§360fff. Definitions — Inbound Citations
21 U.S.C. § 360fff
Cited by 622 provisions in release 119-102.
Citations to §360fff(1)
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(1) The Secretary shall issue regulations to implement this section. Before issuing regulations to implement subsections (b)(1)(A)(i)(III), (b)(1)(C), or (b)(3)(A), the Secretary shall convene and consult an advisory committee on compounding unless the Secretary determines that the issuance of such regulations before consultation is necessary to protect the public health. The advisory committee shall include representatives from the National Association of Boards of Pharmacy, the United States Pharmacopoeia, pharmacy, physician, and consumer organizations, and other experts selected by the Secretary.
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(2) Before issuing regulations to implement subsection (a)(6), the Secretary shall convene and consult an advisory committee on compounding. The advisory committee shall include representatives from the National Association of Boards of Pharmacy, the United States Pharmacopeia, pharmacists with current experience and expertise in compounding, physicians with background and knowledge in compounding, and patient and public health advocacy organizations.
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(C) At least biannually, the Secretary shall seek recommendations from the Drug Safety and Risk Management Advisory Committee (or any successor committee) and from other advisory committees, as appropriate, to the Food and Drug Administration on—(i) priority drug safety questions; and(ii) mechanisms for answering such questions, including through—(I) active risk identification under paragraph (3); and(II) when such risk identification is not sufficient, postapproval studies and clinical trials under subsection (o)(3).
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(6) The Advisory Committee on Risk Communication under section 360bbb–6 of this title shall, on a regular basis, perform a comprehensive review and evaluation of the types of risk communication information provided on the Internet Web site established under paragraph (1) and, through other means, shall identify, clarify, and define the purposes and types of information available to facilitate the efficient flow of information to patients and providers, and shall recommend ways for the Food and Drug Administration to work with outside entities to help facilitate the dispensing of risk communication information to patients and providers.
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(1) refer a drug or biological product to a Food and Drug Administration advisory committee for review at a meeting of such advisory committee prior to the approval of such drug or biological if it is—(A) a drug, no active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations)) of which has been approved in any other application under this section; or(B) a biological product, no active ingredient of which has been approved in any other application under section 262 of title 42; or
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(2) if the Secretary does not refer a drug or biological product described in paragraph (1) to a Food and Drug Administration advisory committee prior to such approval, provide in the action letter on the application for the drug or biological product a summary of the reasons why the Secretary did not refer the drug or biological product to an advisory committee prior to approval.
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(ii) if the sponsor of the application does not agree within 30 days after the Commissioner’s request to make a labeling change requested by the Commissioner, the Commissioner shall refer the matter to the Pediatric Advisory Committee.
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(B) Not later than 90 days after receiving a referral under subparagraph (A)(ii), the Pediatric Advisory Committee shall—(i) review the pediatric study reports; and(ii) make a recommendation to the Commissioner concerning appropriate labeling changes, if any.
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(C) The Commissioner shall consider the recommendations of the Pediatric Advisory Committee and, if appropriate, not later than 30 days after receiving the recommendation, make a request to the sponsor of the application to make any labeling change that the Commissioner determines to be appropriate.
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(E) Nothing in this subsection limits the authority of the United States to bring an enforcement action under this chapter when a drug lacks appropriate pediatric labeling. Neither course of action (the Pediatric Advisory Committee process or an enforcement action referred to in the preceding sentence) shall preclude, delay, or serve as the basis to stay the other course of action.
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(1) Beginning on September 27, 2007, during the 18-month period beginning on the date a labeling change is approved pursuant to subsection (i), the Secretary shall ensure that all adverse event reports that have been received for such drug (regardless of when such report was received) are referred to the Office of Pediatric Therapeutics established under section 393a of this title. In considering the reports, the Director of such Office shall provide for the review of the reports by the Pediatric Advisory Committee, including obtaining any recommendations of such Committee regarding whether the Secretary should take action under this chapter in response to such reports.
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(2) Following the 18-month period described in paragraph (1), the Secretary shall, as appropriate, refer to the Office of Pediatric Therapeutics all pediatric adverse event reports for a drug for which a pediatric study was conducted under this section. In considering such reports, the Director of such Office may provide for the review of such reports by the Pediatric Advisory Committee, including obtaining any recommendation of such Committee regarding whether the Secretary should take action in response to such reports.
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(3) Nothing in this subsection shall prohibit the Office of Pediatric Therapeutics from providing for the review of adverse event reports by the Pediatric Advisory Committee prior to the 18-month period referred to in paragraph (1), if such review is necessary to ensure safe use of a drug in a pediatric population.
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(1) During the one year beginning on the date on which a drug receives a period of market exclusivity under 505A1 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355a], any report of an adverse event regarding the drug that the Secretary of Health and Human Services receives shall be referred to the Office of Pediatric Therapeutics established under section 393a of this title. In considering the report, the Director of such Office shall provide for the review of the report by the Pediatric Advisory Committee, including obtaining any recommendations of such subcommittee2 regarding whether the Secretary should take action under the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.] in response to the report.
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(1) Beginning 270 days after July 9, 2012, the Secretary shall issue a non-compliance letter to such person informing them of such failure to submit or meet the requirements of the applicable subsection. Such letter shall require the person to respond in writing within 45 calendar days of issuance of such letter. Such response may include the person’s request for a deferral extension if applicable. Such letter and the person’s written response to such letter shall be made publicly available on the Internet Web site of the Food and Drug Administration 60 calendar days after issuance, with redactions for any trade secrets and confidential commercial information. If the Secretary determines that the letter was issued in error, the requirements of this paragraph shall not apply. The Secretary shall inform the Pediatric Advisory Committee of letters issued under this paragraph and responses to such letters.
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(ii) if the sponsor does not agree within 30 days after the Commissioner’s request to make a labeling change requested by the Commissioner, the Commissioner shall refer the matter to the Pediatric Advisory Committee.
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(B) Not later than 90 days after receiving a referral under subparagraph (A)(ii), the Pediatric Advisory Committee shall—(i) review the pediatric study reports; and(ii) make a recommendation to the Commissioner concerning appropriate labeling changes, if any.
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(C) The Commissioner shall consider the recommendations of the Pediatric Advisory Committee and, if appropriate, not later than 30 days after receiving the recommendation, make a request to the sponsor of the application or supplement to make any labeling changes that the Commissioner determines to be appropriate.
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(E) Nothing in this subsection limits the authority of the United States to bring an enforcement action under this chapter when a drug lacks appropriate pediatric labeling. Neither course of action (the Pediatric Advisory Committee process or an enforcement action referred to in the preceding sentence) shall preclude, delay, or serve as the basis to stay the other course of action.
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(1) Beginning on September 27, 2007, during the 18-month period beginning on the date a labeling change is made pursuant to subsection (g), the Secretary shall ensure that all adverse event reports that have been received for such drug (regardless of when such report was received) are referred to the Office of Pediatric Therapeutics. In considering such reports, the Director of such Office shall provide for the review of such reports by the Pediatric Advisory Committee, including obtaining any recommendations of such committee regarding whether the Secretary should take action under this chapter in response to such reports.
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(2) Following the 18-month period described in paragraph (1), the Secretary shall, as appropriate, refer to the Office of Pediatric Therapeutics all pediatric adverse event reports for a drug for which a pediatric study was conducted under this section. In considering such reports, the Director of such Office may provide for the review of such reports by the Pediatric Advisory Committee, including obtaining any recommendation of such Committee regarding whether the Secretary should take action in response to such reports.
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(3) Nothing in this subsection shall prohibit the Office of Pediatric Therapeutics from providing for the review of adverse event reports by the Pediatric Advisory Committee prior to the 18-month period referred to in paragraph (1), if such review is necessary to ensure safe use of a drug in a pediatric population.
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(2) In establishing the lists described in paragraph (1), the Secretary shall consult the National Cancer Institute, members of the internal committee under section 355d of this title, and the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee, and shall take into account comments from the meeting under subsection (c).
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(5) The Secretary, through the Drug Safety and Risk Management Advisory Committee (or successor committee) or other advisory committee of the Food and Drug Administration, shall—(A) seek input from patients, physicians, pharmacists, and other health care providers about how elements to assure safe use under this subsection for 1 or more drugs may be standardized so as not to be—(i) unduly burdensome on patient access to the drug; and(ii) to the extent practicable, minimize2 the burden on the health care delivery system;(B) periodically evaluate, for 1 or more drugs, the elements to assure safe use of such drug to assess whether the elements—(ii) are not unduly burdensome on patient access to the drug; and(iii) to the extent practicable, minimize the burden on the health care delivery system; and(C) considering such input and evaluations—(i) issue or modify agency guidance about how to implement the requirements of this subsection; and(ii) modify elements under this subsection for 1 or more drugs as appropriate.
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(5) The Secretary may convene a meeting of 1 or more advisory committees of the Food and Drug Administration to—(A) review a concern about the safety of a drug or class of drugs, including before an assessment of the risk evaluation and mitigation strategy or strategies of such drug or drugs is required to be submitted under subparagraph (B) or (C) of subsection (g)(2);
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(ii) 1 or more meetings of 1 or more advisory committees of the Food and Drug Administration, as provided for under paragraph (6);4 or
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(iv) convening and consulting an advisory committee on issues related to the proposed withdrawal, if requested by the sponsor and if no such advisory committee has previously advised the Secretary on such issues with respect to the withdrawal of the product prior to the sponsor’s request.
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If, regarding an obligation concerning drugs or devices under this Act or section 351 of the Public Health Service Act [42 U.S.C. 262], there is a scientific controversy between the Secretary and a person who is a sponsor, applicant, or manufacturer and no specific provision of the Act involved, including a regulation promulgated under such Act, provides a right of review of the matter in controversy, the Secretary shall, by regulation, establish a procedure under which such sponsor, applicant, or manufacturer may request a review of such controversy, including a review by an appropriate scientific advisory panel described in section 355(n) of this title or an advisory committee described in section 360e(g)(2)(B) of this title. Any such review shall take place in a timely manner. The Secretary shall promulgate such regulations within 1 year after November 21, 1997.
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(1) The Secretary shall establish an advisory committee to be known as the “Advisory Committee on Risk Communication” (referred to in this section as the “Committee”).
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(A) After the expiration of the period for comment on a notice of proposed rulemaking published under paragraph (1) respecting a performance standard and after consideration of such comments and any report from an advisory committee under paragraph (5), the Secretary shall (i) promulgate a regulation establishing a performance standard and publish in the Federal Register findings on the matters referred to in paragraph (1), or (ii) publish a notice terminating the proceeding for the development of the standard together with the reasons for such termination. If a notice of termination is published, the Secretary shall (unless such notice is issued because the device is a banned device under section 360f of this title) initiate a proceeding under section 360c(e) of this title to reclassify the device subject to the proceeding terminated by such notice.
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(A) The Secretary—(i) may on his own initiative refer a proposed regulation for the establishment, amendment, or revocation of a performance standard, or(ii) shall, upon the request of an interested person which demonstrates good cause for referral and which is made before the expiration of the period for submission of comments on such proposed regulation refer such proposed regulation,to an advisory committee of experts, established pursuant to subparagraph (B), for a report and recommendation with respect to any matter involved in the proposed regulation which requires the exercise of scientific judgment. If a proposed regulation is referred under this subparagraph to an advisory committee, the Secretary shall provide the advisory committee with the data and information on which such proposed regulation is based. The advisory committee shall, within sixty days of the referral of a proposed regulation and after independent study of the data and information furnished to it by the Secretary and other data and information before it, submit to the Secretary a report and recommendation respecting such regulation, together with all underlying data and information and a statement of the reason or basis for the recommendation. A copy of such report and recommendation shall be made public by the Secretary.
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(B) The Secretary shall establish advisory committees (which may not be panels under section 360c of this title) to receive referrals under subparagraph (A). The Secretary shall appoint as members of any such advisory committee persons qualified in the subject matter to be referred to the committee and of appropriately diversified professional background, except that the Secretary may not appoint to such a committee any individual who is in the regular full-time employ of the United States and engaged in the administration of this chapter. Each such committee shall include as nonvoting members a representative of consumer interests and a representative of interests of the device manufacturing industry. Members of an advisory committee who are not officers or employees of the United States, while attending conferences or meetings of their committee or otherwise serving at the request of the Secretary, shall be entitled to receive compensation at rates to be fixed by the Secretary, which rates may not exceed the daily equivalent of the rate in effect for grade GS–18 of the General Schedule, for each day (including traveltime) they are so engaged; and while so serving away from their homes or regular places of business each member may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5 for persons in the Government service employed intermittently. The Secretary shall designate one of the members of each advisory committee to serve as chairman thereof. The Secretary shall furnish each advisory committee with clerical and other assistance, and shall by regulation prescribe the procedures to be followed by each such committee in acting on referrals made under subparagraph (A).
