CODE 4910-EX-P DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Petition for Waiver of Compliance In accordance with Part 211 of Title 49 of the Code of Federal Regulations (CFR), notice is hereby given that the Federal Railroad Administration

(City)and BNSF Railway Company

(BNSF)have petitioned for a second extension to the waiver granted on June 21, 2006, in FRA Docket No. FRA-2006-24654. In the June 21, 2006 waiver, FRA agreed to extend the original deadline of June 24, 2006, set forth in 49 CFR 222.42 for continuation of an intermediate partial quiet zone until September 22, 2006. Subsequently, FRA received a waiver requesting an extension of September 22, 2006, to January 20, 2007, from the parties. FRA granted this extension on September 21, 2006. In this current request, the City and BNSF state that they will be unable to meet the January 20, 2007, deadline due to technical problems with the radio communications system that required the ordering of new radio equipment and the need to conduct a 30-day test period of the radio communications system. The City and BNSF seek to retain the current partial quiet zone in order to avoid disruption and confusion in the interim and state that safety will not be compromised. Interested parties are invited to participate in these proceedings by submitting written views, data or comments. Each comment shall specifically set forth the basis upon which it is made and contain a concise statement of the interest of the commenter in the proceeding. FRA does not anticipate the need to schedule a public hearing in connection with this proceeding since the facts do not appear to warrant a hearing. If any interested party desires an opportunity to comment, they should notify FRA in writing within 15 days of the date of publication of this notice and specify the basis for their request. All communications concerning these proceedings should identify the docket number set forth above and may be submitted by any of the following methods: • *Web site: http://dms.dot.gov.* Follow the instructions for submitting comments on the DOT electronic docket site. • *Fax:* 202-493-2251. • *Mail:* Docket Management Facility, U.S. Department of Transportation, 400 Seventh Street, SW., Nassif Building, Room PL-401, Washington, DC 20590-0001. • *Hand Delivery:* Room PL-401 on the plaza level of the Nassif Building, 400 Seventh Street, SW., Washington, DC, between 9 a.m. and 5 p.m., Monday through Friday, except Federal Holidays. to the Docket Clerk, DOT Docket Management Facility, Room PL-401 (Plaza Level), 400 7th Street, SW., Washington, DC 20590. Communications received within 15 days of the date of this notice will be considered by FRA before final action is taken. Comments received after that date will be considered as far as practicable. FRA reserves the right to grant temporary relief to avoid lapse of the existing partial quiet zone while the comment period is open, after consideration of any comments filed prior to the initial date of decision. All written communications concerning this proceeding are available for examination during regular business hours (9 a.m.-5 p.m.) at the above facility. All documents in the public docket are available for inspection and copying on the Internet at the docket facility's Web site: *http://dms.dot.gov.* Anyone is able to search the electronic form of all comments received into any of our dockets by the name of the individual submitting the comment (or signing the comment, if submitted on behalf of an association, business, labor union, etc.). You may review the Department of Transportation's complete Privacy Act Statement, which was published in the **Federal Register** on April 11, 2000 (Volume 65, Number 70; Pages 19477-78). The Privacy Act Statement may also be found at *http://dms.dot.gov.* Issued in Washington, DC on January 9, 2007. Michael Logue, Deputy Associate Administrator, for Safety Compliance and Program Implementation. [FR Doc. E7-319 Filed 1-11-07; 8:45 am] BILLING CODE 4910-06-P DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Petition for Waiver of Compliance In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR), notice is hereby given that the Federal Railroad Administration

(FRA)received a request for a waiver of compliance with certain requirements of its safety standards. The individual petition is described below, including the party seeking relief, the regulatory provisions involved, the nature of the relief being requested, and the petitioner's arguments in favor of relief. New Jersey Transit Corporation [Supplement to Waiver Petition Docket Number FRA-1999-6135] As a supplement to New Jersey Transit Corporation's (NJ Transit) Petition for Approval of Shared Use and Waiver of Certain FRA Regulations (the original shared use waiver was granted by the FRA Railroad Safety Board on December 3, 1999, and a five year extension was granted by the FRA Railroad Safety Board on May 2, 2005), NJ Transit is making signal improvements between CP45 and CP70 in order to create an “Extended Temporal Separation Mode” of operation. This will allow NJ Transit and Conrail to safely share a limited and specific section of the River Line outside of the fixed-windows of temporal separation. NJ Transit submits that this request is consistent with the waiver process for Shared Use. * See Statement of Agency Policy Concerning Jurisdiction Over the Safety of Railroad Passenger Operations and Waivers Related to Shared Use of the Tracks of the General Railroad System by Light Rail and Conventional Equipment, 65 FR 42529 (July 10, 2000); see also Joint Statement of Agency Policy Concerning Shared Use of the Tracks of the General Railroad System by Conventional Railroads and Light Rail Transit Systems, 65 FR 42526 (July 10, 2000). * Currently, River Line passenger operations and Conrail operations are temporally-separated, with light rail having exclusive use of the shared track from 6 a.m. until 10 p.m. during the Passenger Period and Conrail maintaining exclusive rights at all other times during the Freight Period. NJ Transit is proposing to make signal improvements that will maintain temporal separation but provide for superior utilization of the existing infrastructure by expanding the Passenger Period and allow Conrail an increased operating flexibility. Specifically, the intent of these improvements is to: enable the provision of passenger service to Route 73 station in Pennsauken during the extended hours of 5:30 a.m. until 12 a.m.; provide additional flexibility and efficiencies for the operation of freight trains, specifically to enable Conrail to operate between Pavonia Yard and Minson Siding/Pennsauken Industrial Track under vitally enforced separation from light rail vehicles during all hours; provide positive train separation through the utilization of active trip stop transponders for light rail encroachment; and power derails for freight encroachment. NJ Transit further submitted on December 15, 2006, a letter offering clarification and additional information to amend the original petition. First, NJ Transit is formally notifying the FRA that in September of 2004, NJ Transit and Conrail established two separate zones of temporal separation: Zone One from CP45 (Pennsauken) to CP269 (Bordentown), with exclusive Passenger Period from 6 a.m. until 10 p.m., which remains unchanged from the original Shared Use Waiver; Zone Two from CP269 (Bordentown) to CP329 (Trenton) features a revised Passenger Period that starts at 5:45 a.m. until 10 p.m. Second, as part of the current proposed extended temporal separation between CP45 and CP70, there is potential for a new parallel operation between River Line light rail vehicles and Conrail freight equipment at track centerline distances that in some locations are less than 17-ft. NJ Transit is informing FRA that it will not install an Intrusion Detection System

(IDS)in this area as was done previously at two other locations of the River Line. Instead, NJ Transit proposes to maintain an equivalent level of safety by restricting this section of River Line to one mode at a time by prohibiting River Line light rail vehicles from operating between CP45 and CP70 when a Conrail freight train has been authorized through this section. Interested parties are invited to participate in these proceedings by submitting written views, data, or comments. FRA does not anticipate scheduling a public hearing in connection with these proceedings since the facts do not appear to warrant a hearing. If any interested party desires an opportunity for oral comment, they should notify FRA, in writing, before the end of the comment period and specify the basis for their request. All communication concerning these proceedings should identify the appropriate docket number (e.g., Waiver Petition Docket Number FRA-1999-6135) and must be submitted to the Docket Clerk, DOT Docket Management Facility, Room PL-401 (Plaza Level), 400 7th Street, SW., Washington, D.C. 20590. Communications received within 30 days of the date of this notice will be considered by FRA before final action is taken. Comments received after that date will be considered as far as practicable. All written communications concerning these proceedings are available for examination during regular business hours (9 a.m.-5 p.m.) at the above facility. All documents in the public docket are also available for inspection and copying on the Internet at the docket facility's Web site at *http://dms.dot.gov.* Issued in Washington, DC on January 9, 2007. Grady C. Cothen, Deputy Associate Administrator, for Safety Standards and Program Development. [FR Doc. E7-318 Filed 1-11-07; 8:45 am] BILLING CODE 4910-06-P DEPARTMENT OF TRANSPORTATION National Highway Traffic Safety Administration [Docket No. NHTSA 2002006-25975; Notice 2] American Honda Motor Co., Inc., Grant of Petition for Decision of Inconsequential Noncompliance American Honda Motor Co., Inc. (Honda) has determined that the certification labels for certain Pilot trucks that it produced in 2006 do not comply with S5.3 of 49 CFR 571.120, Federal Motor Vehicle Safety Standard (FMVSS) No. 120, “Tire selection and rims for motor vehicles other than passenger cars.” Pursuant to 49 U.S.C. 30118(d) and 30120(h), Honda has petitioned for a determination that this noncompliance is inconsequential to motor vehicle safety and has filed an appropriate report pursuant to 49 CFR Part 573, “Defect and Noncompliance Reports.” Notice of receipt of a petition was published, with a 30-day comment period, on October 4, 2006, in the **Federal Register** (71 FR 58660). NHTSA received no comments. Affected are a total of approximately 23,000 model year 2006 and 2007 Honda Pilot trucks produced between February 17, 2006 and August 10, 2006. S5.3.2 of FMVSS No. 120 requires that the vehicles shall show the size designation appropriate for the tires. The noncompliant vehicles have certification labels stating that the rim size is 6 inches, when in fact the rim size is 16 inches. Honda has corrected the problem that caused these errors so that they will not be repeated in future production. Honda believes that the noncompliance is inconsequential to motor vehicle safety and that no corrective action is warranted. Honda presents the following basis for its petition. Most vehicle owners, dealers, and tire service technicians would refer to the vehicles' existing tires and/or the separate Tire Placard to determine the appropriate size for a replacement tire rather than to the Certification Label. If the vehicle owner, dealer or tire service technician read the incorrect rim size on the certification label, it would be obvious that a full size vehicle could not use 6 inch wheels. The owner's manual contains the correct rim size information. The correct rim size is cast into the wheel itself. NHTSA agrees with Honda that the noncompliance is inconsequential to motor vehicle safety. It would be obvious that a full size vehicle could not be supported by 6 inch wheels. The correct size information is available in the owner's manual, and on the wheel itself, in order to determine the correct size for replacement wheels and tires. In consideration of the foregoing, NHTSA has decided that the petitioner has met its burden of persuasion that the noncompliance described is inconsequential to motor vehicle safety. Accordingly, Honda's petition is granted and the petitioner is exempted from the obligation of providing notification of, and a remedy for, the noncompliance. (Authority: 49 U.S.C. 30118, 30120; delegations of authority at CFR 1.50 and 501.8). Issued on: January 8, 2007. Daniel C. Smith, Associate Administrator for Enforcement. [FR Doc. E7-316 Filed 1-11-07; 8:45 am] BILLING CODE 4910-59-P DEPARTMENT OF TRANSPORTATION Surface Transportation Board [STB Finance Docket No. 34554 (Sub-No. 6)] Union Pacific Railroad Company—Temporary Trackage Rights Exemption—BNSF Railway Company BNSF Railway Company (BNSF), pursuant to a modified written trackage rights agreement entered into between BNSF and Union Pacific Railroad Company (UP), has agreed to extend the expiration date of the local trackage rights granted to UP 1 over BNSF's line of railroad extending from BNSF milepost 579.3 near Mill Creek, OK, to BNSF milepost 631.1 near Joe Junction, TX, a distance of approximately 51 miles. 2 1 UP submits that the trackage rights being granted here are only temporary rights, but, because they are “local” rather than “overhead” rights, they do not qualify for the Board's class exemption for temporary trackage rights at 49 CFR 1180.2(d)(8). *See Railroad Consolidation Procedures* , 6 S.T.B. 910 (2003). Therefore, UP and BNSF concurrently have filed a petition for partial revocation of this exemption in STB Finance Docket No. 34554 (Sub-No. 7), *Union Pacific Railroad Company—Temporary Trackage Rights Exemption—BNSF Railway Company* , wherein UP and BNSF request that the Board permit the proposed local trackage rights arrangement described in the present proceeding to expire on or about December 31, 2007. That petition will be addressed by the Board in a separate decision. 2 The original trackage rights granted in *Union Pacific Railroad Company—Trackage Rights Exemption—The Burlington Northern and Santa Fe Railway Company* , STB Finance Docket No. 34554 (STB served Oct. 7, 2004), also extended from BNSF milepost 579.3 near Mill Creek, OK, to BNSF milepost 631.1 near Joe Junction, TX. By decisions served on November 24, 2004, in STB Finance Docket No. 34554 (Sub-No. 1), on March 25, 2005, in STB Finance Docket No. 34554 (Sub-No. 3), and on March 23, 2006, in STB Finance Docket No. 34554 (Sub-No. 5), the Board granted exemptions to permit the trackage rights authorized in STB Finance Docket No. 34554 and extended in STB Finance Docket No. 34554 (Sub-No. 2), served on February 11, 2005, and in STB Finance Docket No. 34554 (Sub-No. 4), served on March 3, 2006, to expire. At the time of the last extension, it was anticipated by the parties that the rights would expire on or about December 31, 2006. However, this authority has not yet been exercised. The transaction is scheduled to be consummated on January 28, 2007. The purpose of this transaction is to modify the temporary trackage rights exempted in STB Finance Docket No. 34554 (Sub-No. 4) to further extend the expiration date to on or before December 31, 2007. The modified trackage rights will permit UP to continue to move loaded and empty ballast trains for use in its maintenance-of-way projects. As a condition to this exemption, any employees affected by the trackage rights will be protected by the conditions imposed in *Norfolk and Western Ry. Co.—Trackage Rights—BN* , 354 I.C.C. 605 (1978), as modified in *Mendocino Coast Ry., Inc.—Lease and Operate* , 360 I.C.C. 653 (1980). This notice is filed under 49 CFR 1180.2(d)(7). If it contains false or misleading information, the exemption is void *ab initio* . Petitions to revoke the exemption under 49 U.S.C. 10502(d) may be filed at any time. The filing of a petition to revoke will not automatically stay the effectiveness of the exemption. Stay petitions must be filed by January 19, 2007 (at least 7 days before the exemption becomes effective). An original and 10 copies of all pleadings, referring to STB Finance Docket No. 34554 (Sub-No. 6), must be filed with the Surface Transportation Board, 1925 K Street, NW., Washington, DC 20423-0001. In addition, one copy of each pleading must be served on Gabriel S. Meyer, 1400 Douglas Street, STOP 1580, Omaha, NE 68179. Board decisions and notices are available on our Web site at *http://www.stb.dot.gov* . Decided: January 4, 2007. By the Board, David M. Konschnik, Director, Office of Proceedings. Vernon A. Williams, Secretary. [FR Doc. E7-163 Filed 1-11-07; 8:45 am] BILLING CODE 4915-01-P DEPARTMENT OF TRANSPORTATION Surface Transportation Board [STB Docket No. AB-6 (Sub-No. 446X)] BNSF Railway Company—Abandonment Exemption—in Beltrami Country, MN BNSF Railway Company

(BNSF)has filed a notice of exemption under 49 CFR 1152 Subpart F— *Exempt Abandonments* to abandon a 5.29-mile line of railroad between milepost 90.87 and milepost 95.15, including the 1.01-mile depot spur between milepost 94.78 and milepost 93.77, near Bemidji in Beltrami County, MN. The line traverses United States Postal Service Zip Code 56601. BNSF has certified that:

(1)No local traffic has moved over the line for at least 2 years;

(2)there is no overhead traffic on the line;

(3)no formal complaint filed by a user of rail service on the line (or by a state or local government entity acting on behalf of such user) regarding cessation of service over the line either is pending with the Surface Transportation Board or with any U.S. District Court or has been decided in favor of complainant within the 2-year period; and

(4)the requirements at 49 CFR 1105.7 (environmental report), 49 CFR 1105.8 (historic report), 49 CFR 1105.11 (transmittal letter), 49 CFR 1105.12 (newspaper publication), and 49 CFR 1152.50(d)(1) (notice to governmental agencies) have been met. As a condition to this exemption, any employee adversely affected by the abandonment shall be protected under *Oregon Short Line R. Co.—Abandonment—Goshen,* 360 I.C.C. 91 (1979). To address whether this condition adequately protects affected employees, a petition for partial revocation under 49 U.S.C. 10502(d) must be filed. Provided no formal expression of intent to file an offer of financial assistance

(OFA)has been received, this exemption will be effective on February 14, 2007, unless stayed pending reconsideration. Petitions to stay that do not involve environmental issues, 1 formal expressions of intent to file an OFA under 49 CFR 1152.27(c)(2), 2 and trail use/rail banking requests under 49 CFR 1152.29 must be filed by January 22, 2007. Petitions to reopen or requests for public use conditions under 49 CFR 1152.28 must be filed by February 1, 2007 with: Surface Transportation Board, 1925 K Street, NW., Washington, DC 20423-0001. 1 The Board will grant a stay if an informed decision on environmental issues (whether raised by a party or by the Board's Section of Environmental Analysis

(SEA)in its independent investigation) cannot be made before the exemption's effective date. *See Exemption of Out-of-Service Rail Lines,* 5 I.C.C.2d 377 (1989). Any request for a stay should be filed as soon as possible so that the Board may take appropriate action before the exemption's effective date. 2 Each OFA must be accompanied by the filing fee, which currently is set at $1,300. *See* 49 CFR 1002.2(f)(25). A copy of any petition filed with the Board should be sent to BNSF's representative: Sidney L. Strickland, Jr., PLLC, 3050 K Street, NW., Suite 101, Washington, DC 20007. If the verified notice contains false or misleading information, the exemption is void *ab initio.* BNSF has filed environmental and historic reports which address the effects, if any, of the abandonment on the environment and historic resources. SEA will issue an environmental assessment

(EA)by January 19, 2007. Interested persons may obtain a copy of the EA by writing to SEA (Room 500, Surface Transportation Board, Washington, DC 20423-0001) or by calling SEA, at

(202)565-1539. [Assistance for the hearing impaired is available through the Federal Information Relay Service

(FIRS)at 1-800-877-8339.] Comments on environmental and historic preservation matters must be filed within 15 days after the EA becomes available to the public. Environmental, historic preservation, public use, or trail use/rail banking conditions will be imposed, where appropriate, in a subsequent decision. Pursuant to the provisions of 49 CFR 1152.29(e)(2), BNSF shall file a notice of consummation with the Board to signify that it has exercised the authority granted and fully abandoned the line. If consummation has not been effected by BNSF's filing of a notice of consummation by January 12, 2008, and there are no legal or regulatory barriers to consummation, the authority to abandon will automatically expire. Board decisions and notices are available on our Web site at “ *WWW.STB.DOT.GOV.* ” Decided: January 4, 2007. By the Board, David M. Konschnik, Director, Office of Proceedings. Vernon A. Williams, Secretary. [FR Doc. E7-229 Filed 1-11-07; 8:45 am] BILLING CODE 4915-01-P DEPARTMENT OF THE TREASURY Submission for OMB Review; Comment Request January 8, 2006 The Department of the Treasury has submitted the following public information collection requirement(s) to OMB for review and clearance under the Paperwork Reduction Act of 1995, Public Law 104-13. Copies of the submission(s) may be obtained by calling the Treasury Bureau Clearance Officer listed. Comments regarding this information collection should be addressed to the OMB reviewer listed and to the Treasury Department Clearance Officer, Department of the Treasury, Room 11000, 1750 Pennsylvania Avenue, NW., Washington, DC 20220. DATES: Written comments should be received on or before February 12, 2007 to be assured of consideration. Internal Revenue Service

(IRS)*OMB Number:* 1545-1559. *Type of Review:* Extension. *Title:* Revenue Procedures 98-46 and 97-44, LIFO Conformity Requirement. *Description:* This document contains final regulations addressing the carry over of certain attributes, such as earnings and profits and foreign income tax accounts, when two corporations combine in a corporate reorganization or liquidation that is described in both section 367(b) and section 381 of the Internal Revenue Code. *Respondents:* Businesses and other for-profit institutions. *Estimated Total Burden Hours:* 100,000 hours. *OMB Number:* 1545-1130. *Type of Review:* Extension. *Title:* Special Loss Discount Account and Special Estimated Tax Payments for Insurance Companies. *Form:* 8816. *Description:* Form 8816 is used by insurance companies claiming an additional deduction under IRC section 847 to reconcile their special loss discount and special estimated tax payments, and to determine their tax benefit associated with the deduction. The information is needed by the IRS to determine that the proper additional deduction was claimed and to insure the proper amount of special estimated tax was computed and deposited. *Respondents:* Businesses and other for-profit institutions. *Estimated Total Burden Hours:* 1,983 hours. *OMB Number:* 1545-1706. *Title:* Revenue Procedure 2000-42 Section 1503(d) Closing Agreement Requests. *Type of Review:* Extension. *Description:* Revenue Procedure 2000-42 informs taxpayers of the information they must submit to request a closing agreement under Reg. S1.1503-2(g)(2)(iv)(B)(2)(i) to prevent the recapture of dual consolidated losses

(DCLs)upon the occurrence of certain triggering events. *Respondents:* Businesses and other for-profit institutions. *Estimated Total Burden Hours:* 2,000 hours. *OMB Number:* 1545-0240. *Title:* Claim for Refund of Income Tax Return Preparer Penalties. *Form:* 6118. *Type of Review:* Extension. *Description:* Form 6118 is used by preparers to file for a refund of penalties incorrectly charged. The information enables the IRS to process the claim and have the refund issued to the tax return preparer. *Respondents:* Individuals or Households. *Estimated Total Burden Hours:* 9,300 hours. *OMB Number:* 1545-1160. *Title:* CO-93-90 (Final) Corporations; Consolidated Returns-Special Rules Relating To Dispositions and Deconsolidations of Subsidiary Stock. *Type of Review:* Extension. *Description:* These regulations prevent elimination of corporate-level tax because of the operation of the consolidated returns investment adjustment rules. Statements are required for dispositions of a subsidiary's stock for which losses are claimed, for basis reductions within 2 years of the stock's deconsolidation, and for elections by the common parent to retain the NOLs of a disposed subsidiary. *Respondents:* Businesses and other for-profit institutions. *Estimated Total Burden Hours:* 6,000 hours. *OMB Number:* 1545-1724. *Title:* REG-109481-99 (Final) Special Rules Under Section 417(a)(7) for Written Explanations Provided by Qualified Retirement Plans After Annuity Starting Dates. *Type of Review:* Extension. *Description:* The collection of information requirement in sections 1.417(e)-1(b)(3)(iv)(B) and 1.417(e)-1(b)(3)(v)(A) is required to ensure that a participant and the participant's spouse consent to a form of distribution from a qualified plan that may result in reduced periodic payments. *Respondents:* Individuals or households. *Estimated Total Burden Hours:* 12,500 hours. *OMB Number:* 1545-1450. *Title:* FI-59-91 (Final), Debt Instructions With Originals Issue Discount; Contingent Payments; Anti-Abuse Rule. *Type of Review:* Extension. *Description:* The regulations provide definitions, general rules, and reporting requirements for debt instruments that provide for contingent payments. The regulations also provide definitions, general rules, and recordkeeping requirements for integrated debt instruments. *Respondents:* Businesses and other for-profit institutions. *Estimated Total Burden Hours:* 89,000 hours. *OMB Number:* 1545-1451. *Title:* REG-248900-96 (Final), Definition of Private Activity Bonds. *Type of Review:* Extension. *Form:* 8082. *Description:* Section 103 provides generally that interest on certain State or local bonds is excluded from gross income. However, under sections 103(b)(1) and 141, interest on private activity bonds (other than qualified bonds) is not excluded. The regulations provide rules, for purposes of section 141, to determine how bond proceeds are measured and used and how debt service for those bonds is paid or secured. *Respondents:* State, local, or tribal governments. *Estimated Total Burden Hours:* 30,100 hours. *Clearance Officer:* Glenn P. Kirkland,

(202)622-3428, Internal Revenue Service, Room 6516, 1111 Constitution Avenue, NW., Washington, DC 20224. *OMB Reviewer:* Alexander T. Hunt,

(202)395-7316, Office of Management and Budget, Room 10235, New Executive Office Building, Washington, DC 20503. Robert Dahl, Treasury PRA Clearance Officer. [FR Doc. E7-348 Filed 1-11-07; 8:45 am] BILLING CODE 4810-01-P DEPARTMENT OF THE TREASURY Community Development Financial Institutions Fund Proposed Collection; Comment Request ACTION: Notice and request for comments. SUMMARY: The Department of the Treasury, as part of its continuing effort to reduce paperwork and respondent burden, invites the general public and other Federal agencies to take this opportunity to comment on proposed and/or continuing information collections, as required by the Paperwork Reduction Act of 1995, Public Law No. 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the Community Development Financial Institutions Fund (the Fund) of the Department of the Treasury is soliciting comments concerning a voluntary information collection effort involving all Fund Programs. The specific information collection relates to the voluntary collection of narrative descriptions of projects financed by Fund awardees and allocatees in response to the public's request for better and more narrative information on impact and best practices associated with all of the Fund's Programs. The purpose is to more fully describe and record the innovative approaches community development financial institutions (CDFIs) and community development entities

(CDEs)use in revitalizing communities and serving families. Fund awardees and allocatees will be invited to submit narratives on one or more projects that they believe demonstrate best practices or high impact. The project description may be for a project previously reported to the Fund through the Community Investment Impact System

(CIIS)or for a new project that has not yet been reported in CIIS. The Fund plans to use the descriptions in Fund publications and on the Fund's Web site to highlight the work of its awardees and allocatees. DATES: Written comments should be received on or before March 13, 2007 to be assured of consideration. ADDRESSES: Direct all comments to Bob Ibanez, Financial and Program Analyst, Community Development Financial Institutions Fund, U.S. Department of the Treasury, 601 13th Street, NW., Suite 200 South, Washington, DC 20005, Facsimile Number

(202)622-7754. FOR FURTHER INFORMATION CONTACT: A draft of the information collection may be obtained from the Fund's Web site at *http://www.cdfifund.gov.* Requests for additional information should be directed to Bob Ibanez, Financial and Program Analyst, Community Development Financial Institutions Fund, U.S. Department of the Treasury, 601 13th Street, NW., Suite 200 South, Washington, DC 20005, or by phone to

(202)927-6232. SUPPLEMENTARY INFORMATION: *Title:* CDFI/CDE Project Profile Web Form. *Abstract:* The voluntary collection of narrative descriptions of projects financed by Fund awardees and allocatees via the CDFI/CDE Project Profile Web Form is in response to the public's request for better and more narrative information on impact and best practices associated with all of the Fund's Programs. The purpose is to more fully describe and record the innovative approaches community development financial institutions (CDFIs) and community development entities

(CDEs)use in revitalizing communities and serving families. Each best practice is generated by one or more of four CDFI Fund Programs: 1. Through the CDFI Program by directly investing in, supporting and training CDFIs that provide loans, investments, financial services and technical assistance to underserved populations and communities; 2. Through the New Markets Tax Credit

(NMTC)Program by providing an allocation of tax credit authority to community development entities

(CDEs)which enable them to attract investment from the private-sector and to reinvest these amounts in low-income communities; 3. Through the Bank Enterprise Award

(BEA)Program by providing an incentive to banks to invest in their communities and in other CDFIs; and 4. Through the Native American CDFI Assistance

(NACA)Program, by taking action to provide financial assistance, technical assistance, and training to Native CDFIs and other Native entities proposing to become or create Native CDFIs. *Current Actions:* Currently designing and test marketing the CDFI/CDE Project Profile Web Form. *Type of review:* New. *Affected Public:* CDFIs and CDEs; including business or other for-profit institutions, nonprofit entities, and State, local and Tribal entities. *Estimated Number of Respondents:* 100. *Estimated Annual Time per Respondent:* 2.5 Hours. *Estimated Total Annual Burden Hours:* 250 Hours. *Requests for Comments:* Comments submitted in response to this notice will be summarized and/or included in the request for OMB approval. All comments will become a matter of public record. Comments are invited on:

(a)Whether the collection of information is necessary for the proper performance of the functions of the agency, including whether the information shall have practical utility;

(b)the accuracy of the agency's estimate of the burden of the collection of information;

(c)ways to enhance the quality, utility, and clarity of the information to be collected; and

(d)ways to minimize the burden of the collection of information on respondents, including through the use of technology. Authority: 12 U.S.C. 4703, 4703 note, 4704, 4706, 4707, 4717; 12 CFR part 1805; Consolidated Appropriations Act of 2001, Pub. L. No. 106-554; 31 U.S.C. 321. Dated: January 4, 2007. Peter Dugas, Acting Director, Community Development Financial Institutions Fund. [FR Doc. E7-354 Filed 1-11-07; 8:45 am] BILLING CODE 4810-70-P 72 8 Friday, Jnauary 12, 2007 CORRECTIONS Amelia SECURITIES AND EXCHANGE COMMISSION [Release No. 34-54995; File No. SR-Amex-2006-77] Self-Regulatory Organizations; American Stock Exchange, LLC; Notice of Filing of Proposed Rule Change and Amendment No. 1 Thereto to Amend Rules 918 and 918—Ante Regarding Trading Rotations, Halts and Suspensions Correction In notice document E6-22398 beginning on page 78474 in the issue of Friday, December 29, 2006, make the following correction: On page 78474, in the second column, footnote 31 should be footnote 3. [FR Doc. Z6-22398 Filed 1-11-07; 8:45 am] BILLING CODE 1505-01-D Amelia SECURITIES AND EXCHANGE COMMISSION [Release No. 34-55002; File No. SR-NYSEArca-2006-32] Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Order Granting Accelerated Approval of Proposed Rule Change to Trade Various iShares® MSCI Index Funds Pursuant to Unlisted Trading Privileges Correction In notice document E6-22402 beginning on page 78503 in the issue of Friday, December 29, 2006, make the following correction: On page 78504, in the third column, footnote 87 should be footnote 8. [FR Doc. Z6-22402 Filed 1-11-07; 8:45 am] BILLING CODE 1505-01-D Amelia SECURITIES AND EXCHANGE COMMISSION [Release No. 34-54979; File No. SR-NFA-2006-05] Self-Regulatory Organization; National Futures Association; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change and Amendment No. 1 Thereto Relating to the Interpretive Notice Regarding Automated Order-Routing Systems Correction In notice document E6-22657 beginning on page 813 in the issue of Monday, January 8, 2007, make the following correction: On page 813, in the second column, footnote 21 should be footnote 2. [FR Doc. Z6-22657 Filed 1-11-07; 8:45 am] BILLING CODE 1505-01-D 72 8 Friday, January 12, 2007 Proposed Rules Part II Department of Health and Human Services Food and Drug Administration 21 CFR Parts 211, 226, 300, et al. Use of Materials Derived from Cattle in Medical Products Intended for Use in Humans and Drugs Intended for Use in Ruminants; Proposed Rule DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 211, 226, 300, 500, 530, 600, 895, and 1271 [Docket No. 2005N-0373] RIN 0910-AF54 Use of Materials Derived from Cattle in Medical Products Intended for Use in Humans and Drugs Intended for Use in Ruminants AGENCY: Food and Drug Administration, HHS. ACTION: Proposed rule. SUMMARY: The Food and Drug Administration

(FDA)is proposing to prohibit the use of certain cattle material in, or in the manufacture (including processing) of, drugs, biologics, and medical devices intended for use in humans and human cells, tissues, and cellular and tissue-based products (HCT/Ps) (collectively, medical products for humans), and in drugs intended for use in ruminant animals (drugs for ruminants). FDA is also proposing new recordkeeping requirements for medical products for humans and drugs for ruminants that are manufactured from or otherwise contain material from cattle. FDA is proposing these actions as part of its continuing efforts to strengthen defenses against the potential risk of exposure to, and spread of, bovine spongiform encephalopathy

(BSE)and related human disease in the United States. DATES: Submit written or electronic comments on the proposed rule by March 13, 2007. Submit written comments on the information collection requirements by February 12, 2007. Requests for an informal hearing on the proposed ban related to medical devices must be submitted by February 12, 2007. ADDRESSES: You may submit comments, identified by Docket No. 2005N-0373 and RIN number 0910-AF54, by any of the following methods: *Electronic Submissions* Submit electronic comments in the following ways: • Federal eRulemaking Portal: *http://www.regulations.gov* . Follow the instructions for submitting comments. • Agency Web site: *http://www.fda.gov/dockets/ecomments* . Follow the instructions for submitting comments on the agency Web site. *Written Submissions* Submit written submissions in the following ways: • FAX: 301-827-6870. • Mail/Hand delivery/Courier [For paper, disk, or CD-ROM submissions]: Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. To ensure more timely processing of comments, FDA is no longer accepting comments submitted to the agency by e-mail. FDA encourages you to continue to submit electronic comments by using the Federal eRulemaking Portal or the agency Web site, as described in the *Electronic Submissions* portion of this paragraph. *Instructions* : All submissions received must include the agency name and Docket No(s). and Regulatory Information Number

(RIN)(if a RIN number has been assigned) for this rulemaking. All comments received may be posted without change to *http://www.fda.gov/ohrms/dockets/default.htm* , including any personal information provided. For detailed instructions on submitting comments and additional information on the rulemaking process, see section VII “Effective Date and Opportunity for Public Comment” in the SUPPLEMENTARY INFORMATION section of this document. *Docket* : For access to the docket to read background documents or comments received, go to *http://www.fda.gov/ohrms/dockets/default.htm* and insert the docket number(s), found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Information Collection Provisions: To ensure that comments on the information collection are received, Office of Management and Budget

(OMB)recommends that written comments be faxed to the Office of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, FAX: 202-395-6974. FOR FURTHER INFORMATION CONTACT: *For information concerning products regulated by the Center for Drug Evaluation and Research* : Vikki Kinsey, Center for Drug Evaluation and Research (HFD-006), Food and Drug Administration, 5515 Security Lane, rm. 5110, Rockville, MD 20852, 301-443-5578, e-mail: *vikki.kinsey@fda.hhs.gov* . *For information concerning products regulated by the Center for Biologics Evaluation and Research* : Stephen M. Ripley, Center for Biologics Evaluation and Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, rm 594N, Rockville, MD 20852-1448, 301-827-6210, e-mail: *stephen.ripley@fda.hhs.gov* . *For information concerning products regulated by the Center for Devices and Radiological Health* : Scott G. McNamee, Center for Devices and Radiological Health, Food and Drug Administration, 2094 Gaither Rd., rm. 230, Rockville, MD 20850, 240-276-0105, e-mail: *scott.mcnamee@fda.hhs.gov* . *For information concerning products regulated by the Center for Veterinary Medicine* : Michael J. Popek, Center for Veterinary Medicine (HFV-144), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 301-827-6462, e-mail: *michael.popek@fda.hhs.gov* . SUPPLEMENTARY INFORMATION: Table of Contents I. Introduction II. Background A. Transmissible Spongiform Encephalopathies B. Bovine Spongiform Encephalopathy C. Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease D. BSE Risk Assessments 1. Harvard-Tuskegee Study 2. USDA Surveillance Program 3. BSE Testing for Product Safety Purposes 4. BSE Infectivity via Medical Products for Humans and Drugs for Ruminants E. Cattle Materials 1. Specified Risk Material 2. Small Intestine 3. Mechanically Separated Beef 4. Nonambulatory Disabled Cattle 5. Cattle Not Inspected and Passed for Human Consumption 6. Tallow and Tallow Derivatives 7. Fetal Calf Serum 8. Additional Requirements F. Medical Products for Humans and Drugs for Ruminants That May Contain Cattle Material 1. Drugs for Humans 2. Biologics for Humans 3. HCT/Ps 4. Medical Devices for Humans 5. Drugs for Ruminants III. USDA/FSIS IFR IV. FDA Actions on BSE A. Regulations 1. FDA 1997 Ruminant Feed Rule 2. FDA/USDA Animal Feed ANPRM and FDA 2005 Animal Feed Proposed Rule 3. Foods IFR 4. Foods Recordkeeping/Access Final Rule B. FDA Guidance V. Description of Proposed Rule A. Definitions B. Proposed Requirements for Prohibited Cattle Materials and Permission for an Exception or Alternative to These Requirements C. Tallow and Tallow Derivatives D. Proposed Requirements Regarding Extralabel Drug Use in Animals E. Proposed Recordkeeping Requirements 1. Types of Records 2. Proposed Periods for Records Retention 3. Location of Records VI. Legal Authority VII. Effective Date and Opportunity for Public Comment VIII. Analysis of Impacts A. Need for the Proposed Rule B. Scope of the Proposed Rule C. Costs of the Proposed Rule 1. Potential Market Adjustments 2. Cost of Requests for Exception or Alternatives to the Limitation on the Use of Prohibited Cattle Material 3. Cost of Substitutes 4. Recordkeeping Requirements of the Proposed Rule 5. Labeling Costs for Drugs Prohibited from Extralabel Use 6. Summary of the Cost for the Proposed Rule D. Benefits of the Proposed Rule 1. Reduced Risk of Exposure to BSE Infectivity 2. Value of the Potential Reduction of Human Illness E. Summary of the Potential Costs and Benefits of the Proposed Rule F. Regulatory Options Considered G. Regulatory Flexibility Analysis IX. Paperwork Reduction Act Analysis X. Environmental Impact Analysis XI. Federalism XII. References I. Introduction On January 26, 2004, the U.S. Department of Health and Human Services announced its plan to establish new safeguards to strengthen existing firewalls against transmission of BSE in the United States. Consumption of products contaminated with the agent that causes BSE has been linked to the human disease variant Creutzfeldt-Jakob disease (vCJD). Current protections against the spread of BSE in the United States include: • FDA's ruminant feed regulation (the 1997 ruminant feed rule) (62 FR 30936, June 5, 1997) (see section V.A.8 of this document for definition of ruminant), • U.S. Department of Agriculture's (USDA's) Food Safety and Inspection Service

(FSIS)interim final rule banning specified risk materials

(SRMs)and certain other cattle material in human food (the USDA/FSIS IFR) (69 FR 1862, January 12, 2004; as amended, 70 FR 53043, September 7, 2005), • FDA's interim final rule banning the use of SRMs and certain other cattle material in human food, including dietary supplements, and cosmetics (the Foods IFR) (69 FR 42256, July 14, 2004; as amended, 70 FR 53063, September 7, 2005), and • Import controls. FDA also has requirements for establishment and maintenance of records concerning use of materials derived from cattle in human food and cosmetics (the Foods Recordkeeping/Access final rule) (71 FR 59653, October 11, 2006). In addition, FDA, in conjunction with USDA, issued an advance notice of proposed rulemaking (ANPRM) to solicit comment on additional measures under consideration, including measures related to animal feeds (the joint ANPRM) (69 FR 42288, July 14, 2004). On October 6, 2005 (70 FR 58570), we issued a proposed rule that would prohibit certain cattle materials from all animal feed (FDA 2005 Animal Feed proposed rule). In this medical products proposed rule, FDA is proposing to prohibit use of SRMs and certain other cattle material in, or in the manufacture (including processing) of, medical products for humans and drugs for ruminants because of the risk of transmission of BSE. FDA is also proposing recordkeeping requirements for medical products for humans and drugs for ruminants that are manufactured from or otherwise contain material from cattle to ensure compliance with the prohibitions in this proposed rule. The proposed requirements are consistent with the requirements in the USDA/FSIS IFR and the Foods IFR, as well as those in the Foods Recordkeeping/Access final rule. The proposed requirements in this medical products proposed rule only apply to medical products for humans and drugs for ruminants. They do not apply to any other product regulated by FDA. II. Background A. Transmissible Spongiform Encephalopathies Transmissible spongiform encephalopathies

(TSEs)are fatal neurodegenerative disorders that have been identified in humans and a number of animal species (e.g., cattle, sheep, goats, elk, deer, cats, and mink), but primarily in ruminants (i.e., animals that have a stomach with four compartments, such as cattle and buffalo). A TSE is characterized by a long incubation period, followed by a shorter course of neurological symptoms, followed by death (Ref. 1). Postmortem histopathology of the brain tissue from humans and animals with TSEs is characterized by a sponge-like appearance of the brain and deposits of abnormal forms of certain cell-associated proteins (normal prion proteins) in the brain. TSEs in humans include CJD, vCJD, Gerstmann-Sträussler-Scheinker syndrome, kuru, fatal familial insomnia, and sporadic fatal insomnia (Ref. 8). Nonhuman TSEs include BSE in cattle, scrapie in sheep and goats, transmissible mink encephalopathy

(TME)in mink, feline spongiform encephalopathy

(FSE)in cats, and chronic wasting disease

(CWD)in deer and elk (Ref. 8). Scrapie and CWD occur, and TME has occurred, in the United States. On December 23, 2003, USDA diagnosed BSE in an adult cow in the United States that had been imported from Canada. Since then, USDA has confirmed two other cases of BSE in adult cows in the United States. One cow, which was diagnosed on June 24, 2005, was born and raised in Texas. The other cow, which was diagnosed on March 15, 2006, had been on a farm in Alabama for less than a year. The Texas cow was 12 years old and the Alabama cow was determined to be more than 10 years old. Therefore, both cows were born before the 1997 ruminant feed rule was in place. USDA determined that no part of the animals entered the human food or animal feed chains. The pathogenesis of TSEs is poorly understood. TSE agents resist complete inactivation by treatments that destroy conventional microorganisms, like bacteria and viruses. Thus, conventional microorganisms are not likely causes of TSEs (Ref. 9). The most widely accepted explanation for TSEs, the prion theory, suggests that the infectious agents of TSEs are abnormally folded forms of normal prion proteins (Refs. 10 and 11). Normal prion protein genes are found widely in nature. In mammals, normal prion proteins are primarily expressed in neurons, but also can be found in other tissues in lower concentrations, depending on the mammalian species (Ref. 12). It is not well understood how the abnormal folding of prion proteins occurs or why hosts cannot efficiently dispose of or develop immunity to these proteins. The current lack of an antemortem diagnostic test for TSEs in either humans or animals limits surveillance for these diseases, studies of disease pathogenesis, and other research efforts. Diagnosis is confirmed by special postmortem examination of brain tissue by identification of abnormal prion proteins in advanced stages of the disease. At earlier stages of disease development, abnormal prion proteins are undetectable in brain tissue. Presently, there are no effective treatments for TSEs, and all TSEs are invariably fatal (Ref. 1). B. Bovine Spongiform Encephalopathy BSE is a TSE of cattle with a long incubation period (up to 8 years or longer), most likely acquired following consumption of an animal product containing the BSE infectious agent (Refs. 13 and 14). The British Ministry of Agriculture, Fisheries and Food (now known as the Department for Environment, Food, and Rural Affairs) first recognized BSE as a distinct disease in November 1986. The clinical signs of BSE include behavioral, gait, and postural abnormalities. The disease usually presents in cattle as increased apprehension, increased reaction to sound and touch, and a swaying gait. These signs are accompanied by subtle changes in the normal behavior of the cow, such as separation from the herd while at pasture, disorientation, staring, and excessive licking of the nose or flanks. The disease progresses to stumbling and falling, and ends with seizures, coma, and death (Ref. 15). Experiments indicate that the infectious dose for cattle is very low. One gram of homogenized brain from affected cattle caused BSE in 7 out of 10 calves fed the brain sample. Six years after oral consumption of lower doses of brain material, 3 of 15 calves fed 0.1 gram, and 1 of 15 calves fed 0.01 gram, and 1 of 15 calves fed 0.001 gram (1 mg) of brain sample had developed the disease. This experiment is ongoing (Ref. 16). Epidemiological studies have characterized the outbreak of BSE in the United Kingdom as a prolonged epidemic in which early cases were seen simultaneously at various locations, but with all occurrences presumably due to a common point source of infection (Ref. 17). Consistent with this observation, the subsequent spread of BSE was associated with the feeding of meat-and-bone-meal from rendered BSE-infected cattle to non-infected cattle (Ref. 17). It appears likely that the BSE agent was transmitted among cattle at an increasing rate by ruminant-to-ruminant feeding until the United Kingdom ban on such practices went into effect in 1988 (Ref. 13). The United Kingdom instituted a ruminant-to-ruminant feed ban to stop the cycle of infection, restrict the geographic spread of the disease, and eliminate potential sources of new infections. Since BSE was first identified in the United Kingdom, approximately 185,000 cattle have been diagnosed with the disease there (Ref. 18). The precautionary slaughter of millions of British cows and increasingly stringent prohibitions on certain animal feeding practices appear to have slowed, but not eradicated, the BSE epidemic in the United Kingdom. In 1992 (the peak year of the epidemic), there were over 37,000 cases of BSE in the United Kingdom; in 2005, there were 225 cases (Ref. 18). The introduction of BSE into other countries presumably originated from their import of cattle, or animal feed made with cattle material, from the United Kingdom during the BSE epidemic (Ref. 13). In addition to the United Kingdom, BSE has been detected in indigenous cattle in Austria, Belgium, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Israel, Italy, Japan, Liechtenstein, Luxembourg, the Netherlands, Poland, Portugal, the Republic of Ireland, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United States (Ref. 19). C. Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease Creutzfeldt-Jakob Disease

