Sec. 3038. COMBINATION PRODUCT INNOVATION
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## SEC. 3038 COMBINATION PRODUCT INNOVATION ###
(a)In general Section 503(g) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 353(g)) is amended— ####
(1)by striking paragraph (3); ####
(2)by redesignating paragraph
(2)as paragraph (7); ####
(3)by redesignating paragraphs
(4)and
(5)as paragraphs
(8)and (9), respectively; ####
(4)by striking “ (g)(1) ” and all that follows through the end of paragraph
(1)and inserting the following: > > ### “(g) > > > ####
(1)> > > #####
(A)> > The Secretary shall, in accordance with this subsection, assign a primary agency center to regulate products that constitute a combination of a drug, device, or biological product. > > > ##### “(B) > > The Secretary shall conduct the premarket review of any combination product under a single application, whenever appropriate**. > > > ##### “(C) > > For purposes of this subsection, the term ‘primary mode of action’ means the single mode of action of a combination product expected to make the greatest contribution to the overall intended therapeutic effects of the combination product. > > > ##### “(D) > > The Secretary shall determine the primary mode of action of the combination product. If the Secretary determines that the primary mode of action is that of— > > > ###### “(i) > > a drug (other than a biological product), the agency center charged with premarket review of drugs shall have primary jurisdiction; > > > ###### “(ii) > > a device, the agency center charged with premarket review of devices shall have primary jurisdiction; or > > > ###### “(iii) > > a biological product, the agency center charged with premarket review of biological products shall have primary jurisdiction. > > > ##### “(E) > > In determining the primary mode of action of a combination product, the Secretary shall not determine that the primary mode of action is that of a drug or biological product solely because the combination product has any chemical action within or on the human body. > > > ##### “(F) > > If a sponsor of a combination product disagrees with the determination under subparagraph (D)— > > > ###### “(i) > > such sponsor may request, and the Secretary shall provide, a substantive rationale to such sponsor that references scientific evidence provided by the sponsor and any other scientific evidence relied upon by the Secretary to support such determination; and > > > ###### “(ii) > > > ######
(I)> > the sponsor of the combination product may propose one or more studies (which may be nonclinical, clinical, or both) to establish the relevance, if any, of the chemical action in achieving the primary mode of action of such product; > > > ###### “(II) > > if the sponsor proposes any such studies, the Secretary and the sponsor of such product shall collaborate and seek to reach agreement, within a reasonable time of such proposal, not to exceed 90 calendar days, on the design of such studies; and > > > ###### “(III) > > if an agreement is reached under subclause
(II)and the sponsor conducts one or more of such studies, the Secretary shall consider the data resulting from any such study when reevaluating the determination of the primary mode of action of such product, and unless and until such reevaluation has occurred and the Secretary issues a new determination, the determination of the Secretary under subparagraph
(D)shall remain in effect. > > > #### “(2) > > > #####
(A)> > > ######
(i)> > To establish clarity and certainty for the sponsor, the sponsor of a combination product may request a meeting on such combination product. If the Secretary concludes that a determination of the primary mode of action pursuant to paragraph (1)(D) is necessary, the sponsor may request such meeting only after the Secretary makes such determination. If the sponsor submits a written meeting request, the Secretary shall, not later than 75 calendar days after receiving such request, meet with the sponsor of such combination product. > > > ###### “(ii) > > A meeting under clause
(i)may— > > > ###### “(I) > > address the standards and requirements for market approval or clearance of the combination product; > > > ###### “(II) > > address other issues relevant to such combination product, such as requirements related to postmarket modification of such combination product and good manufacturing practices applicable to such combination product; and > > > ###### “(III) > > identify elements under subclauses
(I)and
(II)that may be more appropriate for discussion and agreement with the Secretary at a later date given that scientific or other information is not available, or agreement is otherwise not feasible regarding such elements, at the time a request for such meeting is made. > > > ###### “(iii) > > Any agreement under this subparagraph shall be in writing and made part of the administrative record by the Secretary. > > > ###### “(iv) > > Any such agreement shall remain in effect, except— > > > ###### “(I) > > upon the written agreement of the Secretary and the sponsor or applicant; or > > > ###### “(II) > > pursuant to a decision by the director of the reviewing division of the primary agency center, or a person more senior than such director, in consultation with consulting centers and the Office, as appropriate, that an issue essential to determining whether the standard for market clearance or other applicable standard under this Act or the Public Health Service Act applicable to the combination product has been identified since the agreement was reached, or that deviating from the agreement is otherwise justifiable based on scientific evidence, for public health reasons. > > > #### “(3) > > For