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(A) Upon petition for review of—(i) an order under subsection (d) approving or denying approval of an application or an order under subsection (e) withdrawing approval of an application, or(ii) an order under subsection (f)(6)(A) revoking an approved protocol, under subsection (f)(6)(B) declaring that an approved protocol has not been completed, or under subsection (f)(7) revoking the approval of a device,the Secretary shall refer the application or protocol subject to the order and the basis for the order to an advisory committee of experts established pursuant to subparagraph (B) for a report and recommendation with respect to the order. The advisory committee shall, after independent study of the data and information furnished to it by the Secretary and other data and information before it, submit to the Secretary a report and recommendation, together with all underlying data and information and a statement of the reasons or basis for the recommendation. A copy of such report shall be promptly supplied by the Secretary to any person who petitioned for such referral to the advisory committee.
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(B) The Secretary shall establish advisory committees (which may not be panels under section 360c of this title) to receive referrals under subparagraph (A). The Secretary shall appoint as members of any such advisory committee persons qualified in the subject matter to be referred to the committee and of appropriately diversified professional backgrounds, except that the Secretary may not appoint to such a committee any individual who is in the regular full-time employ of the United States and engaged in the administration of this chapter. Members of an advisory committee (other than officers or employees of the United States), while attending conferences or meetings of their committee or otherwise serving at the request of the Secretary, shall be entitled to receive compensation at rates to be fixed by the Secretary, which rates may not exceed the daily equivalent for grade GS–18 of the General Schedule for each day (including traveltime) they are so engaged; and while so serving away from their homes or regular places of business each member may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5 for persons in the Government service employed intermittently. The Secretary shall designate the chairman of an advisory committee from its members. The Secretary shall furnish each advisory committee with clerical and other assistance, and shall by regulation prescribe the procedures to be followed by each such committee in acting on referrals made under subparagraph (A).
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(C) The Secretary shall make public the report and recommendation made by an advisory committee with respect to an application and shall by order, stating the reasons therefor, either affirm the order referred to the advisory committee or reverse such order and, if appropriate, approve or deny approval of the application, reinstate the application’s approval, approve the protocol, or place in effect a notice of completion.
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(G) provide for advisory committee input, as the Secretary determines appropriate (including in response to the request of the sponsor) for applications submitted under section 360e(c) of this title; and
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(A) may convene a meeting of the Advisory Committee to review such request; and
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(8) In the case of a proposed sunscreen order under paragraph (3), (4), or (5), an Advisory Committee meeting may be convened for the purpose of reviewing and providing recommendations regarding the pending request.
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(I) if the Advisory Committee is not convened under paragraph (8), not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order, which shall include a rationale for not convening such Advisory Committee; or
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(II) if the Advisory Committee is convened under paragraph (8), not later than 270 calendar days after the date on which the sponsor submits such additional information; or
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(1) convene the Advisory Committee—(A) more than once with respect to any request under section 360fff–1 of this title or any pending request; or(B) more than twice in any calendar year with respect to the review under this section; or
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(2) submit more than a total of 3 requests under section 360fff–1 of this title or pending requests to the Advisory Committee per meeting.
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(C) an annual accounting (including information from years prior to November 26, 2014, where such information is available) of the total number of requests submitted, pending, or completed under this part, including whether such requests were the subject of an advisory committee convened by the Secretary;
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(F) to the extent the Secretary determines appropriate, recommendations for process improvements in the handling of requests under this part, including the advisory committee review process.
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(a) Not later than thirty days after—(1) the promulgation of a regulation under section 360c of this title classifying a device in class I, an administrative order changing the classification of a device to class I, or an order under subsection (f)(2) of such section reclassifying a device or denying a petition for reclassification of a device,(2) the promulgation of a regulation under section 360d of this title establishing, amending, or revoking a performance standard for a device,(3) the issuance of an order under section 360d(b)(2) or 360e(b)(2)(B) of this title denying a request for reclassification of a device,(4) the promulgation of a regulation under paragraph (3) of section 360e(b) of this title requiring a device to have an approval of a premarket application, a regulation under paragraph (4) of that section amending or revoking a regulation under paragraph (3), or an order pursuant to section 360e(g)(1) or 360e(g)(2)(C) of this title,(5) the promulgation of a regulation under section 360f of this title (other than a proposed regulation made effective under subsection (b) of such section upon the regulation’s publication) making a device a banned device,(6) the issuance of an order under section 360j(f)(2) of this title,(7) an order under section 360j(g)(4) of this title disapproving an application for an exemption of a device for investigational use or an order under section 360j(g)(5) of this title withdrawing such an exemption for a device,(8) an order pursuant to section 360c(i) of this title, or(9) a regulation under section 360e(i)(2) or 360j(l)(5)(B) of this title,any person adversely affected by such regulation or order may file a petition with the United States Court of Appeals for the District of Columbia or for the circuit wherein such person resides or has his principal place of business for judicial review of such regulation or order. A copy of the petition shall be transmitted by the clerk of the court to the Secretary or other officer designated by him for that purpose. The Secretary shall file in the court the record of the proceedings on which the Secretary based his regulation or order as provided in section 2112 of title 28. For purposes of this section, the term “record” means all notices and other matter published in the Federal Register with respect to the regulation or order reviewed, all information submitted to the Secretary with respect to such regulation or order, proceedings of any panel or advisory committee with respect to such regulation or order, any hearing held with respect to such regulation or order, and any other information identified by the Secretary, in the administrative proceeding held with respect to such regulation or order, as being relevant to such regulation or order.
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(3) To help ensure effective implementation of the system as described in paragraph (1) with respect to devices, the Secretary shall engage outside stakeholders in development of the system, and gather information from outside stakeholders regarding the content of an effective sentinel program, through a public hearing, advisory committee meeting, maintenance of a public docket, or other similar public measures.
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(B) Before the Secretary may promulgate any regulation under subparagraph (A) he shall—(i) afford the advisory committee established under paragraph (3) an opportunity to submit recommendations to him with respect to the regulation proposed to be promulgated;(ii) afford opportunity for an oral hearing; and(iii) ensure that such regulation conforms, to the extent practicable, with internationally recognized standards defining quality systems, or parts of the standards, for medical devices.The Secretary shall provide the advisory committee a reasonable time to make its recommendation with respect to proposed regulations under subparagraph (A).
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(i) afford the advisory committee established under paragraph (3) an opportunity to submit recommendations to him with respect to the regulation proposed to be promulgated;
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(B) The Secretary may refer to the advisory committee established under paragraph (3) any petition submitted under subparagraph (A). The advisory committee shall report its recommendations to the Secretary with respect to a petition referred to it within sixty days of the date of the petition’s referral. Within sixty days after—(i) the date the petition was submitted to the Secretary under subparagraph (A), or(ii) if the petition was referred to an advisory committee, the expiration of the sixty-day period beginning on the date the petition was referred to the advisory committee,whichever occurs later, the Secretary shall by order either deny the petition or approve it.
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(ii) if the petition was referred to an advisory committee, the expiration of the sixty-day period beginning on the date the petition was referred to the advisory committee,
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(3) The Secretary shall establish an advisory committee for the purpose of advising and making recommendations to him with respect to regulations proposed to be promulgated under paragraph (1)(A) and the approval or disapproval of petitions submitted under paragraph (2). The advisory committee shall be composed of nine members as follows:(A) Three of the members shall be appointed from persons who are officers or employees of any State or local government or of the Federal Government.(B) Two of the members shall be appointed from persons who are representative of interests of the device manufacturing industry; two of the members shall be appointed from persons who are representative of the interests of physicians and other health professionals; and two of the members shall be representative of the interests of the general public.Members of the advisory committee who are not officers or employees of the United States, while attending conferences or meetings of the committee or otherwise engaged in its business, shall be entitled to receive compensation at rates to be fixed by the Secretary, which rates may not exceed the daily equivalent of the rate in effect for grade GS–18 of the General Schedule, for each day (including traveltime) they are so engaged; and while so serving away from their homes or regular places of business each member may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5 for persons in the Government service employed intermittently. The Secretary shall designate one of the members of the advisory committee to serve as its chairman. The Secretary shall furnish the advisory committee with clerical and other assistance. Section 1013 of title 5 shall not apply with respect to the duration of the advisory committee established under this paragraph.
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(2) The Secretary shall promulgate regulations under which each advisory committee established under section 360e(g)(2)(B) of this title shall make available to the public a detailed summary of information respecting the safety and effectiveness of a device which information was submitted to the advisory committee and which was the basis for its recommendation to the Secretary made pursuant to section 360e(g)(2)(A) of this title. A summary of information upon which such a recommendation is based shall be made available pursuant to this paragraph only after the issuance of the order with respect to which the recommendation was made and each summary shall include information respecting any adverse effect on health of the device subject to such order.
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(i) Each panel under section 360c of this title and each advisory committee established under section 360d(b)(5)(B) or 360e(g) of this title or under subsection (f) of this section shall make and maintain a transcript of any proceeding of the panel or committee. Each such panel and committee shall delete from any transcript made pursuant to this subsection information which under subsection (c) of this section is to be considered confidential.
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(7) The Secretary shall refer any report of an adverse event regarding a device described in paragraph (6)(A)(i)(I) for which the prohibition under paragraph (3) does not apply pursuant to paragraph (6)(A) that the Secretary receives to the Office of Pediatric Therapeutics, established under section 393a of this title. In considering the report, the Director of the Office of Pediatric Therapeutics, in consultation with experts in the Center for Devices and Radiological Health, shall provide for periodic review of the report by the Pediatric Advisory Committee, including obtaining any recommendations of such committee regarding whether the Secretary should take action under this chapter in response to the report.
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(8) The Secretary, acting through the Office of Pediatric Therapeutics and the Center for Devices and Radiological Health, shall provide for an annual review by the Pediatric Advisory Committee of all devices described in paragraph (6)(A)(i)(I) to ensure that the exemption under paragraph (2) remains appropriate for the pediatric populations for which it is granted.
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(1) The term “advisory committee” means an advisory committee under chapter 10 of title 5 that provides advice or recommendations to the Secretary regarding activities of the Food and Drug Administration.
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(A) develop and implement strategies on effective outreach to potential members of advisory committees at universities, colleges, other academic research centers, professional and medical societies, and patient and consumer groups;
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(C) at least every 180 days, request referrals for potential members of advisory committees from a variety of stakeholders, including—(i) product developers, patient groups, and disease advocacy organizations; and(ii) relevant—(I) professional societies;(II) medical societies;(III) academic organizations; and(IV) governmental organizations; and
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(D) in carrying out subparagraphs (A) and (B), take into account the levels of activity (including the numbers of annual meetings) and the numbers of vacancies of the advisory committees.
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(A) advertising the process for becoming an advisory committee member at medical and scientific society conferences;
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(B) making widely available, including by using existing electronic communications channels, the contact information for the Food and Drug Administration point of contact regarding advisory committee nominations; and
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(C) developing a method through which an entity receiving funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, or the Veterans Health Administration can identify a person whom the Food and Drug Administration can contact regarding the nomination of individuals to serve on advisory committees.
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(1) As soon as practicable, but (except as provided in paragraph (2)) not later than 15 days prior to a meeting of an advisory committee to which a written determination as referred to in section 208(b)(1) of title 18 or a written certification as referred to in section 208(b)(3) of such title, applies, the Secretary shall disclose (other than information exempted from disclosure under section 552 or section 552a of title 5 (popularly known as the Freedom of Information Act and the Privacy Act of 1974, respectively)) on the Internet Web site of the Food and Drug Administration—(A) the type, nature, and magnitude of the financial interests of the advisory committee member to which such determination or certification applies; and(B) the reasons of the Secretary for such determination or certification, including, as appropriate, the public health interest in having the expertise of the member with respect to the particular matter before the advisory committee.