(CJD)is a sporadic disease of humans that exists throughout the world with an annual incidence of approximately one case per million population (Ref. 10). The highest death rates in the United States and the United Kingdom occur in individuals between the ages of 60 and 70 (Ref. 20). Death generally occurs after less than a year of progressive neurological deterioration (Ref. 10). Early symptoms typically include changes in sleeping and eating patterns, followed by inappropriate behavior and eventual dementia, lack of coordination, and myoclonic spasms. CJD is always fatal (Ref. 20). The cause of sporadic CJD is not fully understood, but genetic susceptibility may play a role (Ref. 10). CJD has been inadvertently transmitted between humans during medical treatment or diagnostic procedures via contaminated neurosurgical instruments, transplants of dura mater and corneas, and injection of pituitary extract (Ref. 10). In April 1996, British scientists reported a previously undetected new vCJD in young patients, with symptoms somewhat different from sporadic CJD (Refs. 21 and 22). All cases of vCJD had histopathologic evidence of spongiform changes in the brain, but also showed formation of “florid” plaques (a core of amyloid protein with surrounding halos of vacuoles) not typically seen in other forms of CJD (Ref. 10). Clinically, vCJD usually begins with a psychiatric presentation, such as depression, anxiety, nightmares, or hallucinations. These symptoms are followed by memory impairment, then dementia in the late stages. The clinical course generally ranges from 9 months to 3 years before death occurs (Ref. 23). The probable incubation period for vCJD in humans may range from 5 to more than 20 years (Ref. 39). Scientists have concluded that exposure to the BSE agent is the most plausible explanation for the occurrence of vCJD (Refs. 24 through 27). Monkeys (genetically the closest animal model to humans) inoculated with samples of brain from BSE-infected cattle have been found to develop a TSE that is histopathologically similar to vCJD (Ref. 28), as have mice inoculated or fed with BSE-infected tissue (Ref. 29). Studies have shown that abnormal prion proteins from vCJD patients are molecularly similar to abnormal prion proteins from BSE-infected cattle, but different from abnormal prion proteins from patients with CJD (Ref. 23). Although the exact route of exposure is not known, most scientists believe that vCJD in humans has been caused by consumption of cattle products contaminated with the agent that causes BSE (Refs. 20, 30, and 31). There is thought to be a 10- to 10,000-fold increase in the amount of infectious material needed to cause illness in humans as compared with cattle because of the species barrier, although the European Commission's Scientific Steering Committee cautioned that this range is uncertain and in an unlikely, but worst case scenario, the species barrier may not exist (Ref. 40). As of August 2006, 162 probable and confirmed cases of vCJD have been reported in the United Kingdom (Ref. 32). In addition, there have been 15 vCJD cases in France, 3 in Ireland, 2 in the United States ,and 1 each in Canada, Italy, the Netherlands, Portugal, Japan, Spain, and Saudi Arabia (Refs. 33 through 38 and 70). The two cases in the United States, one of the three from Ireland, and the single cases from Canada and Japan are likely due to the individual's exposure to BSE in the United Kingdom (Refs. 34, 36, and 70). The infectious dose for humans is not known. Despite widespread exposure in the United Kingdom to BSE-contaminated meat products, only a very small percentage of the exposed population has been diagnosed with vCJD to date. This may reflect a partial species barrier to disease transmission from cattle to humans via the oral route of exposure (Ref. 40). D. BSE Risk Assessments 1. Harvard-Tuskegee Study In 1998, USDA asked the Harvard Center for Risk Analysis

(HCRA)and the Center for Computational Epidemiology at Tuskegee University to evaluate United States measures to prevent the spread of BSE to animals and humans if it were to occur in this country. The Harvard-Tuskegee risk assessment (the Harvard-Tuskegee study determined that the United States was highly resistant to any proliferation of BSE or a similar disease (Ref. 41). The risk assessment model also demonstrated that certain new control measures could reduce the small risk even further. The Harvard-Tuskegee study involved a probabilistic simulation model to determine the consequences of introducing BSE into the U.S. cattle population. This simulation indicated that, in a hypothetical situation in which 10 infected cattle were imported into the United States, on average only 4 new cases of BSE would arise, and the disease would be eliminated in 20 years. The Harvard-Tuskegee study determined that these new cases of BSE would most likely arise in the United States from incomplete compliance with the FDA 1997 ruminant feed rule (see section III.A.1 of this document), and also concluded that an epidemic of BSE in this country resulting from scrapie, CWD, or another TSE is unlikely. The Harvard-Tuskegee study estimated the number of cattle infectious doses that might be available for human exposure, but it did not estimate the likelihood of human disease from this exposure because the relationship between the two is not known. According to the study, the estimated total infectivity available for human exposure from the importation of 10 infected cattle is 39 cattle infectious doses over 20 years. The Harvard-Tuskegee study determined that the greatest sources of infectivity to consumers from food are direct consumption of cattle brain and spinal cord and also meat that contains central nervous system tissue from advanced meat recovery systems. The Harvard-Tuskegee study did not address potential human exposure to the BSE agent through food, medical products for humans, or drugs for ruminants that contain ingredients of bovine origin, such as gelatin (from bovine bones and hides), heparin and surfactants (from bovine lung), insulin (from bovine pancreas), hormones (from bovine urine and serum), enzymes (from bovine intestine), or glycosphingolipids (from bovine brains). The Harvard-Tuskegee study identified three pathways that could lead to cattle or human exposure to the BSE agent through food or feed:

(1)Noncompliance with the FDA 1997 ruminant feed rule prohibiting the use of certain proteins in feed for cattle and other ruminants;

(2)rendering of animals that die on the farm and use (through illegal diversion or cross-contamination) of the rendered product in ruminant feed; and

(3)the inclusion of high-risk tissues from cattle, such as brain and spinal cord, in products for human oral consumption. Evaluation of potential risk mitigation measures in the study found that a prohibition against rendering of animals that die on the farm would reduce the potential cases of BSE following hypothetical exposure by 82 percent. In addition, a ban on including SRMs (defined in the study as brain, spinal cord, gut, eyes, and advanced meat recovery products without reference to age of the animals at slaughter) in human and animal food would reduce potential BSE cases in cattle by 88 percent and potential human exposure to BSE by 95 percent. The Harvard-Tuskegee study also noted the value of ensuring that low-risk cattle tissues are not cross-contaminated with high-risk tissue. USDA recently released an updated version of the BSE risk assessment model and report, completed by HCRA (Ref. 42). USDA requested that HCRA utilize an updated risk assessment model to evaluate the impact of measures implemented after the discovery of a BSE-positive cow in Washington State in December 2003, and recommendations made by an international BSE panel. The updated risk assessment estimates that the measures adopted by USDA in January 2004 will result in a 99.6 percent (at the mean) relative reduction in potential human exposure to the BSE agent through consumption of beef and beef products. 2. USDA Surveillance Program The USDA has led targeted BSE surveillance efforts since 1990. On June 1, 2004, in response to a recommendation from the international scientific review panel that assessed USDA's investigation into the discovery of a BSE positive cow in Washington State on December 23, 2003, USDA began an enhanced BSE surveillance effort. This effort continued to focus on the targeted subpopulation of cattle, with a goal to obtain as many samples as possible from the targeted population, to help determine whether BSE is present in the United States. Targeted cattle are defined as nonambulatory cattle; cattle exhibiting signs of a central nervous system disorder; cattle exhibiting other signs that may be associated with BSE, such as emaciation or injury; or dead cattle. To date, USDA has sampled more than 700,000 targeted cattle, only two of which were positive for BSE (Ref. 43). A detailed analysis of surveillance data obtained through March 2006 concluded that the prevalence of BSE in the United States is less than one infected animal per million adult animals (Ref. 7). 3. BSE Testing for Product Safety Purposes No validated antemortem tests for BSE exist. The currently available postmortem tests, although useful for disease surveillance (i.e., determining the rate of disease in the population of cattle), are not appropriate as safety indicators for food, medical products for humans, or drugs for ruminants. This is due, in part, to limitations on the existing testing methods, which rely on the use of postmortem brain tissue. Experimental evidence demonstrates that, in cattle infected orally, certain potentially infective tissues (such as the distal ileum and tonsil) are the first tissues to accumulate infectivity in the incubation period and this infectivity occurs prior to any demonstrated infectivity in brain tissue (Refs. 3, 45, and 46). Therefore, tests conducted on brain tissue may not reflect accurately the potential infectivity in other tissues that develop infectivity earlier, such as the distal ileum. Development of effective safety indicators for food, medical products for humans, and drugs for ruminants will require improved understanding of the pathogenesis of the disease and improved laboratory methods. 4. BSE Infectivity via Medical Products for Humans and Drugs for Ruminants While BSE is usually a concern identified with food safety or animal health, medical products for humans or drugs for ruminants, because of the ways they are used or come into contact with the body, provide another route for human or ruminant exposure to the BSE infectious agent. Medical products for humans and drugs for ruminants may contain or be made using a variety of cattle-derived materials. Examples of materials that are sometimes derived from cattle and that are used in, or in the manufacture of, these products include gelatin, heparin, surfactants, hormones, enzymes, glycosphingolipids, amino acids, glycerol, detergents, blood, collagen, fetal calf serum, bovine meat, and tallow and tallow derivatives. The route by which TSE-contaminated material is introduced into a host is an important determinant of TSE transmissibility. Animal studies have indicated that injection of a TSE agent directly into the brain or spinal cord is the most efficient route of transmission, followed by intravenous, intraperitoneal, and subcutaneous routes, and then by the oral route (Refs. 2 and 47 through 56). Topical administration on intact skin is unlikely to lead to disease transmission, but topical products presumably can cause disease if administered to skin with cuts, abrasions, or open wounds, or if administered to the eyes or other mucosal tissue (Refs. 57 through 59). Currently, no validated method for testing products for humans and ruminants for the agent that causes BSE is available; therefore, we do not have a means of distinguishing products that contain infectious material from products that do not. End users (e.g., consumers, physicians, farmers, veterinarians) also often are not able to determine which products contain prohibited cattle materials and which products do not because such information is generally not included in product labels or labeling. For example, rendered material including brain and spinal cord may become an ingredient in a medical product for humans or a drug for ruminants, although its presence may not be indicated on the label. Furthermore, end users have no way to determine whether cattle material in these products was sourced from nonambulatory disabled cattle or from cattle that were not inspected and passed for human consumption. Based on what is known about transmission of BSE, there is risk of occurrence of vCJD in humans and of TSE in ruminants from the use of high-risk cattle-derived materials in medical products for humans and drugs for animals. While the results from USDA's ongoing testing are reassuring and so far have identified only two additional BSE-infected cows in the United States, one cannot rule out the possibility of future discovery of additional positive animals in the United States or in a country allowed to export cattle material to the United States, or of a future introduction of BSE. To provide consistent protection across the range of FDA-regulated products, it is necessary to put in place measures to reduce further the risk of spread of BSE in cattle and the risk of vCJD in humans. These risks may be reduced by restricting the use of high-risk cattle materials in the manufacture of drugs for ruminants and medical products for humans, similar to existing restrictions for food and cosmetics. E. Cattle Materials This proposed rule would apply to medical products for humans and drugs for ruminants that are manufactured from or otherwise contain certain cattle material. This section discusses the reasons for FDA's decision to propose to restrict the use of such material in medical products for humans and drugs for ruminants. 1. Specified Risk Materials This proposed rule would designate SRMs as prohibited cattle materials in medical products for humans and drugs for ruminants. Specified risk materials would be defined, consistent with the Foods IFR (69 FR 42256 at 42259 and 70 FR 53063 at 53064 through 53065; discussed in section IV.A.3 of this document) and the USDA/FSIS IFR (69 FR 1862 and 70 FR 53043; discussed in section III of this document) as the brain, skull, eyes, trigeminal ganglia (clusters of nerve cells connected to the brain that lie close to the exterior of the skull), spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia (clusters of nerve cells attached to the spinal cord that are contained within the bones of the vertebral column) of cattle 30 months and older, and the tonsils and distal ileum of the small intestine of all cattle. In a pathogenesis study in which cattle were orally inoculated with BSE and then one to three animals were killed and tested at sequential 4- to 6-month intervals, Wells et al. found infectivity using a mouse bioassay at 32 months postinoculation in brain, spinal cord, dorsal root ganglia, and trigeminal ganglia (Ref. 3). Unequivocal clinical disease was first observed at 38 months postinoculation. It is not known how representative these results are, given the extremely small number of cattle tested and the limitations inherent in the mouse bioassay. It also should be noted that only one animal was tested at 26 months postinoculation and no testing was performed again until 32 months postinoculation. Thus, no conclusion can be drawn as to when, in the period between 26 and 32 months postinoculation, infectivity appeared in the tested tissues. The studies will continue for several more years, using a more sensitive cattle assay, to determine if any of the tissues that initially did not appear to be infective actually contain low levels of infection (Refs. 2 through 6 and 60). Infectivity has also been found at 6 months postinoculation in distal ileum and at 10 months postinoculation in tonsils (Refs. 4 and 60). In cattle infected with BSE under field conditions (i.e., not intentionally exposed to BSE as part of an experiment), infectivity has been found in the brain, spinal cord, and retina of the eye in animals with clinical disease (Ref. 60). The Scientific Steering Committee of the European Union (Ref. 31) has reported on the proportion of total infectivity in various tissues. They estimate that in an animal with clinical disease, approximately 64 percent of the infectivity is in the brain, 26 percent is in the spinal cord, 4 percent is in the dorsal root ganglia, 2.5 percent is in the trigeminal ganglia, and 3 percent is in the distal ileum. The eyes are estimated to contain less than 1 percent of the infectivity. In 2003, P. J. Comer and P. J. Huntly reported generally similar estimates of infectivity (i.e., 60.2 percent in brain, 24.1 percent in the spinal cord, 3.6 percent in the dorsal root ganglia, 2.4 percent in the trigeminal ganglia and 9.6 percent in the distal ileum) (Ref. 44). Clinical cases of BSE in cattle under 30 months old are rare. For example, according to the United Kingdom's Department of Environment, Food and Rural Affairs, among the birth cohort of cattle in the United Kingdom that had the highest incidence of BSE (those born in 1987-88), cattle under 3 years old represented less than 0.16 percent of cattle with BSE (61 out of 39,140 cattle with BSE) (Ref. 61). Another report, looking at selected herds whose ages were known, found that in the first 6 months of 1989 and 1990, the BSE incidence in 2-year-old cattle (0.04 percent in 1989 and 0.05 percent in 1990) was approximately 15-fold lower than that in 3-year-old cattle (0.56 percent in 1989 and 0.86 percent in 1990), and was 45- to 75-fold lower than the incidence in 4-year-old cattle (2.83 percent in 1989 and 2.76 percent in 1990) (Ref. 62). Two-year-old cattle represented only about one-half of 1 percent of the total BSE cases in the selected herds in those 6-month periods. The incidence in 2-year-old cattle (0.01 percent) decreased considerably in 1991, presumably reflecting the fact that they were born after July 1988, when the United Kingdom instituted measures prohibiting the use of meat and bone meal in cattle feed. We recognize that certain tissue from infected animals will be infectious a number of months before the animals exhibit clinical symptoms. However, in BSE, as in other TSEs, the total amount of infectivity in an animal increases throughout the incubation period reaching the highest load when an animal begins to demonstrate clinical signs (Ref. 44). Because of this evidence combined with the very low incidence of clinical BSE in cattle younger than 30 months, we are proposing, consistent with the Foods IFR (69 FR 42256 at 42259) and the USDA/FSIS IFR (69 FR 1862), that brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia should be considered SRMs only in cattle 30 months and older. We include the skull and the vertebral column in the list of SRMs because, even though they have not been shown to harbor BSE infectivity, they contain tissues (i.e., brain and spinal cord) that have been shown to be infectious. We did not include, consistent with the Foods IFR (69 FR 42256 at 42259) and the USDA/FSIS IFR (69 FR 1862 at 1868), the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum as SRMs with the rest of the vertebral column because they do not contain spinal cord or dorsal root ganglia. As the science and epidemiology on this issue develop, FDA may find it necessary through future rulemaking to modify the tissues classified as SRMs and the age at which these tissues are classified as SRMs. Based on the previously mentioned experimental evidence indicating that tonsils become infective by 10 months postinoculation and distal ileum by 6 months postinoculation (Refs. 3 and 4), we are proposing, consistent with the Foods IFR (69 FR 42256 at 42259 and 70 FR 53063 at 53064 through 53065) and USDA/FSIS IFR (69 FR 1862 and 70 FR 53043), that the tonsil and distal ileum of the small intestine of all cattle be considered SRMs. 2. Small Intestine The small intestine is not considered prohibited cattle material if the distal ileum is removed by a procedure that removes at least 80 inches of the uncoiled and trimmed small intestine as measured from the caeco-colic junction and progressing proximally towards the jejunum or by a procedure that the establishment can demonstrate is equally effective in ensuring complete removal of the distal ileum. In this medical products proposed rule, we are proposing to prohibit the use of small intestine of all cattle in medical products for humans and drugs for ruminants if procedures that completely remove the distal ileum are not used. This provision is consistent with USDA (70 FR 53043) and FDA (70 FR 53063) requirements. . 3. Mechanically Separated Beef Mechanically Separated (Species) is a standardized food defined by USDA in 9 CFR 319.5 (see section V.A of this document for the proposed definition of mechanically separated beef). The standard does not limit the amount of spinal cord and dorsal root ganglia allowed in vertebral column used to produce the product. Consequently, mechanically separated beef may contain concentrated amounts of such tissues. Because we are proposing that spinal cord, dorsal root ganglia and vertebral column be considered SRMs, we are also proposing, consistent with the USDA/FSIS and Foods IFRs (69 FR 1862 at 1866 through 1867 and 69 FR 42256 at 42259), to include mechanically separated beef as a prohibited cattle material. 4. Nonambulatory Disabled Cattle Experience has shown that nonambulatory disabled cattle (see section V.A of this document for the proposed definition) are the population at greatest risk for harboring BSE. Surveillance data in the European Union in 2002 showed that there were 29 positive/10,000 tests for BSE among healthy-appearing cattle of all ages and 148 positive/10,000 tests for BSE among nonambulatory animals of all ages (Ref. 63). In Switzerland, sampling of particular populations of cattle revealed that BSE-positive animals were 49 to 58 times more likely to be found in the nonambulatory population than in the population selected for passive surveillance (Ref. 64). The Harvard-Tuskegee study estimated that, following importation of 10 infected cattle, a prohibition against rendering animals that die on the farm (these animals could be nonambulatory disabled) would decrease the number of new cases of BSE by 82 percent. Because typical clinical signs of BSE cannot always be observed in nonambulatory disabled cattle, and because evidence has indicated these cattle are more likely to have BSE than apparently healthy cattle, FDA is proposing, consistent with the Foods IFR (69 FR 42256 at 42259), to include material from nonambulatory disabled cattle as prohibited cattle materials. This proposal is also consistent with USDA's requirement that all nonambulatory disabled cattle presented for slaughter be condemned (69 FR 1862 at 1870 and 1871). 5. Cattle Not Inspected and Passed for Human Consumption Cattle that have not been inspected (see section V.A of this document for the proposed definition) are at higher risk of having BSE, as well as other diseases, because they will not have been examined by USDA for their disease status in general and potential for harboring BSE in particular. In addition, such cattle are likely to have died on the farm or en route to slaughter, and these animals are not eligible for inspection by USDA. For cattle that are inspected but not passed, a regulatory authority (USDA or other) has made a determination that they are not appropriate for use in human food (69 FR 42256 at 42259). Such a determination may be based, among other things, on evidence of a neurological disorder associated with a higher risk of BSE. Moreover, material from cattle not inspected or inspected and not passed for human consumption is prohibited from human food (69 FR 42256 at 42259). In this rulemaking, FDA is proposing to extend this prohibition to medical products for humans and drugs for ruminants. By requiring that material from cattle for use in medical products for humans and drugs for ruminants be inspected and passed for human consumption, we would minimize the risk to humans and ruminants of exposure to the agent that causes BSE. 6. Tallow and Tallow Derivatives Tallow is an animal-derived hard fat that has been heat processed; most tallow is derived from cattle. In this proposed rule, we use the term tallow to refer only to tallow derived from cattle. Any risk of BSE transmission from tallow is a result of protein that is present as an impurity in the tallow. Taylor et al. (Refs. 65 and 66) found in rendering studies with abnormal prion protein that the prion protein did not preferentially migrate into the fat fraction, but remained with the protein fraction. Therefore, there is no reason to believe that tallow is likely to contain unusually high amounts of prion protein as a constituent of the insoluble impurities fraction that remains in tallow after rendering. Taylor et al. (Refs. 65 and 66) also reported that the various rendering processes used for tallow production in the United Kingdom were sufficient to produce tallow that did not result in infection when injected into the brains of mice, even though the starting material was highly spiked with the scrapie agent. Wilesmith et al. (Ref. 67) noted that the geographical variation in the incidence of BSE in the United Kingdom was not consistent with the use of tallow in cattle feed and concluded that the most likely source of infection in cattle was BSE-contaminated meat and bone meal. The World Organisation for Animal Health

(OIE)(formerly the Office International des Epizooties), the international animal health standard setting body, categorizes tallow with insoluble impurities of no more than 0.15 percent as protein-free tallow and indicates that tallow that meets this standard can be safely consumed by animals, regardless of the starting materials (Ref. 68). FDA's Transmissible Spongiform Encephalopathies Advisory Committee (TSEAC) considered the safety of tallow in 1998 (Ref. 69). Although members of the TSEAC indicated that tallow is a food with extremely low risk of transmitting BSE to humans or animals, they did not see a need to change FDA's recommendation that tallow not be sourced from cattle born, raised, or slaughtered in countries where BSE is known to exist. Based on the research and the opinions noted previously that show that tallow is inherently a low risk material because of the procedures by which it is manufactured, we are proposing to permit tallow from any country to be used in medical products for humans and drugs for ruminants, as we have for human food and cosmetics (69 FR 42256 at 42260 and 42261), if it contains no more than 0.15 percent insoluble impurities regardless of the starting materials or if it otherwise complies with these regulations (e.g., made without the use of any prohibited cattle materials). We recognize that the TSEAC did not see a need to change FDA's tallow import policy, which recommended against use of tallow from cattle born, raised, or slaughtered in countries where BSE is known to exist. However, the TSEAC was not asked to provide recommendations regarding import of tallow that met our proposed requirements. We believe we are proposing a tallow standard for medical products for humans and drugs for ruminants that is consistent with statutory safety standards and the recommendations by OIE with respect to bovine-derived tallow to prevent BSE in cattle and vCJD in humans. Distinct from tallow are tallow derivatives. These derivatives are produced by subjecting tallow to chemical processes (hydrolysis, trans-esterification, or saponification) that involve high temperature and pressure. The TSEAC considered tallow derivatives in 1998 (Ref. 69) and determined that the rigorous conditions of manufacture are sufficient to further reduce the BSE risk in tallow derivatives. In addition, the OIE also recommends that derivatives of protein-free tallow be freely traded among countries because they pose an insignificant BSE risk to animals (Ref. 68). Because we believe that tallow has negligible risk of transmitting BSE, and tallow derivatives undergo additional processing, we do not believe that tallow derivatives pose a risk of transmitting the agent that causes BSE to humans. Therefore, we are proposing, consistent with the Foods IFR (69 FR 42256 at 42261), that tallow derivatives not be considered a prohibited cattle material. FDA proposes to clarify, as in the amendments to the Foods IFR (70 FR 53063), that the “no more than 0.15 percent insoluble impurities” restriction for tallow does not apply to tallow derivatives. 7. Fetal Calf Serum Current evidence suggests that cow-to-calf transmission of BSE is unlikely to occur (Refs. 14 and 46). Therefore, the serum of fetal calves is unlikely to contain any BSE infectious material, irrespective of the age of the mother. However, because fetal calf serum

(FCS)is generally collected from fetuses of dairy cows culled for low milk production or for health reasons, these cows are often considerably older than 30 months. FDA believes that manufacturers commonly take appropriate steps to prevent contamination of the FCS with specified risk materials from the mother. These steps include the normal dressing procedures used in slaughter houses, consisting of removing the uterus completely from the carcass and other viscera of cows that were inspected and passed, taking it to a separate space free of prohibited cattle materials for cardiac puncture, and collecting the fetal blood in a closed collection system using aseptic technique. Other procedures could also be used to provide adequate assurance that contamination has been prevented. 8. Additional Requirements If the agency finds that additional protections are needed for specific products or classes of products covered by applications (e.g., products with direct routes of exposure into the bloodstream or neural tissue such as injectable, ophthalmic, intranasal, or implanted FDA-regulated products), it intends to provide those protections through the application review process or through other means, such as special controls for Class II devices. The agency believes it is possible that injectable, ophthalmic, intranasal, or implanted FDA-regulated products that contain cattle material other than prohibited cattle materials and that do not have an FDA approval covering use of that material may appear to be adulterated or misbranded under certain circumstances. If the agency finds that classes of such products or specific products do not meet the applicable statutory standards, it may take action even if the products comply with the requirements in this proposed regulation. F. Medical Products for Humans and Drugs for Ruminants That May Contain Cattle Material 1. Drugs for Humans Under this proposed rule, drugs for humans cannot be manufactured from or otherwise contain prohibited cattle materials without written permission from FDA. For drugs subject to applications, the agency may provide additional protections through the application review process on a case-by-case basis to ensure that the products are safe and effective for their intended uses under section 505 of the Federal Food, Drug and Cosmetic Act (the act) (21 U.S.C. 355) and safe, pure, and potent under section 351 of the Public Health Service Act (the PHS Act) (42 U.S.C. 262). For drugs not subject to applications, if the agency finds that specific products or product classes do not meet the applicable statutory standards regarding adulteration and misbranding, it may take action even if the products comply with the requirements in this proposed rule. Many approved human drugs, as well as investigational human drugs, contain ingredients that are derived from cattle. Over the last 10 years, FDA has maintained a database that identifies these drugs and their cattle-derived ingredients. Based on the information in this database, we are aware of no approved drugs and no investigational drugs that are manufactured with cattle material that would be prohibited under this proposed rule based on the type of cattle tissue used. 1 1 All manufacturers would have to ensure that any cattle material they use comes from cattle that are inspected and passed and otherwise complies with the other requirements proposed in this rule. In addition to human drugs with approved applications, a number of human drugs are marketed without an approved application and, therefore, have not been subject to the new drug application

(NDA)review process (e.g., products marketed under FDA's over-the-counter

(OTC)monograph system, Active Pharmaceutical Ingredients, homeopathic preparations, or products that purport to be “grandfathered”). Although FDA's database of these products is incomplete, some of them may contain cattle materials that would be prohibited under this proposed rule. The requirements proposed in this rulemaking apply to all drugs for humans, including those marketed without an approved application. 2. Biologics for Humans Many biological products are manufactured with, or otherwise use, cattle-derived material because this material can provide necessary nutrients for cell growth. For example, microorganisms used for vaccine manufacture are typically grown under controlled conditions in media that may contain cattle materials. Animal-derived products used in vaccine manufacture include amino acids, glycerol, detergents, gelatin, enzymes, and blood. Cattle skeletal muscle is used to prepare broths used in certain complex media. Many microorganisms that are difficult to grow and cells that are used to propagate viruses require serum in the growth media, which is typically derived from cattle blood. Cattle-derived materials (e.g., fetal calf serum, insulin, aprotinin, enzymes) are often used in cell culture techniques to manufacture hematological, cell, and gene-therapy products. Manufacturers of licensed products and sponsors of investigational new drug products are currently requested to provide, in their biologics license application

(BLA)or investigational new drug application (IND), information regarding the source of all bovine-derived materials used in the manufacture of their product. This information is reviewed by FDA along with other information provided in the application. SRMs are not ordinarily used in the manufacture of biological products. Biological products that are not intended for use in or on the body (e.g., in vitro diagnostics) would not be subject to the provisions of this proposed rule. 3. HCT/Ps This proposed rule would affect all HCT/Ps. HCT/Ps are defined in part 1271 (21 CFR part 1271) as “articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. Examples of HCT/Ps include, but are not limited to, bone, ligament, skin, dura mater, heart valve, cornea, hematopoietic stem/progenitor cells derived from peripheral and cord blood, manipulated autologous chondrocytes, epithelial cells on a synthetic matrix, and semen or other reproductive tissue” (§ 1271.3(d)). Certain exceptions apply (§ 1271.3(d)(1) through (d)(7)). HCT/Ps are regulated according to a tiered, risk-based framework. HCT/Ps meeting the criteria listed in § 1271.10 (e.g., minimally manipulated, intended for homologous use only (i.e., perform the same basic function(s) in the recipient as in the donor), not combined with a drug or device, and not having a systemic effect) are regulated solely under the authority of section 361 of the PHS Act (42 U.S.C. 264). These “361” HCT/Ps are required to comply only with the applicable requirements in part 1271. Premarket review is not required for such products; therefore, FDA does not review any information regarding cattle-derived material that might be used in such products. This proposed rule would ban the use of prohibited cattle material in these products, which we believe would help reduce any possible BSE transmission through the use of “361” HCT/Ps manufactured using cattle-derived material. HCT/Ps that do not meet the criteria in § 1271.10 are regulated as drugs and devices under the act, and/or biological products under section 351 of the PHS Act and the act. Establishments that manufacture such HCT/Ps must comply with the requirements in subparts C and D of part 1271 in addition to all other applicable regulations, including submission of the appropriate premarketing applications, and are included in this proposed rule. Information regarding the use of cattle-derived material in the manufacture of such HCT/Ps would be submitted as part of the premarket review, giving us the opportunity to evaluate any potential for risk of BSE transmission. 4. Medical Devices for Humans The Center for Devices and Radiological Health

(CDRH)has an administrative database that FDA reviewers use to record PMA and 510(k) submissions. In 2002, FDA added an “animal tissue flag” to the CDRH administrative database. This “flag” indicates that the device contains or is manufactured with animal tissue of some kind; the species of animal tissue is not identified. The animal tissue flag has been recorded for 68 PMAs and 2,164 510(k)s. These numbers represent only devices for which PMAs or 510(k)s were filed since the animal tissue flag was added in 2002. They do not account for devices cleared or approved for marketing before that time that may contain or that may be manufactured with animal tissue. Examples of cattle material used in devices range from high risk tissues (such as bovine pituitary extract used as a component of growth media) used in a low risk clinical setting (such as a topical application), to low risk cattle tissues (such as collagen from cattle hide or muscle) used in a high risk clinical setting (such as direct application to the central nervous system). Premarket submissions for devices do not always include complete information about the source of animal components. In addition, not all devices are subject to premarket review, either because they are exempt from such review or because they have already been cleared or approved. FDA believes that it is important to help ensure that all devices that are intended for use in or on the body do not contain prohibited cattle materials. Examples of devices intended for use in or on the body include, but are not limited to, vascular grafts, bone fillers, lacrimal plugs, sutures, wound dressings, and heart valves (other than human heart valve allografts regulated solely under section 361 of the PHS Act). FDA has determined that the banning and recordkeeping provisions of this proposed rule are necessary to help ensure the safety of devices intended for use in or on the body. Medical devices that are not intended for use in or on the body (e.g., in vitro diagnostics, x-ray machines) would not be subject to the provisions of this proposed rule. FDA is not aware of any currently marketed device that is manufactured with cattle material that would be prohibited under this proposed rule. 5. Drugs for Ruminants The requirements proposed in this rulemaking would cover new animal drugs for ruminants. Ruminants present the highest risk of any animals for contracting BSE from prohibited cattle materials. Because FDA has other mechanisms to restrict the extralabel use of approved human and animal drugs that contain prohibited cattle materials in ruminants (see section V.D of this document), this proposed rule would only prohibit the use of certain cattle material in drugs intended for use in ruminants. Some drugs for ruminants may contain or be manufactured with cattle-derived materials. We are not aware of any drugs for ruminants that contain, as a component of the drug, cattle material that would be prohibited by the proposed rule. However, although the FDA animal drug database lists materials contained in drugs for animals, it does not identify materials that are used in the manufacture of drugs for animals but that are not intended to be components of the drug (e.g., materials used in fermentation or cell culture production of drugs for animals). Because the FDA database does not contain information on materials used in the manufacture of drugs for animals, we cannot definitively conclude that no drugs for ruminants are manufactured with the use of cattle material that would be prohibited by this proposed rule. However, based on our knowledge of the processes and materials used in manufacture of drugs for ruminants, as well as the fact that very little cattle material is prohibited if sourced from cattle that were inspected and passed and were younger than 30 months old when slaughtered, we do not believe that prohibited cattle material is needed in the manufacture (through fermentation, cell culture or otherwise) of drugs for ruminants. III. USDA/FSIS IFR On January 12, 2004, in response to the diagnosis of BSE in a cow in the United States, USDA published a series of interim final rules, including “Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle” (69 FR 1862). The USDA/FSIS IFR declared that SRMs were inedible and unfit for food and prohibited their use as human food. It also prohibited the use of the entire small intestine of all cattle in human food. In 2005, the USDA/FSIS IFR was amended, in part, to permit use of the small intestine of all cattle in human food if appropriate procedures are used to completely remove the distal ileum (70 FR 53043). In the Foods IFR, FDA extended similar protections to FDA-regulated human food and cosmetics. (See section IV.A.3 of this document for a discussion of the Foods IFR.) The USDA/FSIS and Foods IFRs will reduce but will not, by themselves, eliminate the use of prohibited cattle materials in domestic and imported FDA-regulated medical products for humans and drugs for ruminants. Even when excluded from human food produced in USDA-inspected establishments, prohibited cattle materials that have been denatured may leave the establishments for rendering or destruction. These materials, which previously have not been explicitly prohibited in medical products for humans and drugs for ruminants by FDA, might then be used in FDA-regulated medical products for humans and drugs for ruminants. Under the USDA/FSIS IFR, SRMs and carcasses of nonambulatory disabled cattle are designated as inedible. However, certain products, such as gelatin and collagen (which are both covered by the provisions of this medical products proposed rule) used in FDA-regulated medical products for humans and drugs for ruminants, have traditionally been produced from cattle material deemed inedible by the USDA. Therefore, such a designation by the USDA may not be enough to preclude use of prohibited cattle materials in FDA-regulated products without additional regulation by FDA. Furthermore, some cattle are not slaughtered under continuous USDA inspection (e.g., some are sent directly to rendering without first passing inspection). Cattle material from these animals, such as brains or bones, which include SRMs, could end up as starting material for medical products for humans and drugs for ruminants. If prohibited cattle materials were unlawfully used in FDA-regulated medical products for humans and drugs for ruminants, this proposed rule if finalized would facilitate FDA's ability to use the enforcement mechanisms of the act that apply to adulterated products (e.g., seizure) to prevent human or ruminant exposure to the prohibited cattle materials. Imported products also may contain the types of materials prohibited by the USDA, but would not fall within the scope of the USDA's import regulations either because of the nature of the products or their country of origin. Specifically, although both FSIS and USDA's Animal and Plant Health Inspection Service (APHIS) impose BSE-related prohibitions, these prohibitions collectively do not cover all FDA-regulated medical products for humans and drugs for ruminants. For example, APHIS' BSE-related restrictions on imports do not cover gelatin for human use (beyond requiring a permit) and apply only to a limited number of countries (9 CFR 94.18). IV. FDA Actions on BSE A. Regulations 1. FDA 1997 Ruminant Feed Rule In the **Federal Register** of June 5, 1997 (62 FR 30936), FDA published a regulation that prohibits, with some exceptions, the use of protein derived from mammalian tissue in feed for cattle and other ruminant animals (21 CFR 589.2000). The agency published the FDA 1997 ruminant feed rule to prevent the establishment and amplification of BSE in the United States and thereby minimize any risk to animals and humans. FDA recently proposed changes to these requirements to further strengthen the rule (see section IV.A.2 of this document). 2. FDA/USDA Animal Feed ANPRM and FDA 2005 Animal Feed Proposed Rule Following detection of BSE in an imported dairy cow in Washington State in December 2003, the Secretaries of the U.S. Departments of Agriculture and Health and Human Services announced a series of regulatory actions and policy changes to strengthen protections against the spread of BSE in U.S. cattle and against human exposure to the BSE agent. The Secretary of Agriculture also convened an international panel of experts on BSE to review the U.S. response to the Washington case and make recommendations that could provide meaningful additional public or animal health benefits. In the **Federal Register** of July 14, 2004 (69 FR 42287), FDA and USDA's FSIS and APHIS jointly published an ANPRM to solicit comment on additional measures under consideration based on those recommendations and other factors. FDA has since received comments on the joint ANPRM, and in the **Federal Register** of October 6, 2005 (70 FR 58570), published the FDA 2005 Animal Feed proposed rule to prohibit certain material from all animal food or feed. 3. Foods IFR In the **Federal Register** of July 14, 2004 (69 FR 42256), FDA published an IFR prohibiting the use of certain cattle material to address the potential risk of BSE in human food, including dietary supplements, and cosmetics. This rule took effect immediately upon publication. On September 7, 2005, FDA amended the Foods IFR to revise or clarify provisions with regard to:

(1)Use of small intestine (see section II.E.2 of this document)

(2)use of hide and hide-derived products (see section V.A of this document),

(3)use of milk and milk products (see section V.A of this document),

(4)source tallow for tallow derivatives (see section II.E.6 of this document), and

(5)testing method cited for determining the level of insoluble impurities in tallow (see section V.C of this document). As a result, cattle materials prohibited in human food and cosmetics include SRMs, small intestine of all cattle if procedures that completely remove the distal ileum are not used, material from nonambulatory disabled cattle, material from cattle not inspected and passed for human consumption, and mechanically separated beef. SRMs include the brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle 30 months and older; and the tonsils and distal ileum of the small intestine of all cattle. Prohibited cattle materials do not include tallow that contains no more than 0.15 percent insoluble impurities, tallow derivatives, hides and hide-derived products, and milk and milk products. This action was taken to minimize human exposure to materials that are highly likely to contain the BSE agent in cattle infected with the disease. 4. Foods Recordkeeping/Access Final Rule In the **Federal Register** of October 11, 2006 (71 FR 59653), FDA also published a final rule to require that manufacturers and processors of human food and cosmetics that are manufactured from, processed with, or otherwise contain, material from cattle establish and maintain records sufficient to demonstrate that the food and cosmetics are in compliance with the Foods IFR. FDA believes that records documenting the absence of prohibited cattle materials in human food and cosmetics are critical for manufacturers, processors, and FDA to ensure compliance with the ban on the use of prohibited cattle materials in the Foods IFR. FDA solicited comment on the types of records that may already be available to document the absence of prohibited cattle materials in human food and cosmetics and the types of records that could be established to document the absence of prohibited cattle materials in these FDA-regulated products. The effective date of the Foods Recordkeeping/Access final rule is January 9, 2007. Until the Foods Recordkeeping/Access final rule is effective, FDA is ensuring that it can enforce the new prohibitions in the Foods IFR through the provisions in that rule requiring that FDA be given access to any existing records relevant to compliance with the ban on prohibited cattle materials. This proposed rule for medical products for humans and drugs for ruminants is a companion to the Foods IFR and responds to the same public health concerns. This proposed rule serves as an additional safeguard to reduce human exposure to the agent that causes BSE that may be present in cattle-derived medical products for humans and drugs for ruminants that are from domestic and imported sources. B. FDA Guidance During the past decade, we have communicated with the public and manufacturers, applicants, importers, and processors of FDA-regulated human and animal products regarding appropriate steps to increase product safety and minimize the risk of products being contaminated with the BSE agent. Most of our communications have been in the form of letters and guidance to industry and import alerts. • November 1992—We wrote to manufacturers of dietary supplements to alert them to the developing concern about TSEs in animals and CJD in humans and recommended that they investigate the geographic sources of any bovine and ovine material used in their products. • December 1993—We wrote to manufacturers of drugs, biologics, and medical devices and recommended against the use of bovine-derived materials from cattle that have resided in, or originated from, BSE countries. • August 1994—We published a notice in the **Federal Register** (59 FR 44592, August 29, 1994) entitled “Bovine-Derived Materials; Agency Letters to Manufacturers of FDA-Regulated Products.” In the notice, we published the text of the November 1992 and December 1993 letters previously described and, in addition, the text of letters to manufacturers of FDA-regulated products for animals (August 17, 1994), and manufacturers and importers of dietary supplements and cosmetics (August 17, 1994). • October 1994—We issued Import Alert 17-04, which allowed for the detention, without physical examination, of bulk shipments of high-risk bovine tissues and tissue-derived ingredients from BSE countries. We have updated this alert whenever APHIS has revised the list of countries in 9 CFR 94.18. • October 1997—We published a notice of availability (62 FR 52345, October 7, 1997) of a guidance for industry entitled “The Sourcing and Processing of Gelatin to Reduce the Potential Risk Posed by Bovine Spongiform Encephalopathy

(BSE)in FDA-Regulated Products for Human Use.” The rule, if finalized, will supersede prior communications that address the same issues, including the communications identified previously. V. Description of Proposed Rule A. Definitions For the purposes of this regulation, we are proposing to define the terms “prohibited cattle materials,” “inspected and passed,” “mechanically separated beef,” “nonambulatory disabled cattle,” “specified risk materials,” “tallow,” “tallow derivative,” and “ruminant” (proposed §§ 300.200(a), 500.200(a), 600.16(a), 895.102(a) and 1271.470(a)). The proposed terms and definitions are the same as those used in the Foods IFR (69 FR 42256 and 70 FR 53063), except that we are now including in proposed § 500.200(a) a definition for ruminant and we have revised the definition of prohibited cattle materials as it relates to fetal calf material. We have also made minor editorial revisions to the definition of inspected and passed. The proposed definitions are consistent with definitions used by the USDA (69 FR 1862 and 70 FR 53043). 1. *Prohibited cattle materials* means specified risk materials, small intestine of all cattle if procedures that completely remove the distal ileum are not used, material from nonambulatory disabled cattle, material from cattle not inspected and passed, or mechanically separated beef. Prohibited cattle materials do not include tallow that contains no more than 0.15 percent insoluble impurities, tallow derivatives, hides and hide-derived products, and milk and milk products. Prohibited cattle materials also do not include materials obtained from fetal calves of cows that were inspected and passed as long as the materials were obtained by procedures adequate to prevent contamination with specified risk materials. With regard to hides and hide-derived products, we are proposing that these products not be included in the definition of “prohibited cattle materials.” We are proposing this exemption because cattle hide has been determined to be a tissue with negligible risk of transmitting the agent that causes BSE; the OIE recommends that it be freely traded regardless of the BSE risk status of the exporting countries. Even though we are proposing to exempt hides and hide-derived products from the provisions of this proposed rule, applicants and manufacturers would be required to take precautions to avoid cross contamination of hides and other nonprohibited cattle material with prohibited cattle material during slaughter and processing. With regard to milk and milk products, we are proposing that these products also not be included in the definition of “prohibited cattle materials.” We recognize that milk and milk products present a negligible risk of transmitting the agent that causes BSE. The OIE recommends that milk and milk products be freely traded among countries, regardless of the BSE risk status of the exporting country. In addition, the prohibitions for medical products for humans and drugs for ruminants applies to materials from cattle slaughtered on or after the effective date of the rule and is not meant to apply to milk and milk products, which come from live cattle. 2. *Inspected and passed* means that the material is from an animal that has been inspected and passed for human consumption by the appropriate regulatory authority, and at the time the animal was inspected and passed, it was found to be not adulterated. 3. *Mechanically separated beef* means a meat food product that is finely comminuted, resulting from the mechanical separation and removal of most of the bone from attached skeletal muscle of cattle carcasses and parts of carcasses, that meets the specifications contained in 9 CFR 319.5, USDA's regulation that prescribes the standard of identity for Mechanically Separated (Species). 4. *Nonambulatory disabled cattle* means cattle that cannot rise from a recumbent position or that cannot walk, including, but not limited to, those with broken appendages, severed tendons or ligaments, nerve paralysis, fractured vertebral column, or metabolic conditions. 5. *Specified risk material* means the brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle 30 months and older, and the tonsils and distal ileum of the small intestine of all cattle. 6. *Tallow* means the rendered fat of cattle obtained by pressing or by applying any other extraction process to tissues derived directly from discrete adipose tissue masses or to other carcass parts and tissues. Tallow must be produced from tissues that are not prohibited cattle materials or must contain not more than 0.15 percent insoluble impurities as determined by the method entitled “Insoluble Impurities” (AOCS Official Method Ca 3a-46), American Oil Chemists' Society (AOCS), 5th Edition, 1997, incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS Official Method Ca 3a-46. You may obtain copies of the method from AOCS ( *http://www.aocs.org* ) 2211 W. Bradley Ave., Champaign, IL 61821. Copies may be examined at the Center for Food Safety and Applied Nutrition's Library, 5100 Paint Branch Pkwy., College Park, MD 20740, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to: *http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html* . 7. *Tallow derivative* means any chemical obtained through initial hydrolysis, saponification, or trans-esterification of tallow; chemical conversion of material obtained by hydrolysis, saponification, or trans-esterification may be applied to obtain the desired product. 8. *Ruminant* means any member of the suborder of animals that has a stomach with four compartments (rumen, reticulum, omasum, and abomasum) through which feed passes in digestion. The suborder includes, but is not limited to, cattle, buffalo, sheep, goats, deer, elk, and antelopes. B. Proposed Requirements for Prohibited Cattle Materials and Permission for an Exception or Alternative to These Requirements USDA and FDA prohibit the use of SRMs, and mechanically separated beef in human food (69 FR 1862; 69 FR 42256). USDA also requires that all nonambulatory disabled cattle presented for slaughter be condemned (69 FR 1862), while FDA prohibits use of such cattle in human food (69 FR 42256). USDA and FDA permit use of the small intestine of all cattle in human food if appropriate procedures are used to completely remove the distal ileum (70 FR 53043; 70 FR 53063). FDA imposes these prohibitions for cosmetics as well, and also prohibits material from cattle not inspected and passed in both human food and cosmetics (69 FR 42256; 70 FR 53063). To ensure that the same materials are not incorporated into other FDA-regulated products, we are now proposing to prohibit the use of these materials in, or in the manufacture of, medical products for humans and drugs for ruminants. As with human food and cosmetics, we are proposing the following five categories of material as prohibited cattle materials:

(1)The small intestine from all cattle if procedures that would completely remove the distal ileum are not used,

(2)SRMs,

(3)mechanically separated beef,

(4)material from nonambulatory disabled animals, and

(5)material from cattle not inspected and passed. Scientists believe that the human disease vCJD is likely caused by the consumption of products contaminated with the agent that causes BSE. The relationship between the agent that causes BSE and human cases of vCJD has been described previously in section II.C of this document. Consumption of contaminated material is thought to cause illness in humans, although scientific research has not determined the infectious dose (see section II.C of this document), and there is not a test that would allow screening of cattle materials or derivative products for infectious material (see section II.D of this document). Therefore, we are proposing in § 300.200(b)(1) that, except as provided in proposed § 300.200(b)(2), no human drug be manufactured from or otherwise contain prohibited cattle materials obtained from cattle slaughtered on or after the effective date of the final rule based on this proposal. We are proposing similar limitations for other products: drugs for ruminants, human biological products (including blood products) and medical devices that are intended for use in or on the body, and HCT/Ps (defined at 21 CFR 1271.3(d)) (proposed §§ 500.200(b), 600.16(b), 895.102(b), and 1271.470(b)). With regard to HCT/Ps, this proposed prohibition (proposed § 1271.470(b)) applies to use of prohibited cattle materials in the manufacture of the HCT/P rather than the manufacture of the HCT/P from prohibited cattle materials because HCT/Ps exclude animal tissues (§ 1271.3(d)(2)(vi)). FDA is proposing to apply the requirements of this proposed rule to all products or components of products manufactured for use in the United States or imported into the United States. This proposed rule contains the basic requirements needed to provide further protection of humans and ruminants from the potential risks of BSE posed by the use of cattle material in the manufacture of these products. Additional measures that FDA determines are needed for individual products would be addressed on a case-by-case basis through the application review process. For non-application products, if the agency finds that specific products or product classes do not meet the applicable statutory standards regarding adulteration and misbranding, it may take action even if the products comply with the requirements in this proposed rule. The provisions in this proposed rule would apply to medical products for humans and drugs for ruminants that are manufactured from or that otherwise contain material from cattle slaughtered on or after the effective date of any final rule. The restrictions would not apply to such products (including cell lines used in the manufacture of products) that use or contain materials from cattle slaughtered before the effective date of any final rule. The proposed rule would provide applicants and manufacturers a mechanism for requesting FDA to grant written permission for an exception or alternative to the limitations on the use of prohibited cattle materials in medical products for humans or drugs for ruminants (proposed §§ 300.200(b)(2), 500.200(b)(2), 600.16(b)(2), 895.102(b)(2), and 1271.470(b)(2)). Applicants and manufacturers that choose to request such permission would be required to submit the request in writing to the applicable FDA Center with the requisite information as detailed below. For products subject to an application or premarket notification, this written request would be required to reference the product's application number. The Center Director may permit an exception or alternative to this proposed rule's limitation on the use of prohibited cattle materials upon the submitter's request or on his or her own initiative. Including the application number of the product in a written request for products subject to applications or premarket notifications would ensure that existing applications and clearances reflect when an exception or alternative to these proposed requirements has been submitted and when an exception or alternative has been approved. FDA expects that applicants or manufacturers may submit a request for an exception or alternative when filing a new application or premarket notification for a product containing cattle material that would be prohibited under this proposed rule. Applicants or manufacturers may also submit a request for an exception or alternative if an existing product contains prohibited cattle materials under this proposal. Although FDA believes it is unlikely that applicants or manufacturers who currently are not using prohibited cattle materials in their products will reformulate their products to include prohibited cattle materials, proposing to do so would require not only a request for an exception or alternative but also a supplement to the approved application or a new premarket notification, consistent with existing regulations. A request for an exception or alternative to the requirements would include:

(1)The reasons why an exception or alternative to the requirements is needed,

(2)a description of the product, including the type of prohibited cattle materials used in its manufacturing, its manufacturing and purification processes, and its route of administration,

(3)a description of the source of the prohibited cattle materials, including information on the location where the cattle were born, raised, and slaughtered and any other information relevant to the likelihood of the cattle having ingested material prohibited under § 589.2000, and

(4)any other relevant information (paragraphs (b)(2)(ii)(A) through ((b)(2)(ii)(C) and (b)(2)(ii)(E) of proposed §§ 300.200, 500.200, 600.16, 895.102, and 1271.470). For medical products for humans, the request would be required to include a description of how the requirement is not necessary based on the risks of the prohibited cattle materials in the product and the benefits of the product or how such restrictions are not necessary to ensure the safety of the product (paragraph (b)(2)(ii)(D) of proposed §§ 300.200, 600.16, 895.102, and 1271.470). For drugs for ruminants, the request would be required to include either:

(1)A description of how the requirements are not necessary:

(i)Based on the risks of the prohibited cattle materials in the product to the target animal and the benefits of the product to the target animal and

(ii)to ensure a reasonable certainty of no harm to humans from any food derived from the target animal to which the product was administered, or

(2)a description of how the requirements are not necessary to ensure the safety of the product with respect to both the target animal and any food derived from the target animal to which the product is administered (proposed § 500.200(b)(2)(ii)(D)). FDA would respond to all requests in writing and could impose conditions in granting a request. FDA could also grant permission for an exception or alternative to the requirements on its own initiative based on an evaluation of the criteria described previously. A record of any exception or alternative to the requirements in paragraph (b)(1) of proposed §§ 300.200, 500.200, 600.16, 895.102, and 1271.470 that is granted by FDA would be required to be maintained by the applicant or manufacturer under the proposed recordkeeping requirements discussed in section V.E of this document. Although FDA believes that exceptions or alternatives to the requirements of this proposed rule would be rare, the proposal would allow medical products for humans and drugs for ruminants to be manufactured from or otherwise contain prohibited cattle materials if the agency determines that the risk posed by the use of prohibited cattle materials in the product would be outweighed by the benefits of the particular product or if the agency determines that prohibiting the use of these materials would be otherwise unnecessary to ensure the safety of the product. In the case of drugs intended for use in food-producing ruminant species, the benefits of the product relate primarily to the target animal species (ruminants), whereas the risks relate to both the health of the target animal as well as the safety of the food derived from the target animal. However, the agency does not weigh the benefits of a drug to an animal against the risks of the drug to human health, but rather considers whether there is a reasonable certainty of no harm to humans from the use of the drug in animals. Therefore, the reasonable certainty of no harm standard would be applied when considering requests for exceptions or alternatives to the proposed requirements for drugs intended for use in food-producing ruminant species. In all cases, FDA intends to apply existing statutory safety standards in determining whether to grant a written request for an exception or alternative to the proposed limitations on the use of prohibited cattle materials. (See section V.E of this document for discussion.) In the joint ANPRM, USDA's FSIS sought comment on the issue of equivalence and BSE requirements (whether the agency should consider a country's BSE risk when determining whether a country has implemented equivalent sanitary measures to those required by the United States to prevent human exposure to the BSE agent) (69 FR 42287 at 42299 and 42300). In the Foods IFR, FDA sought comment on the standards that should be applied when determining another country's BSE status, providing an exemption for “BSE-free” countries, and how to determine that countries meet any standards that might be developed (69 FR 42256 at 42263). FDA here again requests comment on whether and, if so, on what basis to exempt products and components of products from “BSE-free” countries from our respective requirements related to BSE, including those issued by this proposed rule. Proposed §§ 211.116 and 226.60, which would be part of FDA's current good manufacturing practice

(CGMP)requirements for finished pharmaceuticals for humans and ruminants and for type A medicated articles for ruminants would prohibit use of certain cattle materials, as described in proposed §§ 300.200, 500.200 and 600.16. The CGMP requirements contain the minimum methods that must be used for the manufacture, processing, packing, or holding of a drug to ensure that the drug meets the quality and purity characteristics that it purports or is represented to possess. The CGMP requirements contained in part 211 (21 CFR part 211) apply to finished pharmaceuticals and components of finished pharmaceuticals for both humans and animals. The CGMP requirements contained in part 226 (21 CFR part 226) apply to Type A medicated articles. Type A medicated products are intended solely for use in the manufacture of another Type A medicated article or a Type B or Type C medicated feed. A Type A medicated article consists of a new animal drug(s), with or without carrier, with or without inactive ingredients. Type A medicated articles are new animal drugs, and the manufacture of a Type A medicated article requires an approved new animal drug application (21 CFR part 514). C. Tallow and Tallow Derivatives Tallow would be defined as “the rendered fat of cattle obtained by pressing or by applying any other extraction process to tissues derived directly from discrete adipose tissue masses or to other carcass parts and tissues” (proposed §§ 300.200(a)(6), 500.200(a)(6), 600.16(a)(6), 895.102(a)(6) and 1271.470(a)(6)). Tallow derivatives would be defined as any chemical obtained through initial hydrolysis, saponification, or trans-esterification of tallow; chemical conversion of material obtained by hydrolysis, saponification, or trans-esterification may be applied to obtain the desired product (proposed §§ 300.200(a)(7), 500.200(a)(7), 600.16(a)(7), 895.102(a)(7) and 1271.470(a)(7)). For the reason described in section II.K of this document, we are proposing that tallow with no more than 0.15 percent insoluble impurities and tallow derivatives would not be defined as prohibited cattle materials under this rule even when manufactured with prohibited materials (proposed §§ 300.200(a)(1), 500.200(a)(1), 600.16(a)(1), 895.102(a)(1) and 1271.470(a)(1)). (Tallow made without using prohibited cattle materials would not be subject to this purity requirement.) We are proposing that the insoluble impurities in tallow be measured by the method entitled “Insoluble Impurities” (AOCS Official Method Ca 3a-46), American Oil Chemists' Society (AOCS), 5th Edition, 1997, incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to the AOCS Official Method Ca 3a-46 (proposed §§ 300.200(a)(6), 500.200(a)(6), 600.16(a)(6), 895.102(a)(6) and 1271.470(a)(6)). The AOCS Official Method Ca 3a-46 is currently used by the domestic tallow industry. Reference to the AOCS Official Method Ca 3a-46 in this proposed definition does not exclude use of another method. Any testing method may be used that is equivalent to the AOCS Official Method Ca 3a-46 in accuracy, precision, and sensitivity. Those wishing to use an alternate test would be responsible for determining that it is equivalent to the AOCS Official Method Ca 3a-46; it would not be necessary for FDA to approve the use of an alternate test. Tallow that contains more than 0.15 percent insoluble impurities could be used if it complies with the proposed requirements for cattle materials in proposed § 300.200 for drugs for humans, proposed § 500.200 for drugs for ruminants, proposed § 600.16 for biological products, proposed § 895.102 for medical devices for humans that are intended for use in or on the body, and proposed § 1271.470 for HCT/Ps (e.g., made without the use of any prohibited cattle materials). We note that, regardless of its purity level, tallow to be used in medical products for humans and drugs for ruminants would be subject to the other provisions of the act and would be adulterated if, for example, it has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth (section 501(a)(2)(A) of the act)(21 U.S.C. 351(a)(2)(A)). D. Proposed Requirements Regarding Extralabel Drug Use in Animals In 1994, Congress enacted the Animal Medicinal Drug Use Clarification Act (AMDUCA)(Public Law 103-396). This act authorizes the extralabel use of approved animal and human drugs in animals. The act, as well as FDA regulations in part 530 (21 CFR part 530), sets out certain conditions for extralabel use and authorizes FDA to prohibit the extralabel use of approved animal or human drugs in animals. Because FDA, elsewhere in this proposed rule, would prohibit the use of certain cattle materials in drugs for ruminants only, the agency is concerned that ruminants could still be exposed to prohibited cattle materials through the extralabel use in ruminants of a drug that was approved for a nonruminant species. Also, the agency is concerned about the extralabel use in ruminants of a drug that was approved for humans to the extent an exception or alternative to these proposed requirements has been granted. Therefore, in order to prevent the intentional or unintentional use of a drug containing prohibited cattle materials in ruminants, FDA is proposing to revise § 530.41 to prohibit in ruminants the extralabel use of drugs containing prohibited cattle material and approved for use in other animals (nonruminants) or for humans (proposed § 530.41(c)). FDA is also proposing to add new § 530.42 that would require labels for drugs prohibited from extralabel use in ruminants and described under proposed § 530.41(c) to bear or be accompanied by labeling information to communicate to the user that extralabel use in ruminants is prohibited. The proposed regulation would require label information to include the statement “Federal law prohibits the extralabel use of this product in ruminants.” AMDUCA and the implementing regulation at § 530.11, however, prohibit the extralabel use of an approved new animal drug or human drug in or on animal feed. Since the extralabel use of all drugs in or on animal feed is excluded from the extralabel use provisions of AMDUCA, FDA believes it is unnecessary and potentially confusing to include the previous statement only on those feed products that contain drugs described in proposed § 530.41(c). Therefore, the labeling requirement under proposed § 530.42 would apply to all products that contain drugs described in proposed § 530.41(c) except those products used in or on an animal feed. FDA intends for sponsors of approved products that would be subject to proposed § 530.42 to revise their labeling by the effective date of the final rule based on this proposal. If necessary, FDA also would have the ability under proposed § 300.200(b)(2)(iii) to impose a labeling condition on a human drug regarding the extralabel use in ruminants of that human drug if an exception or alternative is granted. E. Proposed Recordkeeping Requirements We are proposing that applicants and manufacturers of medical products for humans and drugs for ruminants that are manufactured from or otherwise contain material from cattle be required to establish and maintain records that demonstrate that the material from cattle meets the requirements of this proposed rule (proposed §§ 300.200(c)(1), 500.200(c)(1), 600.16(c)(1), 895.102(c)(1) and 1271.470(c)(1)). Because at this time there is no way to screen reliably for the presence of the BSE agent or for the presence of prohibited cattle materials, applicants and manufacturers of medical products for humans and drugs for ruminants must depend on records from the suppliers of cattle material to demonstrate that their source material is free from prohibited cattle materials. Similarly, without adequate records, FDA may not know whether applicants and manufacturers of medical products for humans and drugs for ruminants have complied with the prohibitions against use of prohibited cattle materials. Therefore, under proposed §§ 300.200(c)(1), 500.200(c)(1), 600.16(c)(1), 895.102(c)(1) and 1271.470(c)(1), applicants and manufacturers of medical products for humans and drugs for ruminants that are manufactured from or otherwise contain material from cattle would be required to establish and maintain records sufficient to demonstrate that the medical products for humans and drugs for ruminants do not contain prohibited cattle materials. 1. Types of Records For example, to satisfy the requirement in proposed §§ 300.200(c)(1), 500.200(c)(1), 600.16(c)(1), 895.102(c)(1), and 1271.470(c)(1) that records show the absence of prohibited cattle materials, applicants and manufacturers of medical products for humans and drugs for ruminants that are manufactured from or otherwise contain brain from cattle would have to establish and maintain records to demonstrate, among other things, that the cattle brain used is not from cattle over 30 months of age. In general, we would expect that having the following types of records on FDA-regulated medical products for humans or drugs for ruminants containing cattle material would be sufficient to demonstrate that the product is not manufactured from and does not otherwise contain prohibited cattle materials: • A signed and dated affirmation (with contact information) by a slaughter establishment that cattle material supplied by that establishment in a particular shipment does not contain prohibited cattle materials. If two or more lots of cattle material from different slaughter establishments are pooled into a final product, then having records from each slaughter establishment should be sufficient. • For products containing tallow, records from a slaughter establishment affirming that the tallow was produced from material containing no prohibited cattle materials or records (i.e., signed, dated, with contact information) from the tallow supplier affirming that the tallow contains no more than 0.15 percent insoluble impurities (e.g., a certificate of analyses). • For products containing fetal calf materials, records from a slaughter establishment affirming that the fetal calf material was obtained:

(1)From cows that were inspected and passed and

(2)using procedures that ensure that the fetal material was not contaminated with prohibited cattle materials during slaughter or processing. Consistent with CGMP recordkeeping requirements, applicants and manufacturers who maintain documentation of compliance should maintain that information on a lot-by-lot basis. The lot-by-lot records would ensure that each time a shipment of cattle material is sent or received, there is documentation that a management official confirmed that the shipment was free of any prohibited cattle material. We request comments on alternative recordkeeping requirements that would ensure the requirements of the proposed rule would be met. We also request comments on whether existing recordkeeping practices include the required information and, if not, what changes the proposal would necessitate. In addition, we request comment on whether the rule should specifically require certain types of records. 2. Proposed Periods for Records Retention The following record retention time periods would be required by this proposal: • For drugs for humans, we are proposing, consistent with our CGMP regulations for these products (§ 211.180), to require that records be retained for at least 1 year after the expiration date of the drug (proposed § 300.200(c)(2)). • For drugs for humans lacking an expiration date, we are proposing, consistent with our CGMP regulations for these products (§ 211.180), to require that records be retained for at least 3 years after distribution of the last lot of the drug (proposed § 300.200(c)(2)). • For drugs for ruminants other than Type A medicated articles, we are proposing, consistent with our CGMP regulations for these products (§ 211.180), to require that records be retained for at least 1 year after the expiration date of the product (proposed § 500.200(c)(2)(ii)). Because all new animal drugs are required to have an expiration date, only the proposed 1-year records retention period would apply to all drugs for ruminants. • For Type A medicated articles intended for use in ruminants, records would be retained, consistent with our CGMP regulations for these products (§ 226.110), for at least 2 years after distribution by the manufacturer (proposed § 500.200(c)(2)(i)). • For human biological products, we reference 21 CFR 600.12(b) for consistency with established recordkeeping periods. Records would be retained for no less than 5 years after the records of manufacture have been completed or 6 months after the latest expiration date for the individual product, whichever represents a later date (proposed § 600.16(c)(2)). • For medical devices that are intended for use in or on the body, we reference 21 CFR 820.180(b) for consistency with established recordkeeping periods. Records would be retained for a period of time equivalent to the design and expected life of the device, but in no case less than 2 years from the date of release for commercial distribution by the manufacturer (proposed § 895.102(c)(2)). • For HCT/Ps, we reference § 1271.270(d) for consistency with established recordkeeping periods. Records would be retained for 10 years after their creation unless otherwise stated in part 1271 (proposed § 1271.470(c)(2)). As discussed previously, records documenting the absence of prohibited cattle materials in medical products for humans and drugs for ruminants are needed to help applicants and manufacturers ensure that they meet the proposed requirements of this rulemaking and to help FDA monitor compliance. It is important for recall purposes that records be retained for the likely period of time during which the product might be used, so that FDA can assess compliance with the requirements for cause or otherwise. The proposed timeframes for retaining records reflect the likely period of time during which medical products for humans and drugs for ruminants covered by this proposed rule might be used. The proposed timeframes for retaining records are consistent with the relevant CGMP requirements in current rules. Because of the lengthy incubation period of BSE (see section II.C of this document), we are requesting comment on whether records should be required for a longer period of time than proposed in this rulemaking. This may assist with traceback and may assist applicants and manufacturers in proving that their products are not the source of BSE infection. In the Foods Recordkeeping/Access final rule, we require that records for FDA-regulated human food and cosmetics be retained for 2 years after the date the records were created (21 CFR 189.5(c)(2) and 21 CFR 700.27(c)(2)). FDA is requiring this timeframe for these products so that the records will be available during the entire shelf life of the products covered by that rule. 3. Location of Records We are proposing that records be maintained at the applicant's or manufacturer's establishment or at a reasonably accessible location. Records would be considered to be reasonably accessible if they are accessible from an onsite location (proposed §§ 300.200(c)(3), 500.200(c)(3), 600.16(c)(3), 895.102(c)(3) and 1271.470(c)(3)). Electronic recordkeeping requirements for all types of FDA required recordkeeping are addressed under part 11 (21 CFR part 11). These requirements would pertain to any records that would be required by this proposed rule. Proposed §§ 300.200(c)(4), 500.200(c)(4), 600.16(c)(4), 895.102(c)(4) and 1271.470(c)(4) provide that records required by this subpart must be readily available to FDA for inspection and copying. All the records would be required to be in English. Because of inherent difficulties in accessing records maintained at foreign establishments, we are proposing requirements for importers of record of medical products for humans and drugs for ruminants (proposed §§ 300.200(c)(5), 500.200(c)(5), 600.16(c)(5), 895.102(c)(5) and 1271.470(c)(5)). When filing entry with the U.S. Customs and Border Protection, importers of record of a product manufactured from or otherwise containing cattle material would be required to affirm that the product for import was manufactured from or otherwise contains cattle material and affirm that the product was manufactured in accordance with proposed §§ 300.200(b), 500.200(b), 600.16(b), 895.102(b) and 1271.470(b), as applicable. If the product was manufactured from or otherwise contains cattle material, then the importer of record would be required, if requested, to provide to FDA within 5 days records that would be sufficient to demonstrate that the product was not manufactured from and does not contain prohibited cattle material. FDA expects that the content of these records would be the same as that described as being sufficient for domestic products. FDA believes 5 days is a reasonable amount of time for the importer of record to respond while still allowing FDA sufficient time to review the documents to make an initial admissibility decision before the conditional release period for the product expires. If the importer of record fails to provide FDA with the records within 5 days, the product would be subject to detention because it would appear to be adulterated, and the owner or consignee would be afforded notice and an opportunity for hearing in accordance with section 801(a) of the act (21 U.S.C. 381). VI. Legal Authority FDA has the authority to take the actions proposed in this rule under various statutory provisions. These provisions include sections 201, 301, 501, 502, 505, 512, 516, 519, 701, 704, and 801(a) of the act (21 U.S.C. 321, 331, 351, 352, 355, 360b, 360f, 360i, 371, 374, and 381(a)) and sections 351, 361, and 368 of the PHS Act (42 U.S.C. 262, 264, and 271). With respect to drugs for humans, including drugs that are biological products, FDA is proposing these regulations under the adulteration provision in section 501(a)(2)(B) of the act, and under sections 201, 505, 701(a) and (b), 704, and 801(a) of the act. Under section 501(a)(2)(B) of the act, FDA has the authority to impose requirements necessary to ensure that drugs meet the requirements of the act with respect to identity, strength, quality, and purity. Under section 501(a)(2)(B) of the act, a drug is adulterated if: “the methods used in, or the facilities and controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.” FDA is proposing to amend its CGMP regulations (proposed § 211.116) to prohibit the use of certain cattle materials in human drug products and components, including biological products, as provided by proposed §§ 300.200 and 600.16. Proposed §§ 300.200 and 600.16 would require that no drug or biological product “be manufactured from or otherwise contain prohibited cattle materials” unless FDA has granted a request for an exception or alternative to the requirements. Proposed § 211.116 would apply to drugs, including biological products, that are directly subject to the CGMP regulations. For drugs not directly subject to the CGMP regulations, such as active pharmaceutical ingredients and source materials, section 501(a)(2)(B) of the act supports the proposed requirements in §§ 300.200 and 600.16. As provided in proposed §§ 300.200(d) and 600.16(d), a drug or biological product that fails to comply with the requirements of §§ 300.200(b) and 600.16(b), respectively, would be adulterated under section 501(a)(2)(B) of the act. Because of the possibility of disease transmission to humans from exposure to prohibited cattle materials, prohibiting such cattle materials in drugs and biological products will help ensure that they meet the requirements of the act with respect to safety and have the identity, and meet the quality and purity characteristics they are purported or represented to possess. Section 201(p) of the act defines a new drug to include “[a]ny drug *** the composition of which is such that such drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling thereof ***.” Based on the scientific data and information available to FDA regarding the possibility of disease transmission to humans from exposure to prohibited cattle materials, under this proposed rule any human drug manufactured from, or otherwise containing, prohibited cattle materials is not generally recognized as safe and effective (GRAS/GRAE), and therefore is a new drug under section 201(p) of the act. Section 505(a) of the act requires that “[n]o person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application filed pursuant to subsection

(b)or

(j)[of section 505] is effective with respect to such drug.” Under section 505 of the act, new drug applications must demonstrate that a drug is safe and effective for its intended use(s). Because of the possibility of disease transmission to humans from exposure to prohibited cattle materials, prohibiting such cattle materials in drugs will help ensure that drugs are safe for their intended use(s). Based on the scientific data and information available to FDA regarding the possibility of disease transmission to humans from exposure to prohibited cattle materials, under this proposed rule FDA would not approve an application or supplement for a drug containing prohibited cattle materials unless an exception or alternative has been granted based upon the Center Director's determination that the safety standard in section 505 of the act would still be met. In addition, under the proposed rule, a drug containing prohibited cattle materials that is already subject to an approval would no longer be shown to be safe based on the presence of prohibited cattle materials, and would be in violation of section 505 of the act unless an exception or alternative for use of the prohibited cattle materials has been granted. Section 505 of the act also allows FDA to impose additional conditions on an application product on a case-by-case basis, should such conditions be necessary to ensure that the product meets the standard for approval set forth in section 505 of the act. Under section 701(a) of the act, FDA is authorized to issue regulations for the act's efficient enforcement. The proposed regulations would require measures to ensure that drugs for humans, including biologics, are being manufactured, processed, packed, or held in conformity with CGMP, and to ensure that new drugs comply with section 505 of the act, which would allow for efficient enforcement of the act. Under the proposed regulations, applicants and manufacturers of drugs for humans that are manufactured from or otherwise contain material from cattle also would be required to establish and maintain records that document the absence of prohibited cattle materials in such products and have such records readily available to FDA for inspection and copying. These proposed recordkeeping requirements are also authorized under sections 501(a)(2)(B) and 505(k) of the act. Once material is removed from cattle, we may not be able to obtain the information necessary to determine whether it is prohibited cattle material. For example, we would not know from examination of a spinal cord whether the source animal was 30 months of age or over at the time of slaughter, or whether it was inspected and passed. Because at this time there is no way to test reliably for the presence of the BSE agent or the presence of the cattle materials prohibited in proposed § 300.200, applicants and manufacturers of drugs for humans would have to depend on records from their suppliers of cattle materials to ensure that their source material does not contain any cattle materials prohibited under proposed § 300.200. Without adequate records, FDA cannot know whether applicants and manufacturers of drugs for humans have complied with the prohibitions against certain cattle materials under proposed § 300.200. Therefore, the proposed recordkeeping requirements are necessary for the efficient enforcement of these rules and authorized under section 701(a) of the act. Under proposed § 300.200(e) and 600.16(e), the failure of an applicant or manufacturer to comply with the requirements of §§ 300.200(c) and 600.16(c), respectively, would render a drug or biological product adulterated. We are also proposing provisions relating to records regarding imported drugs for humans under sections 801(a) and 701(b) of the act. Importers of record of such a drug product manufactured from or otherwise containing cattle material would be required to affirm that such a drug product for import was manufactured from or contains cattle material, and affirm that it was manufactured in compliance with the proposed rule. If such a drug was manufactured from or otherwise contains cattle material, then importers of record would also be required, if requested, to provide records to FDA within 5 days sufficient to demonstrate compliance. Under proposed §§ 300.200(f) and 600.16(f), failure of an importer of record to comply with those requirements causes a drug for humans to appear to be adulterated. Section 801(a) of the act provides requirements with regard to imported drugs and provides for refusal of admission into the United States of drugs for humans that appear to be adulterated. Section 701(b) of the act authorizes the Secretaries of Treasury 2 and Health and Human Services to jointly prescribe regulations for the efficient enforcement of section 801 of the act. 2 Under the Homeland Security Act of 2002 (Public Law 107-296), the Secretary of the Treasury has delegated all relevant Customs revenue authorities to the Secretary of Homeland Security, who has, in turn, delegated them to the Commissioner of Customs and Border Protection (CBP or Customs). If finalized, we will issue this rule jointly with the Department of Homeland Security. Because most biological products, including blood, are also drugs, the sections of the act discussed previously provide legal authority for issuing a regulation limiting the use of prohibited cattle materials in such biological products. There is, however, additional legal authority for the proposed rule's requirements with respect to biological products generally. Section 351(a)(2)(A) of the PHS Act (42 U.S.C. 262(a)(2)(A)) requires that FDA “establish, by regulation, requirements for the approval, suspension, and revocation of biologics licenses.” Approval of a biologics license application

(BLA)must be based on a demonstration that the biological product is “safe, pure, and potent” (section 351(a)(2)(C)(i)(I) of the PHS Act). Limiting the use of prohibited cattle materials in biological products is designed to ensure the safety, purity, and potency of such licensed biological products. Based on the scientific data and information available to FDA regarding the possibility of disease transmission to humans from exposure to prohibited cattle materials, under the proposed rule FDA would not approve a BLA or supplement for a biological product containing prohibited cattle materials unless an exception or alternative has been granted based upon the Center Director's determination that the safety standard in section 351(a)(2)(C) of the PHS Act would still be met. In addition, under the proposed rule, a biological product containing prohibited cattle materials that is already licensed would no longer be demonstrated to be safe based on the presence of prohibited cattle materials, and would be in violation of section 351(a)(1) of the PHS Act and section 505 of the act, unless an exception or alternative for use of the prohibited cattle materials has been granted. Accordingly, FDA is proposing to amend its biological product regulations to prohibit the use of certain cattle materials in biological products as provided by proposed § 600.16. With respect to devices, FDA is proposing to issue these regulations under the adulteration provision in section 501(g) of the act, under the misbranding provision in section 502(t) of the act, and under sections 516, 519(a), 701(a) and (b), and 801 of the act. Under section 516 of the act, FDA may issue a regulation making a device a banned device if the agency determines, on the basis of all available data and information, that a device presents an unreasonable and substantial risk of illness or injury that can not be corrected or eliminated by labeling. A banned device is deemed adulterated under section 501(g) of the act. There are several routes through which devices intended for use in or on the body have the potential to introduce the BSE agent into humans if the devices contain prohibited cattle materials. It is well documented that central nervous system tissue, including the optic nerve, carries infectivity in animals with TSEs and humans with vCJD. Infectivity has also been transmitted to animals via mucosal tissue. Finally, although transmission through intact skin is not likely, the BSE agent has the potential to be introduced into the body through cut or abraded skin. FDA has concluded, therefore, that devices intended for use in or on the body that contain prohibited cattle materials have the potential to expose recipients of those devices if the originating cattle had BSE. Although the over all risk of exposure is low given the low rate of BSE in U.S. cattle, this risk is deemed unacceptable given the fatal nature of vCJD. The agency is not aware of any device that can be manufactured only with prohibited cattle materials; thus, there should be no benefit to the public health from the continued marketing of devices containing these materials. FDA has determined, therefore, that devices intended for use in or on the body that contain prohibited cattle materials present an unreasonable risk to health in relation to the benefit to the public health from their continued marketing. Moreover, because there is no safe way to use these devices, the risk of disease cannot be corrected or eliminated by labeling. It is clear, based on all available data and information, that the risk of BSE exposure may be significantly reduced by banning devices intended for use in or on the body that contain prohibited cattle materials. The agency is proposing to ban such devices, therefore, in accordance with section 516 of the act. Devices already in commercial distribution or already sold to the ultimate user are not subject to this ban because FDA is not aware of any currently marketed device that contains prohibited cattle materials. Manufacturers currently are not required to maintain records that contain information about bovine materials that would be needed to identify devices that might contain such materials. In accordance with section 516 of the act and 21 CFR part 895, interested persons may request an informal hearing on the provisions of the proposed regulation with respect to medical devices within 30 days. If a request for an informal hearing is granted, the hearing will be conducted as a regulatory hearing under 21 CFR part 16. The proposed recordkeeping requirements for devices in this proposed rule are authorized under section 519(a) of the act. Under section 519(a), the agency may, by regulation, require that manufacturers and importers establish and maintain records, make reports, and provide information that the agency determines is necessary to ensure that devices are not adulterated or misbranded and to otherwise ensure their safety and effectiveness. FDA has determined that the recordkeeping requirements in this proposed rule are necessary to ensure that devices intended for use in or on the body do not contain prohibited cattle materials and, thus, are not adulterated under section 501(g) of the act. A device for which there is a failure or refusal to furnish any material or information required under this proposed regulation would be deemed misbranded under section 502(t) of the act. The proposed recordkeeping requirements are also authorized under sections 701(a) and

(b)and 801(a) of the act. Because at this time there is no way to screen reliably for the presence of the BSE agent or the presence of the cattle materials prohibited under this proposed rule, applicants and manufacturers of medical devices would have to depend on records from their suppliers of cattle materials to ensure that their source material does not contain any prohibited cattle materials. The proposed requirements also would allow the agency to monitor compliance with the proposed ban and, therefore, are necessary for the efficient enforcement of the act, in accordance with section 701(a) of the act. Section 801(a) of the act contains requirements with regard to imported devices and provides for refusal of admission into the United States of devices that appear to be adulterated or misbranded. Section 701(b) of the act authorizes the Secretaries of the Treasury and Health and Human Services to jointly prescribe regulations for the efficient enforcement of section 801 of the act. With respect to new animal drugs, FDA is proposing to issue these regulations under the adulteration provision in section 501(a)(2)(B) of the act and sections 512, 701(a) and

(b)and 801(a) of the act. The adulteration provision in section 501(a)(2)(B) of the act provides FDA the same authority for new animal drugs as described for drugs for humans previously in this document. FDA is proposing to amend its CGMP regulations to prohibit the use of certain cattle materials in drug products and components intended for use in ruminant animals (proposed § 211.116). Proposed § 500.200 would require that no drug product or component intended for use in ruminants “be manufactured from or otherwise contain prohibited cattle materials.” Proposed § 211.116 would apply to drugs that are directly subject to the CGMP regulations. For drugs for ruminants that are not directly subject to the CGMP regulations, section 501(a)(2)(B) of the act supports the proposed requirements in proposed § 500.200. As provided in proposed § 500.200(d), a drug that fails to comply with the requirements of § 500.200(b) would be adulterated under section 501(a)(2)(B) of the act. Because of the possibility of disease transmission to ruminants from exposure to prohibited cattle materials and to humans from consuming food from animals exposed to prohibited cattle material, prohibiting such cattle materials in drugs for ruminants would help ensure that new animal drugs for ruminants meet the requirements of the act with respect to safety, and have the identity, and meet the quality and purity characteristics they are purported or represented to possess. Section 201(v) of the act defines a new animal drug to include “[a]ny drug intended for use for animals other than man *** the composition of which is such that such drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling thereof ***.” Based on the scientific data and information available to FDA regarding the possibility of disease transmission to ruminants from exposure to prohibited cattle materials, under this proposed rule any drug for ruminants manufactured from or otherwise containing prohibited cattle materials is not GRAS/GRAE, and therefore is a new animal drug under section 201(v) of the act. Section 512 of the act provides that a new animal drug is unsafe for purposes of the adulteration provisions in section 501(a)(5) and section 402(a)(2)(C)(ii) of the act (21 U.S.C. 342(a)(2)(c)(ii)) unless there is an approval of that new animal drug application in effect. For a new animal drug application to be approved, the drug must be safe and effective for its intended use(s). Based on the scientific data and information available to FDA regarding the possibility of disease transmission to humans from exposure to prohibited cattle materials, under the proposed rule FDA would not approve an application or supplement for a drug for ruminants containing prohibited cattle materials unless an exception or alternative has been granted based upon the Center Director's determination that the safety standard in section 512 of the act would still be met. In addition, under the proposed rule, a drug for ruminants containing prohibited cattle materials that is already subject to an approval would no longer be shown to be safe based on the presence of prohibited cattle materials, and would be in violation of section 512 of the act unless an exception or alternative for use of the prohibited cattle materials has been granted. Under section 512(a)(4) and section (a)(5) of the act, extralabel use of an approved animal drug or human drug in animals is authorized if done under certain conditions set out in FDA regulations. However, section 512(a)(4)(A) of the act also allows FDA to prohibit particular extralabel uses of an approved new animal drug. Thus, for example, a drug approved for use in treating an animal of a nonruminant species could legally be used extralabelly to treat a ruminant animal, if it meets required conditions, unless specifically prohibited. Such drugs for nonruminant animals are allowed to contain cattle materials prohibited from use in drugs for ruminants. Absent a special prohibition, these drugs also could be used in ruminants, through extralabel use, thereby providing an avenue through which ruminants could be exposed to prohibited cattle material. Any human drug for which an exception or alternative is granted could also be used extralabelly in ruminants, which could also provide another avenue through which ruminants could be exposed to prohibited cattle materials. Therefore, under section 512(a)(4)(A) of the act (for drugs for animals) and section 512(a)(5) of the act (for drugs for humans), FDA is proposing to prohibit such extralabel use in ruminants of drugs for nonruminants or for humans containing the prohibited material. FDA is issuing the proposed labeling requirement under sections 502(a) and 201(n) of the act (21 U.S.C. 352(a) and 321(n)). Section 502(a) provides that a drug is deemed misbranded if its labeling is false or misleading in any particular. Section 201(n) provides that “*** in determining whether the labeling *** is misleading, there shall be taken into account (among other things) not only representations made or suggested by statement, word, design, device, or any combination thereof, but also the extent to which the labeling *** fails to reveal facts material in the light of such representations or material with respect to consequences which may result from the use of the article to which the labeling *** relates under the conditions of use *** as are customary or usual.” The proposed rule would require drugs for non-ruminants that contain prohibited materials that are prohibited from extralabel use in ruminants to be labeled “Federal law prohibits the extralabel use of this product in ruminants.” We believe this statement is material with respect to the consequences that may result from the extralabel use of nonruminant drugs with prohibited materials in ruminants. As discussed in other sections of this preamble, the use of materials prohibited in drugs for ruminants presents a risk of BSE. Therefore, under this proposed rule, the failure to include the labeling statement on drugs for nonruminants which contain prohibited materials would render the drugs misbranded under section 502(a) of the act. Under section 701(a) of the act, FDA is authorized to issue regulations for the act's efficient enforcement. Regulations that propose measures to ensure that drugs for animals are being manufactured, processed, packed, or held in conformity with CGMP, and to ensure that they comply with section 512 of the act, allow for efficient enforcement of the act. These proposed regulations would require applicants and manufacturers of drugs for ruminants that are manufactured from or otherwise contain material from cattle to establish and maintain records that document the absence of prohibited cattle materials in such products and make such records readily available to FDA for inspection and copying. These proposed recordkeeping requirements are also authorized under sections 501(a)(2)(B) and 512(l) of the act. Once material is removed from cattle, we may not be able to obtain the information necessary to determine whether it is prohibited cattle material. As noted previously, we would not know from examination of a spinal cord whether the source animal was over 30 months of age at the time of slaughter or whether it was inspected and passed. Because at this time there is no way to test reliably for the presence of the BSE agent or the presence of the cattle materials prohibited in proposed § 500.200, applicants and manufacturers of drugs for ruminants must depend on records from their suppliers of cattle materials to ensure that their source material does not contain any cattle materials prohibited under proposed § 500.200. Therefore, the proposed recordkeeping requirements are necessary for the efficient enforcement of the proposed rule. Under proposed § 500.200(e), the failure of an applicant or manufacturer to comply with the requirements of § 500.200(c) would render a drug for ruminants adulterated. We are also proposing provisions relating to records regarding imported drugs for ruminants under sections 801(a) and 701(b) of the act. Importers of record of a drug for ruminants that was manufactured from or otherwise contains cattle material would be required to affirm that the drug product for import was manufactured from or contains cattle material, and affirm that it was manufactured in compliance with the proposed rule. If a drug was manufactured from or otherwise contains cattle material, then importers of record would also be required, if requested, to provide records to FDA within 5 days sufficient to demonstrate compliance. Under proposed § 500.200(f), failure of an importer of record to comply with these requirements causes a drug to appear to be adulterated. Section 801(a) of the act provides requirements with regard to imported drugs and provides for refusal of admission into the United States of drugs for ruminants that appear to be adulterated. Section 701(b) of the act authorizes the Secretaries of Treasury 3 and Health and Human Services to jointly prescribe regulations for the efficient enforcement of section 801 of the act. 3 Under the Homeland Security Act of 2002 (Public Law 107-296), the Secretary of the Treasury has delegated all relevant Customs revenue authorities to the Secretary of Homeland Security, who has, in turn, delegated them to the Commissioner of Customs and Border Protection (CBP or Customs). If finalized, we will issue this rule jointly with the Department of Homeland Security. FDA has invoked section 361 of the PHS Act (42 U.S.C. 264) to prevent the transmission of numerous communicable diseases, including diseases spread through certain shellfish, turtles, birds, and human tissue intended for transplantation (see 21 CFR 1240.60 (molluscan shellfish), 1240.62 (turtles), 1240.65 (parrots and other psittacine birds), and parts 1270 and 1271 (human tissue)). Recently, FDA also issued under section 361 of the PHS Act regulations designed to prevent the spread of monkeypox from African rodents to humans (21 CFR 1240.63). Section 361 of the PHS Act provides legal authority for FDA to limit the use of prohibited cattle materials in drugs, biological products, devices, new animal drugs for ruminants, and HCT/Ps and to inspect and copy pertinent manufacturing records to ensure compliance. Section 361(a) of the PHS Act authorizes issuance and enforcement of regulations necessary to prevent the introduction, transmission, or spread of communicable diseases from foreign countries or between states. Section 361(a) of the PHS Act also provides for such inspection and destruction of articles found to be so infected or contaminated as to be “sources of dangerous infection to human beings,” as well as other measures that may be necessary to prevent the introduction, transmission, or spread of communicable diseases from a foreign country into a State, or from one State to another State. Because the use of prohibited cattle materials in medical products for humans and drugs for ruminants increases the risk that the agent that causes BSE could be transmitted to humans, limiting the use of prohibited cattle materials in medical products for humans and drugs for ruminants is a needed component of our efforts to prevent the transmission and spread of TSEs including vCJD, in humans. Scientists have concluded that exposure to the BSE agent is the most plausible explanation for the occurrence of vCJD (Refs. 24 through 27). For medical products for humans, by prohibiting use of certain cattle materials, the proposed rule would reduce the risk that the BSE agent would be transmitted directly into any person through exposure to an infectious medical product. For drugs for ruminants, by prohibiting use of certain cattle materials, the proposed rule would reduce the risk that the BSE agent would be transmitted directly into any ruminant. By protecting ruminants from exposure to the BSE agent through animal drugs, the proposed rule would also prevent transmission of the BSE agent to humans who may be exposed to products containing any ruminant materials. Consistent with the authority granted by section 361 of the PHS Act to issue and enforce such regulations as are necessary to prevent communicable disease transmission from foreign countries into the United States and from one State or possession into another, this proposed rule would provide for FDA to be able to inspect and copy pertinent manufacturing records. Because at this time there is no way to screen reliably for the presence of the BSE agent or the presence of the cattle materials prohibited under this proposed rule, the requirements with respect to the maintenance, inspection, and copying of manufacturing records are directly necessary to permit FDA to enforce the other measures designed to prevent transmission of BSE. The proposed rule contains a procedure under which FDA could permit a manufacturer an exception or alternative to the restrictions on the use of prohibited cattle materials under limited circumstances. Specifically, a manufacturer would submit a written request for an exception or alternative to the requirements by describing:

(1)Why an exception or alternative is needed;

(2)the implicated product, including the type of prohibited cattle material, its manufacturing and purification processes, and its route of administration;

(3)the source of the prohibited cattle material including information on the location where the cattle was born, raised, and slaughtered; and

(4)any other information relevant to the likelihood of the cattle having ingested material prohibited under § 589.2000. For medical products for humans, the written request also would include:

(1)How the limitations are not necessary based on the risks of the prohibited cattle materials in the product and the benefits of the product or

(2)how such restrictions are not necessary to ensure the safety of the product. For drugs for ruminants, the written request would also include:

(1)How the requirement is not necessary:

(i)Based on the risks of the prohibited cattle materials in the product to the target animal and the benefits of the product to the target animal and

(ii)to ensure a reasonable certainty of no harm to humans from any food derived from the target animal to which the product is administered, or

(2)how the requirement is not necessary to ensure the safety of the product with respect to both the target animal and any food derived from the target animal to which the product is administered. The relevant Center Director could also grant written permission for an exception or alternative to the proposed requirements on his own initiative, based on these same criteria. As discussed previously, under this proposal, FDA expects that applicants or manufacturers may submit a request for an exception or alternative when filing a new application or premarket notification for a product containing prohibited cattle materials, or if an existing product contains prohibited cattle materials. Although FDA believes it is unlikely that applicants or manufacturers who currently are not using prohibited cattle materials in their products will reformulate their products to include prohibited cattle materials, proposing to do so would require not only a request for an exception or alternative but also a supplement to the approved application or a new premarket notification, consistent with existing regulations. In considering whether an exception or alternative to requirements of this proposed rule would meet the criteria described previously and therefore be appropriate, FDA would be required to ensure that the statutory safety standards would still be met if the exception or alternative were permitted. For drugs for humans, FDA intends to apply the safety standards set forth in sections 501(a)(2)(B) and 505 of the act. Specifically, FDA would only approve a request for an exception or alternative to the proposed limitations on prohibited cattle material if, notwithstanding the exception or alternative:

(1)The drug and the methods used in, or the facilities or controls used for, its manufacturing, processing, packing, or holding conform to or are operated or administered in conformity with CGMP to ensure that such drug meets the requirements of the act as to safety and

(2)the drug is safe for its intended use(s). For biological products, FDA intends to apply the safety standard provided in section 351 of the PHS Act. Specifically, FDA would only approve a request for an exception or alternative to the proposed limitations on prohibited cattle material if, notwithstanding the exception or alternative:

(1)The biological product that is the subject of the application is safe and

(2)the facility in which the biological product is manufactured, processed, packed, or held meets standards designed to ensure that the biological product continues to be safe. For human cells, tissues, and cellular and tissue-based products and other products regulated under the authority of section 361 of the PHS Act, FDA would only approve a request for an exception or alternative to the proposed limitations on prohibited cattle material if such limitations are not necessary to prevent the introduction, transmission, or spread of TSE. For devices, FDA intends to apply the standard in section 516 of the act. Specifically, FDA would approve a request for an exception or alternative to the proposed ban on prohibited cattle materials only if, notwithstanding the exception or alternative, the device does not present an unreasonable and substantial risk of illness or injury. For new animal drugs, FDA intends to apply the safety standards set forth in section 512 and 501(a)(2)(B) of the act. Specifically, FDA would approve a request for an exception or alternative to the proposed limitations on prohibited cattle material only if, notwithstanding the exception or alternative:

(2)the drug is safe for its intended use(s). VII. Effective Date and Opportunity for Public Comment We are proposing that any final rule based on this proposal be effective 30 days after its issuance in the **Federal Register** . Requests for an informal hearing on the proposed ban related to medical devices must be submitted by (see DATES ). FDA invites public comment on this proposed rule, including the proposed effective date for any final rule issued as a result of this proposal. The comment period on this proposed rule will be 60 days. The agency will consider modifications to this proposed rule based on comments made during the comment period. Interested persons may submit to the Division of Dockets Management (see ADDRESSES ) written or electronic comments regarding this proposed rule. Submit a single copy of electronic comments or two paper copies of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday. VIII. Analysis of Impacts FDA has examined the impacts of the proposed rule under Executive Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive Order 12866 directs agencies to assess all costs and benefits of available regulatory alternatives and, when regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health and safety, and other advantages; distributive impacts; and equity). The agency believes that this proposed rule is not an economically significant regulatory action as defined by the Executive Order. The Regulatory Flexibility Act requires agencies to analyze regulatory options that would minimize any significant impact of a rule on small entities. Because FDA has taken regulatory action to reduce the risk of exposure to BSE in the United States and kept affected entities informed on best practices, FDA believes the proposed rule would codify current practices of most affected entities and ensure regulatory consistency across FDA-regulated products. Few entities will need to reformulate with alternative ingredients, submit a request for exception or alternative to the limitation on the use of prohibited cattle material, or cease marketing. The FDA believes most market adjustments have taken place and this rule will not have a significant economic impact on a substantial number of small entities. A few manufacturers of certain drugs prohibited from extralabel use in ruminants would incur one-time costs to add a warning statement to the product labeling. In addition, all manufacturers that use cattle material would incur minor annual incremental recordkeeping costs. Over 10 years, the annualized costs of the proposed rule range from about $235,000 to $922,000 (at a 3 percent discount rate) and from about $235,000 to $923,000 (at a 7 percent discount rate). Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires that agencies prepare a written statement, which includes an assessment of anticipated costs and benefits, before proposing “any rule that includes any Federal mandate that may result in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted annually for inflation) in any one year.” The current threshold after adjustment for inflation is $122 million, using the most current

(2005)Implicit Price Deflator for the Gross Domestic Product. FDA does not expect this rule to result in any 1-year expenditure that would meet or exceed this amount. A. Need for the Proposed Rule The need for this rule stems from inadequate information. Consumers, physicians, farmers, and veterinarians lack the information necessary to determine whether medical products for humans or drugs for ruminants have the potential to contain materials contaminated with the agent that causes BSE. Currently, no validated method exists for testing medical products for humans and drugs for ruminants for the agent that causes BSE; therefore, we do not have a means of distinguishing products that contain infectious material from products that do not. For example, rendered material including brain and spinal cord may become an ingredient in medical products for humans or drugs for ruminants even though its presence may not be indicated as such on the label. Furthermore, end users have no way to determine whether cattle material in these products was sourced from nonambulatory disabled cattle or from cattle that were not inspected and passed for human consumption. Based on what is known about the transmission of BSE, there is some risk of occurrence of vCJD in humans or of BSE in ruminants from the use of certain cattle-derived materials in medical products for humans and drugs for ruminants, respectively. While the results from USDA's ongoing testing 4 are reassuring, one cannot rule out the possible future discovery of other positive animals in the United States or in a country allowed to export cattle material to the United States, or of a future introduction of BSE. To provide consistent protection across the range of FDA-regulated products, it is necessary to put in place measures to reduce further the risk of spread of BSE in cattle and the risk of vCJD in humans. This risk may be reduced by restricting the use of high-risk cattle materials in the manufacture of drugs for ruminants and medical products for humans, similar to existing restrictions for food and cosmetics. 4 USDA began a BSE testing program for cattle on June 1, 2004, after discovery of a case of BSE in a cow in Washington State on December 23, 2003. As discussed in section IV of this document, for over a decade the FDA has taken various actions to reduce the risk of exposure to BSE in agency-regulated medical products for humans and drugs for ruminants, including:

(1)Providing information (through letters to manufacturers), import alerts, and guidances to industry related to bovine materials,

(2)convening TSE advisory committee meetings to provide guidance on the sourcing of certain bovine products, including gelatin,

(3)encouraging companies to be aware of and to document sourcing of bovine material through letters to manufacturers of drugs, biologics, and medical devices, and through the product approval processes, and

(4)recommending that manufacturers develop plans to ensure, with a high degree of certainty, that bovine and ovine materials used in their products were not from countries where BSE exists (“BSE countries” specified by USDA's APHIS in 9 CFR 94.18) or from sheep flocks (foreign or domestic) infected with scrapie. Moreover, manufacturers who also operate in Europe have taken steps to comply with European Union TSE regulations and guidances. The agency has also taken regulatory action to decrease the likelihood of human and ruminant exposure to BSE (e.g., FDA 1997 ruminant feed rule, FDA/USDA Animal Feed ANPRM, FDA 2005 Animal Feed proposed rule, Foods IFR, and Foods Recordkeeping/Access final rule). The agency is proposing additional regulatory action with this rule for medical products for humans and drugs for ruminants that contain certain cattle material. Existing regulations do not explicitly bar the use of prohibited cattle material for these products. By requiring that no medical product for humans or drug for ruminants be manufactured from or otherwise contain prohibited cattle materials, this proposed rule adds another safeguard to minimize human and ruminant exposure to cattle material that scientific studies have demonstrated could contain the BSE agent. This proposed rule is consistent with interim final rules issued by the USDA (USDA/FSIS IFR) and FDA (Foods IFR) that exclude certain cattle material from human food, including dietary supplements, and cosmetics. B. Scope of the Proposed Rule Both the USDA/FSIS and Foods IFRs define SRMs as:

(1)Brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse process of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle 30 months and older, and

(2)the tonsils and distal ileum of the small intestine of all cattle. The USDA/FSIS IFR:

(1)Declares SRMs, mechanically separated beef, and the carcasses and parts of nonambulatory disabled cattle to be inedible and unfit for human food, and prohibits their use in human food and

(2)requires that the entire small intestine of all cattle be removed and disposed of as inedible if procedures that completely remove the distal ileum are not used. The Foods IFR limits the use of prohibited cattle materials in FDA-regulated human food, including dietary supplements, and cosmetics. Prohibited cattle material includes:

(1)All materials declared inedible by the USDA/FSIS IFR and

(2)material from cattle not inspected and passed for human consumption. However, prohibited cattle materials do not include tallow that contains no more than 0.15 percent insoluble impurities, tallow derivatives, hides and hide-derived products, and milk and milk products. This proposed rule would define SRMs consistent with both the USDA/FSIS and Foods IFRs and would define prohibited cattle materials consistent with the Foods IFR. The proposed rule would also clarify for medical products for humans and drugs for ruminants that prohibited cattle materials do not include materials obtained from fetal calves of cows that were inspected and passed, as long as the materials were obtained from suppliers who follow procedures adequate to prevent contamination with SRMs. Current industry practices and full compliance with the USDA/FSIS and Foods IFRs serve as the baseline for this proposed rule. As discussed in section IV of this document, the agency has taken various actions over 10 years to reduce the risk of exposure to the agent that causes BSE in FDA-regulated products. We believe that most affected manufacturers have taken steps to address FDA's existing recommendations regarding the use of cattle material in FDA-regulated products. Because medical products for humans and drugs for ruminants normally use edible cattle material, we assume that the prohibited materials are not widely used in the manufacture and processing of these FDA-regulated products. By determining that medical products for humans and drugs for ruminants manufactured from, or otherwise containing, prohibited cattle materials violate the act and the PHS act, this proposed rule would clarify FDA's ability to bar the use of prohibited cattle materials in medical products for humans and drugs for ruminants that would be outside the scope of other BSE regulations. C. Costs of the Proposed Rule We assume that the recent USDA/FSIS and Foods IFRs have already led to most market adjustments regarding prohibited cattle materials. The manufacturers of products currently using materials from the brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse process of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle would presumably be able to continue to use these ingredients, but exclusively from cattle younger than 30 months of age. However, if manufacturers use cattle tonsils, the distal ileum of small intestine of cattle, or mechanically separated beef in the manufacture of medical products for humans or drugs for ruminants, they would need to reformulate with alternative ingredients, submit a request for exception or alternative to the requirements of the proposed rule, or cease marketing the products. 1. Potential Market Adjustments To the best of our knowledge, there are only a small number of manufacturers with drugs that do not have FDA approval (such as homeopathic drugs) that may be using prohibited cattle material. We believe the recent USDA/FSIS and Foods IFRs may have led any existing manufacturers to find substitutes for prohibited materials. The agency requests information about the impact of the proposed rule on manufacturers or importers of record of drugs that are marketed without an approved application for any reason. 2. Cost of Requests for Exceptions or Alternatives to the Limitation on the Use of Prohibited Cattle Material We estimate that very few firms would submit requests for exceptions or alternatives to the proposed rule's requirements. We estimate that those that do would spend between 60 hours and 120 hours to prepare and submit requests for exceptions or alternatives to the limitation on the use of prohibited cattle material. With an average loaded wage of $41.50, including 33 percent for benefits ($31.16 x 1.33), each request would cost from $2,500 to $5,000 (source: Bureau of Labor Statistics

(BLS)National Compensation Survey: Occupational Wages in the United States, July 2002, for executive, administrative, and managerial employees). Under this proposed rule, we estimate industry would submit three requests in the first year. Depending on the time needed to prepare and submit the request, first-year costs could range from $7,500 to $15,000. Moreover, as markets adjust further, we expect manufacturers would seek and obtain alternatives to prohibited cattle material, eliminating the need for future requests for exceptions or alternatives to the requirements of the proposed rule. 3. Cost of Substitutes Since the USDA/FSIS and Foods IFRs bar prohibited cattle material from edible rendering (i.e., processing of edible cattle waste material into marketable products such as gelatin or tallow), manufacturers of FDA-regulated human medical products for humans and drugs for ruminants using rendered material could continue to use edible rendered products. Some companies may need to find substitutes for other prohibited cattle material used in the manufacture of medical products for humans or drugs for ruminants. Agency records suggest that, because adequate substitutes exist, it is unlikely that the proposed rule would adversely affect markets. Nevertheless, we request comment from affected manufacturers about the costs and extent of substitution. 4. Recordkeeping Requirements of the Proposed Rule The USDA/FSIS IFR and the Foods IFR may affect the availability of prohibited cattle materials, but would not ensure that FDA-regulated medical products for humans or drugs for ruminants are free of prohibited cattle materials. Because at this time there is no way to screen reliably for the presence of the BSE agent or for the presence of cattle materials prohibited under this proposed rule, applicants and manufacturers would have to depend on records from their suppliers of cattle materials to ensure that their source material does not contain any cattle materials prohibited under this proposal. In addition, the agency must be able to determine whether prohibited cattle materials are used in the products it regulates. Without records, FDA may not be able to determine the inspectional status or age of the source animal once cattle material is separated from its source. The proposed rule would require that applicants and manufacturers using cattle material establish and maintain records. Records must be kept at the manufacturing or processing establishment or another reasonably accessible location, and the agency's inspectors must have access to these records. The agency also proposes that importers of record of a medical product for humans or drug for ruminants that was manufactured from or otherwise contains cattle material affirm that the product was manufactured from or otherwise contained cattle material and affirm that the product was manufactured in accordance with the requirements in this proposed rule. Upon agency request, importers of record of affected products would provide to FDA within 5 days records that are sufficient to demonstrate compliance. a. *Number of affected establishments* . The proposed rule is expected to affect all establishments with medical products for humans or drugs for ruminants that are manufactured from, or otherwise contain cattle materials. According to 2002 Economic Census data, up to 6,195 establishments manufactured affected products. In addition, for the current good tissue practice

(CGTP)final rule, the agency estimated there are about 1,300 HCT/P establishments, most of which would be considered small (69 FR 68612 at 68654 and 68674). FDA has developed an automated system, the Operational and Administrative System for Import Support (OASIS), to process shipments of foreign products. According to a preliminary examination of OASIS data from fiscal year 2005, approximately 3,800 unique filers requested entry of FDA-regulated products into the United States. We believe, however, that the actual number of affected filers would be less than this number because some companies may specialize in imports of products such as food, dietary supplements or cosmetics that are outside the scope of this proposed rule. Nevertheless, for this analysis we assume that all filers identified by OASIS could be affected by the proposed requirements for importers of record. As shown in table 1 of this document, about 1,280 manufacturing establishments and 3,800 importers of record could be affected by the recordkeeping requirements. The agency seeks comment on these estimates from affected entities. In addition, although we believe the Foods Recordkeeping/Access final rule accounts for the recordkeeping burden to domestic and foreign suppliers, the agency requests comment from firms supplying cattle material to manufacturers of medical products for humans or drugs for ruminants about any additional burden that may be imposed by the recordkeeping requirements of this proposed rule. Table 1.—Estimated Number of Affected Establishments North American Industry Classification Scheme (NAICS) Code Total Number of Establishments 1 Estimated Percentage of Establishments Using Cattle Material 2 Estimated Number of Affected Establishments Percent of Establishments Considered Small 3 325411—medicinal & botanical manufacturing 367 75 275 98 325412—pharmaceutical preparation manufacturing 4 901 75 674 91 325414—biological product manufacturing 5 296 85 253 96 339112, 339113, 339114, 339115—medical devices 4,631 0.25 12 98 621991—HCT/P 6 1,302 5 65 66 Subtotal 7,497 — 1,278 92 Importers of record 7 3,787 unknown 3,787 unknown Total 11,284 5,065 1 Source: NAICS 325411, 325412, 325414, 339112, 339113, 339114, and 339115, table 4 of the 2002 Economic Census, Manufacturing, Industry Series; NAICS 621991, table 3 in 69 FR 68612 at 68654. Number of importers of record estimated from FDA's OASIS data for FY 2005. 2 Percentages are based on FDA's knowledge of products containing cattle material. We assume equal distribution of affected products across all establishments. 3 The SBA considers entities small if they have less than:

(1)750 employees for NAICS 325411 and 325412,

(2)500 employees for NAICS 32514, 339112, 339113, 339114, and 339115, or

(3)$9.0 million in revenues or receipts for NAICS 621991. Because the Economic Census uses different size categories than SBA, this analysis treats establishments in NAICS 325411 and 325412 with less than 999 employees as small. The agency previously estimated that about 66 percent of establishments in NAICS 621991 are small (table 14 in 69 FR 68612 at 68674). 4 We assume that cattle materials are used by 70 percent of establishments primarily manufacturing products for veterinary use and 75 percent of establishments primarily manufacturing products for human use. Source for the total number of establishments and the number of establishments manufacturing each primary product class: Tables 4 and 5 of the 2002 Economic Census, Manufacturing, Industry Series, EC02-311-325412. 5 We assume that cattle materials are used by 70 percent of establishments primarily manufacturing products for veterinary use and 90 percent of establishments primarily manufacturing products for human use. Source for the total number of establishments and the number of establishments manufacturing each primary product class: Tables 4 and 5 of the 2002 Economic Census, Manufacturing, Industry Series, EC02-311-325412. 6 We assume that from 1 to 5 percent of establishments use cattle materials. 7 Based on FY 2005 data in OASIS; equals the total number of unique filers for all FDA-regulated products. b. *Recordkeeping costs* . Manufacturers of medical products for humans and drugs for ruminants would need to establish and maintain appropriate records that document the absence of prohibited cattle materials in their products. This would require that manufacturers verify and maintain records from suppliers of any material derived from cattle. In addition, when filing an entry with the U.S. Customs and Border Protection, importers of record of affected products would be required to affirm that the product was manufactured from or otherwise contains cattle material and affirm that the product was manufactured in accordance with the proposed provisions. If a product was manufactured from, or otherwise contains, cattle material, then importers of record would also be required, if requested, to provide within 5 days records sufficient to demonstrate that the product was not manufactured from and does not contain prohibited cattle material. As noted previously, we believe that most entities have taken steps to address the sources of cattle materials. Moreover, the CGMP and CGTP regulations covering medical products for humans and drugs for ruminants require that procedures be in place for purchasing controls. We believe, however, that some affected manufacturers currently may not keep adequate records and might incur minor incremental recordkeeping costs. For this analysis, therefore, we assume that, on average, all affected small manufacturers may spend slightly more than 1 hour annually to maintain records. Similarly, we assume that, on average, all affected large manufacturers may spend slightly less than 3 hours annually to maintain records. With a loaded wage rate of $33.00 (source: Bureau of Labor Statistics

(BLS)National Compensation Survey: Occupational Wages in the United States, July 2002, adding 33 percent overhead for a computer programmer), small and large manufacturers might incur about $45 and $90, respectively, to ensure full compliance with the requirements to establish and maintain records. This rule would require importers of record of affected products to affirm that the product was manufactured from or otherwise contains cattle material and affirm that the product was manufactured in accordance with the proposed provisions. Although the marginal burden of each affirmation would be negligible, we believe the cumulative burden might cause smaller importers to spend about the same level of effort as small manufacturers (i.e., $45 annually). In contrast, we assume that larger importers might spend about 5 times the level of effort as small importers (i.e., $225 annually). Because the agency lacks information about importer size, we include a range of possible recordkeeping costs for this analysis. Table 2 shows the estimated recurring recordkeeping costs for this proposed rule. However, because there is some uncertainty about the new burden that might be imposed and the number of firms that might be affected by this proposed rule, the agency requests comment from affected manufacturers and importers of record on this estimated recordkeeping burden. **Table 2.—Estimated Annual Recordkeeping Burden by Industry and Establishment Size** 1 NAICS or Type of Industry Small Number Affected Cost ($) Large Number Affected Cost ($) Total Cost ($) 325411 269 12,100 7 600 12,700 325412 615 27,700 58 5,200 32,900 325414 243 11,000 9 800 11,800 339112, 339113, 339114, 339115 11 500 0 0 500 621991 (HCT/P) 43 1,900 22 2,000 3,900 Subtotal 1,182 53,200 96 8,600 61,800 Lower Bound (i.e., 3,787 small importers) Upper Bound (i.e., 3,787 large importers) Importers of record 2 170,400 852,100 170,400 to 852,100 Total 232,200 to 913,900 1 Totals may not multiply or sum due to rounding. 2 Because we lack data on the size of affected importers of record, we calculate the lower and upper bounds for these costs, assuming that either all firms are small or all firms are large. 5. Labeling Costs for New Animal Drugs Prohibited from Extralabel Use Manufacturers of new animal drugs prohibited from extralabel use in ruminants would need to add a warning statement to the product labeling. We estimate manufacturers of about eight animal products would spend from $1,600 to $6,400 to change the product labeling and file a labeling supplement for each affected product. Costs are based on discussions with experts in the Center for Veterinary Medicine and are presented in table 3 of this document. **Table 3.—Estimated One-Time Costs of Labeling Changes and Filing a Supplement** Cost Component Hours/ Establishment Total Cost 1 ($) Regulatory review and approval 3 to 12 1,000 to 3,980 Artwork 2 - 4,000 Manufacturing 4 to 12 570 to 1,710 Inventory Loss 3 - 6,640 to 40,000 Supplement preparation and Submission 2 to 5 660 to 1,660 Total Cost 4 12,870 to 51,350 1 We calculated using a loaded wage rate for regulatory review and filing a supplement of $41.50, for manufacturing changes $17.80. Source: BLS National Compensation Survey: Occupational Wages in the United States, July 2002, adding 33 percent for benefits. 2 We assume the unit costs for artwork are $500 per product. 3 We assume the unit costs for inventory loss range from $830 to $5,000 per product. 4 Totals may not add or multiply due to rounding. 6. Summary of the Costs for the Proposed Rule Few firms will incur one-time costs for requests for exceptions or alternatives to the limitation on the use of prohibited cattle material. In addition, manufacturers of about eight animal products prohibited from extralabel use in ruminants would incur one-time costs to add a warning statement to the product labeling. All firms that use cattle material or import products that do would incur annual incremental costs for additional recordkeeping. The total one-time costs range from $20,400 to $66,300; annual costs range from $232,200 to $913,900. The total annualized costs of this option range from $234,600 to $921,700 (at a 3 percent discount rate) and from $235,100 to $923,300 (at a 7 percent discount rate) over 10 years. These costs are summarized in table 4 of this document. **Table 4.—Summary of Total Compliance Costs** 1 One-Time Cost Lower Bound ($) Upper Bound ($) Requests for exception or alternative 7,500 15,000 Change labeling and file a supplement 12,900 51,300 Total one-time cost 20,400 66,300 Annual recordkeeping cost 232,200 913,900 Total annualized cost at 3 percent 234,600 921,700 Total annualized cost at 7 percent 235,100 923,300 1 Numbers may not add due to rounding. D. Benefits of the Proposed Rule 1. Reduced Risk of Exposure to BSE Infectivity USDA analyses to date have found the United States is highly resistant to the introduction or establishment of BSE and predict that even if BSE were introduced into the United States, only a small amount of potentially BSE-contaminated tissues would reach the human food supply and be available for consumption (Ref. 41). Moreover, their models predict that implementation of a ban on specified risk materials (e.g., spinal cords, brains, vertebral columns) from both human food and animal feed would reduce substantially the very low risk of additional BSE cases in cattle and the potential human exposure to infectivity from meat and meat products. None of these risk assessments considered the potential exposure to BSE infectivity from certain FDA-regulated products containing bovine material. The risks of exposure to BSE infectivity from medical products for humans and drugs for ruminants are unknown, but the risk of transmission could be higher than for foods and cosmetics assuming the presence of BSE infectivity. For example, the routes of administration for some of these products (such as from injectable and implantable products) are associated with higher risk than oral or topical exposure associated with foods and cosmetics. This proposed rule covers products not included in the recent USDA or Foods IFRs and would ensure that medical products for humans and drugs for ruminants containing cattle material meet specific requirements designed to reduce the risk of human exposure to BSE-infective materials. The proposed rule would decrease the likelihood of human and ruminant exposure to BSE in several ways. First, this rule would provide additional regulatory protection, beyond existing rules, by making clear that prohibited cattle material cannot be used in FDA-regulated medical products for humans or drugs for ruminants. Second, because affected products manufactured from or otherwise containing prohibited cattle materials would be adulterated and the failure of an importer of record to comply with applicable reporting requirements creates the appearance of adulteration under section 801, the proposed rule would clarify FDA's ability to bar importation of medical products for humans or drugs for ruminants that contain prohibited cattle materials. For example, imported products may contain the types of materials prohibited by FDA, but may not fall under the scope of USDA's import restrictions. 2. Value of the Potential Reduction of Human Illness The public health benefit of this proposed rule is the value of the reduction in the risk of the human illness associated with exposure to the agent that causes BSE. If we define the baseline risk as the expected annual number of cases of vCJD per year, then the annual benefits of barring prohibited cattle materials from use in affected products would be: (baseline annual cases of vCJD—annual cases of vCJD under FDA PR) x (value of preventing a case of vCJD). We do not know the baseline expected annual number of cases, but based on the epidemiology of vCJD in the United Kingdom, we anticipate much less than one case of vCJD per year in the United States. Because the proposed rule would reduce rather than eliminate risk of exposure to BSE infectious materials, the reduction in the number of cases would be some fraction of the expected number. FDA uses the concept of the Value of a Statistical Life

(VSL)in order to describe the value of preventing a case of vCJD. This term refers to the sum of risk reductions expected in a population exposed to small changes in risk. It has no application to identifiable individuals or large reductions in risk. Most recent studies suggest values ranging from about $1 million to $10 million. In recent rulemakings, we have used $5 million and $6.5 million as the value of a statistical life, and we believe it is reasonable to use a similar VSL to value the cases of vCJD avoided. E. Summary of the Potential Costs and Benefits of the Proposed Rule The total annualized costs of this proposed rule range from $234,600 to $921,700 (at a 3 percent discount rate) and from $235,100 to $923,300 (at a 7 percent discount rate) over 10 years. By reducing exposure to potentially infectious materials, the requirements of the proposed rule would provide an additional safeguard against a case of vCJD occurring in humans if cattle infected with BSE were used in the manufacture or processing of medical products for humans and drugs for ruminants. We are unable to estimate the value of this potential reduction in the risk of cases of vCJD, even though we estimate the value of avoiding one death at $5.8 million. Nonetheless, we believe the potential benefits of the proposed rule justify the small costs of the rule. F. Regulatory Options Considered For this proposed rule, FDA considered three regulatory options:

(1)*No new regulation* . By definition, no costs and benefits are associated with the baseline. As noted previously, USDA and FDA actions to date would reduce, but not eliminate, the availability and use of prohibited cattle materials in domestic and imported FDA-regulated medical products for humans and drugs for ruminants. Without regulation, FDA would not be explicitly barring the use of prohibited cattle materials that could potentially contain the BSE infectious agent.

(2)*Propose a rule that

(i)bars the use of prohibited cattle materials in medical products for humans and drugs for ruminants, unless a request for exception or alternative to the limitation of the use of prohibited cattle material has been granted, and

(ii)requires establishment, maintenance, and access to records demonstrating that no medical products for humans or drugs for ruminants are manufactured from or otherwise contain prohibited cattle material* . These would be the minimum basic requirements, and would not preclude the imposition of additional measures through the application review process or other means if FDA determined that they were necessary for ensuring the safety of individual products on a case-by-case basis. This is the regulatory option selected. The agency believes that this is the best option to meet its goal of minimizing human and ruminant exposure to materials that scientific studies have demonstrated are likely to contain the BSE agent in cattle infected with the disease. The ban on use of prohibited materials would eliminate exposure to the highest risk animals and the majority of the infectivity in an animal infected with the BSE agent. This option would provide reasonable balance by explicitly barring from medical products for humans and drugs for ruminants the use of potentially infectious materials already deemed unfit for foods by USDA and FDA and by imposing minimal regulatory burden. The agency must be able to determine that the products it regulates contain no prohibited cattle materials. Applicants and manufacturers must depend on records to ensure that affected products do not contain any cattle materials prohibited under the proposal. Without recordkeeping requirements, FDA may not be able to determine the source or age of cattle material once it is separated from the animal. In addition, records would allow the agency to determine the inspectional status of the source animals.

(3)*Propose a rule that, in addition to the requirements listed in option (2), bars the use in medical products for humans and drugs for ruminants of all neural material from cattle from countries with a high or medium risk of BSE if the cattle were slaughtered when over 6 months old, unless a request for exception or alternative to the requirements has been granted* . This approach would be more consistent with recommendations of OIE and would add an additional layer of protection to that provided by option (2). This alternative would put an additional burden on those parts of the affected industries that source cattle materials from such countries and do not already have procedures in place ensuring and documenting compliance with the requirement. Compared to the preferred option (2), we believe this alternative would impose higher costs on, at most, a small segment of the affected industries. In fact, we know of no manufacturers of U.S. licensed or approved medical products for humans and drugs for ruminants for which this alternative would impose any additional burdens beyond those imposed under option (2), because they do not source such materials from such countries. However, we also believe it would not provide significant additional risk reduction because so few animals diagnosed with BSE are younger than 3 years old. For example, cattle born in 1987/1988 in the United Kingdom had the highest incidence of BSE, with over 39,000 cattle diagnosed with BSE. Among those animals, cattle under 3 years old represented only 0.16 percent of cattle with BSE (61 cattle). Once controls were put in place, that number decreased, so that of animals born after 1996, all cattle diagnosed with BSE have been 3 years old or older. G. Regulatory Flexibility Analysis FDA has examined the economic implications of this proposed rule as required by the Regulatory Flexibility Act (5 U.S.C. 601-612). If a rule has a significant economic impact on a substantial number of small entities, the Regulatory Flexibility Act requires agencies to analyze regulatory options that would lessen the economic effect of the rule on small entities. The FDA believes this proposed rule will not have a significant economic impact on a substantial number of small entities and requests comment. The proposed rule may affect entities classified in several industries including Medicinal & Botanical Manufacturing (NAICS 325411), Pharmaceutical Preparation Manufacturing (NAICS 325412), Biological Product (Except Diagnostic) Manufacturing (NAICS 325414), Surgical and Medical Instrument Manufacturing (NAICS 339112), Surgical Appliance and Supplies Manufacturing (NAICS 339113), Dental Equipment and Supplies Manufacturing (NAICS 339114), Ophthalmic Goods Manufacturing (NAICS 339115), and Blood and Organ Banks (NAICS 621991). The Small Business Administration

(SBA)regards an entity as small based on the number of employees or the average annual receipts. The size standards are:

(1)750 employees for NAICS categories 325411 and 325412,

(2)500 employees for NAICS categories 325414, 339112, 339113, 339114 and 339115, and

(3)$9.0 million average annual receipts for NAICS 621991. The U.S. Census gathers employment data for establishments by NAICS and uses size categories that differ from those of the SBA for NAICS 325411 and 325412. For this regulatory flexibility analysis, therefore, we consider entities in these NAICS categories with less than 999 employees to be small. Using these size standards, 2002 Census data, and the CGTP final rule (69 FR 68612 at 68654 and 68674), over 90 percent of these establishments would be considered small (see tables 1 and 2 of this document). However, the agency lacks information on the types of importers of record that might be affected by the proposed rule. Agency data on filers that import FDA-regulated products into the United States does not include the size of the importer of record. Therefore, for the initial regulatory flexibility analysis, we assume that all affected importers of record would be classified as small. The agency requests comment on this assumption. We believe requirements in this proposed rule must apply to all entities, regardless of size. No new skills are needed. To meet the proposed requirements, those applicants and manufacturers of medical products for humans or drugs for ruminants manufactured from or otherwise containing cattle tonsils, the distal ileum of the small intestine of cattle, or mechanically separated beef might need to switch to an alternative source material, submit a request for exception or alternative to the limitation on prohibited cattle material in this proposed rule, or cease marketing the products. We expect that other affected manufacturers would continue to use age-specific cattle material from animals under 30 months of age. A few small entities could incur from $2,500 to $5,000 for each request submitted unless a request for exception or alternative to requirements of the proposed rule has already been granted. In addition, manufacturers of about eight animal products prohibited from extralabel use in ruminants would incur costs of between $1,600 and $6,400 per product to add a warning statement to the product labeling and file a labeling supplement. Although it is uncertain if any small entities will incur these costs, Table 5 shows that for very small establishments with less than 10 employees these one-time costs would equal less than 1.6 percent of the average annual value of shipments. Moreover, for all small establishments in each of the affected industries, the one-time costs to revise labeling or prepare a request for exception or alternative to requirements of the proposed rule would equal no more than 0.15 percent of the average annual value of shipments. **Table 5. Potential direct compliance costs of the proposed rule as a percentage of average annual shipments for affected establishments with less than 10 employees.** 1 NAICS Category Average Annual Shipments Per Establishment ($) Compliance Costs as a Percentage of Average Annual Shipments 2 Recordkeeping ($45 Per Establishment) Labeling Revision ($6,500 Per Product) Request for Exception or Alternative ($5,000 Per Request) 325411, Medicinal and botanical manufacturing 1,059,245 0.004% 0.6% 0.5% 325412, Pharmaceutical preparation manufacturing 1,656,743 0.003% 0.4% 0.3% 325414, Biological product (except diagnostic) manufacturing 1,057,862 0.004% 0.6% 0.5% 339112, Surgical and medical instrument manufacturing 610,138 0.007% 1.0% 0.8% 339113, Surgical appliance and supplies manufacturing 618,207 0.007% 1.0% 0.8% 339114, Dental equipment and supplies manufacturing 396,666 0.011% 1.6% 1.3% 339115, Ophthalmic goods manufacturing 3 1,121,083 0.004% 0.6% 0.4% 621991 Blood and organ banks 4,281,172 0.001% 0.1% 0.1% 1 Source: Table 4 of 2002 Economic Census for NAICS 325411, 325412, 325414, 339112, 339113, 339114, 339115, and 621991. 2 Averages based on the sum of data for establishments with 1 to 4 employees and 5 to 9 employees. For establishments with 1 to 4 employees, recordkeeping costs equal less than 0.02 percent of average annual shipments for all NAICS categories. It is unlikely that entities with 1 to 4 employees would incur compliance costs for a labeling revision or a request for exception or alternative to requirements of the proposed rule. Nevertheless, for these smallest entities, as a percentage of average annual shipments, a labeling revision equals less than 2.6 percent and a request for exemption or alternative equals less than 2.0 percent for all NAICS categories. 3 No information for establishments with 1 to 4 employees. Besides the one-time compliance burden that a few small entities might incur, most affected small manufacturers would incur minor new compliance costs for recordkeeping. For small manufacturers and small importers of record, these annual costs would equal about $45, a negligible amount for even the smallest entities. Table 5 shows that these incremental recordkeeping costs for establishments with less than 10 employees would equal less than 0.02 percent of their average annual value of shipments. FDA lacks the data required to estimate the number of requests, the distribution of one-time labeling costs, and the new annual recordkeeping burden on small entities. We anticipate, however, that the potential costs might represent a very small percentage of their annual revenues and would not be a significant economic impact on affected small entities. Nevertheless, the agency requests detailed data on small business impacts from affected firms. As discussed in section VIII. F. of this document, FDA considered other regulatory options. The proposed rule is the least burdensome option that meets FDA's goal of minimizing human and ruminant exposure to materials that scientific studies have demonstrated are likely to contain the BSE agent in cattle infected with the disease. IX. Paperwork Reduction Act Analysis This proposed rule contains information collection requirements that are subject to review by OMB under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501 3520). A description of these provisions is given below with an estimate of the annual reporting and recordkeeping burden. Included in the estimate is the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing each collection of information. FDA invites comments on the following topics:

(1)Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility;

(2)the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used;

(3)ways to enhance the quality, utility, and clarity of the information to be collected; and

(4)ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology. Title: Use of Materials Derived from Cattle in Medical Products Intended for Use in Humans and Drugs Intended for Use in Ruminants *Description* : As discussed previously in this document, we are proposing to prohibit the use of certain cattle material in medical products for humans and drugs for ruminants because of the risk of BSE and related human disease. The rulemaking contains reporting and recordkeeping requirements that are subject to review by OMB. *Reporting* . Under proposed §§ 300.200(b)(2)(i) and (b)(2)(ii) for drugs for humans, 500.200(b)(2)(i) and (b)(2)(ii) for drugs for ruminants, 600.16(b)(2)(i) and (b)(2)(ii) for biological products, 895.102(b)(2)(i) and (b)(2)(ii) for human medical devices that are intended for use in or on the body, and 1271.470(b)(2)(i) and (b)(2)(ii) for HCT/Ps, applicants and manufacturers could request permission for an exception or alternative to the requirements in proposed §§ 300.200(b)(1), 500.200(b)(1), 600.16(b)(1), 895.102(b)(1), and 1271.470(b)(1) that no medical product for humans or drug for ruminants be manufactured from or otherwise contain prohibited cattle materials obtained from cattle slaughtered on or after the effective date of the regulation. To obtain written permission from FDA for an exception or alternative to the requirements, applicants and manufacturers would send a written request to the director of the Center having jurisdiction over the relevant product. Any request would contain the following: • A statement of the reasons why an exception or alternative is needed; • A description of the product, including the type of prohibited cattle materials used in its manufacturing, its manufacturing and purification processes, and its route of administration; • A description of the source of the prohibited cattle materials, including information on the location where the cattle were born, raised, and slaughtered, and any other information relevant to the likelihood of the cattle having ingested material prohibited under ? 589.2000; • A description, if applicable, of how the requirements that pertain to their product in proposed §§ 300.200(b)(1), 600.16(b)(1), 895.102(b)(1), or 1271.470(b)(1) are not necessary based on the risks of the prohibited cattle materials in the product and the benefits of the product, or how such restrictions are not necessary to ensure the safety of the product; • A description, if applicable, of:

(1)How the requirements that pertain to their product in proposed § 500.200(b)(1) are not necessary:

(i)Based on the risks of the prohibited cattle materials in the product to the target animal and the benefits of the product to the target animal and

(ii)to ensure a reasonable certainty of no harm to humans from any food derived from the target animal to which the product was administered, or

(2)how such restrictions are not necessary to ensure the safety of the product with respect to both the target animal and any food derived from the target animal to which the product is administered; and • Any other relevant information. As discussed in the Analysis of Impacts (see section VIII of this document), we estimate that a request for an exception or alternative to the requirements would take between 60 and 120 hours to complete and submit to FDA. For purposes of this information collection analysis, we estimate, as indicated in table 6 of this document, that each request would take approximately 120 hours. We estimate that only three requests would be submitted to FDA in the first year by applicants and manufacturers of medical products for humans and drugs for ruminants because only a small number of such products are currently manufactured with cattle materials that would be prohibited under this rule. We expect that applicants and manufacturers would seek, and obtain, alternatives to prohibited cattle materials, eliminating the need for future requests for an exception or alternative to the requirements of the proposed rule. We request comments on our estimates of the number of exception/alternative requests, the time for preparation and submission of the request, and the likelihood of requests beyond the first year after the rule would be in effect. Under proposed §§ 300.200(c)(5), 500.200(c)(5), 600.16(c)(5), 895.102(c)(5), and 1271.470(c)(5), when filing entry with the U.S. Customs and Border Protection, importers of record of a medical product for humans or a drug for ruminants that was manufactured from, or otherwise contains, cattle material would be required to affirm that the product was manufactured from or otherwise contained cattle material and affirm that the product was manufactured in accordance with the requirements in this proposed rule. If a product was manufactured from, or otherwise contains, cattle material, then importers of record would also, if requested, have to provide to FDA within 5 days records that would be sufficient to demonstrate that the product was not manufactured from, and does not contain, prohibited cattle material. As discussed in the Analysis of Impacts (see section VIII of this document), we estimate that 3,787 importers of record would be subject to this affirmation and potential record submission and that it would take each of them between 1 and 5 hours annually to process. For purposes of this information collection analysis, we estimate, as indicated in table 6 of this document, that this proposed provision would take each importer of record approximately 2.5 hours annually to process. Under proposed § 530.42, FDA would require that labels for drugs prohibited from extralabel use in ruminants by proposed § 530.41(c) bear or be accompanied by the statement “Federal law prohibits the extralabel use of this product in ruminants.” This labeling statement is not subject to review by OMB because it is “originally supplied by the Federal Government to the recipient for the purpose of disclosure to the public” (5 CFR 1320.3(c)(2)) and, therefore, does not constitute a “collection of information” under the PRA. *Recordkeeping* . Under proposed §§ 300.200(c), 500.200(c), 600.16(c), 895.102(c), and 1271.470(c), applicants and manufacturers of medical products for humans and drugs for ruminants that are manufactured from, or otherwise contain, material from cattle would be required to establish and maintain records demonstrating that their products have not been manufactured from and do not otherwise contain, prohibited cattle materials and make such records available to FDA for inspection and copying. These proposed requirements are necessary because, once materials are separated from an animal, it may not be possible without records to know the following:

(1)Whether the cattle material contains SRMs,

(2)whether the material was sourced from an animal that was inspected and passed for human consumption,