purposes of conducting the premarket review of a combination product that contains an approved constituent part described in paragraph (4), the Secretary may require that the sponsor of such combination product submit to the Secretary only data or information that the Secretary determines is necessary to meet the standard for clearance or approval, as applicable, under this Act or the Public Health Service Act, including any incremental risks and benefits posed by such combination product, using a risk-based approach and taking into account any prior finding of safety and effectiveness or substantial equivalence for the approved constituent part relied upon by the applicant in accordance with paragraph (5). > > > #### “(4) > > For purposes of paragraph (3), an approved constituent part is— > > > ##### “(A) > > a drug constituent part of a combination product being reviewed in a single application or request under section 515, 510(k), or 513(f)(2) (submitted in accordance with paragraph (5)), that is an approved drug, provided such application or request complies with paragraph (5); > > > ##### “(B) > > a device constituent part approved under section 515 that is referenced by the sponsor and that is available for use by the Secretary under section 520(h)(4); or > > > ##### “(C) > > any constituent part that was previously approved, cleared, or classified under section 505, 510(k), 513(f)(2), or 515 of this Act for which the sponsor has a right of reference or any constituent part that is a nonprescription drug, as defined in section 760(a)(2). > > > #### “(5) > > > #####
(A)> > If an application is submitted under section 515 or 510(k) or a request is submitted under section 513(f)(2), consistent with any determination made under paragraph (1)(D), for a combination product containing as a constituent part an approved drug— > > > ###### “(i) > > the application or request shall include the certification or statement described in section 505(b)(2); and > > > ###### “(ii) > > the applicant or requester shall provide notice as described in section 505(b)(3). > > > ##### “(B) > > For purposes of this paragraph and paragraph (4), the term ‘approved drug’ means an active ingredient— > > > ###### “(i) > > that was in an application previously approved under section 505(c); > > > ###### “(ii) > > where such application is relied upon by the applicant submitting the application or request described in subparagraph (A); > > > ###### “(iii) > > for which full reports of investigations that have been made to show whether such drug is safe for use and whether such drug is effective in use were not conducted by or for the applicant submitting the application or request described in subparagraph (A); and > > > ###### “(iv) > > for which the applicant submitting the application or request described in subparagraph
(A)has not obtained a right of reference or use from the person by or for whom the investigations described in clause
(iii)were conducted. > > > ##### “(C) > > The following provisions shall apply with respect to an application or request described in subparagraph
(A)to the same extent and in the same manner as if such application or request were an application described in section 505(b)(2) that referenced the approved drug: > > > ###### “(i) > > Subparagraphs (A), (B), (C), and
(D)of section 505(c)(3). > > > ###### “(ii) > > Clauses (ii), (iii), and
(iv)of section 505(c)(3)(E). > > > ###### “(iii) > > Subsections
(b)and
(c)of section 505A. > > > ###### “(iv) > > Section 505E(a). > > > ###### “(v) > > Section 527(a). > > > ##### “(D) > > Notwithstanding any other provision of this subsection, an application or request for classification for a combination product described in subparagraph
(A)shall be considered an application submitted under section 505(b)(2) for purposes of section 271(e)(2)(A) of title 35, United States Code. > > > #### “(6) > > Nothing in this subsection shall be construed as prohibiting a sponsor from submitting separate applications for the constituent parts of a combination product, unless the Secretary determines that a single application is necessary.” > ; ####
(5)in paragraph
(8)(as redesignated by paragraph (3))— #####
(A)in subparagraph (C)— ######
(i)by amending clause
(i)to read as follows: > > ### “(i) > > In carrying out this subsection, the Office shall help to ensure timely and effective premarket review that involves more than one agency center by coordinating such reviews, overseeing the timeliness of such reviews, and overseeing the alignment of feedback regarding such reviews.” > ; ######
(ii)in clause (ii), by inserting “and alignment” after “the timeliness” each place it appears; and ######
(iii)by adding at the end the following new clauses: > > ###### “(iii) > > The Office shall ensure that, with respect to a combination product, a designated person or persons in the primary agency center is the primary point or points of contact for the sponsor of such combination product. The Office shall also coordinate communications to and from any consulting center involved in such premarket review, if requested by such primary agency center or any such consulting center. Agency communications and commitments, to the extent consistent with other provisions of law and the requirements of all affected agency centers, from the primary agency center shall be considered as communication from the Secretary on behalf of all agency centers involved in the review. > > > ###### “(iv) > > The Office shall, with respect to the premarket review of a combination product— > > > ###### “(I) > > ensure that any meeting between the Secretary and the sponsor of such product is attended by each agency center involved in the review, as appropriate; > > > ###### “(II) > > ensure that each consulting agency center has completed its premarket review and provided the results of such review to the primary agency center in a timely manner; and > > > ###### “(III) > > ensure that each consulting center follows the guidance described in clause