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(A) the type, nature, and magnitude of the financial interests of the advisory committee member to which such determination or certification applies; and
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(B) the reasons of the Secretary for such determination or certification, including, as appropriate, the public health interest in having the expertise of the member with respect to the particular matter before the advisory committee.
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(2) In the case of a financial interest that becomes known to the Secretary less than 30 days prior to a meeting of an advisory committee to which a written determination as referred to in section 208(b)(1) of title 18 or a written certification as referred to in section 208(b)(3) of such title applies, the Secretary shall disclose (other than information exempted from disclosure under section 552 or 552a of title 5) on the Internet Web site of the Food and Drug Administration, the information described in subparagraphs (A) and (B) of paragraph (1) as soon as practicable after the Secretary makes such determination or certification, but in no case later than the date of such meeting.
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(d) The Secretary shall ensure that the public record and transcript of each meeting of an advisory committee includes the disclosure required under subsection (c) (other than information exempted from disclosure under section 552 of title 5 and section 552a of title 5).
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(A) with respect to the fiscal year that ended on September 30 of the previous year, the number of persons nominated for participation at meetings for each advisory committee, the number of persons so nominated, and willing to serve, the number of vacancies on each advisory committee, and the number of persons contacted for service as members on each advisory committee meeting for each advisory committee who did not participate because of the potential for such participation to constitute a disqualifying financial interest under section 208 of title 18;
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(B) with respect to such year, the number of persons contacted for service as members for each advisory committee meeting for each advisory committee who did not participate because of reasons other than the potential for such participation to constitute a disqualifying financial interest under section 208 of title 18;
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(C) with respect to such year, the number of members attending meetings for each advisory committee; and
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(1) review guidance of the Food and Drug Administration with respect to advisory committees regarding disclosure of conflicts of interest and the application of section 208 of title 18; and
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(g) The Secretary shall issue guidance that describes how the Secretary reviews the financial interests and involvement of advisory committee members that are disclosed under subsection (c) but that the Secretary determines not to meet the definition of a disqualifying interest under section 208 of title 18 for the purposes of participating in a particular matter.
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(i) In any proceeding for the issuance, amendment, or repeal of a regulation listing a color additive, whether commenced by a proposal of the Secretary on his own initiative or by a proposal contained in a petition, the petitioner, or any other person who will be adversely affected by such proposal or by the Secretary’s order issued in accordance with paragraph (1) of section 371(e) of this title if placed in effect, may request, within the time specified in this subparagraph, that the petition or order thereon, or the Secretary’s proposal, be referred to an advisory committee for a report and recommendations with respect to any matter arising under subparagraph (B) of this paragraph, which is involved in such proposal or order and which requires the exercise of scientific judgment. Upon such request, or if the Secretary within such time deems such a referral necessary, the Secretary shall forthwith appoint an advisory committee under subparagraph (D) of this paragraph and shall refer to it, together with all the data before him, such matter arising under subparagraph (B) for study thereof and for a report and recommendations on such matter. A person who has filed a petition or who has requested the referral of a matter to an advisory committee pursuant to this subparagraph (C), as well as representatives of the Department, shall have the right to consult with such advisory committee in connection with the matter referred to it. The request for referral under this subparagraph, or the Secretary’s referral on his own initiative, may be made at any time before, or within thirty days after, publication of an order of the Secretary acting upon the petition or proposal.
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(ii) Within sixty days after the date of such referral, or within an additional thirty days if the committee deems such additional time necessary, the committee shall, after independent study of the data furnished to it by the Secretary and other data before it, certify to the Secretary a report and recommendations, together with all underlying data and a statement of the reasons or basis for the recommendations. A copy of the foregoing shall be promptly supplied by the Secretary to any person who has filed a petition, or who has requested such referral to the advisory committee. Within thirty days after such certification, and after giving due consideration to all data then before him, including such report, recommendations, underlying data, and statement, and to any prior order issued by him in connection with such matter, the Secretary shall by order confirm or modify any order theretofore issued or, if no such prior order has been issued, shall by order act upon the petition or other proposal.
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(iii) Where—(I) by reason of subparagraph (B) of this paragraph, the Secretary has initiated a proposal to remove from listing a color additive previously listed pursuant to this section; and(II) a request has been made for referral of such proposal to an advisory committee;the Secretary may not act by order on such proposal until the advisory committee has made a report and recommendations to him under clause (ii) of this subparagraph and he has considered such recommendations, unless the Secretary finds that emergency conditions exist necessitating the issuance of an order notwithstanding this clause.
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(II) a request has been made for referral of such proposal to an advisory committee;
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(D) The advisory committee referred to in subparagraph (C) of this paragraph shall be composed of experts selected by the National Academy of Sciences, qualified in the subject matter referred to the committee and of adequately diversified professional background, except that in the event of the inability or refusal of the National Academy of Sciences to act, the Secretary shall select the members of the committee. The size of the committee shall be determined by the Secretary. Members of any advisory committee established under this chapter, while attending conferences or meetings of their committees or otherwise serving at the request of the Secretary, shall be entitled to receive compensation at rates to be fixed by the Secretary but at rates not exceeding the daily equivalent of the rate specified at the time of such service for grade GS–18 of the General Schedule, including traveltime; and while away from their homes or regular places of business they may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5 for persons in the Government service employed intermittently. The members shall not be subject to any other provisions of law regarding the appointment and compensation of employees of the United States. The Secretary shall furnish the committee with adequate clerical and other assistance, and shall by rules and regulations prescribe the procedure to be followed by the committee.
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(1) if the proceeding is commenced by the filing of a petition, notice of the proposal made by the petition shall be published in general terms by the Secretary within thirty days after such filing, and the Secretary’s order (required by paragraph (1) of section 371(e) of this title) acting upon such proposal shall, in the absence of prior referral (or request for referral) to an advisory committee, be issued within ninety days after the date of such filing, except that the Secretary may (prior to such ninetieth day), by written notice to the petitioner, extend such ninety-day period to such time (not more than one hundred and eighty days after the date of filing of the petition) as the Secretary deems necessary to enable him to study and investigate the petition;
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(2) any report, recommendations, underlying data, and reasons certified to the Secretary by an advisory committee appointed pursuant to subparagraph (D) of subsection (b)(5) of this section, shall be made a part of the record of any hearing if relevant and material, subject to the provisions of section 556(d) of title 5. The advisory committee shall designate a member to appear and testify at any such hearing with respect to the report and recommendations of such committee upon request of the Secretary, the petitioner, or the officer conducting the hearing, but this shall not preclude any other member of the advisory committee from appearing and testifying at such hearing;
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(A) officers and employees of the Food and Drug Administration, contractors of the Food and Drug Administration, advisory committees, and costs related to such officers, employees, and committees and to contracts with such contractors,
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(j) This section may not be construed to require that the number of full-time equivalent positions in the Department of Health and Human Services, for officers, employers, and advisory committees not engaged in the process of the review of human drug applications, be reduced to offset the number of officers, employees, and advisory committees so engaged.
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(A) officers and employees of the Food and Drug Administration, contractors of the Food and Drug Administration, advisory committees, and costs related to such officers, employees, and committees, and to contracts with such contractors;
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(A) officers and employees of the Food and Drug Administration, contractors of the Food and Drug Administration, advisory committees, and costs related to such officers, employees, and committees and to contracts with such contractors;
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(k) This section may not be construed to require that the number of full-time equivalent positions in the Department of Health and Human Services, for officers, employees, and advisory committees not engaged in the process of the review of device applications, be reduced to offset the number of officers, employees, and advisory committees so engaged.
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(A) officers and employees of the Food and Drug Administration, contractors of the Food and Drug Administration, advisory committees consulted with respect to the review of specific animal drug applications, supplemental animal drug applications, or investigational animal drug submissions, and costs related to such officers, employees, committees, and contractors, including costs for travel, education, and recruitment and other personnel activities;
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(j) This section may not be construed to require that the number of full-time equivalent positions in the Department of Health and Human Services, for officers, employees, and advisory committees not engaged in the process of the review of animal drug applications, be reduced to offset the number of officers, employees, and advisory committees so engaged.
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(j) This section may not be construed to require that the number of full-time equivalent positions in the Department of Health and Human Services, for officers, employees, and advisory committees not engaged in the process of the review of abbreviated applications for generic new animal drugs, be reduced to offset the number of officers, employees, and advisory committees so engaged.
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(A) officers and employees of the Food and Drug Administration, contractors of the Food and Drug Administration, advisory committees consulted with respect to the review of specific abbreviated applications, supplemental abbreviated applications, or investigational submissions, and costs related to such officers, employees, committees, and contractors, including costs for travel, education, and recruitment and other personnel activities;
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(A) officers and employees of the Food and Drug Administration, contractors of the Food and Drug Administration, advisory committees, and costs related to such officers and employees and to contracts with such contractors;
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(k) This section may not be construed to require that the number of full-time equivalent positions in the Department of Health and Human Services, for officers, employees, and advisory committees not engaged in human generic drug activities, be reduced to offset the number of officers, employees, and advisory committees so engaged.
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(A) officers and employees of the Food and Drug Administration, contractors of the Food and Drug Administration, advisory committees, and costs related to such officers employees and committees and to contracts with such contractors;
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(i) This section may not be construed to require that the number of full-time equivalent positions in the Department of Health and Human Services, for officers, employers, and advisory committees not engaged in the process of the review of biosimilar biological product applications, be reduced to offset the number of officers, employees, and advisory committees so engaged.
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(A) officers and employees of the Food and Drug Administration, contractors of the Food and Drug Administration, advisory committees, and costs related to such officers, employees, and committees and costs related to contracts with such contractors;
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(h) This section may not be construed to require that the number of full-time equivalent positions in the Department of Health and Human Services, for officers, employers, and advisory committees not engaged in OTC monograph drug activities, be reduced to offset the number of officers, employees, and advisory committees so engaged.
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(i) before promulgating any regulation under subparagraph (A), afford the Tobacco Products Scientific Advisory Committee an opportunity to submit recommendations with respect to the regulation proposed to be promulgated;
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(iii) provide the Tobacco Products Scientific Advisory Committee a reasonable time to make its recommendation with respect to proposed regulations under subparagraph (A);
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(B) The Secretary may refer to the Tobacco Products Scientific Advisory Committee any petition submitted under subparagraph (A). The Tobacco Products Scientific Advisory Committee shall report its recommendations to the Secretary with respect to a petition referred to it within 60 days after the date of the petition’s referral. Within 60 days after—(i) the date the petition was submitted to the Secretary under subparagraph (A); or(ii) the day after the petition was referred to the Tobacco Products Scientific Advisory Committee,whichever occurs later, the Secretary shall by order either deny the petition or approve it.
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(ii) the day after the petition was referred to the Tobacco Products Scientific Advisory Committee,
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(1) After the expiration of the period for comment on a notice of proposed rulemaking published under subsection (c) respecting a tobacco product standard and after consideration of comments submitted under subsections (b) and (c) and any report from the Tobacco Products Scientific Advisory Committee, the Secretary shall—(A) if the Secretary determines that the standard would be appropriate for the protection of the public health, promulgate a regulation establishing a tobacco product standard and publish in the Federal Register findings on the matters referred to in subsection (c); or(B) publish a notice terminating the proceeding for the development of the standard together with the reasons for such termination.
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(A) The Secretary may refer a proposed regulation for the establishment, amendment, or revocation of a tobacco product standard to the Tobacco Products Scientific Advisory Committee for a report and recommendation with respect to any matter involved in the proposed regulation which requires the exercise of scientific judgment.
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(C) If a proposed regulation is referred under this paragraph to the Tobacco Products Scientific Advisory Committee, the Secretary shall provide the Advisory Committee with the data and information on which such proposed regulation is based.
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(D) The Tobacco Products Scientific Advisory Committee shall, within 60 days after the referral of a proposed regulation under this paragraph and after independent study of the data and information furnished to it by the Secretary and other data and information before it, submit to the Secretary a report and recommendation respecting such regulation, together with all underlying data and information and a statement of the reason or basis for the recommendation.
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(1) Immediately upon the establishment of the Tobacco Products Scientific Advisory Committee under section 387q(a) of this title, the Secretary shall refer to the Committee for report and recommendation, under section 387q(c)(4) of this title, the issue of the impact of the use of menthol in cigarettes on the public health, including such use among children, African-Americans, Hispanics, and other racial and ethnic minorities. In its review, the Tobacco Products Scientific Advisory Committee shall address the considerations listed in subsections (a)(3)(B)(i) and (b).