(3)whether the material was sourced from a nonambulatory disabled animal, and

(4)whether the product contains mechanically separated beef. Under the proposed rule, applicants and manufacturers must retain records the varying periods of time consistent with the applicable CGMP or CGTP requirements (e.g., for drugs for humans, it would be at least 1 year after the expiration date of the drug; for drugs for humans lacking an expiration date, it would be at least 3 years after distribution of the last lot of the drug). These records would be required to be maintained at the applicant's or manufacturer's establishment or another reasonably accessible location. Recordkeeping requirements currently exist for applicants and manufacturers of medical products for humans and drugs for ruminants under FDA's CGMP and CGTP regulations. For drugs and biological products for humans and drugs for ruminants, these requirements are at part 210 (21 CFR part 210) and part 211 (CGMP), and the information collection requirements for these regulations are already approved by OMB under OMB Control Number 0910-0139 until September 30, 2008. For blood and blood components, these requirements are at 21 CFR part 606 (CGMP), and the information collection requirements for these regulations are already approved by OMB under OMB Control Number 0910-0116 until December 31, 2008. For Type A medicated articles, these requirements are at part 226 (CGMP), and the information collection requirements for these regulations are already approved by OMB under OMB Control Number 0910-0154 until December 31, 2007. For medical devices for humans, these requirements are at 21 CFR part 820 (CGMP/quality system regulations), and the information collection requirements for these regulations are already approved by OMB under OMB Control Number 0910-0073 until September 30, 2007. For HCT/Ps, these requirements are at part 1271, subpart D (CGTP regulations), and the information collection requirements for these regulations are already approved by OMB under OMB Control Number 0910-0559 until November 30, 2007. In accordance with the previously mentioned CGMP and CGTP regulations, applicants and manufacturers of medical products for humans and drugs for ruminants would be responsible for maintaining records regarding use of cattle materials in, or in the manufacture of, their products. However, FDA estimates that, in accordance with this rulemaking, applicants and manufacturers would expend a small amount of additional effort to comply with the proposed recordkeeping requirements. FDA has determined, as indicated in table 7 of this document, that there are 1,278 applicants and manufacturers of a medical product for humans or drug for ruminants that would be responsible for recordkeeping. This would include verifying records and storing records that contain information on sources of cattle materials that are to be used in medical products for humans and drugs for ruminants. As discussed in the Analysis of Impact (see section VIII of this document), we estimate that this recordkeeping burden will be about 1 to 3 hours per year. For purposes of this document, we estimate, as indicated in table 7, that this burden would take about 2 hours/year. Therefore, the total annual burden will be 2 hrs x 1,278 = 2,556 hours, as shown in table 7 of this document. *Description of Respondents* : Applicants and manufacturers of medical products for humans and drugs for ruminants that are manufactured from, or otherwise contain, material from cattle slaughtered on or after the effective date of the regulation. **Table 6.—Estimated Reporting Burden** 1 21 CFR Section Number of Respondents Frequency per Response Total Responses Hours per Response Total Hours 300.200(b)(2)(i) and (b)(2)(ii), 500.200(b)(2)(i) and (b)(2)(ii), 600.16(b)(2)(i) and (b)(2)(ii), 895.102(b)(2)(i) and (b)(2)(ii), and 1271.470(b)(2)(i) and (b)(2)(ii) 3 1 3 120 360 300.200(c)(5), 500.200(c)(5), 600.16(c)(5), 895.102(c)(5), and 1271.470(c)(5) 3,787 1 3,787 2.5 9,467.5 Total 9,827.5 1 There are no capital costs or operating and maintenance costs associated with this collection of information. **Table 7.—Estimated Annual Recordkeeping Burden** 1 21 CFR Section Number of Respondents Annual Frequency per Response Total Annual Responses Hours per Response Total Hours 300.200(c), 500.200(c), 600.16(c), 895.102(c), and 1271.470(c) 1,278 1 1,278 2 2,556 1 There are no capital costs or operating and maintenance costs associated with this collection of information. In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 3507(d)), the agency has submitted the information collection provisions of this proposed rule to OMB for review. Interested persons are requested to send comments regarding information collection to OMB (see DATES and ADDRESSES ). X. Environmental Impact Analysis FDA has carefully considered the potential environmental effects of this proposed rule (i.e., ban use of prohibited cattle materials in medical products for humans and drugs for ruminants, unless a request for exception or alternative to the requirements has been granted) and of two possible alternative actions:

(1)No action and

(2)in addition to the requirements proposed in this rule, ban use in medical products for humans and drugs for ruminants of all neural material from cattle from countries with a high or medium risk of BSE if the cattle were slaughtered when over 6 months old, unless a request for exception or alternative to the requirements has been granted. In doing so, the agency focused on the environmental impacts of its action, specifically, disposal of unused cattle byproducts (e.g., dead animals and slaughter byproducts) that can no longer be used in medical products for humans or drugs for ruminants after the rule becomes effective. The environmental assessment

(EA)considered each of the alternatives in terms of the need to provide maximum reasonable protection of human health without resulting in a significant impact on the environment. The EA considered environmental impacts related to landfill, incineration, composting, and land burial. The additional waste that might result from the selected action would be an extremely small amount compared to the total amount of waste generated by the cattle industry. The agency has concluded that the proposed rule will not have a significant impact on the human environment and that an environmental impact statement is not required. FDA's finding of no significant impact (FONSI) and the evidence supporting that finding, contained in an EA prepared under 21 CFR 25.40, may be seen in the Dockets Management Branch (see ADDRESSES ) between 9 a.m. and 4 p.m., Monday through Friday. FDA invites comments and submission of data concerning the EA and FONSI. XI. Federalism We have analyzed this proposed rule in accordance with the principles in Executive Order 13132. We have determined that the proposed rule does not contain policies that have substantial direct effects on the States, on the relationship between the National Government and the States, or on the distribution of power and responsibilities among the various levels of government. Accordingly, we have concluded that the proposed rule does not contain policies that have federalism implications as defined in the Executive order and, consequently, a federalism summary impact statement has not been prepared. XII. References The following references have been placed on display in the Division of Dockets Management (see ADDRESSES ) and may be seen by interested persons between 9 a.m. and 4 p.m., Monday through Friday. (FDA has verified the Web site address, but we are not responsible for subsequent changes to the Web site after this document publishes in the **Federal Register** .) 1. Johnson, R. T. and C. J. Gibbs, Jr., “Creutzfeldt-Jakob Disease and Related Transmissible Spongiform Encephalopathies,” *New England Journal of Medicine* , 339(27):1994-2004, 1998. 2. Herzog, C., N. Sales, N. Etchegaray, et al., “Tissue Distribution Of Bovine Spongiform Encephalopathy Agent in Primates After Intravenous or Oral Infection,” *Lancet* , 363(9407):422-28, 2004. 3. Wells, G. A. H., S. A. C. Hawkins, R. B. Green, et al., “Preliminary Observations on the Pathogenesis of Experimental Bovine Spongiform Encephalopathy (BSE): An Update,” *Veterinary Record* , 142:103-106, 1998. 4. Wells, G. A. H., M. Dawson, S. A. C. Hawkins, et al., “Infectivity in the Ileum of Cattle Challenged Orally With Bovine Spongiform Encephalopathy,” *Veterinary Record* , 135:40-41, 1994. 5. Wells, G. A. H., S. A. C. Hawkins, R. B. Green, et al., “Limited Detection of Sternal Bone Marrow Infectivity in the Clinical Phase of Experimental Bovine Spongiform Encephalopathy (BSE),” *Veterinary Record* , 144:292-294, 1999. 6. Brown, K. L, D. L. Ritchie, P. A. McBride, and M. E. Bruce, “Detection of PrP in Extraneural Tissues,” *Microscopy Research and Technique* , 50:40-45, 2000. 7. U. S. Department of Agriculture, APHIS, “Summary of Enhanced BSE Surveillance in the United States,” 2006 accessed online at *http://www.aphis.usda.gov/newsroom/hot_issues/bse/content/printable_version/SummaryEnhancedBSE-Surv4-26-06.pdf.* 8. Council for Agricultural Science and Technology, “Transmissible Spongiform Encephalopathies in the United States,” Task Force Report No. 136, 2000. 9. Prusiner, S. B., “Prions,” *Proceedings of the National Academy of Sciences of the United States of America* , 95(23):13363-13383, 1998. 10. Prusiner, S. B., “Shattuck Lecture—Neurodegenerative Diseases and Prions,” *New England Journal of Medicine* , 344(20): 1516-1526, 2001. 11. Legname, G., I.V. Baskakov, H. B. Nguyen, et al., “Synthetic Mammalian Prions,” *Science* , 305:673-676, 2004. 12. Collins, S. J., V. A. Lawson, and C. L. Masters, “Transmissible Spongiform Encephalopathies,” *Lancet* , 363(9402):51-61, 2003. 13. Collee, J. G. and R. Bradley, “BSE: A Decade On—Part I,” *Lancet* , 349:636-641, 1997. 14. Anderson, R. M., C. A. Donnelly, N. M. Ferguson, et al., “Transmission Dynamics and Epidemiology of BSE in British Cattle,” *Nature* , 382:779-788, 1996. 15. Wells, G. A. H., A. C. Scott, C. T. Johnson, et al., “A Novel Progressive Spongiform Encephalopathy in Cattle,” *Veterinary Record* , 121:419-420, 1987. 16. Vossen, P., J. Kreysa, and M. Goll, “Overview of the BSE Risk Assessments of the European Commission's Scientific Steering Committee

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(HER)via Food With Respect to BSE,” 1999. 32. The National Creutzfeldt-Jakob Disease Surveillance Unit, United Kingdom, accessed online at *http://www.cjd.ed.ac.uk/figures.htm* . 33. Public Health Agency of Canada, “First Canadian Case of Variant Creutzfeldt-Jakob Disease (Variant CJD),” accessed online at *http://www.phac-aspc.gc.ca/cjd-mcj/vcjd-ca_e.html* . 34. Wiersma, S., S. Cooper, R. Knight et al., “Probable Variant Creutzfeldt-Jakob Disease in a U.S. Resident-Florida, 2002,” *Morbidity and Mortality Weekly Report* , 51:927-929, 2002. 35. “Probable Case of Indigenous vCJD diagnosed in Ireland,” *Eurosurveillance Weekly* , accessed online at *http://www.eurosurveillance.org/ew/2004/041111.asp* . 36. Belay, E.D., J.J. Sejvar, W-J Shieh, et al., “Variant Creutzfeldt-Jakob disease death, United States,” *Emerging Infectious Diseases* , 11 (9), 1351-1354, 2005, accessed online at *http://www.cdc.gov/ncidod/EID/vol11no09/05-0371.htm* . 37. 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Schultz, et al., “Prion Diseases: Infectious and Lethal Doses Following Oral Challenge,” *Journal of General Virology* , 84(Pt 7):1927-1929, 2003. 51. Gibbs, C. J., Jr., H. L. Amyx, A. Bacote, et al., “Oral Transmission of Kuru, Creutzfeldt-Jakob Disease, and Scrapie to Nonhuman Primates,” *Journal of Infectious Diseases* , 142(2):205-208, 1980. 52. Pattison, I. H., M. N. Hoare, J.N. Jebbett, and W.A. Watson, “Spread of Scrapie to Sheep and Goats by Oral Dosing With Foetal Membranes From Scrapie-Affected Sheep,” *Veterinary Record* , 90(17):465-468, 1972. 53. Pattison, I. H., M. N. Hoare, J.N. Jebbett, and W.A. Watson, “Further Observations on the Production of Scrapie in Sheep by Oral Dosing With Foetal Membranes From Scrapie-Affected Sheep,” *British Veterinary Journal* , 130(4):lxv-lxvii, 1974. 54. Pattison, I. H. and G. C. Millson, “Experimental Transmission of Scrapie to Goats and Sheep by the Oral Route,” *Journal of Comparative Pathology* , 71:171-176, 1961. 55. Race, R., M. Oldstone, and B. Chesebro, “Entry Versus Blockade Of Brain Infection Following Oral or Intraperitoneal Scrapie Administration: Role of Prion Protein Expression in Peripheral Nerves and Spleen,” *Journal of Virology* , 74(2):828-833, 2000. 56. Kimberlin, R. H. and Walker, C. A., “Pathogenesis of Experimental Scrapie” in *Novel Infectious Agents and the Central Nervous System* , Eds. G. Bock and J. Marsh, Wiley, Chichester (Ciba Foundation Symposium 135): Wiley, 37-62, 1988. 57. Scott, J. R., J. D. Foster and H. Fraser, “Conjunctival Instillation of Scrapie in Mice Can Produce Disease,” *Veterinary Microbiology* , 34(4):305-309, 1993. 58. Klitzman R. L., M. P. Alpers, and D. C. Gajdusek, et al., “The Natural Incubation Period of Kuru and the Episodes of Transmission in Three Clusters of Patients,” *Neuroepidemiology* , 3(1):3-20, 1984. 59. Sugaya, M., K. Nakamura, T. Watanabe, et al., “Expression of Cellular Prion-Related Protein by Murine Langerhans Cells and Keratinocytes,” *Journal of Dermatological Science* , 28:126-134, 2002. 60. Scientific Steering Committee, European Commission, “Update of the Opinion on TSE Infectivity Distribution in Ruminant Tissues,” initially adopted by the Scientific Steering Committee at its meeting of January, 10-11, 2002, and amended at its meeting of November 7-8, 2002, following the submission of

(1)a risk assessment by the German Federal Ministry of Consumer Protection, Food and Agriculture and

(2)new scientific evidence regarding BSE infectivity distribution in tonsils, accessed online at *http://www.europa.eu.int/comm/food/fs/bse/scientific_advice08_en.html* . 61. Department for Environment Food and Rural Affairs, United Kingdom, “BSE: Statistics—Age at Clinical Onset in Years by Birth Cohort,” accessed online at *http://www.defra.gov.uk/animalh/bse/statistics/bse/age.htm* . 62. Wilesmith, J. W. and J. B. M. Ryan, “Bovine Spongiform Encephalopathy: Recent Observations on the Age-Specific Incidences,” *Veterinary Record* , 130:491-492, 1992. 63. Health and Consumer Protection Directorate-General, European Commission, “Report on the Monitoring and Testing of Ruminants for the Presence of Transmissible Spongiform Encephalopathy

(TSE)in 2002,” 2003, accessed online at *http://www.europa.eu.int/comm/food/food/biosafety/bse/annual_report_2002_en.pdf* . 64. Doherr, M. G., D. Heim, R. Fatzer, et al., “Targeted Screening of High-Risk Cattle Populations for BSE to Augment Mandatory Reporting of Clinical Suspects,” *Preventive Veterinary Medicine* , 51:3-16, 2001. 65. Taylor, D. M., S. L. Woodgate, and M. J. Atkinson, “Inactivation of the Bovine Spongiform Encephalopathy Agent by Rendering Procedures,” *Veterinary Record* , 137:605-610, 1995. 66. Taylor, D. M., S. L. Woodgate, A. J. Fleetwood, and R. J. G. Cawthorne, “The Effect of Rendering Procedures on the Scrapie Agent,” *Veterinary Record* , 141:643-649, 1997. 67. Wilesmith, J. W., G. A. H. Wells, M. P. Cranwell, and J. B. M. Ryan, “Bovine Spongiform Encephalopathy: Epidemiological Studies,” *Veterinary Record* , 123:638-644, 1988. 68. World Organisation for Animal Health (OIE), “Terrestrial Animal Health Code, Bovine Spongiform Encephalopathy,” 2005, accessed online at *http://www.oie.int/eng/normes/mcode/en_chapitre_2.3.13.htm* . 69. U.S. Department of Health and Human Services, Food and Drug Administration, Transcript of meeting of the Transmissible Spongiform Encephalopathies Advisory Committee, April 16, 1998, accessed online at *http://www.fda.gov/ohrms/dockets/ac/98/transcpt/3406t2.pdf* . 70. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, “Probable Variant Creutzfeldt-Jakob Disease in a U.K. Citizen Who Had Temporarily Resided in Texas, 2001-2005, November 18, 2005, accessed online at *http://www.cdc.gov/ncidod/dvrd/vcjd/other/probablevcjd_texas2001_2005_111805.htm* . List of Subjects 21 CFR Part 211 Drugs, Labeling, Laboratories, Packaging and containers, Prescription drugs, Reporting and recordkeeping requirements, Warehouses. 21 CFR Part 226 Animal drugs, Animal feeds, Labeling, Packaging and containers, Reporting and recordkeeping requirements. 21 CFR Part 300 Drugs, Incorporation by reference, Prescription drugs. 21 CFR Part 500 Animal drugs, Animal feeds, Cancer, Incorporation by reference, Labeling, Packaging and containers, Polychlorinated biphenyls (PCBs). 21 CFR Part 530 Administrative practice and procedure, Advertising, Animal drugs, Labeling, Reporting and recordkeeping requirements. 21 CFR Part 600 Biologics, Incorporation by reference, Reporting and recordkeeping requirements. 21 CFR Part 895 Administrative practice and procedure, Incorporation by reference, Labeling, Medical devices. 21 CFR Part 1271 Biologics, Drugs, Human cells and tissue-based products, Incorporation by reference, Medical devices, Reporting and recordkeeping requirements. Therefore, under the Federal Food, Drug, and Cosmetic Act, and under authority delegated to the Commissioner of Food and Drugs, FDA proposes to amend 21 CFR parts 211, 226, 300, 500, 530, 600, 895, and 1271 as follows: PART 211—CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS 1. The authority citation for 21 CFR part 211 continues to read as follows: Authority: 21 U.S.C. 321, 351, 352, 355, 360b, 371, 374; 42 U.S.C. 216, 262, 263a, 264. 2. Section 211.116 is added to subpart F to read as follows: § 211.116 Use of cattle material. Use of certain cattle material in drug products and components is prohibited as provided by §§ 300.200, 500.200, and 600.16 of this chapter. PART 226—CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES 3. The authority citation for 21 CFR part 226 continues to read as follows: Authority: 21 U.S.C. 351, 352, 360b, 371, 374. 4. Section 226.60 is added to subpart C to read as follows: § 226.60 Use of cattle material. Use of certain cattle material in Type A medicated articles for ruminants is prohibited as provided by § 500.200 of this chapter. PART 300—GENERAL 5. The authority citation for 21 CFR part 300 is revised to read as follows: Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360b, 361, 371, 381; 42 U.S.C. 264, 271. 6. Section 300.200 is added to subpart C to read as follows: § 300.200 Prohibited cattle materials.

(a)*Definitions* . The definitions and interpretations of terms contained in section 201 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321) apply to such terms when used in this section. The following definitions also apply:

(1)*Prohibited cattle materials* means specified risk materials; small intestine of all cattle except as provided in paragraph (b)(3) of this section; material from nonambulatory disabled cattle; material from cattle not inspected and passed; or mechanically separated beef. Prohibited cattle materials do not include tallow that contains no more than 0.15 percent insoluble impurities, tallow derivatives, hides and hide-derived products, and milk and milk products. Prohibited cattle materials also do not include materials obtained from fetal calves of cows that were inspected and passed, as long as the materials were obtained by procedures adequate to prevent contamination with specified risk materials.

(2)*Inspected and passed* means that the material is from an animal that has been inspected and passed for human consumption by the appropriate regulatory authority, and at the time the animal was inspected and passed, it was found to be not adulterated.

(3)*Mechanically separated beef* means a meat food product that is finely comminuted, resulting from the mechanical separation and removal of most of the bone from attached skeletal muscle of cattle carcasses and parts of carcasses, that meets the specifications contained in 9 CFR 319.5, the U. S. Department of Agriculture's (USDA's) regulation that prescribes the standard of identity for Mechanically Separated (Species).

(4)*Nonambulatory disabled cattle* means cattle that cannot rise from a recumbent position or that cannot walk, including, but not limited to, those with broken appendages, severed tendons or ligaments, nerve paralysis, fractured vertebral column, or metabolic conditions.

(5)*Specified risk materials* means the brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle 30 months and older, and the tonsils and distal ileum of the small intestine of all cattle.

(6)*Tallow* means the rendered fat of cattle obtained by pressing or by applying any other extraction process to tissues derived directly from discrete adipose tissue masses or to other carcass parts and tissues. Tallow must be produced from tissues that are not prohibited cattle materials or must contain not more than 0.15 percent insoluble impurities as determined by the method entitled “Insoluble Impurities” (AOCS Official Method Ca 3a-46), American Oil Chemists' Society (AOCS), 5th Edition, 1997, incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS Official Method Ca 3a-46. You may obtain copies of the method from the AOCS ( *http://www.aocs.org* ) 2211 W. Bradley Ave., Champaign, IL 61821. Copies may be examined at the Center for Food Safety and Applied Nutrition's Library, 5100 Paint Branch Pkwy., College Park, MD 20740, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to: *http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html* .

(7)*Tallow derivative* means any chemical obtained through initial hydrolysis, saponification, or trans-esterification of tallow; chemical conversion of material obtained by hydrolysis, saponification, or trans-esterification may be applied to obtain the desired product.

(b)*Requirements* .

(1)At a minimum, except as provided in paragraph (b)(2) of this section, no drug intended for use in humans shall be manufactured from, or otherwise contain, prohibited cattle materials obtained from cattle slaughtered on or after [effective date of final rule].

(2)The requirements in paragraph (b)(1) of this section with respect to prohibited cattle materials shall not apply if FDA grants written permission for an exception or alternative to such requirements.

(i)To obtain written permission from FDA, you must send a written request to the Director of the Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. For a drug subject to an application, your written request must reference its application number. The Center Director may also grant written permission for an exception or alternative to the requirements in paragraph (b)(1) of this section on his own initiative and shall base such a determination on an evaluation of the criteria described in paragraph (b)(2)(ii) of this section. You must maintain a record of any exception or alternative to the requirements in paragraph (b)(1) of this section that is granted by FDA, in accordance with paragraph

(c)of this section.

(ii)A written request for an exception or alternative to the requirements in paragraph (b)(1) of this section must include, for each applicable product:

(A)A statement of the reasons why an exception or alternative is needed;

(B)A description of the product, including the type of prohibited cattle materials used in its manufacturing, its manufacturing and purification processes, and its route of administration;

(D)A description of how the requirements in paragraph (b)(1) of this section are not necessary based on the risks of the prohibited cattle materials in the product and the benefits of the product or how such restrictions are not necessary to ensure the safety of the product; and

(E)Any other relevant information.

(iii)FDA shall respond in writing to all requests for an exception or alternative to the requirements and may impose conditions in granting any such request.

(3)The small intestine is not considered prohibited cattle material if the distal ileum is removed by a procedure that removes at least 80 inches of the uncoiled and trimmed small intestine, as measured from the caeco-colic junction and progressing proximally towards the jejunum, or by a procedure that the establishment can demonstrate is equally effective in ensuring complete removal of the distal ileum.

(c)*Records* .

(1)Applicants and manufacturers of a drug that is manufactured from, or otherwise contains, cattle material must establish and maintain records sufficient to demonstrate that the material is not manufactured from, and does not contain, prohibited cattle materials.

(2)Records must be retained for at least 1 year after the expiration date of the drug or, for drugs lacking an expiration date, at least 3 years after distribution of the last lot of the drug.

(3)Records must be retained at the applicant's or manufacturer's establishment or at a reasonably accessible location. Records are considered to be reasonably accessible if they are accessible from an onsite location.

(4)Records required by this section must be readily available to FDA for inspection and copying. All the records must be in English.

(5)When filing entry with the U.S. Customs and Border Protection, the importer of record of a drug manufactured from, or otherwise containing, cattle material must affirm that the drug was manufactured from, or otherwise contains, cattle material and must affirm that the drug was manufactured in accordance with this section. If a drug was manufactured from, or otherwise contains, cattle material, then the importer of record must, if requested, provide to FDA within 5 days records that are sufficient to demonstrate that the drug is not manufactured from, and does not contain, prohibited cattle material.

(d)A human drug that is not in compliance with the requirements of paragraph

(b)of this section is adulterated under section 501(a)(2)(B) of the act (21 U.S.C. 351(a)(2)(B)).

(e)Failure of an applicant or manufacturer to comply with the requirements of paragraph

(c)of this section renders a drug adulterated under section 501(a)(2)(B) of the act (21 U.S.C. 351(a)(2)(B)).

(f)Failure of an importer of record to comply with the requirements of paragraph

(c)of this section causes a drug to appear to be adulterated under section 801(a) of the act (21 U.S.C. 381(a)).

(g)A human drug that is a new drug and that is not in compliance with the requirements of paragraph

(b)of this section is in violation of section 505 of the act (21 U.S.C. 355).

(h)Failure of an applicant or manufacturer to comply with the requirements of paragraph

(c)of this section is a violation of section 301(e) of the act (21 U.S.C. 331(e)).

(i)Any person who violates the requirements of paragraph

(b)or

(c)of this section shall be subject to the penalties provided in section 368 of the Public Health Service Act (42 U.S.C. 271). PART 500—GENERAL 7. The authority citation for 21 CFR part 500 is revised to read as follows: Authority: 21 U.S.C. 321, 331, 342, 343, 348, 351, 352, 353, 360b, 371, 381; 42 U.S.C. 264, 271. 8. New subpart F is added to part 500 to read as follows: Subpart F—Substances Prohibited From Animal Drugs § 500.200 Prohibited cattle materials in drugs intended for use in ruminants.

(5)*Specified risk materials* means the brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle 30 months and older and the tonsils and distal ileum of the small intestine of all cattle.

(6)*Tallow* means the rendered fat of cattle obtained by pressing or by applying any other extraction process to tissues derived directly from discrete adipose tissue masses or to other carcass parts and tissues. Tallow must be produced from tissues that are not prohibited cattle materials or must contain not more than 0.15 percent insoluble impurities as determined by the method entitled “Insoluble Impurities” (AOCS Official Method Ca 3a-46), American Oil Chemists' Society (AOCS), 5th Edition, 1997, incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS Official Method Ca 3a-46. You may obtain copies of the method from AOCS ( *http://www.aocs.org* ) 2211 W. Bradley Ave., Champaign, IL 61821. Copies may be examined at the Center for Food Safety and Applied Nutrition's Library, 5100 Paint Branch Pkwy., College Park, MD 20740, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to: *http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html* .

(8)*Ruminant* means any member of the suborder of animals that has a stomach with four compartments (rumen, reticulum, omasum, and abomasum) through which feed passes in digestion. The suborder includes, but is not limited to, cattle, buffalo, sheep, goats, deer, elk, and antelopes.

(b)*Requirements* .

(1)At a minimum, except as provided in paragraph (b)(2) of this section, no drug intended for use in ruminants shall be manufactured from, or otherwise contain, prohibited cattle materials obtained from cattle slaughtered on or after [effective date of final rule].

(i)To obtain written permission from FDA, you must send a written request to the Director of the Center for Veterinary Medicine, 7519 Standish Place, Rockville, MD 20855. For a drug intended for use in ruminants that is subject to a new animal drug application, your written request must reference its application number. The Center Director may also grant written permission for an exception or alternative to the requirements in paragraph (b)(1) of this section on his own initiative and shall base such a determination on an evaluation of the criteria described in paragraph (b)(2)(ii) of this section. You must maintain a record of any exception or alternative to the requirements in paragraph (b)(1) of this section that is granted by FDA, in accordance with paragraph

(c)of this section.

(ii)A written request for an exception or alternative to the requirements in paragraph (b)(1) of this section must include, for each applicable product:

(A)A statement of the reasons why the exception or alternative is needed;

(B)A description of the product, including the type of prohibited cattle materials used in its manufacturing, its manufacturing and purification processes, and its route of administration;

(C)A description of the source of the prohibited cattle materials, including information on the location where the cattle were born, raised, and slaughtered, and any other information relevant to the likelihood of the cattle having ingested material prohibited under § 589.2000 of this chapter; (D)( *1* ) A description of how the requirements in paragraph (b)(1) of this section are not necessary: ( *i* ) Based on the risks of the prohibited cattle materials in the product to the target animal and the benefits of the product to the target animal; and ( *ii* ) To ensure a reasonable certainty of no harm to humans from any food derived from the target animal to which the product was administered; or ( *2* ) A description of how the requirements in paragraph (b)(1) of this section are not necessary to ensure the safety of the product with respect to both the target animal and any food derived from the target animal to which the product is administered; and

(E)Any other relevant information.

(iii)FDA shall respond in writing to all requests for an exception or alternative to the requirements and may impose conditions in granting any such request.

(c)*Records* .

(1)Applicants and manufacturers of a drug intended for use in ruminants that is manufactured from, or otherwise contains, any cattle material must establish and maintain records sufficient to demonstrate that the material is not manufactured from, and does not contain, prohibited cattle materials.

(2)The following record retention periods apply:

(i)Records for a Type A medicated article intended for use in ruminants that is manufactured from, or otherwise contains, any cattle material must be retained for at least 2 years after distribution by the manufacturer.

(ii)Records for a drug intended for use in ruminants, other than a Type A medicated article, that is manufactured from, or otherwise contains, any cattle material must be retained for at least 1 year after the expiration date of the drug.

(4)Records required by this section must be available to FDA for inspection and copying. All the records must be in English.

(5)When filing entry with the U.S. Customs and Border Protection, the importer of record of a drug intended for use in ruminants that was manufactured from, or otherwise contains, cattle material must affirm that the drug was manufactured from, or otherwise contains, cattle material and must affirm that the drug was manufactured in accordance with this section. If a drug was manufactured from, or otherwise contains, cattle material, then the importer of record must, if requested, provide to FDA within 5 days records that are sufficient to demonstrate that the drug is not manufactured from, and does not contain, prohibited cattle material.

(d)A drug intended for use in ruminants that is not in compliance with the requirements of paragraph

(b)of this section is adulterated under section 501(a)(2)(B) of the act (21 U.S.C. 351(a)(2)(B)).

(e)Failure of an applicant or manufacturer to comply with the requirements of paragraph

(c)of this section renders a drug intended for use(s) in ruminants adulterated under section 501(a)(2)(B) of the act (21 U.S.C. 351(a)(2)(B)).

(f)Failure of an importer of record to comply with the requirements of paragraph

(c)of this section causes a drug intended for use(s) in ruminants to appear to be adulterated under section 801(a) of the act (21 U.S.C. 381(a)).

(g)A drug intended for use in ruminants that is a new animal drug and that is not in compliance with the requirements of paragraph

(b)of this section is in violation of section 512 of the act (21 U.S.C. 360b).

(h)Failure of an applicant or manufacturer to comply with the requirements of paragraph

(c)of this section is in violation of section 301(e) of the act (21 U.S.C. 331(e)).

(i)Any person who violates the requirements of paragraph

(b)or

(c)of this section shall be subject to the penalties provided in section 368 of the Public Health Service Act (42 U.S.C. 271). PART 530—EXTRALABEL DRUG USE IN ANIMALS 9. The authority citation for 21 CFR part 530 is revised to read as follows: Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 351, 352, 353, 355, 357, 360b, 371, 379e; 42 U.S.C. 264, 271. 10. Section 530.41 is amended by removing the word “for” from the section heading, paragraph

(a)introductory text, and paragraph

(b)and adding in its place the word “from”; and by adding paragraph

(c)to read as follows: § 530.41 Drugs prohibited from extralabel use in animals.

(c)Drugs that contain prohibited cattle material as defined in §§ 300.200(a)(1) and 500.200(a)(1) of this chapter are prohibited from extralabel use in ruminants. 11. Section 530.42 is added to subpart E to read as follows: § 530.42 Labeling requirements for new animal drugs prohibited from extralabel use in animals.

(a)The labeling of any approved new animal drug that is prohibited from extralabel use in ruminants by § 530.41(c) must bear the statement “Federal law prohibits the extralabel use of this product in ruminants.”

(b)Failure to comply with the labeling requirements in paragraph

(a)of this section renders a drug misbranded under section 502(a) of the act. PART 600—BIOLOGICAL PRODUCTS: GENERAL 12. The authority for 21 CFR part 600 is revised to read as follows: Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 360i, 371, 374, 381; 42 U.S.C. 216, 262, 263, 263a, 264, 271, 300aa-25. 13. Section 600.16 is added to subpart B to read as follows: § 600.16 Prohibited cattle materials.

(a)*Definitions* . The definitions and interpretations of terms contained in section 201 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321), section 351 of the Public Health Service Act (the PHS Act) (42 U.S.C. 262), and § 600.3 apply to such terms when used in this section. The following definitions also apply:

(6)*Tallow* means the rendered fat of cattle obtained by pressing or by applying any other extraction process to tissues derived directly from discrete adipose tissue masses or to other carcass parts and tissues. Tallow must be produced from tissues that are not prohibited cattle materials or must contain not more than 0.15 percent insoluble impurities as determined by the method entitled “Insoluble Impurities” (AOCS Official Method Ca 3a-46), American Oil Chemists' Society (AOCS), 5th Edition, 1997, incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS Official Method Ca 3a-46. You may obtain copies of the method from AOCS ( *http://www.aocs.org* ) 2211 W. Bradley Ave., Champaign, IL 61821. Copies may be examined at the Center for Food Safety and Applied Nutrition's Library, 5100 Paint Branch Pkwy., College Park, MD 20740, or at the National Archives and records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to: *http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html* .

(b)*Requirements* .

(1)At a minimum, except as provided in paragraphs (b)(2) and (b)(4) of this section, no biological product intended for use in humans shall be manufactured from, or otherwise contain, prohibited cattle materials obtained from cattle slaughtered on or after [effective date of final rule].

(i)To obtain written permission from FDA, you must send a written request to the Director of the Center for Biologics Evaluation and Research (see § 600.2 for mailing address) or the Director of the Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers lane, Rockville, MD 20857, depending on the Center with primary jurisdiction over the product. Your written request must reference its application number. The Center Director may also grant written permission for an exception or alternative to the requirements in paragraph (b)(1) of this section on his own initiative and shall base such a determination on an evaluation of the criteria described in paragraph (b)(2)(ii) of this section. You must maintain a record of any exception or alternative to the requirements in paragraph (b)(1) of this section that is granted by FDA, in accordance with paragraph

(c)of this section.

(ii)A written request for an exception or alternative to the requirements in paragraph (b)(1) of this section must include, for each applicable product:

(A)A statement of the reasons why an exception or alternative is needed;

(B)A description of the product, including the type of prohibited cattle materials used in its manufacturing, its manufacturing and purification processes, and its route of administration;

(D)A description of how the requirements in paragraph (b)(1) in this section are not necessary based on the risks of the prohibited cattle materials in the product and the benefits of the product or how such restrictions are not necessary to ensure the safety of the product; and

(E)Any other relevant information.

(iii)FDA shall respond in writing to all requests for an exception or alternative to the requirements and may impose conditions in granting any request.

(4)Biological products that are not intended for use in or on the body (e.g., in vitro diagnostics) are not subject to the requirements of paragraph (b)(1) of this section.

(c)*Records* .

(1)Establishments that manufacture a biological product intended for use in or on the body that is manufactured from, or otherwise contains, cattle material must establish and maintain records sufficient to demonstrate that the material is not manufactured from, and does not contain, prohibited cattle materials.

(2)Records must be retained consistent with § 600.12(b).

(3)Records must be retained at the manufacturer's establishment or at a reasonably accessible location. Records are considered to be reasonably accessible if they are accessible from an onsite location.

(4)Records required by this section must be available to FDA for inspection and copying. All the records must be in English.

(5)When filing entry with the U.S. Customs and Border Protection, the importer of record of a biological product intended for use in or on the body that was manufactured from, or otherwise contains, cattle material must affirm that the product was manufactured from, or otherwise contains, cattle material and must affirm that the product was manufactured in accordance with this section. If a product was manufactured from, or otherwise contains, cattle material, then the importer of record must, if requested, provide to FDA within 5 days records that are sufficient to demonstrate that the product is not manufactured from, and does not contain, prohibited cattle material.

(d)A biological product that is a drug and that is not in compliance with the requirements of paragraph

(b)of this section is adulterated under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 351(a)(2)(B)) and not safe, pure, and potent under section 351 of the PHS Act (42 U.S.C. 262).

(e)Failure of an applicant or manufacturer of a biological product that is a drug to comply with the requirements of paragraph

(c)of this section renders such product adulterated under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 351(a)(2)(B)) and not safe, pure, and potent under section 351 of the PHS Act (42 U.S.C. 262).

(f)Failure of an importer of record to comply with the requirements of paragraph

(c)of this section causes a biological product to appear to be adulterated under section 801(a) of the act (21 U.S.C. 381).

(g)A biological product that is a new drug and that is not in compliance with the requirements of paragraph

(b)of this section is in violation of section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) and section 351 of the PHS Act (42 U.S.C. 262).

(h)A biological product that is a device and that is not in compliance with the requirements of paragraph

(b)of this section is adulterated under section 501(g) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 351(g)) and in violation of section 351 of the PHS Act (42 U.S.C. 262).

(i)Failure of an applicant or manufacturer to comply with the requirements of paragraph

(c)of this section is a violation of section 301(e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 331(e)).

(j)Any person who violates the requirements of paragraph

(b)or

(c)of this section shall be subject to the penalties provided in section 368 of the PHS Act (42 U.S.C. 271). PART 895—BANNED DEVICES 14. The authority citation for 21 CFR part 895 is revised to read as follows: Authority: 21 U.S.C. 331, 351, 352, 360f, 360h, 360i, 371, 381; 42 U.S.C. 264, 271. 15. Section 895.102 is added to subpart B to read as follows: § 895.102 Prohibited cattle materials.

(1)*Prohibited cattle materials* means specified risk materials; small intestine of all cattle except as provided in paragraph (b)(3) of this section; material from nonambulatory disabled cattle; material from cattle not inspected and passed; or mechanically separated beef. Prohibited cattle materials do not include tallow that contains no more that 0.15 percent insoluble impurities, tallow derivatives, hides and hide-derived products, and milk and milk products. Prohibited cattle materials also do not include materials obtained from fetal calves of cows that were inspected and passed, as long as the materials were obtained by procedures adequate to prevent contamination with specified risk materials.

(5)*Specified risk materials* means the brain, skull, eyes, trigeminal ganglia, spinal cord, vertebral column (excluding the vertebrae of the tail, the transverse processes of the thoracic and lumbar vertebrae, and the wings of the sacrum), and dorsal root ganglia of cattle 30 months or older and the tonsils and distal ileum of the small intestine of all cattle.

(6)*Tallow* means the rendered fat of cattle obtained by pressing or by applying any other extraction process to tissues derived directly from discrete adipose tissue masses or to other carcass parts and tissues. Tallow must be produced from tissues that are not prohibited cattle materials or must contain not more than 0.15 percent insoluble impurities determined by the method entitled “Insoluble Impurities” (AOCS Official Method Ca 3a-46), American Oil Chemists' Society (AOCS), 5th Edition, 1997, incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS Official Method Ca 3a-46. You may obtain copies of the method from AOCS ( *http://www.aocs.org* ) 2211 W. Bradley Ave., Champaign, IL 61821. Copies may be examined at the Center for Food Safety and Applied Nutrition's Library, 5100 Paint Branch Pkwy., College Park, MD 20740, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to: *http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html* .

(b)*Requirements* .

(1)At a minimum, except as provided in paragraph (b)(2) of this section, no medical device for humans that is intended for use in or on the body shall be manufactured from, or otherwise contain, prohibited cattle materials obtained from cattle slaughtered on or after [effective date of final rule].

(i)To obtain written permission from FDA, you must send a written request to the Director of the Center for Devices and Radiological Health, 9200 Corporate Blvd., Rockville, MD 20850. For a device subject to premarket approval or premarket clearance, your written request must reference its application number. The Center Director may also grant written permission for an exception or alternative to the requirements in paragraph (b)(1) of this section on his own initiative and shall base such a determination on an evaluation of the criteria described in paragraph (b)(2)(ii) of this section. You must maintain a record of any exception or alternative to the requirements in paragraph (b)(1) of this section that is granted by FDA, in accordance with paragraph

(c)of this section.

(ii)A written request for an exception or alternative to the requirements in paragraph (b)(1) of this section must include, for each applicable product:

(A)A statement of the reasons why an exception or alternative is needed;

(B)A description of the product, including the type of prohibited cattle materials used in its manufacturing, its manufacturing and purification processes, and its route of administration;

(E)Any other relevant information.

(iii)FDA shall respond in writing to all requests for an exception or alternative to the requirements and may impose conditions in granting any such request.

(c)*Records* .

(1)Applicants and manufacturers of a medical device that is intended for use in or on the body that is manufactured from, or otherwise contains, cattle material must establish and maintain records sufficient to demonstrate that the material is not manufactured from, and does not contain, prohibited cattle materials.

(2)Records must be retained consistent with § 820.180(b) of this chapter.

(4)Records required by this section must be available to FDA for inspection and copying. All the records must be in English.

(5)When filing entry with the U.S. Customs and Border Protection, the importer of record of a medical device intended for use in or on the body that was manufactured from, or otherwise contains, cattle material must affirm that the device was manufactured from, or otherwise contains, cattle material and must affirm that the device was manufactured in accordance with this section. If a device was manufactured from, or otherwise contains, cattle material, then the importer of record must, if requested, provide to FDA within 5 days records that are sufficient to demonstrate that the device is not manufactured from, and does not contain, prohibited cattle material.

(d)A medical device that is intended for use in or on the body that is not in compliance with the requirements of paragraph

(b)of this section is adulterated under section 501(g) of the act (21 U.S.C. 351(g)).

(e)Failure of an applicant or manufacturer of a medical device that is intended for use in or on the body to comply with the requirements of paragraph

(c)of this section renders the device misbranded under section 502(t) of the act (21 U.S.C. 352(t)).

(f)Failure of an importer of record to comply with the requirements of paragraph

(c)of this section causes a medical device that is intended for use in or on the body to appear to be adulterated under section 801 of the act (21 U.S.C. 381).

(g)Failure of an applicant or manufacturer to comply with the requirements of paragraph

(c)of this section is a violation of section 301(e) of the act (21 U.S.C. 331(e)).

(h)Any person who violates the requirements of paragraph

(b)or

(c)of this section shall be subject to the penalties provided in section 368 of the Public Health Service Act (42 U.S.C. 271). PART 1271—HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS 16. The authority citation for 21 CFR part 1271 continues to read as follows: Authority: 42 U.S.C. 216, 243, 263a, 264, 271. 17. Part 1271 is amended by adding new subpart G to read as follows: Subpart G—Prohibited Cattle Materials § 1271.465 Applicability. The provisions set forth in this subpart are applicable only to HCT/Ps described in § 1271.10 and regulated solely under section 361 of the Public Health Service Act (the PHS Act) (42 U.S.C. 264) and the regulations in this part, and to the establishments that manufacture those HCT/Ps. HCT/Ps that are drugs or devices regulated under the Federal Food, Drug, and Cosmetic Act, or are biological products regulated under section 351 of the PHS Act (42 U.S.C. 262), are not subject to the regulations set forth in this subpart. Such products are subject to the applicable regulations for biological products and for drugs or devices. § 1271.470 Prohibited cattle materials.

(a)*Definitions* . The following definitions apply to this section:

(6)*Tallow* means the rendered fat of cattle obtained by pressing or by applying any other extraction process to tissues derived directly from discrete adipose tissue masses or to other carcass parts and tissues. Tallow must be produced from tissues that are not prohibited cattle materials or must contain not more than 0.15 percent insoluble impurities as determined by the method entitled “Insoluble Impurities” (AOCS Official Method Ca 3a-46), American Oil Chemists' Society (AOCS), 5th Edition, 1997, incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS Official Method Ca 3a-46. You may obtain copies of the method from AOCS ( *http://www.aocs.org* ) 2211 W. Bradley Ave., Champaign, IL 61821. Copies may be examined at the Center for Food Safety and Applied Nutrition's Library, 5100 Paint Branch Pkwy., College Park, MD 20740, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to: *http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html* .

(b)*Requirements* .

(1)At a minimum, except as provided in paragraph (b)(2) of this section, no HCT/P intended for use in humans shall be manufactured using, or otherwise contain, prohibited cattle materials obtained from cattle slaughtered on or after [effective date of final rule].

(i)To obtain written permission from FDA, you must send a written request to the Director of the Center for Biologics Evaluation and Research (see § 600.2 of this chapter for mailing address). The Center Director may also grant written permission for an exception or alternative to the requirements in paragraph (b)(1) of this section on his own initiative and shall base such a determination on an evaluation of the criteria described in paragraph (b)(2)(ii) of this section. You must maintain a record of any exception or alternative from the requirements in paragraph (b)(1) of this section that is granted by FDA, in accordance with paragraph

(c)of this section.

(ii)A written request for an exception or alternative to the requirements in paragraph (b)(1) of this section must include, for each applicable product:

(A)A statement of the reasons why an exception or alternative is needed;

(B)A description of the product, including the type of prohibited cattle materials used in its manufacturing, its manufacturing and purification processes, and its route of administration;

(E)Any other relevant information.

(iii)FDA shall respond in writing to all requests for an exception or alternative to the requirements and may impose conditions in granting any request.

(c)*Records* .

(1)Establishments that manufacture an HCT/P that is manufactured using, or otherwise contains, cattle material must establish and maintain records sufficient to demonstrate that the material is not manufactured using, and does not contain, prohibited cattle materials.

(2)Records must be retained for the period specified in § 1271.270(d).

(4)Records required by this section must be available to FDA for inspection and copying. All the records must be in English.

(5)When filing entry with the U.S. Customs and Border Protection, the importer of record of an HCT/P manufactured using, or otherwise containing, cattle material must affirm that the HCT/P was manufactured using, or otherwise contains, cattle material and must affirm that the HCT/P was manufactured in accordance with this section. If an HCT/P was manufactured using, or otherwise contains, cattle material, then the importer of record must, if requested, provide to FDA within 5 days records that are sufficient to demonstrate that the HCT/P is not manufactured using, and does not contain, prohibited cattle material.