(vi)and advises, as appropriate, on other relevant regulations, guidances, and policies. > > > ### “(v) > > In seeking agency action with respect to a combination product, the sponsor of such product— > > > #### “(I) > > shall identify the product as a combination product; and > > > #### “(II) > > may request in writing the participation of representatives of the Office in meetings related to such combination product, or to have the Office otherwise engage on such regulatory matters concerning the combination product. > > > ### “(vi) > > Not later than 4 years after the date of enactment of the 21st Century Cures Act, and after a public comment period of not less than 60 calendar days, the Secretary shall issue a final guidance that describes— > > > #### “(I) > > the structured process for managing pre-submission interactions with sponsors developing combination products; > > > #### “(II) > > the best practices for ensuring that the feedback in such pre-submission interactions represents the Agency’s best advice based on the information provided during such pre-submission interactions; > > > #### “(III) > > the information that is required to be submitted with a meeting request under paragraph (2), how such meetings relate to other types of meetings in the Food and Drug Administration, and the form and content of any agreement reached through a meeting under such paragraph (2);” > ; and #####
(B)in subparagraph (G)— ######
(i)in the matter preceding clause (i), by inserting “(except with respect to clause (iv), beginning not later than one year after the date of the enactment of the 21st Century Cures Act)” after “enactment of this paragraph”; ######
(ii)in clause (ii), by striking “and” at the end; ######
(iii)in clause (iii), by striking the period at the end and inserting “; and”; and ######
(iv)by adding at the end the following new clause: > > ###### “(iv) > > identifying the percentage of combination products for which a dispute resolution, with respect to premarket review, was requested by the combination product’s sponsor.” > ; and ####
(6)in paragraph
(9)(as redesignated by paragraph (3))— #####
(A)in subparagraph (C)— ######
(i)in clause (i), by striking the comma at the end and inserting a semicolon; ######
(ii)in clause (ii), by striking “, and” at the end and inserting a semicolon; ######
(iii)in clause (iii), by striking the period at the end and inserting “; and”; and ######
(iv)by adding at the end the following: > > ###### “(iv) > > de novo classification under section 513(a)(1).” > ; and #####
(B)by adding at the end the following: > > ##### “(D) > > The terms ‘premarket review’ and ‘reviews’ include all activities of the Food and Drug Administration conducted prior to approval or clearance of an application, notification, or request for classification submitted under section 505, 510(k), 513(f)(2), 515, or 520 of this Act or under section 351 of the Public Health Service Act, including with respect to investigational use of the product.” > . ###
(b)Information for Approval of Combination Products Section 520(h)(4) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360j(h)(4)) is amended— ####
(1)in subparagraph (A), by striking “Any information” and inserting “Subject to subparagraph (C), any information”; and ####
(2)by adding at the end the following new subparagraph: > > ##### “(C) > > No information contained in an application for premarket approval filed with the Secretary pursuant to section 515(c) may be used to approve or clear any application submitted under section 515 or 510(k) or to classify a product under section 513(f)(2) for a combination product containing as a constituent part an approved drug (as defined in section 503(g)(5)(B)) unless— > > > ###### “(i) > > the application includes the certification or statement referenced in section 503(g)(5)(A); > > > ###### “(ii) > > the applicant provides notice as described in section 503(g)(5)(A); and > > > ###### “(iii) > > the Secretary’s approval of such application is subject to the provisions in section 503(g)(5)(C).” > . ###
(c)Variations From CGMP Streamlined Approach **[**[21 U.S.C. 355 note](/us/usc/t21/s355)**]** Not later than 18 months after the date of enactment of this Act, the Secretary of Health and Human Services (referred to in this subsection as the “Secretary”) shall identify types of combination products and manufacturing processes with respect to which the Secretary proposes that good manufacturing processes may be adopted that vary from the requirements set forth in section 4.4 of title 21, Code of Federal Regulations (or any successor regulations) or that the Secretary proposes can satisfy the requirements in section 4.4 through alternative or streamlined mechanisms. The Secretary shall identify such types, variations from such requirements, and such mechanisms, in a proposed list published in the Federal Register. After a public comment period regarding the appropriate good manufacturing practices for such types, the Secretary shall publish a final list in the Federal Register, notwithstanding section 553 of title 5, United States Code. The Secretary shall evaluate such types, variations, and mechanisms using a risk-based approach. The Secretary shall periodically review such final list. ## Subtitle E Antimicrobial Innovation and Stewardship
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