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(2) Not later than 1 year after its establishment, the Tobacco Product Scientific Advisory Committee shall submit to the Secretary the report and recommendations required pursuant to paragraph (1).
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(1) The Secretary shall refer to the Tobacco Products Scientific Advisory Committee for report and recommendation, under section 387q(c)(4) of this title, the issue of the nature and impact of the use of dissolvable tobacco products on the public health, including such use among children. In its review, the Tobacco Products Scientific Advisory Committee shall address the considerations listed in subsection (a)(3)(B)(i).
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(2) Not later than 2 years after its establishment, the Tobacco Product Scientific Advisory Committee shall submit to the Secretary the report and recommendations required pursuant to paragraph (1).
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(2) Upon receipt of an application meeting the requirements set forth in paragraph (1), the Secretary—(A) may, on the Secretary’s own initiative; or(B) may, upon the request of an applicant,refer such application to the Tobacco Products Scientific Advisory Committee for reference and for submission (within such period as the Secretary may establish) of a report and recommendation respecting the application, together with all underlying data and the reasons or basis for the recommendation.
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(1) The Secretary shall, upon obtaining, where appropriate, advice on scientific matters from the Tobacco Products Scientific Advisory Committee, and after due notice and opportunity for informal hearing for a tobacco product for which an order was issued under subsection (c)(1)(A)(i), issue an order withdrawing the order if the Secretary finds—(A) that the continued marketing of such tobacco product no longer is appropriate for the protection of the public health;(B) that the application contained or was accompanied by an untrue statement of a material fact;(C) that the applicant—(i) has failed to establish a system for maintaining records, or has repeatedly or deliberately failed to maintain records or to make reports, required by an applicable regulation under section 387i of this title;(ii) has refused to permit access to, or copying or verification of, such records as required by section 374 of this title; or(iii) has not complied with the requirements of section 387e of this title;(D) on the basis of new information before the Secretary with respect to such tobacco product, evaluated together with the evidence before the Secretary when the application was reviewed, that the methods used in, or the facilities and controls used for, the manufacture, processing, packing, or installation of such tobacco product do not conform with the requirements of section 387f(e) of this title and were not brought into conformity with such requirements within a reasonable time after receipt of written notice from the Secretary of nonconformity;(E) on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when the application was reviewed, that the labeling of such tobacco product, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary of such fact; or(F) on the basis of new information before the Secretary, evaluated together with the evidence before the Secretary when such order was issued, that such tobacco product is not shown to conform in all respects to a tobacco product standard which is in effect under section 387g of this title, compliance with which was a condition to the issuance of an order relating to the application, and that there is a lack of adequate information to justify the deviation from such standard.
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(1) The Secretary shall refer to the Tobacco Products Scientific Advisory Committee any application submitted under this section.
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(2) Not later than 60 days after the date an application is referred to the Tobacco Products Scientific Advisory Committee under paragraph (1), the Advisory Committee shall report its recommendations on the application to the Secretary.
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(iii) proceedings of any panel or advisory committee with respect to such regulation or order;
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(a) Not later than 6 months after June 22, 2009, the Secretary shall establish a 12-member advisory committee, to be known as the Tobacco Products Scientific Advisory Committee (in this section referred to as the “Advisory Committee”).
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(A) The Secretary shall appoint as members of the Tobacco Products Scientific Advisory Committee individuals who are technically qualified by training and experience in medicine, medical ethics, science, or technology involving the manufacture, evaluation, or use of tobacco products, who are of appropriately diversified professional backgrounds. The committee shall be composed of—(i) 7 individuals who are physicians, dentists, scientists, or health care professionals practicing in the area of oncology, pulmonology, cardiology, toxicology, pharmacology, addiction, or any other relevant specialty;(ii) 1 individual who is an officer or employee of a State or local government or of the Federal Government;(iii) 1 individual as a representative of the general public;(iv) 1 individual as a representative of the interests of the tobacco manufacturing industry;(v) 1 individual as a representative of the interests of the small business tobacco manufacturing industry, which position may be filled on a rotating, sequential basis by representatives of different small business tobacco manufacturers based on areas of expertise relevant to the topics being considered by the Advisory Committee; and(vi) 1 individual as a representative of the interests of the tobacco growers.
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(v) 1 individual as a representative of the interests of the small business tobacco manufacturing industry, which position may be filled on a rotating, sequential basis by representatives of different small business tobacco manufacturers based on areas of expertise relevant to the topics being considered by the Advisory Committee; and
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(2) The Secretary may not appoint to the Advisory Committee any individual who is in the regular full-time employ of the Food and Drug Administration or any agency responsible for the enforcement of this chapter. The Secretary may appoint Federal officials as ex officio members.
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(c) The Tobacco Products Scientific Advisory Committee shall provide advice, information, and recommendations to the Secretary—(1) as provided in this subchapter;(2) on the effects of the alteration of the nicotine yields from tobacco products;(3) on whether there is a threshold level below which nicotine yields do not produce dependence on the tobacco product involved; and(4) on its review of other safety, dependence, or health issues relating to tobacco products as requested by the Secretary.
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(1) Members of the Advisory Committee who are not officers or employees of the United States, while attending conferences or meetings of the committee or otherwise engaged in its business, shall be entitled to receive compensation at rates to be fixed by the Secretary, which may not exceed the daily equivalent of the rate in effect under the Senior Executive Schedule under section 5382 of title 5, for each day (including travel time) they are so engaged; and while so serving away from their homes or regular places of business each member may be allowed travel expenses, including per diem in lieu of subsistence, as authorized by section 5703 of title 5 for persons in the Government service employed intermittently.
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(2) The Secretary shall furnish the Advisory Committee clerical and other assistance.
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(3) Section 1013 of title 5 does not apply to the Advisory Committee.
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(e) The Advisory Committee shall make and maintain a transcript of any proceeding of the panel or committee. Each such panel and committee shall delete from any transcript made under this subsection information which is exempt from disclosure under section 552(b) of title 5.
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(I) referred to the Tobacco Products Scientific Advisory Committee.
Citations to §360fff(2)
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(III) subject to a final sunscreen order (as defined in section 360fff(2)(A) of this title); or
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(iii) subject to a final sunscreen order (as defined in section 360fff(2)(A) of this title).
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(A) the Secretary shall issue a final sunscreen order—(i) in the case of a proposed sunscreen order described in subparagraph (A) or (B) of section 360fff(7) of this title, not later than 90 calendar days after the end of the public comment period under paragraph (3); or(ii) in the case of a proposed sunscreen order described in subparagraph (C) of section 360fff(7) of this title, not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order; or
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(B) if the Secretary does not issue such final sunscreen order within such 90- or 210-calendar-day period, as applicable, the sponsor of such request may notify the Office of the Commissioner of such request and request review by the Office of the Commissioner.
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(6) The Commissioner shall issue a final sunscreen order with respect to a proposed sunscreen order subject to paragraph (5)(B) not later than 60 calendar days after the date of notification under such paragraph.
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(A) the Secretary shall issue a final sunscreen order with respect to the request—(i) in the case of a proposed sunscreen order described in subparagraph (A) or (B) of section 360fff(7) of this title, not later than 90 calendar days after the end of the public comment period under paragraph (6); or(ii) in the case of a proposed sunscreen order described in subparagraph (C) of section 360fff(7) of this title—(I) if the Advisory Committee is not convened under paragraph (8), not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order, which shall include a rationale for not convening such Advisory Committee; or(II) if the Advisory Committee is convened under paragraph (8), not later than 270 calendar days after the date on which the sponsor submits such additional information; or
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(B) if the Secretary does not issue such final sunscreen order within such 90-, 210-, or 270-calendar-day period, as applicable, the sponsor of such request may notify the Office of the Commissioner about such request and request review by the Office of the Commissioner.
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(10) The Commissioner shall issue a final sunscreen order with respect to a proposed sunscreen order subject to paragraph (9)(B) not later than 60 calendar days after the date of notification under such paragraph.
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(A) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded, a sunscreen containing such ingredient or combination of ingredients shall be permitted to be introduced or delivered into interstate commerce for use under the conditions described in such final sunscreen order, in accordance with all requirements applicable to drugs not subject to section 353(b)(1) of this title, for so long as such final sunscreen order remains in effect.
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(B) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded, a sunscreen containing such ingredient or combination of ingredients shall not be introduced or delivered into interstate commerce, for use under the conditions described in such final sunscreen order, unless an application is approved pursuant to section 355 of this title with respect to a sunscreen containing such ingredient or combination of ingredients, or unless conditions are later established under which such ingredient or combination of ingredients is later determined to be GRASE and not misbranded under the over-the-counter drug monograph system.
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(A) In the event that information relevant to a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients becomes available to the Secretary after issuance of a final sunscreen order, the Secretary may amend such final sunscreen order by issuing a new proposed sunscreen order under subsection (a)(1) and following the procedures set forth in this section.
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(B) Any interested person may petition the Secretary to amend a final sunscreen order under section 10.30, title 21 Code of Federal Regulations (or any successor regulations). If the Secretary grants any petition under such section, the Secretary shall initiate the process for amending a final sunscreen order by issuing a new proposed sunscreen order under subsection (a)(1) and following the procedures set forth in this section.
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(C) Once the Secretary issues a new proposed sunscreen order to amend a final sunscreen order under subparagraph (A) or (B), such final sunscreen order shall remain in effect and paragraph (3) shall not apply to such final sunscreen order until the Secretary has issued a new final sunscreen order or has determined not to amend the final sunscreen order.
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(3) A final sunscreen order shall be deemed to be a final order under section 355h of this title.
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(1) A final sunscreen order shall have the effect of authorizing solely the order requestor (or the licensees, assignees, or successors in interest of such requestor with respect to the subject of such request and listed under paragraph (5)) for a period of 18 months, to market a sunscreen ingredient under this section incorporating changes described in paragraph (2) subject to the limitations under paragraph (4), beginning on the date the requestor (or any licensees, assignees, or successors in interest of such requestor with respect to the subject of such request and listed under paragraph (5)) may lawfully market such sunscreen ingredient pursuant to the order.
Citations to §360fff(2)(A)
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(III) subject to a final sunscreen order (as defined in section 360fff(2)(A) of this title); or
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(iii) subject to a final sunscreen order (as defined in section 360fff(2)(A) of this title).
Citations to §360fff(3)
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Any person may submit a request to the Secretary for a determination of whether a nonprescription sunscreen active ingredient or a combination of nonprescription sunscreen active ingredients, for use under specified conditions, to be prescribed, recommended, or suggested in the labeling thereof (including dosage form, dosage strength, and route of administration) is GRASE and should be included in part 352 of title 21, Code of Federal Regulations (or any successor regulations) concerning nonprescription sunscreen.
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(A) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded, a sunscreen containing such ingredient or combination of ingredients shall be permitted to be introduced or delivered into interstate commerce for use under the conditions described in such final sunscreen order, in accordance with all requirements applicable to drugs not subject to section 353(b)(1) of this title, for so long as such final sunscreen order remains in effect.
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(B) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded, a sunscreen containing such ingredient or combination of ingredients shall not be introduced or delivered into interstate commerce, for use under the conditions described in such final sunscreen order, unless an application is approved pursuant to section 355 of this title with respect to a sunscreen containing such ingredient or combination of ingredients, or unless conditions are later established under which such ingredient or combination of ingredients is later determined to be GRASE and not misbranded under the over-the-counter drug monograph system.
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(ii) the data required to meet the safety and efficacy standard for determining whether a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded;
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(C) If the sponsor elects to use the processes and procedures for review in accordance with clause (i) or (iii) of paragraph (1)(B), the Secretary may incorporate any resulting final order into a regulation addressing the conditions under which other drugs in the same therapeutic category are GRASE and not misbranded, including through direct final rulemaking, and the final order so incorporated shall cease to be effective on the effective date of the final regulation that addresses such drug.