(d)An HCT/P that is not in compliance with the requirements of paragraph

(b)or

(c)of this section is a violative HCT/P that is subject to retention, recall, destruction, and/or cessation of manufacturing under § 1271.440. Dated: December 7, 2006. Jeffrey Shuren, Assistant Commissioner for Policy. [FR Doc. E6-22329 Filed 1-11-07; 8:45 am] BILLING CODE 4160-01-S 72 8 Friday, January 12, 2007 Proposed Rules Part III Fish and Wildlife Service 50 CFR Parts 17 Endangered and Threatened Wildlife and Plants; Withdrawal of Proposed Rule To List Lepidium papilliferum (Slickspot Peppergrass); Proposed Rule DEPARTMENT OF THE INTERIOR Fish and Wildlife Service 50 CFR Part 17 RIN 1018-AU99 Endangered and Threatened Wildlife and Plants; Withdrawal of Proposed Rule To List Lepidium papilliferum (Slickspot Peppergrass) AGENCY: Fish and Wildlife Service, Interior. ACTION: Proposed rule; withdrawal. SUMMARY: We, the U.S. Fish and Wildlife Service (Service), again withdraw our July 15, 2002, proposal (67 FR 46441) to list *Lepidium papilliferum* (slickspot peppergrass) as an endangered species under the Endangered Species Act of 1973, as amended (Act). The best available data for *L. papilliferum* indicates that, while its sagebrush-steppe matrix habitat is degraded, there is little evidence of negative impacts on the abundance of *L. papilliferum* , which inhabits slickspot microsites within this system. Annual abundance of the plant is strongly correlated with spring precipitation, therefore a high degree of variability in annual abundance is to be expected. Data on overall population trends are inconsistent; although recent declines that do not correlate with spring rainfall are noted in one portion of the species' range, range-wide data demonstrate increases in abundance that continue to track consistently with rainfall during those same years. The best available range-wide data indicate that abundance of the population range-wide is strongly correlated with precipitation and has increased in recent years in association with increased rainfall, as expected. ADDRESSES: Supporting documentation for this action is available for public inspection, by appointment, during normal business hours at the Snake River Fish and Wildlife Office, 1387 S. Vinnell Way, Boise, ID 83709. FOR FURTHER INFORMATION CONTACT: Jeffery Foss, Field Supervisor, Snake River Fish and Wildlife Office at the above address; by telephone at 208/378-5243; by facsimile at 208/378-5262; or by electronic mail at: *fw1srbocomment@fws.gov* . SUPPLEMENTARY INFORMATION: Species Information *Lepidium papilliferum* was originally described as *L. montanum* var. *papilliferum* in 1900 by Louis Henderson. It was renamed *L. papilliferum* by Aven Nelson and J. Francis Macbride in 1913, based on its distinctive growth habit, short lifespan, and unusual pubescence (Nelson and Macbride 1913, p. 474). Hitchcock regarded *L. papilliferum* as *L. montanum* var. *papilliferum* (Hitchcock *et al.* 1964, p. 516; Hitchcock and Cronquist 1973). In a review of taxa in the mustard family (Brassicaceae), Rollins

(1993)maintained the species based on differences in the physical features between *L. papilliferum* and *L. montanum* . More recently, a taxonomic review concluded that *L. papilliferum* warrants species recognition based on distinct morphological features (Lichvar 2002), and a contrasting life history when compared to *L. montanum* regarding seed dormancy and its seed bank (Meyer *et al.* 2005, p. 21). The preliminary results of recent genetic studies comparing *L. papilliferum* with *L. montanum* indicate that *L. papilliferum* forms a monophyletic group or subgroup that is genetically distinct from *L. montanum* (Larson *et al.* 2006, p. 13 and Figs. 4, 8; Smith 2006, pp. 5-7, Fig. 1). The currently accepted taxonomy recognizes *Lepidium papilliferum* (Henderson) A. Nels and J.F. Macbr as a full species (Taxonomic Serial No. 53383, Integrated Taxonomic Information System (ITIS), 2006). Biology *Lepidium papilliferum* is a taprooted, intricately branched plant. The plant flowers once and then dies (it is monocarpic), and displays two different life cycles, an annual and a biennial form. The plant averages 2 to 8 inches

(in)(5 to 20 centimeters (cm)), but can reach up to 16 in (40 cm) in height. Leaves and stems are covered with fine, soft hairs, and the leaves are divided into linear segments. Flowers are numerous, 0.1 in (3 to 4 millimeter (mm)) diameter, white, and 4-petalled. Fruits (siliques) are 0.1 in (3 mm), round in outline, flattened, and 2-seeded (Moseley 1994, pp. 3 and 4; Holmgren *et al.* 2005, p. 260). The annual form of the *Lepidium papilliferum* matures, reproduces by setting seed, and dies in one growing season. The biennial life form initiates growth in the first year as a rosette, but does not produce seed and die until the second year. Biennial rosettes must survive dry summers on the Snake River Plain and Owyhee Plateau, and consequently many of these rosettes die before flowering and producing seed. The proportion of annuals versus biennials in a population can vary greatly (Meyer *et al.* 2005, p. 15). Depending on individual plant vigor and the effectiveness of pollination, dozens, if not thousands, of seeds can be produced by a single *L. papilliferum* plant (Quinney 1998, pp. 15 and 17), with individual biennial plants producing a much greater number of seeds than annual plants (Meyer *et al.* 2005, p. 15). Average seed output for annual plants at the Orchard Training Area

(OTA)(an Idaho Army National Guard training area on BLM land) in 1993, was 125 seeds per plant, and in 1994, was 46 seeds per plant. Biennial seed production in 1993 and 1994 averaged 787 and 105 seeds per plant, respectively (Meyer *et al.* 2005, p. 16). *Lepidium papilliferum* seeds produced in a given year are dormant for at least a year before any germination takes place. Following this year of dormancy, approximately 6 percent of seeds produced in a given year germinate annually and approximately 3 percent die annually (Meyer *et al.* 2005, pp. 17, 18). After 12 years, all seeds in a given cohort will likely have either died or germinated (Meyer *et al.* 2005, p. 18). Seeds are released in late June or early July. Like many short-lived plants growing in arid environments, above-ground numbers of *Lepidium papilliferum* individuals can fluctuate widely from one year to the next, depending on seasonal precipitation patterns (Mancuso and Moseley 1998, p. 1; Meyer *et al.* 2005, pp. 4, 12, 15; Palazzo *et al.* 2005, p. 9; Menke and Kaye 2006a, p. 8; Menke and Kaye 2006b, pp. 10, 11). In an analysis of monitoring data, minimum and maximum temperatures were not statistically correlated with *L. papilliferum* abundance (Menke and Kaye 2006b, p. 8). Above-ground plants represent only a portion of the population; the seed bank (a reserve of dormant seeds, generally found in the soil) contributes the other portion, and apparently in many years constitutes the majority of the population (Mancuso and Moseley 1998, p. 1). According to Meyer *et al.* (2005, p. 21), “Without a persistent seedbank, *L. papilliferum* could probably not succeed as an annual in its stochastically varying habitat.” Seed banks are adaptations for survival in a “risky environment,” because they buffer a species from stochastic impacts such as lack of soil moisture (Baskin and Baskin 2001, p. 160). *Lepidium papilliferum* seeds have an extremely patchy distribution, making it difficult to estimate seed density without taking a large number of samples (Meyer and Allen 2005, pp. 5, 6). The vast majority of *L. papilliferum* seeds in slickspots (see Ecology and Habitat section) have been located near the soil surface, with lower numbers of seeds located in deeper soils (Meyer * et al. * 2005, p. 19; Palazzo *et al.* 2005, p. 3). *L. papilliferum* seeds have been found in slickspots with no above-ground plants (Meyer *et al.* in press, p. 18; Palazzo *et al.* 2005, p. 10). Viable seeds have also been located outside of slickspots, indicating that some seed dispersal is occurring beyond slickspot habitat (Palazzo *et al.* 2005, p. 10). The primary seed dispersal mechanism for *L. papilliferum* has not been identified and is not known (Robertson and Ullappa 2004, p. 1708). *Lepidium papilliferum* seeds located near the soil surface show higher rates of germination and viability (Meyer and Allen 2005, pp. 6 to 8; Palazzo *et al.* 2005, p. 10), and the greatest seedling emergence success rate (Meyer and Allen 2005, pp. 6 to 8). Seeds were more abundant, more viable, and had greater germination percentages and rates from the upper 2 in (5 cm) of soil (Palazzo *et al.* 2005, pp. 8, 10). In another study, the highest level (60 percent) of seedling emergence was observed at a seed depth of 0.1 in (approximately 2 mm), with a marked decrease in seedling emergence at 0.2 in (approximately 5 mm) (Meyer and Allen 2005, pp. 6, 7). Deep burial of slickspot peppergrass seeds (average depths greater than 5.5 in (14 cm)) entombs seeds that are still viable and preserves them beyond the 12-year period previously assumed as the maximum period of viability for *Lepidium papilliferum* seeds (Meyer and Allen 2005, pp. 6, 9). While there may be processes such as badger ( *Taxidea taxus* ) burrow-digging that could return these buried viable seeds to the near-surface, the successful establishment of seedlings may be reduced due to modification of soil layers following previous disturbance events (Meyer and Allen 2005, pp. 6, 8). The effects of environmental threats such as wildfire on *L. papilliferum* seed dormancy and viability are currently unknown. *Lepidium papilliferum* has low seed set in the absence of pollinators, and is primarily an outcrossing species requiring pollen from separate plants for more successful fruit production (Robertson 2003a, p. 5; Robertson and Klemash 2003, p. 339; Robertson and Ulappa 2004, p. 1707). In pollination experiments where researchers moved pollen from one plant to another, fruit production was observed to be higher with pollen from distant sources 246 to 330 feet

(ft)(75 to 100 meters (m)) away within a plant patch, and 4 to 12.4 miles

(mi)(6.5 to 20 kilometers (km)) away from another patch of plants (Robertson and Ulappa 2004, p. 1705). Genetic exchange can occur either thorough pollen or seed dispersal. *Lepidium papilliferum* has been observed to be visited by at least 25 families of insects, although only some of these insects serve as effective pollinators (Robertson 2003b, pp. 10, 11; Robertson and Klemash 2003, p. 336). Scarcity of pollinators were not found to limit seed set at any site (Robertson *et al.* 2004, p. 14). Pollinators include insects from several families of bees and ants (Hymenoptera), including Apidae, Halictidae, Sphecidae, and Vespidae; beetles (Coleoptera), including Dermestidae, Meloidae, and Melyridae; flies (Diptera), including Bombyliidae, Syrphidae, and Tachinidae; and others (Robertson and Klemash 2003, p. 336). The pollen transfer efficiency for *L. papilliferum* varies among these insects. Pollinators of *L. papilliferum* with high pollen transfer efficiencies and visitation rates include sphecid and vespid wasps, bombyliid and tachnid flies, and honeybees, with lesser contributions from halictid bees. The genetics of *Lepidium papilliferum* were studied using samples collected from areas across the entire range of the species, including both the Snake River Plain and a disjunct range on the Owyhee Plateau (Stillman *et al.* 2005, pp. 6, 8, 9). The largest amounts of genetic difference occurred between the Snake River Plain and the Owyhee Plateau populations. The Snake River Plain and the Owyhee Plateau populations are separated by 44 mi (70 km), which is considered beyond the distance that insect pollinators can travel or that seed dispersal can occur. Despite the distance that separates the Snake River Plain and the Owyhee Plateau populations, plants from these two areas share a 94-percent similarity in allelic diversity. This high degree of similarity suggests that they were either part of one continuous distribution or they originated from similar ancestral material (Stillman *et al.* 2005, pp. 6, 8, 9). Sites in the Snake River Plain with fewer numbers of plants had less genetic diversity than sites with larger numbers of plants. Interestingly, a correlation between population size and genetic diversity did not exist in the Owyhee Plateau region. The authors suggested that this may be because the Owyhee Plateau region is less fragmented than the Snake River Plain, but suggested further genetic research is needed. Larson (2006, p. 14 and Fig. 4) also found geographically well-defined populations of *Lepidium papilliferum* between the Snake River Plain and Owyhee Plateau based on genetics. In contrast to the Stillman *et al.*

(2005)study, Larson's findings indicate the possibility of depressed genetic diversity in *L. papilliferum* based on significantly greater average similarity coefficients within collection sites of *L. papilliferum* compared to those of *L. montanum,* (Larson *et al.* 2006, p. 13). Ecology and Habitat The habitat of *Lepidium papilliferum* is found within semiarid sagebrush-steppe habitats in southern Idaho. This plant is known from the extensive volcanic plains of the Snake River Plain (and foothills) and the Owyhee Plateau, with most element occurrences

(EOs)occurring on flat to gently sloping terrain (see Figure 1 below). Element occurrences are defined as “an area of land in which a species is or was present” (NatureServe 2002). *L. papilliferum* is associated with basalt ridges and plains, stable piedmont, and older alluvial floodplains and deposits (Fisher *et al.* 1996, pp. 14, 16). BILLING CODE 4310-55-C EP12JA07.000 BILLING CODE 4310-55-P Range-wide, *Lepidium papilliferum* is associated with visually distinct microsites known as slickspots (mini-playas or natric sites) (Moseley 1994, p. 7). Slickspots are distinguished from the surrounding sagebrush matrix as having the following characteristics—microsites where water pools when rain falls (Fisher *et al.* 1996, pp. 2, 4); little vegetation; more distinct soil layers with a more columnar or prismatic structure; higher alkalinity and clay content and natric (higher sodium) properties (Fisher *et al.* 1996, pp. 15, 16; Meyer and Allen 2005, pp. 3 to 5, 8); and reduced levels of organic matter and nutrients due to lower biomass production (Meyer and Quinney 1993, pp. 3, 6; Fisher *et al.* 1996, p. 4). The slickspots range in size from less than 10 square feet (ft 2 ) (1 square meter (m 2 )) to about 110 ft 2 (10 m 2 ) (Mancuso *et al.* 1998, p. 1), but most are between 10 ft 2 and 20 ft 2 (1 m 2 and 2 m 2 ). Slickspots cover a relatively small cumulative area within the larger sagebrush-steppe matrix, and only a small percentage of slickspots are known to be occupied by *Lepidium papilliferum* . For example, a thorough field inventory within the Juniper Butte Range in 2002 found that of the 11,070 acres

(ac)(4,480 hectares (ha)) surveyed, approximately 1 percent (109 ac (44 ha)) consisted of slickspot habitat, and only 4 percent of the slickspot habitat was occupied by above-ground *L. papilliferum* plants (U.S. Air Force 2002, p. 9). The total amount of occupied slickspot habitat (above-ground plants and known occurrences of seed in the soil) within this large occurrence was approximately 4 ac (1.6 ha) at the time it was surveyed (0.1 percent of the acreage). Based on studies in 2004 on the Orchard Training Area (OTA), a training area of the Idaho Army Reserve National Guard (IARNG) on the Snake River Plain, slickspots have three primary layers: the surface silt layer, the restrictive layer, and the moist clay layer beneath. The top two layers (surface silt and restrictive) of slickspots are very thin; the surface silt layer varies in thickness from 0.1 to 1.2 in (a few mm to 3 cm) in slickspots known to support *Lepidium papilliferum* , and the restrictive layer varies in thickness from 0.4 to 1.2 in (1 to 3 cm) (Meyer and Allen 2005, p. 3). The moist clay basal layer, which continues down to bedrock, is consistently below the restrictive layer (Meyer and Allen 2005, p. 3). All slickspots have variations in surface silt thickness. As part of the *Lepidium papilliferum* Habitat Integrity and Population

(HIP)monitoring conducted range-wide in 2005, the depth of the surface silt layer was measured 3 times in every slickspot along 79 transects across the range of *L. papilliferum* ; a total of 769 slickspots were sampled. Measurements were taken directly adjacent to live *L. papilliferum* plants; the range-wide mean surface silt layer depth was 0.31 in (0.78 cm) (Colket 2006a). The surrounding sagebrush matrix soils are distinguished from slickspot soils by a deeper silt layer with a clay layer beneath, and usually the restrictive layer is lacking (Meyer and Allen 2005, pp. 3 to 5). Non-slickspot soils at the OTA had thick silt layers with a mean depth of 4.7 in (12 cm); the silt layer typically transitioned directly into the clay layer beneath, although some samples had restrictive layers which were abnormally thickened (over 3.9 in (10 cm)) (Meyer and Allen 2005, pp. 3 to 5, 8). It is unknown how long slickspots take to form, but it is hypothesized to take several thousands of years (Nettleton and Petersen 1983, p. 193; Seronko 2006, p. 1). The conditions that allowed for the formation of slickspots in southwestern Idaho are thought to have occurred during a wetter Pleistocene climate. Holocene additions of wind-carried salts (often loess deposits) produced soils high in sodium (natric) (Nettleton and Petersen 1983, p. 191; Seronko 2006, p. 1). It may take several hundred years to alter or lose slickspots through natural climate change or severe natural erosion (Seronko 2006, p. 1). Some researchers hypothesize that, given current climatic conditions, new slickspots are no longer being created (Nettleton and Petersen 1983, pp. 166, 191, 206), but that some slickspots subjected to light disturbance in the past may re-form (Seronko 2006, p. 1). Slickspots may be destroyed and lost to disturbances that alter the physical properties of the soil layers. The forces that hold clay particles together are greatly weakened when sodium-clay and water come into contact. In this condition, clay particles are easily detached or dispersed from larger aggregates, i.e., slickspot soils are especially susceptible to mechanical disturbances when wet (Rengasmy *et al.* 1984, p. 63; Seronko 2004, pp. 1, 2). Such disturbances disrupt the soil layers important to *Lepidium papilliferum's* seed germination and seedling growth. Meyer and Allen (2005, p. 9) suggest that if sufficient time passes following the disturbance of slickspot soil layers, it is possible that the slickspot soil layers may reform similar to their pre-disturbance configuration. Slickspots that no longer support *L. papilliferum* , but still retain the thin silt and restrictive layer structure, are the most likely sites to support reintroductions. Restoration and species reintroduction potential for *L. papilliferum* habitat have not been studied. The highest monthly temperatures within the range of *Lepidium papilliferum* normally occur in July (approximately in the low 90 degrees Fahrenheit (approximately 33 degrees Celsius)), and lowest monthly temperatures occur in January (approximately in the low 20 degrees Fahrenheit (minus 7 degrees Celsius)). Average precipitation within the species' range is 11.7 in (29.7 cm) for Boise, 7.4 in (18.8 cm) for Bruneau, and 9.9 in (25.1 cm) for Mountain Home. Precipitation tends to fall as rain, primarily in winter and spring (November to May); the lowest rainfall occurs in July and August, and June, September, and October receive slightly more. Freeze-free days average about 120 days in Boise, 146 days in Bruneau, and 138 days in Mountain Home (WRCC 2006). Spring precipitation has been correlated with above-ground numbers of *Lepidium papilliferum* in several analyses. Palazzo *et al.* (2005, p. 9) and Menke and Kaye (2006a, p. 8) utilized Habitat Integrity Index

(HII)range-wide data collected from 1998 to 2001. Menke and Kaye (2006b, pp. 10, 11) utilized HII data collected from 1998 to 2002, as well as 2004 Habitat Integrity and Population

(HIP)data. Meyer *et al.* (2005, p. 15) utilized demographic data from the OTA collected from 1993 to 1995. Palazzo *et al.* (2005, p. 9) found a positive relationship (p-value of less than 0.01) between above-ground plants and February to June precipitation. Menke and Kaye (2006a, p. 8) found March to May precipitation accounted for 99.4 percent (2006a, p. 8) and 89 percent (2006b, pp. 10, 11) of the variation in *L. papilliferum* numbers. Meyer *et al.* (2005, p. 15) found that an increase in February through May precipitation increased the number of *L. papilliferum* seedlings at the OTA. This correlation of abundance with spring rainfall is important, as it at least partially explains past fluctuations in population numbers, and suggests that perceived declines were largely a result of years with low precipitation levels. Menke and Kaye (2006b, p. 8) also found that minimum and maximum temperatures were not statistically correlated with *L. papilliferum* abundance. The sparse native vegetation naturally present at slickspots suggests that *Lepidium papilliferum* is more tolerant than surrounding vegetation at surviving in alkaline soils and spring inundation. Plant ecology literature suggests that plants tolerant of stress ( *e.g.* , alkaline soils) are poor competitors (Grime 1977, p. 1185). Range and Distribution *Lepidium papilliferum* is known only from the Snake River Plain and its adjacent northern foothills (an area 90 by 25 mi (145 by 40 km)) in southwest Idaho, and a disjunct population on the Owyhee Plateau in Idaho (see Figure 1 above). The plant occurs at elevations ranging from approximately 2,200 ft (670 m) to 5,400 ft (1,645 m) in Ada, Canyon, Gem, Elmore, Payette, and Owyhee Counties (Moseley 1994, pp. 3 to 9). The separation of population centers into two physiographic regions is important for the conservation of *L. papilliferum* . We regard the two physiographic regions as two distinct metapopulations, the Snake River Plain metapopulation and the Owyhee Plateau metapopulation. Metapopulation concepts are useful when considering fragmented habitats, such as those within *L. papilliferum's* range, because they include discussion of when extinction events exceed colonization events, which can cause the species to not persist (Husband and Barrett 1996, pp. 461 to 462). In 2003, a “Candidate Conservation Agreement for Slickspot Peppergrass ( *Lepidium papilliferum* )”

(CCA)was developed by several State, Federal, and private entities in Idaho (State of Idaho *et al.* 2003) (see Previous Federal Actions section). The CCA is based on two geographical management areas that include known EOs, one on the Snake River Plain and a second on the Owyhee Plateau, called “consideration zones.” Although somewhat arbitrary in nature, this designation is useful for management purposes. There are 1,595,205 ac (645,597 ha) within the Snake River Plain consideration zone, and 126,946 ac (51,373 ha) within the Owyhee Plateau consideration zone. Factors affecting the species vary between the two physiographic regions. For example, urban and rural development, agriculture, and infrastructure development of sagebrush-steppe habitat has been substantial within the Snake River Plain, but little development has occurred within the Owyhee Plateau portion of *L. papilliferum* 's range. Element occurrences have been used to describe distribution of *Lepidium papilliferum* by assuming that slickspots within 1 kilometer (0.6 mi) of each other are capable of genetic exchange through pollination (Colket and Robertson, pers. comm. 2006). As of February 2006, there were 85 delineated EOs that occupied 13,359 ac (5,406 ha) (Colket *et al.* 2006). We estimate that the actual acreage occupied by *L. papilliferum* is only a fraction of a percent of this total acreage number because the majority of slickspots are not occupied by *L. papilliferum* and slickspots occupy a small percentage of the landscape (see U.S. Air Force 2002, p. 9, for an example). Of these EOs, 60 (11,025.3 ac (4,461.8 ha)) occur on the Snake River Plain, and 25 (2,333.8 ac (944.5 ha)) occur on the Owyhee Plateau (Colket *et al.* 2006, Table 14). Of the total EO acreage, 521 ac (211 ha) (3.9 percent) occur on private lands, 1,254 ac (507 ha) (9.4 percent) occur on lands managed by the State of Idaho, and 11,582 ac (4,687 ha) (86.7 percent) occur on Federal lands (USFWS 2006c). On the Snake River Plain, 85 percent of the EO acreage occurs on federally managed lands, 10.3 percent of the EO acreage occurs on State-managed lands, and 4.7 percent of the EO acreage occurs on private lands. On the Owyhee Plateau, 94.7 percent of the EO acreage occurs on Federally managed lands, with the remaining 5.3 percent occurring on State managed lands; no EOs on the Owyhee Plateau occur on private lands. The approximate extant range of the plant was first described in 1994 (Moseley 1994, p. 6), and has not changed substantially since, although the amount of known occupied habitat, particularly on the Owyhee Plateau, has expanded in recent years. Since 2003, sixteen new occurrences, all within 3 mi (4.8 km) of previously existing occurrences, have been documented: 2 on the Snake River Plain with an area of 2.7 ac (1 ha) and approximately 2,500 individuals, and 14 on the Owyhee Plateau with an area of 46.6 ac (18 ha) and approximately 650 individuals (Colket *et al.* 2006, Tables and Appendix A). It should be noted that not all potential *L. papilliferum* habitat in southwest Idaho has been surveyed, and it is likely that additional occupied *L. papilliferum* sites will be found. Estimating the number of individuals (abundance) of *Lepidium papilliferum* is confounded by its annual or biennial life cycle, because the number of individuals of each life form can fluctuate widely depending on precipitation. To assess abundance, we utilized four available data sets: range-wide EO records maintained by the Idaho Conservation Data Center (CDC), range-wide data associated with the HII/HIP monitoring, transect monitoring data collected on the OTA, and special use plot data from the OTA. As of February 2006, the Idaho CDC had ranked 101 EO records for *Lepidium papilliferum* (Colket *et al.* 2006a, pp. 15 to 41); 9 are ranked as extirpated

(lost)or probably extirpated, and 7 are considered historical (information for most is too vague for relocation). All 9 extirpations were verified locations from old herbarium collections, the most recent from 1955, where the habitat has been completely converted to urban or agricultural lands (Colket *et al.* 2006, Table 13). The remaining 85 records (as of February 2006) are for EOs considered extant (existing). In the review of EO specifications and ranks conducted in February 2006, observed abundance was categorized as being greater than 1,000 plants, 400 to 999 plants, 50 to 399 plants, less than 50 plants, 0 plants, or an unknown number of plants. This classification was based on the number of plants present at the last survey, regardless of year and associated precipitation patterns. Existing data provide an estimated abundance for extant EOs: 15 (18 percent) have over 1,000 plants, 11 (13 percent) have between 400 and 999 plants, 1 (1 percent) has about 400 plants, 18 (21 percent) have between 50 and 399 plants, 22 (26 percent) have fewer than 50 plants, 9 (11 percent) had no plants at the last visit, and 9 (11 percent) have an unknown number of individuals. Two monitoring methods, HII and HIP, have been used range-wide for *Lepidium papilliferum* . Each included different methodologies, but are still useful for tracking abundance at transects across the two efforts. HII monitoring was developed to assess the overall habitat condition that includes attributes associated with the slickspots and the sagebrush-steppe habitat, occurred for 4 years (1998 to 2001), and is presented in various reports (Mancuso and Moseley 1998; Mancuso *et al.* 1998; Mancuso 2000, 2001, 2002; Menke and Kaye 2006a, b). HIP monitoring was developed to assess the overall habitat condition that includes those attributes associated with the slickspots and the sagebrush-steppe habitat, and also the effectiveness of the CCA. HIP monitoring was conducted in 2004 and 2005 (State of Idaho *et al.* 2006, p. 18), and is expected to continue. HIP monitoring results in 2004 are reported in Menke and Kaye 2006b, and results through 2005 are included in our report “Best Available Biological Information for Slickspot Peppergrass ( *Lepidium papilliferum* )” (USFWS 2006f, Figures 8, 9). Although neither the HII nor HIP methodologies have been peer reviewed, they represent the best available survey and monitoring techniques for *L. papilliferum* . Abundance data for *Lepidium papilliferum* have been collected range-wide since 1998, and collected at the OTA since the early 1990s. The range-wide HII and HIP transect data illustrate that plant abundance is positively correlated with spring precipitation, and specifically that rainfall in the months of March through May accounts for 89 percent of the variability in plant numbers (Menke and Kaye 2006b, p. 10). Plant abundance therefore fluctuates widely between years in association with precipitation. In the areas monitored by HII and HIP, Menke and Kaye (2006b, p. 10) report that *L. papilliferum* abundance decreased range-wide between 1998 and 1999, remained low through 2002, and began to increase again beginning in 2002. This pattern closely tracks that of rainfall during those same years. Abundance data from transects at the OTA illustrate declines in abundance first noted in 1996, with a declining trend in recent years that is not correlated with spring precipitation (Weaver 2006, pp. 1-6). Abundance data from the range-wide HII and HIP transects showed increasing trends in *L. papilliferum* between the years 2002 and 2005 (no data were collected in 2003) (USFWS 2006f, Figures 8, 9). Thus range-wide abundance data from the HII and HIP transects continue to show a consistently positive correlation with spring precipitation. We consider this range-wide data to be the best available at this time. We conducted a review of the abundance data and study methodology following the reopened comment period on the proposal to list *L. papilliferum* as endangered (October 23, 2006, to November 13, 2006; 71 FR 62078). A review of the special use plot counts at the OTA (USFWS 2006e, Figure 7) shows a decline in plant numbers during the drought years of 1992 (249 plants), 1997 (624 plants), and 2002 (270 plants) followed by a positive response in plant numbers as spring precipitation increased in subsequent years 1993 (6,369 plants), 1998 (3,330 plants), and 2003 (4,080 plants). Reviewing the special use plot data at OTA for 2004-2006 illustrates a relatively stable or declining number of plants despite increases in spring precipitation. We reviewed the OTA population monitoring transect study and updated the description of the study methods from our BAI based upon clarification of new information provided by IARNG staff during the reopened comment period on the proposal to list *L. papilliferum* as endangered (October 23, 2006, to November 13, 2006; 71 FR 62078). The BAI cited study methods as described by IARNG staff and stated that the census effort occurred annually at the OTA and that observers cover 98 percent of the plants' habitat at OTA. New information obtained since the BAI was written suggests that 90 percent may be a more accurate estimate of the amount of habitat surveyed at OTA. Since 2003, additional plant inventories have increased the size of the known population of *L. papilliferum* at OTA, including the documentation of 365 new occupied slickspots in 2005 (URS Corporation 2005, pp. 6-7). The OTA population monitoring transects for 2005 reported 18,599 plants in the transect areas; the survey inventory by URS corporation reported 43,925 plants (365 new slickspots with *L. papilliferum* , 125 historic slickspots with *L. papilliferum* , 66 historic slickspots without *L. papilliferum* ) in the areas surveyed at OTA (URS Corporation 2005, p. 7). We reviewed the results of range-wide HII and HIP monitoring, including reported plant abundance since these studies were initiated in 1998, and new information available to us since the time we last issued a listing finding on this species. These data illustrate a general pattern of plant numbers correlating with spring precipitation (USFWS 2006f, Figures 8, 9). Data are incomplete for 2002 and 2003. Menke and Kaye (2006b, p. 19) report that “populations generally decreased during 1998-2004 and these trends appear to be strongly influenced by spring precipitation.” In contrast to the results reported from the OTA, range-wide abundance of *Lepidium papilliferum* as measured by the HII and HIP increased as spring precipitation increased in the years 2002 through 2005 (USFWS 2006f, Figures 8, 9). Comparing years 1998 and 2005, which are relatively comparable in terms of range-wide spring precipitation (6.6 inches and 6.3 inches, respectively), plant numbers are also similar (17,611 and 15,226 respectively), indicating little change in overall abundance of *L. papilliferum* range-wide over this time interval, despite the intervening fluctuations in yearly abundance that are to be expected for an ephemeral annual plant. In general, the HII and HIP data from 1998-2005 indicate that the abundance of *L. papilliferum* range-wide remained relatively stable over this time interval (USFWS 2006f, Figure 8). We consider this range-wide data to be the best available at this time. Habitat Quality Vegetation community data are collected as one component of *Lepidium papilliferum* HIP monitoring. One of the attributes documented in HIP monitoring is the fire history pattern. Observations are recorded to document if there is evidence of fires at four landscape scales; in the HIP transects, and in the surrounding habitat at 65 meters, 250 meters, and 500 meters from the transect. Given the mosaic pattern of wildfire burns, often the surrounding habitat may be burned while an individual HIP transect is unburned or predominately unburned. In 2004, vegetation communities were sampled at 71 HIP transects, and 41 (58 percent) of the transects were classified as unburned, with predominantly big sagebrush cover and less than 33 percent introduced annual cover; 7 (10 percent) were classified as unburned, with moderate big sagebrush cover and at least 33 percent introduced annual cover; 6 (8 percent) were classified as burned, with predominantly native vegetation, although introduced annual cover sometimes comprised up to 50 percent of the total plant cover; 2 (3 percent) were classified as burned, with predominantly introduced annual cover ( *Salsola kali* (Russian thistle or tumbleweed) and *Ceratocephala testiculata* (bur buttercup, formerly *Ranunculus testiculatus* )), with low cheatgrass ( *Bromus tectorum* ) and some crested wheatgrass ( *Agropyron cristatum* ); 11 (14 percent) were classified as burned and dominated by cheatgrass; and 4 (6 percent) were classified as burned and seeded with crested wheatgrass (Colket 2005a, p. 8). In summary, over 42 percent of the HIP vegetation plots along HIP transects were in habitats with over 33 percent nonnative, invasive plant cover. Menke and Kaye (2006b) evaluated the association between measures of habitat quality measured by HIP and abundance of *L. papilliferum* . For the one year for which data were available (2004), they report that *L. papilliferum* abundance was not significantly correlated with soil crust cover or weedy species cover in slickspots, and that the proportion of flowering plants had a positive correlation with soil crust cover, but was not significantly correlated with livestock print cover or weedy species cover (Menke and Kaye 2006b, p. 15). In their overall evaluation of habitat condition, they report that total vascular plant cover, species richness, and species diversity had declined between 1998 and 2004, and suggest that past fires have been a factor in degrading slickspot condition (Menke and Kaye 2006b, p. 19). Several features of slickspots, including soil crust cover and weedy species cover, were consistently more degraded in burned areas. Although slickspots in burned areas had more dense weedy annual species cover (Menke and Kaye 2006b, p. 19), Menke and Kaye state that “Competition from weedy annual species (which may be promoted by fire), does not appear to influence abundance of *L. papilliferum* plants in a given year, but may influence reproductive output, other plant traits, and other life history stages' (Menke and Kaye 2006b, p. 17). Soil crust cover was significantly lower in 2004 transects with evidence of livestock grazing, but there was no direct relationship between abundance of *L. papilliferum* and total livestock print cover or cover of print penetrating to the slickspot clay layer (Menke and Kaye 2006b, p. 15). Another measure of habitat quality within *Lepidium papilliferum* 's range is the EO ranking by the Idaho CDC. The first EO ranks for *L. papilliferum* were assigned in 1993 (Colket *et al.* 2006, Tables 1-13). In 2006, EO specifications and ranking were revised by the Idaho CDC (Colket *et al.* 2006, pp. 15 to 44). Due to the change in methodology, it is difficult to draw conclusions about changes in EO rankings over time. EO ranks are designed as an assessment of estimated viability or probability of persistence and help prioritize conservation planning or actions (NatureServe 2002, p. 36). We consider EO rankings to be part of the best available data on the species at this time. Table 1 summarizes the rankings for 85 EOs based on the 2006 revised methodology. A-ranked EOs have one or more of the following conditions that are summarized through a formula:

(1)Over 1,000 detectable above-ground plants;

(2)intact native plant communities with trace nonnative species cover;

(3)slickspots with zero or trace nonnative cover or livestock disturbance;

(4)zero or few minor anthropogenic disturbances;

(5)a lack of burning; and

(6)a surrounding landscape within 0.6 mi (1 km) that is not fragmented by agricultural lands, residential or commercial development, introduced annual grasslands, or drill seeding projects (Colket *et al.* 2006, p. 3). By contrast, D-ranked EOs exist in the most highly degraded habitats, with the fewest plants, and with the most degraded surrounding landscape (Colket *et al.* 2006, p. 3). Table 1.—Number of Element Occurrences in 2006 by CDC Ranking (Percent of Total) [Colket *et al.* 2006, Tables 1 to 13 and Appendix C] A B BC C pC 1 D pD 1 E 2 F Total 0 15

(18)1

(1)26

(31)4

(5)19

(22)1

(1)10

(12)9

(11)85 1 Probable ranks assigned when incomplete information available. 2 Not enough habitat information available to make a ranking. Of the 66 EOs with B through D rankings (13,123 ac (5,310 ha)), 51 occur on the Snake River Plain (10,804 ac (4,372 ha)), and 15 on the Owyhee Plateau (2,318 ac (938 ha)). Of these 66 middle-ranked EOs, 50 are ranked as a C or D (averaging fewer than 399 plants, partial to nonexistent native plant communities that are partially to predominately burned, and partially to predominantly fragmented landscapes). The 40 EOs on the Snake River Plain cover 3,170 ac (1,283 ha), and the 10 EOs on the Owyhee Plateau cover 73 ac (30 ha). Habitat data (HII, HIP) have been collected annually for approximately one-half of the extant EOs since 1998. Given that monitoring methodologies and the specifications for determining EO rank changed in 2004/2005, and not every EO is monitored annually, it is not possible to draw definitive conclusions about the change in habitat quality over time. It is possible, however, to gain an understanding of the current condition of habitat quality from the available data. Based on the most recent EO ranks, at least 75 percent (n = 49) were ranked as C, D, or F, indicating that most EOs occurred in partially or predominantly fragmented landscapes with partial to nonexistent native plant communities. As discussed below we don't have any data that correlate *L. papilliferum* population numbers with effects to habitat. Previous Federal Actions For a description of Federal actions concerning *Lepidium papilliferum* that occurred prior to January 22, 2004, please refer to the document to withdraw our July 15, 2002, proposal published in the **Federal Register** on January 22, 2004 (69 FR 3094). On January 22, 2004, we published a document withdrawing our proposed rule to list *Lepidium papilliferum* as endangered (69 FR 3094). That action was based on our conclusion that there was “a lack of strong evidence of a negative population trend, and the formalized conservation plans ( *e.g.* , the CCA and INRMPs) had sufficient certainty that they would be implemented and effective such that the risk to the species was reduced to a level below the statutory definition of endangered or threatened.” On April 5, 2004, Western Watersheds Project filed a lawsuit challenging our decision to withdraw the proposed rule to list *Lepidium papilliferum* as threatened or endangered ( *Western Watersheds Project* v. *Jeffery Foss, et al.* , Case No. CV 04-168-S-EJL). On August 19, 2005, the U.S. District Court for the District of Idaho reversed the decision to withdraw the proposed rule, with directions that the case be remanded to the Secretary of the Department of Interior for reconsideration of “whether a proposed rule listing the slickspot peppergrass as either threatened or endangered should be adopted.” After issuance of the District Court's remand order, we notified Federal, State and local agencies, county governments, elected officials, and other interested parties of the Court's decision in a letter dated October 13, 2005. We requested new scientific data and comments about *Lepidium papilliferum.* We also stated that scientific data received from the public would be included in an updated “Draft Best Available Biological Information for Slickspot Peppergrass ( *Lepidium papilliferum* )”

(BAI)document. In response to our request, we received a total of 13 comment letters. The updated BAI combined all existing and new information about the species and its habitat, and we utilized it in making this final listing determination. On February 27, 2006, we opened a 30-day public comment and peer review period, through an electronic process referred to as VOCUS, for our comprehensive document entitled “Draft Best Available Biological Information for Slickspot Peppergrass ( *Lepidium papilliferum* )” (USFWS 2006f). Following public and peer review, we used new data and technical corrections, along with existing data, for our analysis described below as the best available scientific and commercial data. After an order by the district Court on October 4, 2006, which requires “a final listing determination on the slickspot peppergrass by January 4, 2007,” we opened a 22-day public comment period that closed on November 13, 2006 (71 FR 62078). A variety of documents were posted on the FWS Web site for public comment, including peer review comments on the draft BAI and results of the expert panel. Summary of Comments and Responses We received a total of 13 comment letters in response to our October 13, 2005, request for additional information to assist with the listing determination for *Lepidium papilliferum;* 17 public comment letters and 19 peer review responses on the Draft BAI released on February 27, 2006; and 20 public comment letters in response to our October 23, 2006, reopening of the public comment period. The majority of comments were specific to the draft BAI and associated data as well as issues surrounding the 2003 CCA developed to conserve *L. papilliferum.* Comments that were substantive or that provided new information were incorporated into the final determination where appropriate, or are addressed below. We consolidated the comments into categories by issue. *Issue 1:* Several commenters provided new data and information regarding the biology, ecology, life history, genetics, and factors affecting *Lepidium papilliferum* , and requested that it be incorporated into the body of existing knowledge concerning the species and considered by us in making any future management determinations. *Our response:* In making this final listing determination, we have considered scientific and commercial data contained in over 75 technical reports, published journal articles, and other general literature documents, including nearly 30 reports received since the January 23, 2004. The body of available information specific to this species has greatly expanded since 2004, with new information regarding species locations, known condition of its habitat, slickspot soil characteristics and disturbance, *Lepidium papilliferum's* pollinators, seed viability and germination, ongoing conservation efforts, genetics, and factors affecting the species. This information was contained in various State agency reports (Colket 2005a; Colket 2006; Colket *et al.* 2006; IDARNG 2005; State of Idaho *et al.* 2006) and other scientific reports and peer reviewed articles (Menke and Kaye 2006a, b; Meyer and Allen 2005; Meyer *et al.* 2005; Meyer *et al.* 2006; Palazzo *et al.* 2005; Robertson 2003a; Robertson and Klemesh 2003; Robertson and Ulappa 2004; Robertson *et al.* 2005; Stillman *et al.* 2005). Additionally, we reviewed and considered data from ongoing *L. papilliferum* conservation efforts (Binder 2006; Boise Airport 2003; Hoffman 2005; IDARNG 2005; State of Idaho *et al.* 2006; U.S. Air Force 2004). Further research and continued monitoring would provide a more thorough understanding of the species; however, we have a legal obligation to make a final listing determination based on the best available scientific and commercial data. *Issue 2:* Some commenters stated that an urgent need to list *Lepidium papilliferum* exists due to ongoing and current threats. One commenter suggested that there is evidence for widespread and rapid population decline. Another commenter stated that the species is at such risk of extinction that it should be listed to ensure that the BLM and other Federal land management agencies implement management actions that result in substantive conservation. Other commenters stated that existing regulations are insufficient in providing for the long-term persistence of the species. Conversely, some commenters stated that existing regulatory mechanisms, primarily through the CCA and its associated conservation measures, are sufficient or more than sufficient to preclude the need to list *L. papilliferum* under the Act. *Our response:* The Act requires us to make listing decisions based solely on the best scientific and commercial data available at the time the decision is made (section 4(b)(1)(A) of the Act). We thoroughly reviewed all available scientific and commercial data for *Lepidium papilliferum* in preparing this final determination. We reviewed historical and recent publications, and unpublished reports concerning *L. papilliferum* and the sagebrush-steppe habitat of southwestern Idaho. From this information, we produced the document “Draft Best Available Biological Information for Slickspot Peppergrass ( *Lepidium papilliferum* )” (BAI); we solicited public comment and peer review on the BAI in February 2006. We also convened a panel of seven scientific experts to review the scientific information available to us pertaining to *L. papilliferum* . Additionally, we reopened the public comment period on the proposed rule in October 2006 (71 FR 62078) to solicit additional review and comment on new data that we have considered in this final determination. We followed our Policy on Information Standards Under the Endangered Species Act, published in the **Federal Register** on July 1, 1994 (59 FR 34272), and our associated Information Quality Guidelines in preparing this final determination. Our evaluation of the significance of these numerous ongoing threats across the range of *Lepidium papilliferum* is presented in the Summary of Factors Affecting the Species section of this final determination. This analysis includes the adequacy of existing regulatory mechanisms, including public land management practices. During the listing process, we provided 6 public comment periods that were open for a total of 262 days, and held 2 public hearings. We received new information since the proposed rule specific to *L. papilliferum* that ranged from additional Idaho CDC survey data to slickspot soils information. While the body of available information specific to this species is limited, our legal obligation is to make a final listing determination based on the best available data. *Issue 3:* Several comments regarded the effectiveness of the CCA (first approved in 2003 and subsequently revised in 2006) in conserving *Lepidium papilliferum.* Some commenters stated that the voluntary commitment of non-governmental cooperators developed during the CCA process is equal to or better for conservation of *L. papilliferum* than mandated actions that would be associated with listing the species. One commenter suggested that the commitment to better livestock grazing management by the *L. papilliferum* Conservation Committee and permittees continues, and is still strong after 2 years of implementation, and that the follow-through on implementing CCA conservation measures, such as responding to grazing triggers and off-highway vehicle

(OHV)events during 2005, was good. The State of Idaho reported that, of the 203 conservation measures identified in the CCA, 193 were accomplished in either 2004 or 2005, and 7 measures were not implemented due to wildfire or ongoing litigation. One commenter stated that the inclusion of an adaptive management process within the CCA will ensure that the identified conservation measures, if initially ineffective, would become effective well before the probable extinction of *L. papilliferum* given existing threats. The U.S. Air Force provided comments on our October 23, 2006 draft description and analysis of conservation measures (71 FR 62078). The U.S. Air Force believed that several more conservation measures have been implemented and are effective in conserving *L. papilliferum* at the Juniper Butte Range than what we had determined. Conversely, some comments suggested that there is little certainty that implementation of *Lepidium papilliferum* conservation measures identified in the CCA will occur. One commenter stated that the adaptive management approach used in the CCA provides no certainty of protection for *L. papilliferum.* Another commenter suggested that any cooperator can drop out of the CCA at any time without repercussion. Another comment asserted that the adaptive management approach as currently described in the CCA allows for a one-time disturbance event that could result in irreversible harm to L. *papilliferum habitat.* Comments indicated that the CCA provides vast opportunity for a one-time livestock penetrating trampling event to occur, and is therefore insufficient. Other comments suggested that the CCA does not protect *L. papilliferum* and its habitat from soil disturbance, and did not include active restoration measures for the vast majority of the species' habitats. Commenters stated that, due to the downward trend in *L. papilliferum* abundance, reintroduction of the species should be considered. One commenter stated that management under an Instruction Memorandum

