Proposed Rules. Notice

Agency: Food and Drug Administration, HHS
Action: Notice
Citation: FR Doc. 01-2789 · Docket No. 01D-0027

Summary

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled “Statistical Approaches to Establishing Bioequivalence.” This guidance provides recommendations to sponsors and/or applicants who intend to use equivalence criteria in analyzing in vivo or in vitro bioequivalence (BE) studies for investigational new drug applications (IND’s), new drug applications (NDA’s), abbreviated new drug applications (ANDA’s) and supplements to these applications. The guidance discusses the use of average, population, and individual BE approaches to compare in vivo and in vitro bioavailability (BA) measures. (This guidance replaces the draft guidance that was issued in 1999 entitled “Average, Population, and Individual Approaches to Establishing Bioequivalence.”)

Dates

Submit written comments on agency guidances at any time.

Supplementary Information

FDA is announcing the availability of a guidance for industry entitled “Statistical Approaches to Establishing Bioequivalence.” This guidance provides information on statistical approaches for sponsors and/or applicants intending to provide BA and BE information to the agency in IND’s, NDA’s, ANDA’s, and their supplements. Over the years, BA/BE data have been analyzed using an average BE approach. This statistical guidance describes two new approaches for analysis, population and individual BE. This guidance does not provide information about when an approach should be used; that information is provided in other FDA BA/BE guidances. Instead, the guidance provides recommendations on how to use each of these approaches once one has been selected. This guidance is a final revision of a document that began with the publication of a preliminary draft guidance on this subject entitled “In Vivo Bioequivalence Studies Based on Population and Individual Bioequivalence Approaches” in 1997 (62 FR 67880, December 30, 1997), and was followed by a draft guidance entitled “Average, Population, and Individual Approaches to Establishing Bioequivalence,” published in 1999 (64 FR 48842, September 8, 1999). This final guidance replaces both of these draft guidances and a 1992 FDA guidance entitled “Statistical Procedure for Bioequivalence Studies Using a Standard Two-Treatment Crossover Design.” In September 1999, FDA announced the availability of a draft guidance entitled “BA and BE Studies for Orally Administered Drug Products—General Considerations” (64 FR 48409, September 3, 1999). That draft guidance was intended to provide general information on how to comply with the BA and BE requirements in part 320 (21 CFR part 320) for orally administered dosage forms. When that draft guidance was published, FDA received a total of 16 public comments, a number of which expressed concern about the use of the individual BE approach. FDA acknowledged the public concerns about the use of the individual BE approach when the final guidance entitled “BA and BE Studies for Orally Administered Drug Products—General Considerations” (65 FR 64449, October 27, 2000) was issued. In that guidance, FDA recommends the continued use of the average BE approach for both replicated and nonreplicated studies. However, that guidance states that sponsors have the option to choose another approach, e.g., an individual BE approach for highly variable drugs. The final statistical guidance being made available today provides recommendations on how to use this approach if it is chosen. This statistical guidance is one of a set of core guidances being developed to provide recommendations on how to meet the provisions of part 320. Taken together, these guidances are designed to address the studies that should be provided to document product quality BA/BE for all drug products regulated by CDER in accordance with the provisions of part 320. This guidance is being issued consistent with FDA’s good guidance practices regulation (65 FR 56468, September 19, 2000). This Level 1 guidance document represents the agency’s current thinking on the statistical approaches used in BA and BE studies. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such an approach satisfies the requirements of the applicable statutes, regulations, or both. Interested persons may, at any time, submit written comments on the guidance to the Dockets Management Branch (address above). Two copies of any comments are to be submitted, except that individuals may submit one copy. Comments are to be identified with the docket number found in brackets in the heading of this document. The guidance and received comments are available for public examination in the Documents Management Branch between 9 a.m. and 4 p.m., Monday through Friday. Dated: January 24, 2001. Ann M. Witt, Acting Associate Commissioner for Policy. [FR Doc. 01-2789 Filed 2-1-01; 8:45 am]