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(ii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded;
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(iii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded and the reasons for such determinations; and
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(ii) resulting in a determination that the nonprescription sunscreen active ingredient, combination of nonprescription sunscreen active ingredients, or other ingredient is GRASE and is not misbranded;
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(iii) resulting in a determination that the nonprescription sunscreen active ingredient, combination of nonprescription sunscreen active ingredients, or other ingredient is not GRASE and is misbranded and the reasons for such determinations; and
Citations to §360fff(4)
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(1) In the case of a request under section 360fff–1 of this title that is determined to be eligible under subsection (a) for further review under this section and section 360fff–3 of this title, the Secretary shall, in notifying the public under subsection (a)(1)(C) of such eligibility determination, post the eligibility determination on the Internet website of the Food and Drug Administration, invite the sponsor of such request and any other interested party to submit comments, and provide a period of not less than 45 calendar days for comments in support of or otherwise relating to a GRASE determination, including published and unpublished data and other information related to the safety and efficacy of such request.
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(A) If, prior to November 26, 2014, an application was submitted pursuant to section 330.14 of title 21, Code of Federal Regulations for a GRASE determination for a drug other than a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients and such drug was found to be eligible to be considered for inclusion in the over-the-counter drug monograph system pursuant to section 330.14 of title 21, Code of Federal Regulations, the sponsor of such application may request that the Secretary provide a framework under paragraph (2) for the review of such application.
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(4) Not later than 18 months after November 26, 2014, the Secretary shall report to the Committee on Health, Education, Labor, and Pensions of the Senate and the Committee on Energy and Commerce of the House of Representatives, in writing, regarding all pending applications subject to paragraph (1). In such letter, the Secretary shall provide a report on the review of such applications, including the timelines, in calendar days, for the review and GRASE determination for each application. Such timelines shall account for the considerations under paragraph (5).
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(1) Not later than 18 months after November 26, 2014, the Secretary shall issue proposed regulations establishing timelines for the review of applications for GRASE determinations for drugs other than nonprescription sunscreen active ingredients or combinations of nonprescription sunscreen active ingredients that are submitted to the Secretary after November 26, 2014, under section 330.14 of title 21, Code of Federal Regulations (or any successor regulations), and that are found to be eligible to be considered for inclusion in the over-the-counter drug monograph system pursuant to section 330.14 of title 21, Code of Federal Regulations (or any successor regulations), or that are subject to this subsection pursuant to paragraph (1) or (3) of subsection (a), as applicable, providing—(A) timely and efficient completion of evaluations of applications under section 330.14 of title 21, Code of Federal Regulations (or any successor regulations) for drugs other than sunscreens; and(B) timely and efficient completion of the review of the safety and effectiveness submissions pursuant to such applications, including establishing—(i) reasonable timelines, in calendar days, for the applicable proposed and final regulations for applications of various content, complexity, and format, and timelines for internal procedures related to such processes; and(ii) measurable metrics for tracking the extent to which the timelines set forth in the regulations are met.
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(A) a review of the progress made in issuing GRASE determinations for pending requests, including the number of pending requests—(i) reviewed and the decision times for each request, measured from the date of the original request for an eligibility determination submitted by the sponsor;(ii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded;(iii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded and the reasons for such determinations; and(iv) for which a determination has not been made, and an explanation for the delay, a description of the current status of each such request, and the length of time each such request has been pending, measured from the date of original request for an eligibility determination by the sponsor;
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(B) a review of the progress made in issuing GRASE determinations for requests not included in the reporting under subparagraph (A), including the number of such requests—(i) reviewed and the decision times for each request;(ii) resulting in a determination that the nonprescription sunscreen active ingredient, combination of nonprescription sunscreen active ingredients, or other ingredient is GRASE and is not misbranded;(iii) resulting in a determination that the nonprescription sunscreen active ingredient, combination of nonprescription sunscreen active ingredients, or other ingredient is not GRASE and is misbranded and the reasons for such determinations; and(iv) for which a determination has not been made, and an explanation for the delay, a description of the current status of each such request, and the length of time each such request has been pending, measured from the date of original request for an eligibility determination by the sponsor;
Citations to §360fff(5)
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(ii) the established name and quantity or, if determined to be appropriate by the Secretary, the proportion of each active ingredient, including the quantity, kind, and proportion of any alcohol, and also including whether active or not the established name and quantity or if determined to be appropriate by the Secretary, the proportion of any bromides, ether, chloroform, acetanilide, acetophenetidin, amidopyrine, antipyrine, atropine, hyoscine, hyoscyamine, arsenic, digitalis, digitalis glucosides, mercury, ouabain, strophanthin, strychnine, thyroid, or any derivative or preparation of any such substances, contained therein, except that the requirement for stating the quantity of the active ingredients, other than the quantity of those specifically named in this subclause, shall not apply to nonprescription drugs not intended for human use; and
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(iii) the established name of each inactive ingredient listed in alphabetical order on the outside container of the retail package and, if determined to be appropriate by the Secretary, on the immediate container, as prescribed in regulation promulgated by the Secretary, except that nothing in this subclause shall be deemed to require that any trade secret be divulged, and except that the requirements of this subclause with respect to alphabetical order shall apply only to nonprescription drugs that are not also cosmetics and that this subclause shall not apply to nonprescription drugs not intended for human use.
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(ee) If it is a nonprescription drug that is subject to section 355h of this title, is not the subject of an application approved under section 355 of this title, and does not comply with the requirements under section 355h of this title.
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(x) If it is a nonprescription drug (as defined in section 379aa of this title) that is marketed in the United States, unless the label of such drug includes a domestic address or domestic phone number through which the responsible person (as described in section 379aa of this title) may receive a report of a serious adverse event (as defined in section 379aa of this title) with such drug.
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(C) any constituent part that was previously approved, cleared, or classified under section 355, 360(k), 360c(f)(2), or 360e of this title for which the sponsor has a right of reference or any constituent part that is a nonprescription drug, as defined in section 379aa(a)(2) of this title.
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(A) Any person planning to submit an application for an Rx-to-nonprescription switch may submit to the Secretary a written request for a meeting, for purposes of developing a plan for such application that addresses the potential risks to public health of such switch and the evidence necessary to support such application, including the design of any necessary studies, and the format and content of the planned application. The Secretary may grant such a meeting, as appropriate, consistent with established procedures for granting meetings with, and providing written responses to, applications under this section. Each such meeting shall be documented in meeting minutes.
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(i) Not later than 18 months after November 12, 2025, the Secretary shall issue guidance to increase the clarity and predictability of the process and standards for approval of applications for nonprescription drugs under this section, including in the case of applications for an Rx-to-nonprescription switch, especially with respect to prescription drugs with well-established safety profiles for which an applicant may seek approval for nonprescription use.
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(I) describe how published reports in medical literature, any previous finding of safety or effectiveness for the drug under this section, the results of significant human experience with the drug, unpublished studies and other data, and other sources of information may be used to support an application for a nonprescription drug, including in the context of an application for an Rx-to-nonprescription switch;
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(III) describe evidentiary expectations to support approval of an application for a nonprescription drug, including in the context of an application for an Rx-to-nonprescription switch, including how sponsors can demonstrate that consumers can appropriately self-select and use the drug and comprehend the nonprescription drug label; and
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(IV) provide recommendations for how mechanisms, in addition to the required Drug Facts Label, such as mobile applications and decisions aids, can be incorporated into the information submitted in support of an application for an Rx-to-nonprescription switch.
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(C) Not later than 1 year after November 12, 2025, the Secretary shall develop and make publicly available on the website of the Food and Drug Administration a plan to engage stakeholders on steps and factors for application holders and other stakeholders to consider in identifying approved prescription drugs that may be promising candidates for applications for an Rx-to-nonprescription switch.
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(D) For purposes of this paragraph, the term “Rx-to-nonprescription switch” means the approval of an application, or supplemental application, as applicable, submitted under this section by the holder of an approved application for a prescription drug seeking approval to market such drug as a nonprescription drug, including for—(i) a full Rx-to-nonprescription switch, under which a drug previously approved for prescription use only is—(I) approved for nonprescription use under the same conditions as applied to the drug when approved for prescription use; or(II) approved for nonprescription use subject to one or more additional conditions for nonprescription use; and(ii) a partial Rx-to-nonprescription switch, under which the drug is approved for nonprescription use only under certain conditions described in the approved labeling, while the drug otherwise remains approved for prescription use only.
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(i) a full Rx-to-nonprescription switch, under which a drug previously approved for prescription use only is—(I) approved for nonprescription use under the same conditions as applied to the drug when approved for prescription use; or(II) approved for nonprescription use subject to one or more additional conditions for nonprescription use; and
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(I) approved for nonprescription use under the same conditions as applied to the drug when approved for prescription use; or
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(II) approved for nonprescription use subject to one or more additional conditions for nonprescription use; and
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(ii) a partial Rx-to-nonprescription switch, under which the drug is approved for nonprescription use only under certain conditions described in the approved labeling, while the drug otherwise remains approved for prescription use only.
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(a) Nonprescription drugs marketed without an approved drug application under section 355 of this title, as of March 27, 2020, shall be treated in accordance with this subsection.(1) A drug is deemed to be generally recognized as safe and effective under section 321(p)(1) of this title, not a new drug under section 321(p) of this title, and not subject to section 353(b)(1) of this title, if—(A) the drug is—(i) in conformity with the requirements for nonprescription use of a final monograph issued under part 330 of title 21, Code of Federal Regulations (except as provided in paragraph (2)), the general requirements for nonprescription drugs, and conditions or requirements under subsections (b), (c), and (k); and(ii) except as permitted by an order issued under subsection (b) or, in the case of a minor change in the drug, in conformity with an order issued under subsection (c), in a dosage form that, immediately prior to March 27, 2020, has been used to a material extent and for a material time under section 321(p)(2) of this title; or(B) the drug is—(i) classified in category I for safety and effectiveness under a tentative final monograph that is the most recently applicable proposal or determination issued under part 330 of title 21, Code of Federal Regulations;(ii) in conformity with the proposed requirements for nonprescription use of such tentative final monograph, any applicable subsequent determination by the Secretary, the general requirements for nonprescription drugs, and conditions or requirements under subsections (b), (c), and (k); and(iii) except as permitted by an order issued under subsection (b) or, in the case of a minor change in the drug, in conformity with an order issued under subsection (c), in a dosage form that, immediately prior to March 27, 2020, has been used to a material extent and for a material time under section 321(p)(2) of this title.(2) With respect to sunscreen drugs subject to this section, the applicable requirements in terms of conformity with a final monograph, for purposes of paragraph (1)(A)(i), shall be the requirements specified in part 352 of title 21, Code of Federal Regulations, as published on May 21, 1999, beginning on page 27687 of volume 64 of the Federal Register, except that the applicable requirements governing effectiveness and labeling shall be those specified in section 201.327 of title 21, Code of Federal Regulations.(3) A drug that is not described in paragraph (1), (2), or (4) is not required to be the subject of an application approved under section 355 of this title, and is not subject to section 353(b)(1) of this title, if—(A) the drug is—(i) classified in category III for safety or effectiveness in the preamble of a proposed rule establishing a tentative final monograph that is the most recently applicable proposal or determination for such drug issued under part 330 of title 21, Code of Federal Regulations;(ii) in conformity with—(I) the conditions of use, including indication and dosage strength, if any, described for such category III drug in such preamble or in an applicable subsequent proposed rule;(II) the proposed requirements for drugs classified in such tentative final monograph in category I in the most recently proposed rule establishing requirements related to such tentative final monograph and in any final rule establishing requirements that are applicable to the drug; and(III) the general requirements for nonprescription drugs and conditions or requirements under subsection (b) or (k); and(iii) in a dosage form that, immediately prior to March 27, 2020, had been used to a material extent and for a material time under section 321(p)(2) of this title; or(B) the drug is—(i) classified in category I for safety and effectiveness under a proposed monograph or advance notice of proposed rulemaking that is the most recently applicable proposal or determination for such drug issued under part 330 of title 21, Code of Federal Regulations;(ii) in conformity with the requirements for nonprescription use of such proposed monograph or advance notice of proposed rulemaking, any applicable subsequent determination by the Secretary, the general requirements for nonprescription drugs, and conditions or requirements under subsection (b) or (k); and(iii) in a dosage form that, immediately prior to March 27, 2020, has been used to a material extent and for a material time under section 321(p)(2) of this title.(4) A drug that is classified in category II for safety or effectiveness under a tentative final monograph or that is subject to a determination to be not generally recognized as safe and effective in a proposed rule that is the most recently applicable proposal issued under part 330 of title 21, Code of Federal Regulations, shall be deemed to be a new drug under section 321(p) of this title, misbranded under section 352(ee) of this title, and subject to the requirement for an approved new drug application under section 355 of this title beginning on the day that is 180 calendar days after March 27, 2020, unless, before such day, the Secretary determines that it is in the interest of public health to extend the period during which the drug may be marketed without such an approved new drug application.(5) A drug that the Secretary has determined not to be generally recognized as safe and effective under section 321(p)(1) of this title under a final determination issued under part 330 of title 21, Code of Federal Regulations, shall be deemed to be a new drug under section 321(p) of this title, misbranded under section 352(ee) of this title, and subject to the requirement for an approved new drug application under section 355 of this title.(6) Except as provided in subsection (m), a drug is deemed to be a new drug under section 321(p) of this title and misbranded under section 352(ee) of this title if the drug—(A) is not subject to section 353(b)(1) of this title; and
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(i) in conformity with the requirements for nonprescription use of a final monograph issued under part 330 of title 21, Code of Federal Regulations (except as provided in paragraph (2)), the general requirements for nonprescription drugs, and conditions or requirements under subsections (b), (c), and (k); and
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(ii) in conformity with the proposed requirements for nonprescription use of such tentative final monograph, any applicable subsequent determination by the Secretary, the general requirements for nonprescription drugs, and conditions or requirements under subsections (b), (c), and (k); and
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(III) the general requirements for nonprescription drugs and conditions or requirements under subsection (b) or (k); and
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(ii) in conformity with the requirements for nonprescription use of such proposed monograph or advance notice of proposed rulemaking, any applicable subsequent determination by the Secretary, the general requirements for nonprescription drugs, and conditions or requirements under subsection (b) or (k); and
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(iii) meets the general requirements for nonprescription drugs; and
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(i) may file such request, if the request includes information specified under subparagraph (C) with respect to safe nonprescription marketing and use of such drug; or
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(ii) if the request fails to include information specified under subparagraph (C), shall refuse to file such request and require that nonprescription marketing of the drug be pursuant to a new drug application as described in subparagraph (D).