(IM)is uncertain, and that because the IM is not a legal requirement, interpretation will be inconsistent among field staff. *Our response:* We support utilizing a collaborative conservation approach to address factors affecting species being considered for listing under the Act. Prior to July 18, 2003, we worked with various agencies and individuals to assess the status of *Lepidium papilliferum,* and also to identify and implement conservation actions. Since February 2000, we have been an active technical advisor in an interagency group of biologists and stakeholders to share data and coordinate conservation actions for *L. papilliferum.* Using our Policy for Evaluation of Conservation Efforts When Making Listing Decisions

(PECE)(68 FR 15100), we reviewed the conservation measures in five plans, or conservation strategies, for *L. papilliferum:*

(1)The Candidate Conservation Agreement for Slickspot Peppergrass (CCA), which was initially approved in 2003 and revised in 2006;

(2)the Idaho Army National Guard Integrated Natural Resource Management Plan for Gowen Field/Orchard Training Area;

(3)the U.S. Air Force Integrated Natural Resource Management Plan for Mountain Home Air Force Base, which was modified in 2004 and contains more measures that promote the conservation of *L. papilliferum* than the 2000 version;

(4)the Conservation Agreement (Hull's Gulch Agreement) by and between Boise City and the U.S. Fish and Wildlife Service for *Allium aasea* (Aase's onion), *Astragalus mulfordiae* (Mulford's milkvetch), and *Lepidium papilliferum* (slickspot peppergrass), which was in place until it expired on October 22, 2006, and

(5)the Conservation Agreement for slickspot peppergrass ( *Lepidium papilliferum* ) at the Boise Airport, Ada County, Idaho. These five agreements and plans include a wide array of conservation measures to address the need to maintain and enhance slickspot peppergrass, and to potentially avoid or reduce adverse effects that might occur in relation to various types of activities. We recognize that many of the conservation efforts identified in the plans are having conservation benefits for the species, particularly as they relate to limiting the effects of wildfire and livestock use. We believe conservation efforts are important for this species because, while we do not have sufficient information to determine that potential threats are having a population level impact on the species, further research is necessary. To the extent that there are effects from activities, these conservation efforts should offset them. We evaluated conservation efforts within each plan under PECE (60 FR 15100). PECE is relevant in situations where it is necessary to determine whether individual conservation efforts that have not been implemented, or that have been implemented but have not yet demonstrated whether they are effective, are sufficiently certain to be implemented and effective so as to have contributed to the elimination or adequate reduction of one or more threats to the species identified through our threats analysis conducted pursuant to section 4(a)(1) of the Act. In this case, the efforts that met the standard in PECE for sufficient certainty of implementation and effectiveness were not used as a basis for our conclusion, because our analysis did not show that the species met the definition of threatened or endangered. However, this does not mean that conservation efforts which have yet to be implemented, or which have yet to be demonstrated to be effective, are unimportant. In fact we strongly encourage continued implementation of all on-going and planned conservation efforts, as they can contribute to maintaining or improving the status of *L. papilliferum.* *Issue 4* : There were several comments regarding the use of available monitoring and survey data in determining the historical and existing distribution, population size, and trend information for *Lepidium papilliferum.* One commenter suggested there have been no comprehensive systematic surveys for *L. papilliferum,* and therefore, we do not fully understand the distribution or status of the species. Numerous commenters stated that monitoring protocols and methods used to gather data regarding *L. papilliferum* trends and distribution were biased toward documenting declines, were insufficient, or were poorly timed, and therefore conclusions are poor. Several commenters stated that there is no clear relationship between *L. papilliferum* trends and threat factors affecting the species. Some commenters suggested that the data demonstrate a negative population trend for *L. papilliferum;* other commenters suggested the data are inconclusive, and no trend can be determined. One commenter thought the trend from 2004 to 2005 was positive or stable due to implementation of the CCA, a wet spring, and a minimal wildfire season. Another commenter identified that the number of extant EOs have increased from 45 in 1998 to 85 in 2006, and there has been only 1 EO that has been extirpated since 1955. Several commenters cited information relating *L. papilliferum* annual abundance to precipitation, while other commenters disputed the claim that annual abundance is related to precipitation. Several commenters stated that the number of element occurrences has increased from 1998 (45 extant EOs) to 2006 (85 extant EOs). Several commenters thought that the soil type (slickspots) used by *Lepidium papilliferum* is a limited resource that is not reforming, because the processes that originally created it no longer occur. Slickspots being modified, altered, or developed are lost to the ecosystem forever. *Our response:* In this determination, we have reviewed and considered scientific and commercial data contained in over 75 technical reports, published journal articles, and other documents, including nearly 30 reports received since January 22, 2004. We must base our listing determination for *Lepidium papilliferum* on the best available data regarding the plant's current known population status, the known condition of its habitat, and the current factors affecting the species, along with ongoing conservation efforts, as described in the Summary of Factors Affecting the Species section of this final determination. We also acknowledge that uncertainties exist. While a systematic survey, utilizing similar techniques, has not been conducted for *Lepidium papilliferum* range-wide, at least 30 separate survey efforts for *L. papilliferum* have occurred (Baczkowski 2006; USFWS 2006d). Some of these surveys were within the known range of *L. papilliferum* habitat, and others were outside of the known distribution, for example, in the State of Oregon, in the Saylor Creek area between the Snake River Plain and the Owyhee Plateau, and the City of Hagerman. In 2003, for example, 2,350 acres were surveyed in the Saylor Creek area between the Snake River Plain metapopulations and the Owyhee Plateau metapopulations. During these surveys, 1,727 slickspots were documented, but no *L. papilliferum* individuals were found (U.S. Air Force 2003, p. 16). We agree that undiscovered sites occupied by *L. papilliferum* likely exist. Inventories for *L. papilliferum* have not been completed on the majority of private lands within its range due to restricted access. Recent discoveries of new occupied slickspot sites and new EOs since 1998 have not added substantially to our knowledge of where the species exists. For example, an inventory survey at the OTA in 2005 found 365 new slickspots with *L. papilliferum* all within the range of known habitat on the OTA (URS Corporation 2005, p. 6). Since 2003, 16 new EOs on approximately 50 ac (28 ha) (0.4 percent of the total acreage) have been documented, all within 3 mi (4.8 km) of previously existing EOs (Colket *et al.* 2006, Tables 1 to 14). Although there has been only one documented extirpation since 1955, up to 9 small and isolated EOs had no plants detected during one or more recent monitoring surveys. Numerous monitoring efforts have been conducted for *Lepidium papilliferum,* including population trend monitoring transects at the OTA (IDARNG 2005) completed since 1991, demographic monitoring at the OTA from 1993 to 1996 (Meyer *et al.* 2005), Habitat Integrity Index

(HII)monitoring done by the Idaho CDC at *L. papilliferum* EOs range-wide conducted from 1998 to 2002 (Mancuso and Moseley 1998; Mancuso *et al.* 1998; Mancuso 2000; Mancuso 2001; Mancuso 2002), Habitat Integrity Population

(HIP)monitoring built on HII monitoring at *L. papilliferum* EOs range-wide conducted by the Idaho CDC in 2004 and 2005 (Colket 2005a, Colket 2005b), and monitoring done at the Juniper Butte Range in 2003 and 2005 (U.S. Air Force 2003). HIP monitoring, the most extensive range-wide effort to date, was developed by the Idaho CDC in conjunction with the *L. papilliferum* Technical Team to statistically analyze and detect trends in *L. papilliferum* and its habitat (the technical team includes IDARNG, BLM, Air Force, the Service, Idaho Department of Agriculture, and other interested parties) (Colket 2005a, p. 3). Both the HII and HIP monitoring, because of the difficulties associated with tracking numbers of *L. papilliferum* individuals across years, utilize habitat information as a metric of *L. papilliferum* health (Mancuso *et al.* 1998, pp. 1 to 7). Because of the fluctuations in *Lepidium papilliferum* numbers associated with precipitation (Meyer *et al.* 2005, pp. 4, 12, 15; Palazzo *et al.* 2005, p. 9; Menke and Kaye 2006b, p. 10), determining trends requires long-term monitoring data sets. Two long-term monitoring data sets in which we see a downward trend in recent years in numbers of individuals that do not mimic precipitation are the population trend monitoring transect data and special use plot data at the OTA. In contrast, an analysis by Palazzo *et al.* (2005, p. 9) for all 4 years of HII data found a relationship (p-value less than 0.01) between February to June precipitation and numbers of *L. papilliferum* . In their analysis of range-wide HII and HIP data collected from 1998-2002 and 2004 (no data was collected in 2003), Menke and Kaye (2006b, p. 10) further refined this relationship and found a strong positive relationship between precipitation from March through May and *L. papilliferum* abundance. In contrast to the monitoring data from OTA, the range-wide data shows that *L. papilliferum* continues to track consistently with precipitation throughout all years of the data set (Menke and Kaye 2006b, p. 10 and Figs. 1, 2). We consider this range-wide data to be the best available at this time. The conditions that allowed for the formation of slickspots in southwestern Idaho are thought to have occurred during a wetter Pleistocene climate (Nettleton and Petersen 1983, p. 191; Seronko 2006). Under natural conditions, several hundred years may be necessary to alter or lose slickspots, generally through climate change or severe natural erosion (Seronko 2006). Meyer and Allen (2005, p. 9) suggest that if sufficient time passes following the disturbance of slickspot soil layers, it is possible that slickspots can reform similar to their pre-disturbance configuration. *Issue 5:* Numerous commenters provided information or opinions regarding how various threats may or may not affect *Lepidium papilliferum* , its habitat, and its possible probability of extirpation. Threats specifically mentioned included residential, commercial, and agricultural development; military training; OHV use; nonnative, invasive plant species; wildfire; wildfire rehabilitation methods (including drill seeding and invasive, nonnative plant seedings); fragmentation; soil disturbance; herbicide spraying; wildlife grazing; herbivory; and agricultural pesticides ( *e.g.* , insecticide for grasshoppers or Mormon crickets) affecting *L. papilliferum* pollinators. One commenter suggested that the decreased quality of sagebrush grassland (steppe) habitat is the primary problem with the apparent decline of *L. papilliferum* . *Our response:* Our evaluation of the significance of the various threats across the range of *Lepidium papilliferum* is discussed in the Summary of Factors Affecting the Species section of this final determination. We analyzed the adequacy of existing regulatory mechanisms, including the effectiveness of ongoing, recently implemented, and proposed conservation efforts that attempt to conserve *L. papilliferum* in three conservation agreements, and two INRMPs from the IDARNG and the U.S. Air Force. The primary factors impacting *L. papilliferum* and its surrounding habitat include habitat degradation and modification of the sagebrush-steppe ecosystem from the current wildfire regime (i.e., increasing frequency, size, and duration of wildfires), invasion of nonnative weed species ( *e.g.* , cheatgrass), effects of livestock use ( *e.g.* , trampling and disruption of soils), and habitat loss due to agricultural and urban development. Less important factors that may affect the species include effects from rangeland revegetation projects, wildfire management practices, recreation, and military use. Herbivory is reported as sparse or at low levels, and is mainly by insects. Herbivory impacts to *L. papilliferum* from native ungulates such as elk, deer, and antelope have not been observed. However, pronghorn antelope tracks and droppings (U.S. Air Force 2003, p. 14), and elk tracks and droppings (State of Idaho *et al.* 2006, Appendix A) have been infrequently documented in slickspots that support *L. papilliferum* . Herbicide spraying was not considered by the Expert Panel to be an important threat to *L. papilliferum* , and is not discussed in this listing determination. While the decreased quality of sagebrush-steppe and the development and implementation of successful habitat restoration may impact the species, we have found no correlation to date between the existence of these threats and population numbers. *Issue 6:* Several comments referred to the effects of livestock use on *Lepidium papilliferum* and its habitat. They suggested that livestock use (past, current, or future) adversely affects *L. papilliferum* by trampling and uprooting individual plants, transporting nonnative invasive seeds, disturbing slickspot habitat soil crusts, burying *L. papilliferum* seeds to a soil depth at which germination cannot occur, accelerating erosion of slickspots, compacting soils, and changing slickspot soil chemistry through the deposition of manure. Conversely, several commenters suggested that livestock use has minimal effects and can even provide beneficial effects to *Lepidium papilliferum* and its habitat. One commenter suggested that only three documented examples exist in which livestock use has been implicated as the primary factor in either a reduction or elimination of *L. papilliferum* from a given area. In each case, the incident was isolated and occurred prior to implementation of the CCA. Several commenters suggested that *L. papilliferum* co-evolved with historical livestock use and wild ungulate grazing pressure; therefore the impact of existing livestock use is as likely to be beneficial as it is to be adverse, although effects generally remain unknown. Commenters suggested that potential benefits to *L. papilliferum* from livestock use include reduced frequency, intensity, and magnitude of wildfire; reduced nonnative invasive annual grasses; and improved germination of *L. papilliferum* seeds as a result of abrasion and reduced physical resistance of the surface soil crust. One commenter suggested that without authorized livestock grazing permits on Federal lands, some conservation benefits would not occur, including weed control, wildfire suppression, habitat rehabilitation, and a ready source of information regarding the land upon which ranchers run their livestock. Other commenters suggested that insufficient information exists, so we cannot draw conclusions regarding the effects of livestock use on *L. papilliferum* and its habitat. *Our response:* The most visible effect on *Lepidium papilliferum* and its slickspot habitat from livestock use is trampling impacts. Penetrating trampling is defined as livestock trampling of water-saturated slickspot soils that break through the restrictive soil layer (see Ecology and Habitat section above). Penetrating livestock trampling can affect the fragile soil layers of slickspots (Meyer *et al.* 2005, pp. 21, 22; Seronko 2004, pp. 1, 2), especially when it occurs during wet periods when slickspots are most vulnerable to disturbance. Penetrating trampling also potentially affects the seed bank for *L. papilliferum* by pushing the seeds below their ability to germinate (i.e., below 1.5 in (3 cm)) (Meyer *et al.* in press, pp. 3, 24, 25). Livestock use at an appropriate level, and during dry conditions, may reduce the spread of nonnative annual grasses at some *L. papilliferum* sites. However, using livestock to control nonnative annual grasses would need to occur during early spring when the grasses are growing strongly, and spring is when slickspots are most likely to be wet and most susceptible to damage. Responsive management, involving quickly removing livestock during rain events and moving them regularly to prevent soil disturbance, would be difficult over large areas. Livestock use has been documented (Colket *et al.* 2006, Appendix C) within 62 of the 75 *Lepidium papilliferum* EOs for which habitat information has been collected (49 of 60 on the Snake River Plain and 13 of 15 on the Owyhee Plateau). Penetrating hoof prints have been documented within 21 EOs on the Snake River Plain, and 9 on the Owyhee Plateau (Colket *et al.* 2006, Appendix C). Data limitations have made it difficult to establish impact (or effect) thresholds from livestock management activities for *Lepidium papilliferum* . Based on a single year of HIP data (2004), there was no correlation between *L. papilliferum* abundance in the short-term and total livestock print cover or cover of prints penetrating to the slickspot clay layer (Menke and Kaye 2006b, p. 15). The HIP data are observational in nature; controlled experiments are needed to more accurately assess the effects of livestock on *L. papilliferum* and its habitat. At this time we have no data that long-term declines in abundance will arise from livestock grazing. Adaptive management techniques for areas occupied by *L. papilliferum* and affected by livestock use could result in new information from ongoing and proposed livestock use studies and monitoring conservation efforts for the species. We anticipate that additional information regarding *L. papilliferum* and livestock use, from research currently underway by the U.S. Air Force and University of Idaho will be available for use in species conservation. A more complete discussion on the effects of livestock use on *Lepidium papilliferum* and its habitat is found in the Summary of Factors Affecting the Species section. *Issue 7:* One commenter suggested that wildfire historically (prior to European influence) occurred on a 60- to 100-year frequency and resulted in small burned areas where wind erosion could scour slickspots, maintaining the thin silt layer on the slickspot and the mini-playa as a depression. Wind scour likely occurred, since the only species growing on the slickspot was *Lepidium papilliferum* . With exotic species currently occupying slickspots, wind erosion may not be effectively scouring them, and in fact, deposition may be occurring. One commenter suggested that historical wildfire intervals in Wyoming big sagebrush communities were much longer, and some areas rarely, if ever, burned. Conversely, one commenter stated that while an abundance of information exists regarding wildfire in *Lepidium papilliferum* habitat, no long-term monitoring data confirmed the significance of its effect on *L. papilliferum* . *Our response:* As previously stated in the July 15, 2002, proposed rule (67 FR 46441) and January 22, 2004, document to withdraw the proposed rule (69 FR 3094), wildfire affects *Lepidium papilliferum* EOs throughout the species' range. Where habitat information is known, 42 of 60 EOs on the Snake River Plain and 6 of 15 on the Owyhee Plateau have been at least partially burned; 57 EOs on the Snake River Plain and 12 on the Owyhee Plateau have adjacent landscapes that are at least partially burned (Colket *et al.* 2006, Appendix C). Current research indicates wildfire frequency in the sagebrush-steppe ecosystem throughout the range of *Lepidium papilliferum* has increased, from a historical average of once every 60 to 110 years to once every 5 years at many sites, due to the invasion of nonnative annuals such as cheatgrass that became common on the Snake River Plain rangelands in the 1950's (Wright and Bailey 1982, p. 158; Billings 1990, pp. 307 to 308; Whisenant 1990, p. 4; USGS 1999, pp. 1 to 9; West and Young 2000, p. 262). Wildfires in cheatgrass tend to be larger, burn more uniformly, and leave fewer patches of unburned vegetation, all of which influence the post-fire recovery of native sagebrush-steppe vegetation (Whisenant 1990, p. 4). The result of this altered wildfire regime has been the conversion of vast areas of the former sagebrush-steppe ecosystem into nonnative annual grasslands (USGS 1999, pp. 1 to 9). Frequent wildfires can also promote soil erosion and sedimentation (Bunting *et al.* 2003, p. 82) in arid environments such as the sagebrush-steppe ecosystem. Increased sedimentation can result in a silt layer that is too thick for optimal *L. papilliferum* seed germination (Meyer and Allen 2005, pp. 6 to 7), and that allows weedy species to invade slickspots. See the Summary of Factors Affecting the Species section for a more complete discussion. Following wildfire events, the use of nonnative forage grass species (such as crested wheatgrass and Russian wildrye ( *Elymus junceus* )) for rehabilitation can result in successful establishment of perennial plants, ultimately reducing and diminishing the impacts of cheatgrass and its accelerated wildfire frequency. The use of nonnative species that closely mimic the biology and ecological function of species native to the area may be a necessary first step in restoring a site following wildfire if native seed cannot be used due to limited availability or prohibitive cost. Of the known *Lepidium papilliferum* occurrences, 14 (19 percent) are located within areas where wildfire rehabilitation projects and crested wheatgrass seedings have occurred (Colket *et al.* 2006, Appendix C). Although *L. papilliferum* still occurs in these areas, most support lower numbers of plants (Mancuso and Moseley 1998). See “Factor A” in the Summary of Factors Affecting the Species section below for a more detailed discussion. In a review of available information, the Expert Panel considered the current wildfire regime the most important factor affecting *Lepidium papilliferum* and its remaining habitat. *Issue 8:* One commenter expressed concerns regarding the U.S. Air Force's development of the Juniper Butte Range (beginning in 1998) on the Owyhee Plateau where *Lepidium papilliferum* and its habitat occur. Development and use of this training range, along with resulting road construction, human presence, and proposed use of aerial flares/white phosphorus munitions during training exercises, has increased the risk of wildfire within a substantial portion of *L. papilliferum* 's range. *Our response:* Currently, the impact of military training activities does not represent a principal threat to *Lepidium papilliferum* . Both the IDARNG and U.S. Air Force are implementing conservation efforts that potentially avoid or reduce adverse effects of military training on the species and its habitat. Threats from military activities are localized and have little significance across the range of the species. Military activities within the range of *Lepidium papilliferum* include ordnance use, facility development, and transportation, all of which create an increased risk of wildfire and nonnative plant invasions. Military training occurs on the Snake River Plain at the OTA, on all or portions of seven EOs, and on the Owyhee Plateau at the Juniper Butte Range on a portion of one EO (sub EO 704). The U.S. Air Force intends to use 300 ac (121 ha) of the 11,070-acre Juniper Butte Range as the actual bombing impact area (U.S. Air Force 2000). It anticipates that a small amount of ordnance will be dropped outside the bombing impact area, but the potential impact to *L. papilliferum* would likely be minimal. The Integrated Natural Resource Management Plan (INRMP) developed for the Juniper Butte Range provides management directions that ameliorate many of the threats from military training exercises. Range-wide, the most intact *Lepidium papilliferum* habitat occurs at the OTA, where similar conservation efforts have been implemented for 14 years (Colket *et al.* 2006, pp. 22 to 23; Meyer 2005, p. 1). The IDARNG has implemented a variety of actions to meet the conservation needs of *L. papilliferum* , while still providing for military training activities. These actions include wildfire suppression efforts, and restricting ground-operated military training to areas where the plants are not found. *Issue 9:* Some commenters asserted the taxonomic status of *Lepidium papilliferum* is problematic and warrants further evaluation. For example, one commenter suggested that our failure to complete a genetic study of *Lepidium montanum* seriously flaws any discussion assessing *L. papilliferum* as a species on its own. A few commenters suggested that if *L. papilliferum* is a subspecies or variety it is not eligible for protection under the Act. *Our response: Lepidium papilliferum* was originally described as *L. montanum* var. *papilliferum* in 1900 by Louis Henderson. It was renamed *L. papilliferum* by Aven Nelson and J. Francis Macbride in 1913 based on its distinctive growth habit, short lifespan, and unusual pubescence (Nelson and Macbride 1913, p. 474). Hitchcock regarded *L. papilliferum* as *L. montanum* var. *papilliferum* , influencing several publications including *Flora of Idaho* and *Flora of the Pacific Northwest* (Hitchcock *et al.* 1964, p. 516; Hitchcock and Cronquist 1973, p. 170; Steele 1981, p. 55; Moseley 1994, p. 2). In a review of taxa in the mustard family (Brassicaceae), Rollins

(1993)maintained the species based on differences in the physical features between *L. papilliferum* and *L. montanum* such as:

(1)*L. papilliferum* has trichomes (hair-like structures) occurring on the filaments of stamens (part of flower that produces pollen), and *L. montanum* does not;

(2)all the leaves on *L. papilliferum* are pinnately divided, and *L. montanum* has some leaves that are not divided;

(3)the shape of the silicle [silique] (seed capsule) of *L. papilliferum* is different from that of *L. montanum* ; and

(4)the silicle of *L. papilliferum* has no wings, or even vestiges of wings, at its apex (end of the capsule), unlike that of *L. montanum* (Rollins 1993, p. 578; Moseley 1994, p. 2). A review of the taxonomic status by Lichvar (2002), using classic morphological features and study of herbarium specimens, concluded that *L. papilliferum* has distinct morphological features that warrant species recognition. Meyer *et al.* (2005, p. 17) described a life history contrast when compared to *L. montanum* regarding seed dormancy and the seed bank. *L. papilliferum* seeds can remain dormant (and viable) and persist in the seed bank for about 12 years, whereas *L. montanum* has largely non-dormant seeds (Meyer *et al.* 2005, p. 17). Most recently, *L. papilliferum* has been accepted as a distinct species by Intermountain Flora, a recognized regional text (Holmgren *et al.* 2005, p. 259); the U.S. Department of Agriculture's “PLANTS Database” (USDANRCS 2006); and the Biota of North America Project, the recognized taxonomic reference for the United States (ITIS 2006). The preliminary results of two studies on the genetics of *Lepidium papilliferum* recently became available. The first, based on a relatively small sample size and more limited methodology, found that *L. papilliferum* forms a distinct monophyletic group that is most closely related to *L. fremontii* (Smith 2006, pp. 5 to 7 and Fig. 1). The second, utilizing larger sample sizes and additionally applying the methodology of AFLP (amplified fragment length polymorphisms, recognized for greater resolution or discriminatory power in detecting genetic differentiation) (Mueller and Wolfenbarger 1999, pp. 389 to 393; Savelkoul *et al.* 1999, p. 3085)), found that *L. papilliferum* forms a distinct monophyletic group or subgroup, and indicates that it is most closely related to *L. montanum* var. montanum (Larson *et al.* 2006, p. 13, 15, and Fig. 4). These genetic studies are consistent with the interpretation that *L. papilliferum* is either a variety or subspecies of *L. montanum* , or that it is a full and distinct species that has recently diverged from *L. montanum* . Plant species and subspecies (or varieties) are eligible for protection under the Act. *Issue 10:* One commenter stated that very little scientific research has been conducted on *Lepidium papilliferum* , and subsequently very little peer-reviewed literature is available for the species. Most of the information we have is based on technical reports and personal communications. *Our response:* The Act requires us to make listing decisions based on the best scientific and commercial data available at the time the decision is made (section 4(b)(1)(A) of the Act). Following the August 19, 2005, Federal Court decision regarding our January 22, 2004, document to withdraw the proposed rule to list *Lepidium papilliferum* as endangered, we sought and received new scientific and commercial data pertaining to the species. We incorporated all relevant new information into the “Draft Best Available Information

(BAI)for Slickspot peppergrass ( *Lepidium papilliferum* )” document, which was updated from the 2003 version. We solicited public comment and peer review on the draft BAI document and requested additional scientific data pertaining to the species. We followed our Information Quality Guidelines in preparing this final determination (see Information Quality Act discussion below). We also convened a panel of seven scientific experts (see Expert Panel discussion below) to review the available data pertaining to *L. papilliferum* prior to making this final determination. Information Quality Act In our review of the status of *Lepidium papilliferum* , we assembled information that addressed the current biological and ecological condition of the plant and its habitats. This information included reports from private industry, public universities, State and Federal resource agencies, published texts on a variety of biological topics, and peer-reviewed literature from the primary scientific journals. Additionally, we included unpublished scientific and commercial data , documents written and included in literature, and personal communications. Personal communications were used when they represented information that was pertinent and not available through other sources such as technical reports or published texts. We carefully evaluated each piece of data for its usefulness in the review process, and used those that contributed important information to the review. State and Federal government documents are generally considered to be of high utility, objectivity, and integrity. These documents are often subject to public review and comment, and State and Federal agencies generally employ the current standards in resource survey, monitoring, and analysis methodologies. The peer-reviewed scientific literature and scientific textbooks are rigorously reviewed and edited at several levels before publication, and represent the highest degree of utility, objectivity, and integrity. In compiling this document, we tried to present the information in an accurate, clear, complete, and unbiased manner. Given that the data available on this species covered a wide spectrum from peer-reviewed literature to personal communications, we developed this document with the goal of providing a high degree of transparency regarding the source of data. We followed our Information Quality Act Guidelines in developing this document. These guidelines provide direction for ensuring and maximizing the quality of information disseminated to the public. The guidelines define quality as an encompassing term that includes utility, objectivity, and integrity. Utility refers to the usefulness of the information to its intended users, including the public. Objectivity includes disseminating information in an accurate, clear, complete, and unbiased manner and ensuring accurate, reliable, and unbiased information. If data and analytic results have been subjected to formal, independent peer review, we generally presume that the information is of acceptable objectivity. Integrity refers to the security of information, i.e., protection of the information from unauthorized access or revision to ensure that the information is not compromised through corruption or falsification. One of our goals in obtaining public comment and peer review of the draft BAI was to ensure that we were considering the best available data while accurately representing the source of the information. Background information on the taxonomy, distribution, abundance, life history, conservation actions, and needs of *Lepidium papilliferum,* and threats affecting the species, were derived from previous petition findings, previous **Federal Register** notices, Idaho's Conservation Data Center EO records, and other pertinent references from 1897 (when the species was first collected) through 2006. The supporting information, administrative finding, and other relevant materials can be reviewed in person at the address listed in the ADDRESSES section, or copies of information can be made available to you (see References Cited at the end of this rule). Summary of Factors Affecting the Species Section 4 of the Act and its implementing regulations (50 CFR part 424) set forth the procedures for adding species to the Federal Lists of Endangered and Threatened Wildlife and Plants. A species may be determined to be an endangered or threatened species due to one or more of the five factors described in section 4(a)(1) of the Act. The five listing factors are:

(A)The present or threatened destruction, modification, or curtailment of its habitat or range;

(B)overutilization for commercial, recreational, scientific, or educational purposes;

(C)disease or predation;

(D)the inadequacy of existing regulatory mechanisms; and

(E)other natural or manmade factors affecting its continued existence. A. The Present or Threatened Destruction, Modification, or Curtailment of its Habitat or Range Current Wildfire Regime The invasion of nonnative plant species, particularly annual grasses such as cheatgrass and medusahead ( *Taeniatherum caput-medusae* ), beginning in the early 1900's has increased the amount and continuity of fine fuels across the landscape. As cheatgrass became more dominant on the rangelands of the Snake River Plain in the 1950's, wildfire frequency intervals began to shorten from the historic average of between 60 to 110 years to the current frequency intervals of less than 5 years in many areas on the Snake River Plain where *Lepidium papilliferum* resides (Whisenant 1990, p. 4) and within the sagebrush-steppe ecosystem as a whole (Wright and Bailey 1982, p. 158; Billings 1990, pp. 307 to 308; USGS 1999, pp. 1 to 9, West and Young 2000, p. 262). Wildfires tend to be larger and burn more uniformly when annual grasses are present, resulting in fewer patches of unburned vegetation, which can affect the post-fire recovery of native sagebrush-steppe vegetation (Whisenant 1990, p. 4). This altered wildfire regime has contributed to the conversion of vast areas of sagebrush-steppe ecosystem into nonnative annual grasslands (USGS 1999, pp. 1 to 9). More frequent wildfires also promote soil erosion and sedimentation (Bunting *et al.* 2003, p. 82) in arid environments such as the sagebrush-steppe ecosystem. Increased sedimentation can result in a silt layer that is too thick for optimal *L. papilliferum* germination (Meyer and Allen 2005, pp. 6 to 7). Of the 75 EOs for which habitat information is known, 48 (42 of 60 on the Snake River Plain and 6 of 15 on the Owyhee Plateau) have been at least partially burned, and 69 (57 on the Snake River Plain and 12 on the Owyhee Plateau) have adjacent landscapes that are at least partially burned (Colket *et al.* 2006, Appendix C). Within the Snake River Plain, approximately 448,917 acres (181,670 ha) (28 percent) were burned between 1970 and 2003 (calculated from USBLM 2004). Within the Owyhee Plateau 60,467 acres (24,470 ha) (47 percent) have burned between 1970 and 2003 (calculated from BLM 2004). Table 3 shows the evidence of wildfire documented through HIP range-wide transect monitoring in 2005. Wildfire evidence can remain on the landscape for up to 20 years, and evidence documented in Table 3 includes both recent and historical fires. Table 3.—Evidence of Wildfire Documented at HIP Transects in 2005 (Colket 2005a, Tables 1 and 2) Number of transects at least partially burned Number of transects not burned Total transects Adjacent landscapes within 0.31 mi (500 m) of EOs burned or partially burned Snake River Plain 26 31 57 45 Owyhee Plateau 12 10 22 21 Total 38 41 79 66 In a statistical analysis of HII data between 1998 and 2001, burned areas at the beginning of the study had depleted shrub and soil crust cover that persisted throughout the monitoring period (Menke and Kaye 2006a, p. iii). In addition, burned areas had less native plant cover, greater nonnative plant cover, increased slickspot perimeter compromise, and increased organic debris accumulation (Menke and Kaye 2006a, p. iii). Similarly, in a statistical analysis of HII and HIP data between 1998 and 2004, burned areas had less soil crust cover and higher nonnative plant cover (Menke and Kaye 2006b, p. 3). Although the proportion of flowering plants was positively correlated with soil crust cover, there was no relationship between *L. papilliferum* plant abundance and soil crust cover or weedy species cover in slickspots based on the 2004 HIP data (Menke and Kaye 2006b, p. 15). In their analysis, Menke and Kaye (2006b, p. 17) concluded that competition from weedy annual species does not appear to influence abundance of *L. papilliferum* plants in a given year, although it may influence reproductive output or other traits, and that past fire disturbance does not appear to significantly alter longer-term trends in plant abundance. Past fires have apparently degraded slickspot condition, as evidenced by lower soil crust cover and greater exotic species cover (Menke and Kaye 2006b, p. 19), however *Lepidium papilliferum* abundance was statistically similar between burned and unburned transects from 1998 to 2004 (Menke and Kaye 2006b, p. 10), and the proportion of *L. papilliferum* in flower was similar between burned and unburned transects in 2004 (Menke and Kaye 2006b, p. 15). Past fires appear to have had a lasting negative impact on the plant community surrounding slickspots, including increased exotic species cover and decreased soil crust cover (Menke and Kaye 2006b, p. 19). Menke and Kaye (2006b, p. 17) note that the HII and HIP data are observational only, and controlled experiments are needed to more accurately assess the impacts of factors such as fire and grazing on *L. papilliferum* (Menke and Kaye 2006b, p. 17). At this point, given the equivocal nature of the habitat integrity and population monitoring data, the effects of an altered sagebrush steppe wildfire regime on *L. papilliferum* need further study. We have no data at this point that indicates that fire has a long-term impact on the species abundance; the available data show no correlation between fire and *L. papilliferum* population numbers. Existing conservation measures designed to reduce the adverse effects of wildfire apply to approximately 96 percent of *Lepidium papilliferum* 's occupied range. For example, the IDARNG, U.S. Air Force, and BLM will continue their rapid response or mutual support agreement for wildfire control. BLM has established wildfire suppression goals for management areas in the CCA (State of Idaho *et al.* 2006, Table 5). The military is implementing a number of efforts that address wildfire suppression that have been shown to be effective in certain respects at controlling this threat. However, we are not relying on the implementation of conservation measures to make this finding. Implemented and effective conservation measures will, however, help to counter habitat degradation generally and may help conserve the species. Since the late 1980s, the policies of the IDARNG included immediate wildfire suppression during military activities to prevent damage to intact sagebrush-steppe and *Lepidium papilliferum* sites within the OTA (IDARNG 2004, pp. 65 to 67). Seven occurrences of *L. papilliferum* occur within this area (Colket *et al.* 2006, pp. 8 to 9). Since 2002, the U.S. Air Force has instituted a high-level rapid response for wildfire suppression on the Juniper Butte Range (U.S. Air Force 2004, pp. 6-45 to 6-47). The U.S. Air Force addresses wildfire prevention through reducing standing fuels and weeds, planting fire-resistant vegetation in areas with a higher potential for ignition sources ( *e.g.* , along roads), and using wildfire indices to determine wildfire hazard ratings and restricting activities when the rating is extreme (U.S. Air Force 2004, pp. 6-45 through 6-47). The BLM and IDARNG are continuing their mutual support agreement for wildfire suppression in the Snake River Birds of Prey National Conservation Area (IDARNG 2004, p. 83). On the OTA, the reduction in wildfires within EOs has demonstrated that management efforts to suppress wildfire can be effective. The 7 EOs on the OTA represent nearly 40 percent of the total area occupied by *Lepidium papilliferum* (see Figure 1 above), and aggressive wildfire suppression has occurred for over 12 years. The feasibility of implementing rapid response wildfire suppression techniques elsewhere is complicated by the fact that many of the remaining *L. papilliferum* EOs are in remote areas away from wildfire control facilities. The current wildfire regime is interrelated with several other factors that may affect *L. papilliferum,* including the replacement of large areas of native vegetation with more flammable nonnative grasses, increased sedimentation of slickspots, and habitat fragmentation. While these effects may be occurring, the existing data do not correlate them with declines in abundance of *L. papilliferum* . Invasive Nonnative Species The most common nonnative annual grasses known to occur in *Lepidium papilliferum's* habitat include cheatgrass and medusahead. Annual forbs most commonly associated with slickspots include clasping pepperweed ( *Lepidium perfoliatum* ), tumbleweed (also known as Russian thistle), tumble mustard ( *Sisymbrium altissimum* ) (also known as tall tumble mustard), and bur buttercup (Colket 2005a, p. 6). Nonnative plants may become established in *L. papilliferum* habitats by spreading through natural dispersal (unseeded) or may be intentionally planted through re-vegetation projects (seeded). Invasive nonnative plants can alter attributes of ecosystems, including geomorphology, wildfire regime, hydrology, microclimate, nutrient cycle, and productivity (Dukes and Mooney 2003, pp. 1 to 35). They can also negatively affect native plants through competitive exclusion, niche displacement, hybridization, and competition for pollinators; examples are widespread among taxa and ecosystems (D'Antonio and Vitousek 1992, pp. 63 to 87; Olson 1999, p. 5; Mooney and Cleland 2001, p. 1). All 75 EOs for which habitat information is available have nonnative, unseeded plants present (Colket *et al.* 2006a, Appendix C). The results from 2004 HIP monitoring revealed that all 71 HIP transects monitored within EOs (49 on the Snake River Plain and 22 on the Owyhee Plateau) had nonnative, unseeded plant cover. For example, within the Snake River Plain (49 transects), 1 had nonnative plant cover occurring over 50 percent of the transect, 7 transects had nonnative plant cover between 25 and 50 percent of the transect, and 10 transects had nonnative plant cover between 10 and 25 percent. Two transects on the Owyhee Plateau had nonnative plant cover between 10 and 25 percent (Colket 2005a, pp. 46 to 47). In their analysis of *Lepidium papilliferum* population trends in association with plant community trends and habitat quality based on HII and HIP monitoring data from 1998-2002 and 2004, Menke and Kaye (2006b, p. 12) report that species diversity and species richness of the plant community had declined, but that exotic species cover and shrub cover had remained the same. Total exotic species cover and exotic grass cover was high in burned transects in all years (Menke and Kaye 2006b, p. 15). Weedy species cover was higher in burned slickspots, but there was no significant correlation between weedy species cover and either abundance of *L. papilliferum* or proportion of *L. papilliferum* in flower (Menke and Kaye 2006b, p. 15). The authors note that although competition from weedy annuals does not appear to influence the short-term abundance of *L. papilliferum,* it may be influencing other plant traits or life history stages not assessed in this study (Menke and Kaye 2006b, p. 17). However, we have no data to corroborate that this threat will result in future declines in abundance. Existing conservation measures designed to reduce the potential adverse effects of nonnative, unseeded species apply to approximately 96 percent of *Lepidium papilliferum* 's occupied range (CCA, U.S. Air Force INRMP, IDARNG INRMP). Conservation measures identified within the CCA include protecting remnant blocks of native vegetation, prioritized weed control measures at *L. papilliferum* EOs, protective weed control techniques, revegetation requirements in disturbed areas, education on nonnative species and their spread, vehicle wash points and stations, and research support and funding for nonnative species control (State of Idaho *et al.* 2006, pp. 131 to 132). The military has a number of ongoing efforts to suppress non-native species. The IDARNG requires all military vehicles entering the OTA from a distance greater than 50 mi (80.4 km) to be washed at a high-pressure wash rack facility to prevent weed seed introduction. Noxious weeds at small sites are hand-pulled when they are found by IDARNG staff, and noxious weed sites on the OTA are reported annually to BLM for treatment (IDARNG 2004, p. 67). The U.S. Air Force reduces the spread of exotic annual species by reseeding disturbed areas with native vegetation to the maximum extent practicable, eradicating noxious weeds prior to spread, and requiring cleaning of U.S. Air Force vehicles and equipment on a wash rack upon return to base. They avoid the use of pesticides within 25 feet of slickspots and use pesticides only if wind conditions are favorable (away from the slickspot) to prevent the loss of *Lepidium papilliferum* (U.S. Air Force 2004, pp. R-4, R-5). The OTA has demonstrated that management efforts to suppress wildfire, rehabilitating areas with native species, and using wildfire rehabilitation activities with minimal ground disturbance can be effective in reducing the wildfire threat and reducing rates of spread of nonnative unseeded species. Nonnative, unseeded species are increasing at the OTA, although not as rapidly as at other areas where these conservation efforts are not being implemented or have only been implemented for a short period. We have no evidence that correlates invasive species presence with declines of *L. papilliferum* or the proportion of *L. papilliferum* in flower (Menke and Kaye 2006b, p. 15). Livestock Use Trampling of *Lepidium papilliferum* and slickspots can result from livestock use. Table 4 documents the extent of livestock use at HIP transects. Livestock trampling can affect the soil layers of slickspots (Colket 2005a, p. 34; Meyer *et al.* 2005, pp. 21 and 22; Seronko 2004, pp. 1 and 2). Trampling when slickspots are dry can lead to mechanical damage to the slickspot soil crust, potentially resulting in invasion of nonnative plants into the slickspots and altering the hydrologic function of slickspots. Livestock trampling of water-saturated slickspot soils that breaks through the restrictive layer, which is referred to as penetrating trampling (State of Idaho *et al* . 2006, p. 9), has the potential to alter the soil structure and the functionality of slickspots (Rengasamy *et al.* 1984, p. 63; Seronko 2004, pp. 1 and 2). Penetrating trampling, which occurs when slickspots are wet, also has the potential to affect the seed bank for *L. papilliferum.* Meyer and Allen (2005, pp. 6 and 7); seed emergence success decreased with increasing depth from a mean of 54 percent at the shallowest plant depth of 2 mm to a mean of 5 percent at 30 mm depth. Table 4.—Livestock Use Documented at Element Occurrences and HIP Transects in 2004 (Colket *et al.* 2006, Appendix C). [Evidence of livestock use does not infer effects throughout a transect or EO] Evidence of penetrating trampling