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(B) A drug described in this subparagraph is a nonprescription drug which contains an active ingredient not previously incorporated in a drug—(ii) subject to a final order under this section; or(iii) subject to a final sunscreen order (as defined in section 360fff(2)(A) of this title).
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(i) information sufficient for a prima facie demonstration that the drug subject to such request has a verifiable history of being marketed and safely used by consumers in the United States as a nonprescription drug under comparable conditions of use;
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(ii) if the drug has not been previously marketed in the United States as a nonprescription drug, information sufficient for a prima facie demonstration that the drug was marketed and safely used under comparable conditions of marketing and use in a country listed in section 382(b)(1)(A) of this title or designated by the Secretary in accordance with section 382(b)(1)(B) of this title—(I) for such period as needed to provide reasonable assurances concerning the safe nonprescription use of the drug; and(II) during such time was subject to sufficient monitoring by a regulatory body considered acceptable by the Secretary for such monitoring purposes, including for adverse events associated with nonprescription use of the drug; or
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(I) for such period as needed to provide reasonable assurances concerning the safe nonprescription use of the drug; and
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(II) during such time was subject to sufficient monitoring by a regulatory body considered acceptable by the Secretary for such monitoring purposes, including for adverse events associated with nonprescription use of the drug; or
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(i) the drug is marketed as a nonprescription drug, under conditions of use comparable to the conditions specified in the request, for such period as the Secretary determines appropriate (not to exceed 5 consecutive years) pursuant to an application approved under section 355 of this title; and
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(h) The Secretary shall establish procedures under which sponsors, requestors, or organizations nominated by sponsors or requestors to represent their interests in a proceeding may meet with appropriate officials of the Food and Drug Administration to obtain advice on the studies and other information necessary to support submissions under this section and other matters relevant to the regulation of nonprescription drugs and the development of new nonprescription drugs under this section.
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(1) Except as provided in this subsection, nothing in this section supersedes regulations establishing general requirements for nonprescription drugs, including regulations of general applicability contained in parts 201, 250, and 330 of title 21, Code of Federal Regulations, or any successor regulations. The Secretary shall establish or modify such regulations by means of rulemaking in accordance with section 553 of title 5.
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(B) Regulations in effect on the day before March 27, 2020, establishing requirements for specific nonprescription drugs marketed pursuant to this section (including such requirements in parts 201 and 250 of title 21, Code of Federal Regulations), shall be deemed to be final orders under subsection (b), only as they apply to drugs—(ii) otherwise subject to an order under this section.
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(1) This section shall not affect the treatment or status of a nonprescription drug—(A) that is marketed without an application approved under section 355 of this title as of March 27, 2020;(B) that is not subject to an order issued under this section; and
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(1) The term “nonprescription drug” refers to a drug not subject to the requirements of section 353(b)(1) of this title.
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(A) in evaluating the generally recognized as safe and effective status of active ingredients used in nonprescription drugs intended for topical administration for purposes of subsection (a), utilize standards that allow for the use of real world evidence (as defined in section 355g(b) of this title), as appropriate, as part of a comprehensive evaluation of scientific evidence to demonstrate the safety and effectiveness of such active ingredients, to supplement evidence from traditional clinical trials, provided that such standards allow the Secretary to evaluate whether the benefits of such active ingredients outweigh the risks; and
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Any person may submit a request to the Secretary for a determination of whether a nonprescription sunscreen active ingredient or a combination of nonprescription sunscreen active ingredients, for use under specified conditions, to be prescribed, recommended, or suggested in the labeling thereof (including dosage form, dosage strength, and route of administration) is GRASE and should be included in part 352 of title 21, Code of Federal Regulations (or any successor regulations) concerning nonprescription sunscreen.
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(A) To be eligible for review under subsection (b) and section 360fff–3 of this title, a request shall be for a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients, for use under specified conditions, to be prescribed, recommended, or suggested in the labeling thereof, that—(i) is not included in part 352 of title 21, Code of Federal Regulations (or any successor regulations) concerning nonprescription sunscreen; and(ii) has been used to a material extent and for a material time under such conditions, as described in section 321(p)(2) of this title.
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(i) is not included in part 352 of title 21, Code of Federal Regulations (or any successor regulations) concerning nonprescription sunscreen; and
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(A) If a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is determined under paragraph (1)(A) to be eligible for further review, the Secretary shall make the request publicly available, with redactions for information that is treated as confidential under section 552(b) of title 5, section 1905 of title 18, or section 331(j) of this title.
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(A) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded, a sunscreen containing such ingredient or combination of ingredients shall be permitted to be introduced or delivered into interstate commerce for use under the conditions described in such final sunscreen order, in accordance with all requirements applicable to drugs not subject to section 353(b)(1) of this title, for so long as such final sunscreen order remains in effect.
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(B) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded, a sunscreen containing such ingredient or combination of ingredients shall not be introduced or delivered into interstate commerce, for use under the conditions described in such final sunscreen order, unless an application is approved pursuant to section 355 of this title with respect to a sunscreen containing such ingredient or combination of ingredients, or unless conditions are later established under which such ingredient or combination of ingredients is later determined to be GRASE and not misbranded under the over-the-counter drug monograph system.
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(A) In the event that information relevant to a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients becomes available to the Secretary after issuance of a final sunscreen order, the Secretary may amend such final sunscreen order by issuing a new proposed sunscreen order under subsection (a)(1) and following the procedures set forth in this section.
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(ii) the data required to meet the safety and efficacy standard for determining whether a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded;
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(3) Except as otherwise provided in section 360fff–6 of this title, nothing in this part shall be construed to affect the authority of the Secretary under this chapter or the Public Health Service Act (42 U.S.C. 201 et seq.) with respect to a drug other than a nonprescription sunscreen.
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(A) If, prior to November 26, 2014, an application was submitted pursuant to section 330.14 of title 21, Code of Federal Regulations for a GRASE determination for a drug other than a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients and such drug was found to be eligible to be considered for inclusion in the over-the-counter drug monograph system pursuant to section 330.14 of title 21, Code of Federal Regulations, the sponsor of such application may request that the Secretary provide a framework under paragraph (2) for the review of such application.
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(1) Not later than 18 months after November 26, 2014, the Secretary shall issue proposed regulations establishing timelines for the review of applications for GRASE determinations for drugs other than nonprescription sunscreen active ingredients or combinations of nonprescription sunscreen active ingredients that are submitted to the Secretary after November 26, 2014, under section 330.14 of title 21, Code of Federal Regulations (or any successor regulations), and that are found to be eligible to be considered for inclusion in the over-the-counter drug monograph system pursuant to section 330.14 of title 21, Code of Federal Regulations (or any successor regulations), or that are subject to this subsection pursuant to paragraph (1) or (3) of subsection (a), as applicable, providing—(A) timely and efficient completion of evaluations of applications under section 330.14 of title 21, Code of Federal Regulations (or any successor regulations) for drugs other than sunscreens; and(B) timely and efficient completion of the review of the safety and effectiveness submissions pursuant to such applications, including establishing—(i) reasonable timelines, in calendar days, for the applicable proposed and final regulations for applications of various content, complexity, and format, and timelines for internal procedures related to such processes; and(ii) measurable metrics for tracking the extent to which the timelines set forth in the regulations are met.
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(ii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded;
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(iii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded and the reasons for such determinations; and
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(ii) resulting in a determination that the nonprescription sunscreen active ingredient, combination of nonprescription sunscreen active ingredients, or other ingredient is GRASE and is not misbranded;
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(iii) resulting in a determination that the nonprescription sunscreen active ingredient, combination of nonprescription sunscreen active ingredients, or other ingredient is not GRASE and is misbranded and the reasons for such determinations; and
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(1) For purposes of enforcement of this chapter, officers or employees duly designated by the Secretary, upon presenting appropriate credentials and a written notice to the owner, operator, or agent in charge, are authorized (A) to enter, at reasonable times, any factory, warehouse, or establishment in which food, drugs, devices, tobacco products, or cosmetics are manufactured, processed, packed, or held, for introduction into interstate commerce or after such introduction, or to enter any vehicle being used to transport or hold such food, drugs, devices, tobacco products, or cosmetics in interstate commerce; and (B) to inspect, at reasonable times and within reasonable limits and in a reasonable manner, such factory, warehouse, establishment, or vehicle and all pertinent equipment, finished and unfinished materials, containers, and labeling therein. In the case of any person (excluding farms and restaurants) who manufactures, processes, packs, transports, distributes, holds, or imports foods, the inspection shall extend to all records and other information described in section 350c of this title, when the standard for records inspection under paragraph (1) or (2) of section 350c(a) of this title applies, subject to the limitations established in section 350c(d) of this title. In the case of a facility (as defined in section 364 of this title) that manufactures or processes cosmetic products, the inspection shall extend to all records and other information described in sections 364a, 364b, and 364f of this title, when the standard for records inspection under such section applies. In the case of any factory, warehouse, establishment, or consulting laboratory in which prescription drugs, nonprescription drugs intended for human use, devices, or tobacco products are manufactured, processed, packed, or held, the inspection shall extend to all things therein (including records, files, papers, processes, controls, and facilities) bearing on whether prescription drugs, nonprescription drugs intended for human use, devices, or tobacco products which are adulterated or misbranded within the meaning of this chapter, or which may not be manufactured, introduced into interstate commerce, or sold, or offered for sale by reason of any provision of this chapter, have been or are being manufactured, processed, packed, transported, or held in any such place, or otherwise bearing on violation of this chapter. No inspection authorized by the preceding sentence or by paragraph (3) shall extend to financial data, sales data other than shipment data, pricing data, personnel data (other than data as to qualification of technical and professional personnel performing functions subject to this chapter), and research data (other than data relating to new drugs, antibiotic drugs, devices, and tobacco products and subject to reporting and inspection under regulations lawfully issued pursuant to section 355(i) or (k) of this title, section 360i of this title, section 360j(g) of this title, or subchapter IX and data relating to other drugs, devices, or tobacco products which in the case of a new drug would be subject to reporting or inspection under lawful regulations issued pursuant to section 355(j) of this title). A separate notice shall be given for each such inspection, but a notice shall not be required for each entry made during the period covered by the inspection. Each such inspection shall be commenced and completed with reasonable promptness.
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(1) The term “adverse event” means any health-related event associated with the use of a nonprescription drug that is adverse, including—(A) an event occurring from an overdose of the drug, whether accidental or intentional;(B) an event occurring from abuse of the drug;(C) an event occurring from withdrawal from the drug; and(D) any failure of expected pharmacological action of the drug.