(EO)Evidence of penetrating trampling (HIP Transects) Snake River Plain 21/60 19/49 Owyhee Plateau 9/15 20/22 Total 30/75 33/71 In a statistical analysis of HII data from 1998 to 2001, it was found that recent livestock use had neutral effects on *Lepidium papilliferum* , slickspot attributes, and plant community attributes (Menke and Kaye 2006a, p. iii). Recent livestock use estimated by HIP monitoring in the year 2004 resulted in decreased soil crust cover in slickspots, decreased vascular plant cover, and decreased plant litter cover in the surrounding plant community (Menke and Kaye 2006b, p. 3). There was no significant correlation between total livestock print cover or cover of prints penetrating to the slickspot clay layer and abundance of *L. papilliferum* , and both the abundance of *L. papilliferum* per slickspot and proportion of flowering plants was similar between grazed and ungrazed transects for the single year of data reported in 2004 (Menke and Kaye 2006b, p. 15). In the surrounding plant community, grazed and ungrazed transects had similar species richness, diversity, and soil crust cover, but total vascular plant cover and plant litter cover were significantly lower in grazed transects (Menke and Kaye 2006b, pp. 15 and 16). Livestock trampling events that are most likely to adversely affect *Lepidium papilliferum* usually occur when large numbers of livestock are concentrated on or around slickspots that are saturated with water (Hoffman 2005; Meyer *et al.* 2005, pp. 21 to 22). Saturated conditions typically exist for short periods each year and may never occur in some (drought) years (Hoffman 2005). Predicting when soils will be wet in a climate with few and inconsistent precipitation events is difficult. Consequently, managing livestock to avoid penetrating tramping events is difficult. Supplemental salt and watering sites can alter livestock distribution, and depending on location, can increase or decrease trampling of slickspots. At least two penetrating trampling events have been suggested as the cause of substantial losses in *Lepidium papilliferum* numbers. In 1996, when other sites at the OTA had a reasonably high numbers of *L. papilliferum* individuals, a study site referred to as the “States site” experienced substantial declines. In 1993, this site had thousands of plants. In the spring of 1996, a trampling event disrupted or buried the in-situ seed bank (Meyer *et al.* 2005, pp. 21 and 22). Since this trampling event, fewer than 10 plants have been observed at the site despite yearly visits (Meyer *et al.* 2005, pp. 21 and 22). In another study area, four of five sites experienced increases in plant numbers; the fifth site, Glenn's Ferry, was the only one that incurred a trampling event, and the only one with a dramatic reduction in *L. papilliferum* numbers (Robertson 2003b, p. 8). Research designed to specifically examine the relationship between livestock use trampling effects and *L. papilliferum* is currently being conducted by University of Idaho and the State of Idaho in cooperation with us (State of Idaho *et al.* 2006, p. 119). However, at this point we have nothing but this anecdotal evidence to indicate a threat. Information we do have does not suggest that habitat threats are correlated with declines in species population levels. There are also indirect effects from livestock use that have impacted the sagebrush-steppe ecosystem. The spread of both native and nonnative plant species has been attributed to livestock use (Frost and Launchbaugh 2003, pp. 43 to 45). The spread of cheatgrass on the Snake River Plain has been attributed to several causes, including the past practice of heavy livestock use in the late 1800s (Mack 1981, pp. 145 to 165). Today, nonnative, annual plants such as cheatgrass are so widespread that they have been documented spreading into areas that have not been disturbed (Piemeisal 1951, p. 71; Tisdale *et al.* 1965, pp. 349 and 351; Stohlgren *et al.* 1999, p. 45); therefore, the absence of livestock use does not protect the landscape from invasive, nonnative weeds (Frost and Launchbaugh 2003, p. 44). With careful management, livestock grazing may be used as a tool to select for certain native species or even to control cheatgrass (Frost and Launchbaugh 2003, p. 43). There was no significant difference in cover of exotic plant species in slickspots between grazed and ungrazed areas in the 2004 HIP dataset, although soil crust cover was significantly lower in grazed transects (Menke and Kaye 2006b, p. 19). Analysis of HII data from 1999 through 2001 found no effect of livestock grazing on slickspot perimeter integrity, weedy species density, perennial forb or grass establishment, or organic debris accumulation in slickspots (Menke and Kaye 2006a, p. 10). Cumulative livestock sign had a significant negative correlation with exotic grass dominance around slickspots (Menke and Kaye 2006a, p. 11) and with the frequency of slickspots with dense weedy annuals in 2001 (Menke and Kaye 2006a, p. 10). The analysis of grazing effects was limited since the HII data were observational only (no controlled experiments were performed), all areas were likely grazed at some point in the past, and grazing effects could only be observed in habitats that had been burned in the past (Menke and Kaye 2006a, p. 18). The conservation plans (CCA, U.S. Air Force INRMP, IDARNG INRMP) contain numerous measures to avoid, mitigate, and monitor effects of livestock use on the species. Livestock grazing conservation measures implemented through the CCA and the U.S. Air Force INRMP apply to all Federal and State-managed lands (96 percent of the acreage) within the occupied range of *Lepidium papilliferum* . Conservation measures prescribed by the CCA include minimum distances for placement of salt and water troughs away from occurrences of the species, and several troughs and salt blocks have been moved as a result of these measures (State of Idaho *et al.* 2006, p. 133; State of Idaho *et al.* 2005). The CCA also includes measures to reduce trampling during wet periods, including trailing (moving cattle to, or between, allotments repeatedly on the same path) restrictions (State of Idaho *et al.* 2006, pp. 132 to 134). High priority EOs, as identified in the CCA, tend to have more restrictive conservation measures, such as no early spring grazing, fencing to exclude livestock, and delaying turnout of livestock when soils are saturated (State of Idaho *et al.* 2006, pp. 133 to 134). High priority EOs were designated based on existing habitat quality, geographic location relative to other existing EOs, minimal land use activities, the absence or presence of resources to address threats, and the need to preserve enough EOs throughout the species' range to prevent extinction in case of a catastrophic event. In high priority EOs, greater emphasis is placed on protection and restoration of habitat. BLM has changed the season of grazing use from spring to fall, and implemented a deferred rotation management system on some allotments to protect flowering annuals from grazing (State of Idaho *et al.* 2006, pp. 133 to 134). Under the revised Juniper Butte Range INRMP, the U.S. Air Force will continue to use livestock throughout the majority of the Juniper Butte Range to reduce the amount of standing grass biomass to reduce wildfire risk (U.S. Air Force 2004, pp. 6-37 to 6-39). The grazing component plan for the INRMP states that livestock use will occur annually for up to 60 days while the bombing range is shut down for clean-up and target maintenance. The shutdown period lasts a maximum of 60 days within a 90-day period, from April 1 through June 30 (U.S. Air Force 2000, pp. B-18 to B-21). The INRMP emphasizes avoiding grazing when slickspots are wet in order to reduce trampling of slickspot habitats. It also provides guidance for annual monitoring of slickspot soil moisture to determine livestock turnout dates for Juniper Butte Range (U.S. Air Force 2000, pp. B-18 to B-21). The U.S. Air Force established three fenced areas of 173 ac (70.0 ha), 8 ac (3.2), and 30 ac (12.1 ha), respectively, in 2002, with the intent of promoting *Lepidium papilliferum* research and seed collection (Binder 2006), when compatible with the Air Force mission. There was no significant correlation between total livestock print cover or cover of prints penetrating to the slickspot clay layer and abundance of *L. papilliferum* , and both the abundance of *L. papilliferum* per slickspot and proportion of flowering plants was similar between grazed and ungrazed transects for the single year of data reported in 2004 (Menke and Kaye 2006b, p. 15) and no other data were available that indicated otherwise. Therefore, we do not believe that livestock impacts are a threat to the species. Residential and Agricultural Development Past residential and agricultural development has been responsible for five documented local extirpations and four probable local extirpations of *Lepidium papilliferum* (Colket *et al.* 2006, p. 4). The long-term viability of *L. papilliferum* occurrences on private land on the Snake River Plain has the potential to be compromised due to the continuation of residential and urban development in and around Boise (Moseley 1994, p. 20). Today, all or portions of 18 *L. papilliferum* EOs covering 457 acres (3.5 percent) (not including EOs managed by cities or counties) occur on private land. However, half of these 18 EOs are smaller than one acre, and most are classified as having fair to poor habitat quality (Colket *et al.* 2006, pp. 39 to 41). Residential and agricultural development can affect *L. papilliferum* and slickspot habitat through habitat conversion, increased nonnative plant invasions, increased off-highway vehicle use, increased wildfire, changes to insect populations, and increased fragmentation. Future residential and agricultural development on private land occupied by the species is a potential threat that is limited to 3.5 percent of the total known element occurrence acreage, therefore such development is not a significant threat. Gravel or cinder mining may affect *Lepidium papilliferum* on State and Federal lands (Mancuso 2000, p. 13). One site was impacted by illegal mining activity in 1999 on BLM and private lands (DeBolt 1999). No other impacts from gravel or cinder mining have been documented, therefore gravel or cinder mining does not constitute a significant threat to the species. Power, gas, and other lines, and related roads, affect and fragment *Lepidium papilliferum* EOs. Utility lines and accompanying roads have been documented running through at least four EOs, gas lines run through two EOs, and roads run through at least six EOs (Colket *et al.* 2006, Appendix C). In addition to direct habitat destruction, these corridors allow off-road vehicle access and increase the chance of nonnative plant invasions and human-ignited wildfires. Transportation corridors associated with development also increase the probability of human-ignited wildfires and the spread of nonnative, invasive plants. Future developments associated with power, gas, other lines, and related roads through habitat occupied by the species may be a potential threat depending upon design and mitigation measures associated with the developments. But at this time we have no data that such development constitutes a significant threat to the species. Of the *Lepidium papilliferum* EOs for which habitat information has been collected, 14 of 75 (13 of 60 on the Snake River Plain and 1 of 15 on the Owyhee Plateau) have development ( *e.g.* , utility lines, mining, agricultural development, and residential development) within them, and 28, all on the Snake River Plain, have development adjacent to them within 0.31 mi (500 m) (Colket *et al.* 2006, Appendix C). On the Owyhee Plateau, one EO has development occurring within it, and no EOs have development within 0.31 mi (500 m) (Colket *et al.* 2006, Appendix C). Within the Snake River Plain, an estimated 327,549 ac (132,554 ha) (20 percent) has been converted to agriculture (IDWR 1999), and 94,974 ac (38,435 ha) (6 percent) has been converted to urban areas (University of Idaho 2001). Development was not a parameter that was measured in 2004 through the HIP transect monitoring program (Colket 2005a). In 2005, 79 HIP transects were monitored (57 on the Snake River Plain and 22 on the Owyhee Plateau); of these transects only one transect on the Snake River Plain had development occurring at the transect (in this case residential/commercial). Monitoring in 2005 on the Snake River Plain also documented residential and commercial development occurring within 0.31 mi (500 m) of 17 transects, and agricultural development was documented adjacent to 10 transects (Colket 2005b, Table 2). Currently, the effects from development to *Lepidium papilliferum* are confined geographically to the Snake River Plain, however these threats are not significant. Development does not appear to be a threat at all for *L. papilliferum* EOs on the Owyhee Plateau. Nonnative Seeded Species A decline in habitat quality for *Lepidium papilliferum* since 1998 in terms of decreased vascular plant cover, species richness, and species diversity was noted by Menke and Kaye (2006b, p. 19), although they found no change in the cover of exotic grasses or forbs in the plant community between 1998 and 2004, and no relationship between short-term abundance of *L. papilliferum* and weedy species cover in slickspots (Menke and Kaye 2006b, p. 15). At this time, we have no data supporting a conclusion that longer-term abundance will be negatively affected by the presence of exotic grasses. Rangeland revegetation priorities on public lands in southeast Idaho have included providing forage for livestock, erosion control, wildfire prevention, reducing nonnative annual grass density, and watershed rehabilitation. Some nonnative perennials can out-compete native species and decrease biodiversity (summarized by Harrison *et al.* 1996, 62 pp.). For example, crested wheatgrass, a forage species that was once commonly planted within the range of *Lepidium papilliferum* , is a competitor and its seedlings are better than some native species at acquiring moisture at low temperatures (Lesica and DeLuca 1998, p. 1; Pyke and Archer 1991, p. 4; Bunting *et al.* 2003, p. 82). The results from surveys conducted on the Owyhee Plateau by (Popovich 2002, p. 16) indicated that the number of *L. papilliferum* plants per site was lower in habitat with crested wheatgrass seedings, compared to native sagebrush-steppe habitat areas or burned areas that had not been seeded (Popovich 2002, p. 16). Forage kochia ( *Bassia prostrata* , formerly *Kochia prostrata* ) is another nonnative species that has been used for rangeland habitat restoration. Thousands of forage kochia plants have been observed in relatively small slickspots, and it is documented as a direct competitor with *L. papilliferum* in slickspots (DeBolt 2002; Quinney 2005). In one study area within the Poen fire rehabilitation project, post-wildfire monitoring over a 6-year period following aerial seeding with forage kochia showed eventual loss of *L. papilliferum* along the monitoring transect, and a dramatic increase in forage kochia (DeBolt 2002). Four other slickspots, containing a total of 31 individual *L. papilliferum* plants and numerous forage kochia plants in 2000, were void of *L. papilliferum* and dominated by forage kochia in 2005 (Quinney 2005). Blue flax ( *Linum lewisii* ) is another nonnative seeded plant that was found within HIP transects (Colket 2005a, p. 6). It is not clear why these *L. papilliferum* plants were absent. Nonnative seeded species exist in 23 of the 75 EOs with documented habitat information (17 of 60 on the Snake River Plain and 6 of 15 on the Owyhee Plateau), and 18 (14 on the Snake River Plain and 4 on the Owyhee Plateau) have non-native seeded species adjacent to the EO within 0.31 mi (500 m). The effects of invasive, nonnative seeded plants are monitored as parts of HIP range-wide transect monitoring for *Lepidium papilliferum* . In 2004, 71 *L. papilliferum* HIP transects (49 on the Snake River Plain and 22 on the Owyhee Plateau) were measured (Colket 2005a, pp. 46 to 47). Results indicate that 11 transects within the Snake River Plain and 13 transects within the Owyhee Plateau had introduced perennial plant cover (nonnative, seeded species) (Colket 2005a, pp. 46 to 47). In general, the documented high percentage of plant cover in the 2004 HIP transect monitoring is attributable to crested wheatgrass, except at the site with the highest percent cover. This site in the Snake River Plain contained 26.8 percent cover in forage kochia (Colket 2005a, pp. 17, 32). Approximately 80 percent (9,163 ac (3,708 ha)) of the Juniper Butte Range is dominated by nonnative perennial plant communities as a result of wildfire rehabilitation efforts (U.S. Air Force 1998, pp. 31-120 to 3-121). Although the use of native plant species for wildfire rehabilitation is preferable, previously there have been problems with the availability and high cost of native seed (Jirik 1999, p. 110; Brooks and Pyke 2001, p. 9). In recent years, with an increase in research and agencies ( *e.g.* , BLM) investing heavily in projects such as the Great Basin Native Plant Selection and Increase Project and the Great Basin Restoration Initiative, native seeds and plants are more available to use in restoration of sagebrush-steppe habitat. However, restoration of sagebrush-steppe habitat, and *Lepidium papilliferum* habitat in particular, is still considered a difficult and expensive task. Under current policies, BLM no longer uses forage kochia as a wildfire rehabilitation species in *Lepidium papilliferum* habitat (USBLM 2002). BLM emphasizes the use of native plants, including forbs, in seed mixes and avoids the use of invasive, nonnative species (State of Idaho *et al.* 2006, p. 26). In January 2004, BLM issued an Instruction Memorandum to employees on compliance with CCA requirements for emergency stabilization and wildfire rehabilitation activities (State of Idaho *et al.* 2006, p. 71). The military has a number of ongoing efforts to address invasive nonnative, seeded plants. These efforts are implemented and effective in reducing this threat. The U.S. Air Force uses only non-invasive plant materials and will not use forage kochia, intermediate wheatgrass ( *Thinopyrum intermedium* , formerly *Agropyron intermedium* ), or salt-tolerant species such as four-wing saltbush ( *Atriplex canescens* ) in revegetation efforts, with native plants being used to the maximum extent practicable and in concert with the military mission for rehabilitation efforts (U.S. Air Force 2004, p. R-4). The IDARNG INRMP for the OTA includes the objectives for maintenance; where possible, improvement of *Lepidium papilliferum* habitat; and restoration of areas damaged by wildfire, through native species and broadcast seeding, collecting, and planting small amounts of native seed not commercially available, and monitoring the success of seeding efforts (IDARNG 2004, p. 72 to 73). Since 1991, the IDARNG has examined historical records and has seeded areas back to the native vegetation that was present prior to past wildfires. Care is taken to ensure that restoration does not damage *L. papilliferum* or its habitat, or introduce species into the habitat that were not present in presettlement times (IDARNG 2004, p. 73). The IDARNG has demonstrated that diligent efforts to suppress wildfire, the use of native species, and minimal ground-disturbing wildfire rehabilitation activities can be effective in reducing the wildfire threat and rates at which nonnative species spread. Because of limited rainfall and harsh conditions, restoration is a difficult task and often requires repeated seedings on the OTA (IDARNG 2004, p.73). Methods currently used by the IDARNG may not be economically feasible for revegetation of large areas of damaged habitat found in other parts of the range of the species. Menke and Kaye (2006b, p. 19) evaluated rangewide data from 1998-2004 and found a decline in the quality of habitat surrounding slickspots occupied with *Lepidium papilliferum* in terms of decreased vascular plant cover, species richness, and species diversity. They found no change in the cover of exotic grasses or forbs in the plant community between 1998 and 2004, and no relationship between short-term abundance of *L. papilliferum* and weedy species cover in slickspots (Menke and Kaye 2006b, p. 15). Because abundance cannot be correlated with habitat changes, we find that a decline in habitat quality is not threatening the species. Wildfire Management and Post-Wildfire Rehabilitation Activities associated with wildfire management include fuel management projects ( *e.g.* , greenstrips, prescribed fire), wildfire suppression activities, and post-wildfire rehabilitation. These activities can potentially impact existing *Lepidium papilliferum* occurrences and damage slickspot habitat (ILPG 1999) by the establishment of nonnatives or by mechanical disturbances. Drill seeding is a rehabilitation technique that is used after wildfire. Drill seeding uses a rangeland drill that plants and covers seed simultaneously in furrows. It is designed to give the seeds moisture and temperature advantages that will enhance their competitive fitness and, consequently, their success rate (Scholten and Bunting 2001, p. 3). Drill seeding has been used on wildfire rehabilitation projects on BLM lands where *Lepidium papilliferum* occurs. It impacts slickspots through mechanical disturbance and introduces other, often nonnative, plant materials. Historically, slickspots were not understood to have any special ecological value, and so no attempt was made to avoid them during rehabilitation activities. We have no data on the extent that drill seeding may still be affecting *L. papilliferum* habitat, although some habitat areas have buffers established to protect them. Disk or drill seeding has occurred on 14 of 60 EOs on the Snake River Plain and 10 of 15 EOs on the Owyhee Plateau (Colket *et al.* 2006, Appendix C). Drill seeding may have less severe impacts on slickspot habitat than disking the soil, but the success of restoring slickspots and *Lepidium papilliferum* plants varies considerably. The benefits of post-fire revegetation, and subsequent recovery of soil surfaces conducive to germination and establishment of native perennial grass and shrub communities, may outweigh the initial short-term disturbance associated with drill seeding (Young and Allen 1996, pp. 533 to 534; Bunting *et al.* 2003, pp. 82 to 85). Ground disturbance associated with wildfire control, such as establishment of fire lines (areas with vegetation removed to break fuel continuity), fire camps, and staging areas, and the use of wildfire suppression vehicles, can also impact existing *Lepidium papilliferum* occurrences and damage slickspot habitat (ILPG 1999). Similarly, construction of fuel breaks, while beneficial in slowing the movement of wildfire, may also impact *L. papilliferum* through ground disturbance or the use of invasive, nonnative, seeded species. Only two EOs, both on the Snake River Plain, are documented as having wildfire lines within them, although neither has documented wildfire lines within slickspots (Colket *et al.* 2006, Appendix C). Herbicides used to pretreat rehabilitation areas prior to seeding may also impact *L. papilliferum* . These activities may injure or kill individual plants or the seed bank through mechanical disturbance or direct exposure to herbicides. Indirect effects associated with mechanical disturbance of slickspot soils include increased probability of establishment of invasive, nonnative plants, burying of the seed bank to a depth where seedlings cannot emerge from the soil, and mixing of slickspot soil layers, which affects the suitability of a microsite for the species. The effect of drill seeding is monitored as part of the HIP range-wide transect monitoring. In 2004, of the 71 *Lepidium papilliferum* transects monitored, 3 transects on the Snake River Plain and 5 transects on the Owyhee Plateau had evidence of old drill seedings within slickspots; no transects had evidence of firefighting disturbances within slickspots (Colket 2005a, pp. 44 to 45). Through the CCA, BLM has implemented a number of conservation measures to avoid or minimize impacts to the species from wildfire prevention, wildfire suppression, and post-wildfire emergency rehabilitation activities. These measures are effective to reduce this threat at least partially. BLM and fire cooperators distribute maps and inform crew members of the location of *Lepidium papilliferum* to maximize wildfire protection in those areas, and to minimize potential impacts from suppression related activities (State of Idaho *et al.* 2006, p. 26). Per conservation measure .08 of the CCA, BLM uses seeding techniques that minimize soil disturbance, such as no-till drills and rangeland drills equipped with depth bands, when rehabilitation and restoration projects have the potential to impact occupied or suitable habitat (State of Idaho *et al.* 2006, p. 26). Rehabilitation and restoration standard operating procedures for *L. papilliferum* were issued in an Instruction Memorandum in January 2004 (State of Idaho *et al.* 2005, p. 33). BLM avoids spraying herbicides within or near known occupied habitat, and conducts pretreatment surveys of at least 5 percent of previously unsurveyed habitat prior to herbicide or ground disturbing treatments associated with emergency wildfire rehabilitation activities (State of Idaho *et al.* 2006, p. 27). The military has a number of ongoing, effective efforts to address wildfire management activities. The potential for wildfire ignition and spread are decreased by the placement of appropriate restrictions on activities, and the use of wildfire indices to restrict activities when the wildfire rating hazard is extreme (U.S. Air Force 2004, p. R-3). The U.S. Air Force uses drill seeders equipped with depth bands to avoid unnecessary disturbance to soils, avoids slickspots to the maximum extent practicable in drill seeding efforts, and uses broadcast seeding to the maximum extent practicable consistent with reseeding goals (U.S. Air Force 2004, p. R-4). The IDARNG restores wildfire-damaged areas using native species and broadcast seeding. Similarly, the IDARNG provides their fire crews with maps of all known occupied habitat, and actively suppresses all wildfires on the OTA. Blading is not permitted in *Lepidium papilliferum* habitat areas on the OTA. Existing roadways serve as fuel breaks within the OTA, and allow for quick access for wildfire management (IDARNG 2004, p. 73). Since 1987, the IDARNG has demonstrated that efforts to suppress wildfire and the use of native species with minimal ground-disturbing fire rehabilitation activities can be effective in reducing the wildfire threat and reducing establishment rates of nonnative, unseeded species associated with wildfire management activities (IDARNG 2004, p. 73). Wildfire management has positive consequences (i.e., the control of wildfires) and potentially negative consequences (i.e., destruction of slickspots through habitat restoration and wildfire control practices), depending on how the activity is implemented. The Expert Panel considered wildfire management to be less of an impact than the first four factors discussed above. After our review of the available data, we have determined that wildfire management can potentially impact *Lepidium papilliferum* , although this activity is not threatening the species. Recreation Recreational activities that may affect *Lepidium papilliferum* include hiking, horseback riding, and off-highway vehicles. Juniper Butte Range and areas of the OTA are protected from recreational activities because of military restrictions. Off-highway vehicle use has been documented in 16 of the 75 EOs (16 of 60 on the Snake River Plain, none on the Owyhee Plateau) for which habitat information has been collected (Colket *et al.* 2006, Appendix C). Effects from recreational activities are monitored as part of the HIP range-wide transect monitoring for *Lepidium papilliferum* . In 2004, 3 of 49 transects on the Snake River Plain showed off-highway vehicle tracks within the EO area, and 1 transect had off-highway vehicle tracks directly through it (Colket 2005b, Table 1). In 2005, two EOs on the Snake River Plan had tracks in the general occurrence area, and one had tractor tracks running through the transect (Colket 2005b, Table 1). New tracks are documented each year, so monitoring reports are not cumulative. Off-highway vehicle use was also monitored within the Owyhee Plateau *L. papilliferum* EOs in 2004 and 2005, but no off-highway use was documented. An analysis of HII transects between 1998 and 2001 indicated that only a few transects had OHV use in each year, that impacts appeared to be minimal, and that OHV use regionally does not appear to be a major agent of habitat degradation, while noting that concentrated OHV use in localized areas could potentially be more problematic (Menke and Kaye 2006a, p. 18). Therefore, we have determined from the available data that any potential impact to *Lepidium papilliferum* from recreation appears to be localized. Additionally, we have no data indicating that recreation is a major agent of habitat degradation and therefore is not threatening the species. Military Training Military activities within the range of *Lepidium papilliferum* include ordnance impact areas, training activities, military development, and an increased risk of wildfire and nonnative plant invasions. Military training occurs on the Snake River Plain at the OTA (seven EOs) and on the Owyhee Plateau at the Juniper Butte Range (a portion of one EO). INRMPs developed for both the Juniper Butte Range and the OTA provide management direction reducing or eliminating many of these threats from military training exercises. The OTA, where 14 years of INRMP conservation efforts have been implemented, is considered the most intact, native *L. papilliferum* habitat range-wide (Colket *et al.* 2006, pp. 22 to 23; Meyer 2005, p. 1). The IDARNG and the U.S. Air Force are implementing various conservation efforts to avoid or reduce adverse effects of military training on the species and its habitat, and the IDARNG has had measures in place that promote the conservation of *Lepidium papilliferum* prior to revisions to the IDARNG INRMP made in 2004. The threat of military training is localized in area, and minimal in significance across the range of the species. Summary of Factor A There is little disagreement that the quality and composition of the sage-brush steppe ecosystems that surrounds the slickspot microsites inhabited by *Lepidium papilliferum* has become degraded over time. Increased fire frequencies largely caused by the invasion of exotic annual grasses are of particular concern, as are potentially destructive penetrating trampling events of slickspots by livestock. What is not clear is the relationship between these factors and the long-term persistence or viability of *L. papilliferum* . What little data we have at this time does not indicate any direct relationship between the abundance of *L. papilliferum* and factors such as livestock use and weedy species cover. Burning appears to have a negative impact on slickspot conditions, such as increasing exotic species cover and decreasing soil crust cover, but these factors were not significantly correlated with *L. papilliferum* abundance. Accordingly we find that *L. papilliferum* is not threatened by habitat changes to the extent that protection under the Act is needed. B. Overutilization for Commercial, Recreational, Scientific, or Educational Purposes We have no data indicating that overutilization for commercial, recreational, scientific, or educational purposes is a threat to *Lepidium papilliferum* . C. Disease or Predation Herbivory of *Lepidium papilliferum* is reported as sparse. Herbivory by rodents and insects has been occasionally observed on *L. papilliferum* plants. In one instance, grasshoppers (possibly Acrididae) were observed consuming *L. papilliferum* flower petals (Geertson 2004, p. 3). We are unaware of any specific studies documenting foraging on *L. papilliferum* by Mormon crickets ( *Anabrus simplex* ). Insect herbivores have been studied as part of pollinator and reproductive biology studies (Robertson *et al.* 2004). Flower petal herbivory of *L. papilliferum* by chrysomelid beetles ( *Phyllotreta* spp.) was shown to be detrimental to seed production because of decreased pollinator visitation; pollinators did not visit flowers with missing flower petals. Other insect herbivores include plutellid moth larvae, which eat all portions of the plant; harvester ants which eat entire fruits or leaves from plants; mirid bugs, which probably suck phloem; grasshoppers (Acrididae); and leafhoppers (Cicadellidae), which probably suck phloem (Robertson *et al.* 2004, p. 12). At three different sites (one at Kuna Butte and two at the Orchard Training Area), 35 percent, 37 percent, and 23 percent of plants showed evidence of insect herbivore damage (Robertson *et al.* 2004). Herbivory impacts to *L. papilliferum* from large, native ungulates, such as elk, deer and antelope, have not been observed. However, pronghorn antelope tracks and droppings (U.S. Air Force 2003, p. 14) and elk tracks and droppings (State of Idaho *et al.* 2006, Appendix A) have been infrequently documented in slickspots that support *L. papilliferum* . Domestic sheep have been observed pulling the plants from the ground and spitting them out (Quinney and Weaver 1998). Herbivory by cattle has not been observed. We have no data to support the conclusion that disease or predation are a significant threat to *Lepidium papilliferum* . D. Inadequacy of Existing Regulatory Mechanisms *Lepidium papilliferum* is considered a sensitive species by BLM (BLM 2003, p. 2-1). BLM has regulations that address the need to protect sensitive, candidate, and federally listed species, and BLM has initiated monitoring of *L. papilliferum* on Federal lands. Monitoring can be used to identify threats, which can result in management actions necessary for controlling *L. papilliferum* habitat degradation. As a signatory of the CCA (State of Idaho *et al.* 2003, 2006), BLM is the primary land management agency implementing conservation efforts for this species. The majority of implemented conservation efforts associated with the CCA occur on BLM lands. In recent years, BLM has initiated efforts to conserve the species, and the CCA represents a major commitment by BLM for management of lands that account for a majority of the range of the species (87 percent of the total area and portions of 71 of the 85 extant EOs). Conservation efforts are not a basis for our finding here, but ongoing conservation efforts will be helpful in offsetting any effects that do occur from potential threats, and further voluntary conservation efforts are encouraged. Therefore, available data does not suggest that existing regulatory mechanisms are inadequate. E. Other Natural or Manmade Factors Affecting Its Continued Existence The Expert Panel identified unpredictable rain events and drought as climate factors affecting *Lepidium papilliferum,* but did not consider them to be significant threats to the species. We have no data that climatic patterns of rainfall will significantly change over time. Therefore, we do not consider drought or lack of rainfall to pose an extinction risk, although it can cause a short-term decline in population numbers. No other threats to *L. papilliferum* were identified under Factor E. Summary of Factors Affecting the Species—Conclusion The primary factors affecting *Lepidium papilliferum* are habitat based. We examined other potential threats and determined that the available data does not suggest that the other factors are threatening the species. We examined data available for effects of wildfire frequency, invasive nonnative plants (especially annual grasses), livestock impacts, and residential and agricultural development. While disturbances to *L. papilliferum* can result from wildfire, commercial and residential development, livestock use, and ground-disturbing wildfire management practices or recreation activities the available data did not support a finding that the species is threatened by one or more of these potential threats. Our analysis of the factors affecting the species indicates that there is cause for concern regarding the decline in quality of the sagebrush-steppe ecosystem and the slickspot microhabits within. We examined the increased frequency of fires, fueled largely by invasive exotic annual grasses, and how it is altering the diversity and composition of the native plant community. We found that there was no evidence that habitat degradation is a threat to the species such that listing is warranted at this time. However, the concerns generated by our analysis emphasize the need for further research and support for ongoing efforts to restore and manage the sagebrush steppe ecosystem. This also underscores the necessity for close monitoring of *L. papilliferum* and other components of the sagebrush community to better determine the response of these species to the alteration of their environment. The best available data do not demonstrate any relationship between altered habitat conditions and the status of *L. papilliferum.* The limited data available do not demonstrate any significant relationship between the abundance of *L. papilliferum* and factors such as livestock use or weedy species cover. The two available datasets of abundance monitoring present conflicting results regarding the trend of the population over time. The population of *L. papilliferum* is positively correlated with spring precipitation. *L. papilliferum* evolved in an arid environment and has adapted to fluctuations in precipitation. We have no data demonstrating that precipitation levels are varying significantly from historical patterns. Accordingly, we do not find that fluctuation in precipitation is a threat to the species. Status Review Process Section 4(b)(1)(A) of the Act requires us to consider the best scientific and commercial data available, as well as efforts being made by States or other entities to protect a species, when making a listing decision. To meet this standard, we systematically collected information on *Lepidium papilliferum,* its habitats, and environmental factors affecting the species from a wide array of sources. In addition, we received a substantial amount of unpublished information from other Federal agencies, States, private industry, and individuals. We solicited information on all Federal, State, or local conservation efforts currently in operation or planned for either *L. papilliferum* or its habitat. In addition, we convened an Expert Panel of seven independent scientists who assisted in evaluating the available data and discussed threats to *L. papilliferum.* Expert Panels are not a required component of our analysis, but are used occasionally by the Service to help inform decision makers when there is uncertainty. Scientific information on *Lepidium papilliferum* and associated habitat is limited; data gaps and uncertainty exist in the scientific community's knowledge of threats that may affect *L. papilliferum* populations across its geographical range of sagebrush-steppe habitat. For these reasons, we requested input from scientific experts to help us assess the status of *L. papilliferum.* The Expert Panel consisted of experts in the fields of small populations/fragmentation, annual desert plants, sagebrush community ecology, wildfire/nonnative species, soils and livestock use, and *L. papilliferum.* The discussion of the Expert Panel, and other available data, was then considered by our Manager Panel in order to develop the decision reported in this finding. We conducted three phases of information synthesis and evaluation. First, the information on individual planned conservation efforts was evaluated to determine which of the efforts that have not yet been implemented, or have been implemented but have not yet demonstrated whether they are effective, met the standard for sufficient certainty of implementation and effectiveness in the Policy for Evaluating Conservation Efforts (68 FR 15115, March 28, 2003). Second, we employed the assistance of an Expert Panel that evaluated all factors possibly affecting the species' current status. Subsequent to the work done by the expert panel new information became available. Our Manager Panel evaluated all the information, including the new information, on status, trends, ongoing conservation efforts, and potential risk to determine whether the species should be listed as threatened, listed as endangered, or not warranted for listing. We structured these three phases by differentiating two distinct stages of the analysis:

(1)A risk analysis phase that included compiling biological information and estimating the risk to the species; and

(2)a risk management phase where our Manager Panel evaluated whether the potential threats identified as part of our section 4(a)(1) analysis, and summarized in this finding, qualify *Lepidium papilliferum* as a threatened or endangered species under the Act. Policy for Evaluation of Conservation Efforts PECE provides a framework and criteria for evaluating conservation efforts that have not been implemented or have not demonstrated whether they are effective at the time of a listing decision. Recognizing that the certainty of implementation and effectiveness of various planned efforts within a conservation plan, strategy, or agreement may vary, PECE requires that we evaluate each individual conservation effort that has not been implemented or for which effectiveness has not been demonstrated, and the policy provides criteria to direct our analysis. PECE specifies that to consider that a conservation effort(s) contributes to forming a basis for not listing a species or listing a species as threatened rather than endangered, we must find that the conservation effort is sufficiently certain to be implemented and effective so as to have contributed to the elimination or adequate reduction of one or more threats to the species identified through the section 4(a)(1) analysis. (68 FR 15115, March 28, 2003). Thus, PECE is relevant in situations where a threats analysis, conducted without consideration of conservation efforts that meet the standard in PECE, indicates that listing is warranted. In such situations, we then consider the effect of conservation efforts that meet the “sufficient certainty” standard in PECE to determine whether such efforts have contributed to the elimination or adequate reduction of threats, leading to a determination that the species does not meet the definition of threatened or endangered and therefore does not warrant listing, or that that listing as threatened, rather than endangered, is appropriate. Because of the time needed to evaluate large numbers of individual conservation efforts under PECE, it sometimes is necessary to proceed with the evaluation process prior to completing the threats analysis pursuant to section 4(a)(1) of the Act, i.e., before we have determined whether efforts that meet the standard in PECE will actually play a role in our determination. That was the case in this situation. For the PECE analysis, we reviewed activities identified in five plans or conservation strategies. The five plans were:

(1)The Candidate Conservation Agreement for Slickspot Peppergrass;

(2)the Idaho Army National Guard Integrated Natural Resource Management Plan for Gowen Field/Orchard Training Area;

(3)the U.S. Air Force Integrated Natural Resource Management Plan for Mountain Home Air Force Base;

(4)the Conservation Agreement by and between Boise City and the U.S. Fish and Wildlife Service for *Allium aasea* (Aase's onion), *Astragalus mulfordiae* (Mulford's milkvetch), and *Lepidium papilliferum* (slickspot peppergrass); and

(5)the Conservation Agreement for Slickspot Peppergrass ( *Lepidium papilliferum* ) at the Boise Airport, Ada County, Idaho. We reviewed each conservation effort contained in the five conservation plans to determine which had been implemented and demonstrated effectiveness in reducing one or more threats. We relied on available documentation to determine if the effort was implemented by the time of our analysis. As explained above, conservation efforts that have been implemented and demonstrated effectiveness are not subject to evaluation under PECE, and are considered as part of the section 4(a)(1) threats analysis (below). We also used the criteria in PECE to evaluate efforts that had not been implemented, and efforts that had been implemented but had not yet demonstrated whether they were effective. We did not rely on those efforts that met the PECE standard in our determination. We made our determination on the basis of the threats analysis and information about population status and trends (see below). However, we consider the conservation plans and the continued commitment of stakeholders to implement the conservation efforts important to the long-term sustainability of *Lepidium papilliferum* . Expert Panel In May 2006, we convened a panel composed of seven experts to provide assistance in understanding the ecology and biology of *Lepidium papilliferum,* to assess the threats and extinction risk to the species, and to identify areas of scientific uncertainty. The panelists brought a variety of expertise to the discussion, including knowledge and experience with wildfire, nonnative species, range and grazing issues, soils, small populations and fragmentation, annual desert plants, and sagebrush community ecology, and included a *L. papilliferum* species expert. The top two potential threats identified by the Expert Panel were the invasion of cheatgrass and the subsequent changes to the fire regime in the sagebrush-steppe ecosystem. Several members of the panel agreed that the expansion of cheatgrass will likely create annual grasslands that will dominate the Snake River Plain within the next 50 years, and would impact *Lepidium papilliferum* and its habitat. The invasion of exotic annual grasses in turn increases the frequency of fire, leading to further alterations of the native plant community. Following the May 2006 Expert Panel, the Service received additional information including new analysis of *Lepidium papiliferum* population and habitat monitoring data ( *e.g.* , Menke and Kaye 2006b). This information was not available to the expert panel and did not factor into their extinction risk estimates. The Service considers the extinction risk estimates by the expert panel to be informative in that they provide a context in which we were able to assess the new information. However, the estimates have limited applicability to our determination in light of this new information. In particular, the new information limits the Service's confidence in extrapolation of * L. papilliferum* population trends at the OTA to population trends in the remaining Snake River Plain metapopulation and the range-wide population. Manager Panel Our Manager Panel reviewed background materials, interacted with the Expert Panel during their exercises, and participated in discussions about the application of the Act and specific terms contained in the Act. The managers based their assessments on the data in the record, including comments previously received; the data presented by the individual members of the Expert Panel, as well as data received subsequent to the Expert Panel process; known information gaps and uncertainty; the number and severity of the threats affecting the species; and mitigating circumstances that might ameliorate one or more of the threats. The Manager Panel convened on three occasions. This rule is based on the record of these discussions and all relevant and available information pertaining to the threats to and status of the species. Determination We examined the data regarding *L. papilliferum* populations and occurrence as well as the specific habitat needs of the species. We included an examination of habitat degradation and modification to the sagebrush-steppe ecosystem and the slickspot microhabitats from the current wildfire regime (i.e., increasing frequency, size, and duration), invasion of non-native weed species ( *e.g.* , cheatgrass), effects of livestock use ( *e.g.* , penetrating trampling, disruption of soil crust covers), and residential and agricultural development to determine whether there were any resulting effects on *L. papilliferum.* While the sagebrush steppe-ecosystem has experienced decreased native shrub cover and increased exotic grass cover, we have no data demonstrating that these factors affect *L. papilliferum* populations. Data at this point are limited and based on observational measures rather than controlled experiments, but indicate no significant relationship between the abundance of *L. papilliferum* and factors such as livestock use or weedy species cover in slickspots. The data limitations point to the value of the conservation activities and collection of data and to improve our understanding of the species, as well as preventive actions. However, we do not have evidence that the factors evaluated here have led to a negative population trend range-wide in *L. papilliferum.* Determining range-wide abundance and population trends of *Lepidium papilliferum* is complicated by its annual and biennial life histories and its correlation to spring precipitation, which can vary widely from year to year. Spring rainfall patterns also vary at the local scale, which can influence abundance of the plant from one population to another in the same local area. Abundance estimates are confounded because seeds can remain dormant (and viable) in the seed bank for at least 12 years. All of these factors lead to great natural variability in the abundance of *L. papilliferum* from year to year, which confounds our assessment of population trends. Currently we have two relatively long-term datasets of abundance monitoring for *Lepidium papilliferum* on which to base our evaluation of population trends for this species, the data from the OTA and the data from range-wide HII and HIP monitoring (which includes several transects on the OTA). The dataset from the OTA indicates recent declines in the abundance of the species that do not correlate as expected with patterns of spring precipitation, beginning in 2003 (Weaver 2006, pp. 1-6). Data from the range-wide HII and HIP transects demonstrate that although the population declined following one of its highest recorded peaks in abundance in 1998 (the first year for which HII data was available), the range-wide population then stabilized and began increasing after 2003 (Menke and Kaye 2006b, Figure 3; USFWS 2006f, Figures 8, 9). The range-wide data show increases in populations since 2003, and populations have continued to show a positive relationship to spring precipitation. The available data are not consistent with regard to an overall population trend for *L. papilliferum.* The data from OTA indicate that plant abundance declined after 1995 and was generally correlating with spring precipitation until 2003 through present when plant abundance did not increase with higher levels of spring precipitation. Range-wide data indicate that *L. papilliferum* abundance has correlated with spring precipitation and abundance of the plant range-wide has increased since 2004 to levels comparable to 1998 range-wide data. We consider this range-wide data to be the best available at this time. Identification of data gaps and uncertainties helps explain the limits of our understanding of future risk to *Lepidium papilliferum.* We are required to make a determination whether the species qualifies as threatened or endangered under the Act based solely on the best available scientific and commercial data. To ensure that we considered this data in the proper context, the Manager Panel (see Status Review Process) participated in a structured analysis that included an evaluation of the Act's statutory requirements, in particular the Act's definitions of threatened and endangered, and a review of the data from the risk analysis and all other compiled biological information. They considered the data about risks to *L. papilliferum,* including explicit measures of uncertainty, and the data supporting the existence of those risks, in the context of the requirements of the Act. The definitions in the Act include: an endangered species is in danger of extinction throughout all or a significant portion of its range, and a threatened species is likely to become an endangered species within the foreseeable future throughout all or a significant portion of its range (16 U.S.C. 1532(6), (20)). The Manager Panel convened on three occasions: once during the science panel and shortly after the science panel in May 2006, and again in November 2006. When the Manager Panel convened in November 2006, focal points of discussion included results of the Menke and Kaye 2006 report that was not available at the time of the science panel and new insights gained from public comment and review of monitoring results. Of particular note were the results that spring precipitation (March-May) explained 89 percent of the variation in plant abundance for the years 1998-2001, 2002, and 2004 sampled by range-wide HII and HIP transects (Menke and Kaye 2006b, p. 10). In addition, this report demonstrated a consistent correlation between the abundance of *Lepidium papilliferum* and spring rainfall throughout all years and reported population increases range-wide since 2003, which contradicted trends reported based on data from the OTA. Upon reviewing the studies and plant abundance data, the Manager Panel concluded that indications of declines in plant abundance at OTA cannot be reasonably extrapolated to the range-wide population of *Lepidium papilliferum,* and that the conflicting data indicating range-wide population increases in recent years from the HII and HIP transects add additional uncertainty to our ability to assess the nature of any population trend for *L. papilliferum.* The high variability in plant numbers from year to year, expected for an ephemeral annual plant with a dormant seed bank that is highly dependent on seasonal rainfall, increases the difficulty of discerning any trend in abundance data over time. Although the quality of the sagebrush-steppe slickspot habitat of *L. papilliferum* has become degraded due to a variety of threats, the existing data do not support a determination that those threats are affecting *L. papilliferum* across all or a significant portion of its range sufficient to require the protections of the Act at this time. The managers decided that the data before them did not support a determination that *L. papilliferum* is exhibiting a population decline. The available data do not lead us to conclude that the species is declining range-wide, thus we are unable to establish that there is a point in time when the species is likely to be in danger of extinction throughout all or a significant part of its range. The district court decision found that our previous analysis of foreseeable future was unsupported in the record. In particular, the court noted that the expert panel concluded that there was a 64-80 percent chance that *L. papilliferum* would become extinct in the next 100 years. Thus, the court thought that our ultimate conclusion that the species was not likely to become in danger of extinction in the foreseeable future depended upon a preliminary conclusion that the foreseeable future was in this case a period of time considerably less than 100 years. Because the court found that we had not adequately explained why the Service selected the timeperiod it did for foreseeable future, the court held that our determination was arbitrary and capricious. In contrast, given the new information, the question of how much of the future is foreseeable is no longer relevant. We conclude that apparent abundance of the plant can fluctuate widely from one year to the next, and abundance is strongly correlated with spring precipitation. We have no data demonstrating that precipitation levels are varying significantly from historical patterns. *L. papilliferum* evolved in an arid environment and has adapted to fluctuations in precipitation by a strategy of relatively long-term seed viability and by increased seed production during favorable conditions. Thus, there is no current evidence that threats are working to threaten the species with endangerment and we cannot predict extinction at any point in time in the foreseeable future, regardless of whether the foreseeable future is defined as less than 100 years, 100 years, or more than 100 years. In summary, the Act requires us to make a decision based on the best available data at the time of the listing determination. The best available data for *Lepidium papilliferum* indicate that, while the broad scale habitat in which the species exists is degraded, we have no data that correlates this with species abundance. We know that annual abundance is strongly correlated with spring precipitation (March-May) and a high degree of variability in annual abundance is therefore to be expected. The best available range-wide data indicate that abundance of the population range-wide is strongly correlated with precipitation and has increased in recent years in association with increased rainfall, as expected. Accordingly based solely on the best available data, we find that *Lepidium papilliferum* is not presently in danger of extinction throughout all or a significant portion of its range nor is it likely to become an endangered species throughout all or a significant portion of its range in the foreseeable future. References Cited A complete list of all references cited herein, as well as others, is available upon request from our Snake River Basin Office (see ADDRESSES section). Author(s) The primary authors of this final rule are staff of the U.S. Fish and Wildlife Service. Authority: 16 U.S.C. 1531 *et seq.* Dated January 4, 2007. H. Dale Hall, Director, U.S. Fish and Wildlife Service. [FR Doc. 07-60 Filed 1-11-07; 8:45 am]

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