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(2) The term “nonprescription drug” means a drug that is—(A) not subject to section 353(b) of this title; and(B) not subject to approval in an application submitted under section 355 of this title.
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(1) The manufacturer, packer, or distributor whose name (pursuant to section 352(b)(1) of this title) appears on the label of a nonprescription drug marketed in the United States (referred to in this section as the “responsible person”) shall submit to the Secretary any report received of a serious adverse event associated with such drug when used in the United States, accompanied by a copy of the label on or within the retail package of such drug.
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(2) A retailer whose name appears on the label described in paragraph (1) as a distributor may, by agreement, authorize the manufacturer or packer of the nonprescription drug to submit the required reports for such drugs to the Secretary so long as the retailer directs to the manufacturer or packer all adverse events associated with such drug that are reported to the retailer through the address or telephone number described in section 352(x) of this title.
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(d) Each serious adverse event report under this section shall be submitted to the Secretary using the MedWatch form, which may be modified by the Secretary for nonprescription drugs, and may be accompanied by additional information.
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(g) The submission of any adverse event report in compliance with this section shall not be construed as an admission that the nonprescription drug involved caused or contributed to the adverse event.
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(1) No State or local government shall establish or continue in effect any law, regulation, order, or other requirement, related to a mandatory system for adverse event reports for nonprescription drugs, that is different from, in addition to, or otherwise not identical to, this section.
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(5) The term “OTC monograph drug” means a nonprescription drug without an approved new drug application which is governed by the provisions of section 355h of this title.
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(C) the status of implementation of evidence and testing standards under section 355h(r) of this title for nonprescription drugs intended for topical administration, including—(i) the application of evidence or testing standards; and(ii) the number of active ingredient requests for nonprescription drugs intended for topical administration reviewed using the standards under section 355h(b) of this title; and
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(ii) the number of active ingredient requests for nonprescription drugs intended for topical administration reviewed using the standards under section 355h(b) of this title; and
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(2) collaboration or partnerships with other institutions of higher education, nonprofit organizations, and large and small pharmaceutical manufacturers, including generic and nonprescription manufacturers, contract manufacturers, and other relevant entities;
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(A) experience in participating in and leading advanced and continuous pharmaceutical manufacturing technology partnerships with other institutions of higher education, nonprofit organizations, and large and small pharmaceutical manufacturers, including generic and nonprescription manufacturers, contract manufacturers, and other relevant entities to—(i) support the implementation of advanced or continuous pharmaceutical manufacturing for companies manufacturing or seeking to manufacture in the United States;(ii) support Federal agencies with technical assistance and workforce training, which may include regulatory and quality metric guidance as applicable, and hands-on training, for advanced and continuous pharmaceutical manufacturing;(iii) organize and conduct advanced research and development activities, with respect to advanced or continuous pharmaceutical manufacturing, needed to develop new and more effective technology, and to develop and support technological leadership;(iv) develop best practices for designing, developing, and implementing advanced and continuous pharmaceutical manufacturing processes; and(v) identify and assess workforce needs for advanced and continuous pharmaceutical manufacturing, and address such workforce needs, which may include the development and implementing of training programs; or
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(3) to develop, along with industry partners (which may include large and small pharmaceutical manufacturers, including generic and nonprescription manufacturers, and contract research organizations or contract manufacturers that carry out drug development and manufacturing activities) and another institution or consortium designated under this section, if any, a strategic plan for developing an advanced and continuous pharmaceutical manufacturing workforce;
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(D) a summary of relevant feedback related to improving advanced and continuous pharmaceutical manufacturing solicited from the public, which may include other institutions of higher education, nonprofit organizations, and large and small pharmaceutical manufacturers, including generic and nonprescription manufacturers, and contract manufacturers, and other relevant entities.
Citations to §360fff(6)
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(1) The review of a pending request shall be carried out by the Secretary in accordance with this subsection.
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(2) Sections 360fff–1 and 360fff–2 of this title shall not apply with respect to any pending request.
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(3) Notwithstanding the requirements of section 360fff(7) of this title, a letter issued pursuant to section 330.14(g) of title 21, Code of Federal Regulations before November 26, 2014, with respect to a pending request, shall be deemed to be a proposed sunscreen order and displayed on the Internet website of the Food and Drug Administration. Notification of the availability of such letter shall be published in the Federal Register not later than 45 calendar days after November 26, 2014.
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(4) In the case of a pending request for which the Secretary has not issued a letter pursuant to section 330.14(g) of title 21, Code of Federal Regulations before November 26, 2014, the Secretary shall complete review of such request and, not later than 90 calendar days after November 26, 2014, issue a proposed sunscreen order with respect to such request.
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(6) A proposed sunscreen order issued under paragraph (4) or (5), or a notification of the availability of a letter under paragraph (3), with respect to a pending request shall provide for a period of 45 calendar days for public comment.
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(8) In the case of a proposed sunscreen order under paragraph (3), (4), or (5), an Advisory Committee meeting may be convened for the purpose of reviewing and providing recommendations regarding the pending request.
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(A) more than once with respect to any request under section 360fff–1 of this title or any pending request; or
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(2) submit more than a total of 3 requests under section 360fff–1 of this title or pending requests to the Advisory Committee per meeting.
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(i) the format and content of information submitted by a sponsor in support of a request under section 360fff–1 of this title or a pending request;
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(iii) the process by which a request under section 360fff–1 of this title or a pending request is withdrawn; and
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(iv) the process by which the Secretary will carry out section 360fff–3(c) of this title, including with respect to how the Secretary will address the total number of requests received under section 360fff–1 of this title and pending requests.
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(i) the processes and procedures set forth for pending requests under section 360fff–3(b) of this title, except that specific timelines shall be determined in accordance with other applicable requirements under this section;
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(iii) an initial filing determination under the processes and procedures described in section 360fff–2(b) of this title and the processes and procedures set forth for pending requests under section 360fff–3(b) of this title, except that specific timelines shall be determined in accordance with other applicable requirements under this section; or
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(B) the timelines for the various processes and procedures shall not be shorter than the timelines set forth for pending requests under sections 360fff–2(b) and 360fff–3(b) of this title, as applicable.
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(A) a review of the progress made in issuing GRASE determinations for pending requests, including the number of pending requests—(i) reviewed and the decision times for each request, measured from the date of the original request for an eligibility determination submitted by the sponsor;(ii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded;(iii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded and the reasons for such determinations; and(iv) for which a determination has not been made, and an explanation for the delay, a description of the current status of each such request, and the length of time each such request has been pending, measured from the date of original request for an eligibility determination by the sponsor;
Citations to §360fff(7)
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(B) shall complete the review of such request and issue a proposed sunscreen order with respect to such request.
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(2) If the Secretary does not issue a proposed sunscreen order under paragraph (1)(B) within such 300-day period, the sponsor of such request may notify the Office of the Commissioner of such request and request review by the Office of the Commissioner. If such sponsor so notifies the Office of the Commissioner, the Commissioner shall, not later than 60 calendar days after the date of notification under this paragraph, issue a proposed sunscreen order with respect to such request.
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(3) A proposed sunscreen order issued under paragraph (1)(B) or (2) with respect to a request shall provide for a period of 45 calendar days for public comment.
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(4) A sponsor may request, in writing, a meeting with respect to a proposed sunscreen order issued under this subsection and described in subparagraph (B) or (C) of section 360fff(7) of this title, not later than 30 calendar days after the Secretary issues such order. The Secretary shall convene a meeting with such sponsor not later than 45 calendar days after such request for a meeting.
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(5) With respect to a proposed sunscreen order under paragraph (1)(B) or (2)—(A) the Secretary shall issue a final sunscreen order—(i) in the case of a proposed sunscreen order described in subparagraph (A) or (B) of section 360fff(7) of this title, not later than 90 calendar days after the end of the public comment period under paragraph (3); or(ii) in the case of a proposed sunscreen order described in subparagraph (C) of section 360fff(7) of this title, not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order; or(B) if the Secretary does not issue such final sunscreen order within such 90- or 210-calendar-day period, as applicable, the sponsor of such request may notify the Office of the Commissioner of such request and request review by the Office of the Commissioner.
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(i) in the case of a proposed sunscreen order described in subparagraph (A) or (B) of section 360fff(7) of this title, not later than 90 calendar days after the end of the public comment period under paragraph (3); or
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(ii) in the case of a proposed sunscreen order described in subparagraph (C) of section 360fff(7) of this title, not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order; or
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(6) The Commissioner shall issue a final sunscreen order with respect to a proposed sunscreen order subject to paragraph (5)(B) not later than 60 calendar days after the date of notification under such paragraph.
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(3) Notwithstanding the requirements of section 360fff(7) of this title, a letter issued pursuant to section 330.14(g) of title 21, Code of Federal Regulations before November 26, 2014, with respect to a pending request, shall be deemed to be a proposed sunscreen order and displayed on the Internet website of the Food and Drug Administration. Notification of the availability of such letter shall be published in the Federal Register not later than 45 calendar days after November 26, 2014.
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(4) In the case of a pending request for which the Secretary has not issued a letter pursuant to section 330.14(g) of title 21, Code of Federal Regulations before November 26, 2014, the Secretary shall complete review of such request and, not later than 90 calendar days after November 26, 2014, issue a proposed sunscreen order with respect to such request.
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(5) If the Secretary does not issue a proposed sunscreen order under paragraph (4), or the Secretary does not publish a notification of the availability of a letter under paragraph (3), as applicable, the sponsor of such request may notify the Office of the Commissioner of such request and request review by the Office of the Commissioner. The Commissioner shall, not later than 60 calendar days after the date of notification under this paragraph, issue a proposed order with respect to such request.
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(6) A proposed sunscreen order issued under paragraph (4) or (5), or a notification of the availability of a letter under paragraph (3), with respect to a pending request shall provide for a period of 45 calendar days for public comment.
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(A) A sponsor may request, in writing, a meeting with respect to a proposed sunscreen order issued under this subsection, including a letter deemed to be a proposed sunscreen order under paragraph (3), not later than 30 calendar days after the Secretary issues such order or the date upon which such feedback letter is deemed to be a proposed sunscreen order, as applicable. The Secretary shall convene a meeting with such sponsor not later than 45 calendar days after the date of such request for a meeting.
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(B) A sponsor may request one or more confidential meetings with respect to a proposed sunscreen order, including a letter deemed to be a proposed sunscreen order under paragraph (3), to discuss matters relating to data requirements to support a general recognition of safety and effectiveness involving confidential information and public information related to such proposed sunscreen order, as appropriate. The Secretary shall convene a confidential meeting with such sponsor in a reasonable time period. If a sponsor requests more than one confidential meeting for the same proposed sunscreen order, the Secretary may refuse to grant an additional confidential meeting request if the Secretary determines that such additional confidential meeting is not reasonably necessary for the sponsor to advance its proposed sunscreen order, or if the request for a confidential meeting fails to include sufficient information upon which to base a substantive discussion. The Secretary shall publish a post-meeting summary of each confidential meeting under this subparagraph that does not disclose confidential commercial information or trade secrets. This subparagraph does not authorize the disclosure of confidential commercial information or trade secrets subject to 552(b)(4)1 of title 5 or section 1905 of title 18.
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(8) In the case of a proposed sunscreen order under paragraph (3), (4), or (5), an Advisory Committee meeting may be convened for the purpose of reviewing and providing recommendations regarding the pending request.
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(9) In the case of a proposed sunscreen order under paragraph (3), (4), or (5)—(A) the Secretary shall issue a final sunscreen order with respect to the request—(i) in the case of a proposed sunscreen order described in subparagraph (A) or (B) of section 360fff(7) of this title, not later than 90 calendar days after the end of the public comment period under paragraph (6); or(ii) in the case of a proposed sunscreen order described in subparagraph (C) of section 360fff(7) of this title—(I) if the Advisory Committee is not convened under paragraph (8), not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order, which shall include a rationale for not convening such Advisory Committee; or(II) if the Advisory Committee is convened under paragraph (8), not later than 270 calendar days after the date on which the sponsor submits such additional information; or(B) if the Secretary does not issue such final sunscreen order within such 90-, 210-, or 270-calendar-day period, as applicable, the sponsor of such request may notify the Office of the Commissioner about such request and request review by the Office of the Commissioner.
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(i) in the case of a proposed sunscreen order described in subparagraph (A) or (B) of section 360fff(7) of this title, not later than 90 calendar days after the end of the public comment period under paragraph (6); or
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(ii) in the case of a proposed sunscreen order described in subparagraph (C) of section 360fff(7) of this title—(I) if the Advisory Committee is not convened under paragraph (8), not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order, which shall include a rationale for not convening such Advisory Committee; or(II) if the Advisory Committee is convened under paragraph (8), not later than 270 calendar days after the date on which the sponsor submits such additional information; or
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(I) if the Advisory Committee is not convened under paragraph (8), not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order, which shall include a rationale for not convening such Advisory Committee; or
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(10) The Commissioner shall issue a final sunscreen order with respect to a proposed sunscreen order subject to paragraph (9)(B) not later than 60 calendar days after the date of notification under such paragraph.
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(A) In the event that information relevant to a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients becomes available to the Secretary after issuance of a final sunscreen order, the Secretary may amend such final sunscreen order by issuing a new proposed sunscreen order under subsection (a)(1) and following the procedures set forth in this section.
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(B) Any interested person may petition the Secretary to amend a final sunscreen order under section 10.30, title 21 Code of Federal Regulations (or any successor regulations). If the Secretary grants any petition under such section, the Secretary shall initiate the process for amending a final sunscreen order by issuing a new proposed sunscreen order under subsection (a)(1) and following the procedures set forth in this section.
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(C) Once the Secretary issues a new proposed sunscreen order to amend a final sunscreen order under subparagraph (A) or (B), such final sunscreen order shall remain in effect and paragraph (3) shall not apply to such final sunscreen order until the Secretary has issued a new final sunscreen order or has determined not to amend the final sunscreen order.
Citations to §360fff(8)
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(ggg) The failure of a sponsor of a product approved under accelerated approval pursuant to section 356(c) of this title—(1) to conduct with due diligence any postapproval study required under section 356(c) of this title with respect to such product; or(2) to submit timely reports with respect to such product in accordance with section 356b(a)(2) of this title.
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(5) Not later than 1 year after December 29, 2022, the Secretary shall issue guidance regarding information sponsors may consider including in submissions required under section 412(d) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(d)), including considerations for meeting each of the requirements of paragraphs (1), (2), and (3) of subsection (d).
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(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(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.
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(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.
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(A) 1 (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.
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(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—(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 chapter or the Public Health Service Act [42 U.S.C. 201 et seq.] 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 chapter 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 360e, 360(k), or 360c(f)(2) of this title (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 360e of this title that is referenced by the sponsor and that is available for use by the Secretary under section 360j(h)(4) of this title; or(C) any constituent part that was previously approved, cleared, or classified under section 355, 360(k), 360c(f)(2), or 360e of this title for which the sponsor has a right of reference or any constituent part that is a nonprescription drug, as defined in section 379aa(a)(2) of this title.(A) If an application is submitted under section 360e or 360(k) of this title or a request is submitted under section 360c(f)(2) of this title, 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 355(b)(2) of this title; and(ii) the applicant or requester shall provide notice as described in section 355(b)(3) of this title.(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 355(c) of this title;(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 355(b)(2) of this title that referenced the approved drug:(i) Subparagraphs (A), (B), (C), and (D) of section 355(c)(3) of this title.(ii) Clauses (ii), (iii), and (iv) of section 355(c)(3)(E) of this title.(iii) Subsections (b) and (c) of section 355a of this title.(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 355(b)(2) of this title for purposes of section 271(e)(2)(A) of title 35.(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.(7) Nothing in this subsection shall prevent the Secretary from using any agency resources of the Food and Drug Administration necessary to ensure adequate review of the safety, effectiveness, or substantial equivalence of an article.(A) Not later than 60 days after October 26, 2002, the Secretary shall establish within the Office of the Commissioner of Food and Drugs an office to ensure the prompt assignment of combination products to agency centers, the timely and effective premarket review of such products, and consistent and appropriate postmarket regulation of like products subject to the same statutory requirements to the extent permitted by law. Additionally, the office shall, in determining whether a product is to be designated a combination product, consult with the component within the Office of the Commissioner of Food and Drugs that is responsible for such determinations. Such office (referred to in this paragraph as the “Office”) shall have appropriate scientific and medical expertise, and shall be headed by a director.(B) In carrying out this subsection, the Office shall, for each combination product, promptly assign an agency center with primary jurisdiction in accordance with paragraph (1) for the premarket review of such product.(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 order to ensure the timeliness and alignment of the premarket review of a combination product, the agency center with primary jurisdiction for the product, and the consulting agency center, shall be responsible to the Office with respect to the timeliness and alignment of the premarket review.
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(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 chapter 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).
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(B) a device constituent part approved under section 360e of this title that is referenced by the sponsor and that is available for use by the Secretary under section 360j(h)(4) of this title; or
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(C) any constituent part that was previously approved, cleared, or classified under section 355, 360(k), 360c(f)(2), or 360e of this title for which the sponsor has a right of reference or any constituent part that is a nonprescription drug, as defined in section 379aa(a)(2) of this title.
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(B) The Secretary shall meet with a sponsor of an investigation or an applicant for approval for a drug under this subsection or section 262 of title 42 if the sponsor or applicant makes a reasonable written request for a meeting for the purpose of reaching agreement on the design and size—(I) of clinical trials intended to form the primary basis of an effectiveness claim; or(II) in the case where human efficacy studies are not ethical or feasible, of animal and any associated clinical trials which, in combination, are intended to form the primary basis of an effectiveness claim; or(ii) with respect to an application for approval of a biological product under section 262(k) of title 42, of any necessary clinical study or studies.
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(C) Any agreement regarding the parameters of the design and size of clinical trials of a new drug under this paragraph that is reached between the Secretary and a sponsor or applicant shall be reduced to writing and made part of the administrative record by the Secretary. Such agreement shall not be changed after the testing begins, except—(i) with the written agreement of the sponsor or applicant; or(ii) pursuant to a decision, made in accordance with subparagraph (D) by the director of the reviewing division, that a substantial scientific issue essential to determining the safety or effectiveness of the drug has been identified after the testing has begun.
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(i) with the written agreement of the sponsor or applicant; or
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(D) A decision under subparagraph (C)(ii) by the director shall be in writing and the Secretary shall provide to the sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant will be present and at which the director will document the scientific issue involved.
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(II) set forth procedures for sponsors to request meetings described in subparagraph (A) and document the recommendations made in such meetings;
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(III) describe evidentiary expectations to support approval of an application for a nonprescription drug, including in the context of an application for an Rx-to-nonprescription switch, including how sponsors can demonstrate that consumers can appropriately self-select and use the drug and comprehend the nonprescription drug label; and
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(B) the manufacturer or the sponsor of the investigation of a new drug proposed to be distributed to investigators for clinical testing obtaining a signed agreement from each of such investigators that patients to whom the drug is administered will be under his personal supervision, or under the supervision of investigators responsible to him, and that he will not supply such drug to any other investigator, or to clinics, for administration to human beings;
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(C) the establishment and maintenance of such records, and the making of such reports to the Secretary, by the manufacturer or the sponsor of the investigation of such drug, of data (including but not limited to analytical reports by investigators) obtained as the result of such investigational use of such drug, as the Secretary finds will enable him to evaluate the safety and effectiveness of such drug in the event of the filing of an application pursuant to subsection (b); and
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(D) the submission to the Secretary by the manufacturer or the sponsor of the investigation of a new drug of a statement of intent regarding whether the manufacturer or sponsor has plans for assessing pediatric safety and efficacy.
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(2) Subject to paragraph (3), a clinical investigation of a new drug may begin 30 days after the Secretary has received from the manufacturer or sponsor of the investigation a submission containing such information about the drug and the clinical investigation, including—(A) information on design of the investigation and adequate reports of basic information, certified by the applicant to be accurate reports, necessary to assess the safety of the drug for use in clinical investigation; and
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(A) At any time, the Secretary may prohibit the sponsor of an investigation from conducting the investigation (referred to in this paragraph as a “clinical hold”) if the Secretary makes a determination described in subparagraph (B). The Secretary shall specify the basis for the clinical hold, including the specific information available to the Secretary which served as the basis for such clinical hold, and confirm such determination in writing.
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(C) Any written request to the Secretary from the sponsor of an investigation that a clinical hold be removed shall receive a decision, in writing and specifying the reasons therefor, within 30 days after receipt of such request. Any such request shall include sufficient information to support the removal of such clinical hold.
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(4) Regulations under paragraph (1) shall provide that such exemption shall be conditioned upon the manufacturer, or the sponsor of the investigation, requiring that experts using such drugs for investigational purposes certify to such manufacturer or sponsor that they will inform any human beings to whom such drugs, or any controls used in connection therewith, are being administered, or their representatives, that such drugs are being used for investigational purposes and will obtain the consent of such human beings or their representatives, except where it is not feasible, it is contrary to the best interests of such human beings, or the proposed clinical testing poses no more than minimal risk to such human beings and includes appropriate safeguards as prescribed to protect the rights, safety, and welfare of such human beings. Nothing in this subsection shall be construed to require any clinical investigator to submit directly to the Secretary reports on the investigational use of drugs. The Secretary shall update such regulations to require inclusion in the informed consent documents and process a statement that clinical trial information for such clinical investigation has been or will be submitted for inclusion in the registry data bank pursuant to subsection (j) of section 282 of title 42.
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(B) The Secretary shall meet with a sponsor of an investigation or an applicant for approval for a drug under this subsection if the sponsor or applicant makes a reasonable written request for a meeting for the purpose of reaching agreement on the design and size of bioavailability and bioequivalence studies needed for approval of such application. The sponsor or applicant shall provide information necessary for discussion and agreement on the design and size of such studies. Minutes of any such meeting shall be prepared by the Secretary and made available to the sponsor or applicant.
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(C) Any agreement regarding the parameters of design and size of bioavailability and bioequivalence studies of a drug under this paragraph that is reached between the Secretary and a sponsor or applicant shall be reduced to writing and made part of the administrative record by the Secretary. Such agreement shall not be changed after the testing begins, except—(i) with the written agreement of the sponsor or applicant; or(ii) pursuant to a decision, made in accordance with subparagraph (D) by the director of the reviewing division, that a substantial scientific issue essential to determining the safety or effectiveness of the drug has been identified after the testing has begun.
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(i) with the written agreement of the sponsor or applicant; or
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(D) A decision under subparagraph (C)(ii) by the director shall be in writing and the Secretary shall provide to the sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant will be present and at which the director will document the scientific issue involved.
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(II) for the reporting (in a standardized form) of data on all serious adverse drug experiences (as defined in section 355–1(b) of this title) submitted to the Secretary under paragraph (1), and those adverse events submitted by patients, providers, and drug sponsors, when appropriate;
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(ii) update the list quarterly to include each authorized generic drug included in an annual report submitted to the Secretary by the sponsor of a listed drug during the preceding 3-month period.
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(2) The Commissioner shall include in the list described in paragraph (1) each authorized generic drug included in an annual report submitted to the Secretary by the sponsor of a listed drug after January 1, 1999.
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(A) Notwithstanding any provision of the Food and Drug Administration Modernization Act of 1997 or any other provision of law, a sponsor of a drug that is the subject of an application described in subparagraph (B)(i) shall be eligible for, with respect to the drug, the 3-year exclusivity period referred to under clauses (iii) and (iv) of subsection (c)(3)(E) and under clauses (iii) and (iv) of subsection (j)(5)(F), subject to the requirements of such clauses, as applicable.
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(A) Notwithstanding any provision of the Food and Drug Administration Modernization Act of 1997 or any other provision of law, a sponsor of a drug that is the subject of an application described in subparagraph (B)(i) may elect to be eligible for, with respect to the drug—(I) the 3-year exclusivity period referred to under clauses (iii) and (iv) of subsection (c)(3)(E) and under clauses (iii) and (iv) of subsection (j)(5)(F), subject to the requirements of such clauses, as applicable; and(II) the 5-year exclusivity period referred to under clause (ii) of subsection (c)(3)(E) and under clause (ii) of subsection (j)(5)(F), subject to the requirements of such clauses, as applicable; or(ii) a patent term extension under section 156 of title 35, subject to the requirements of such section.
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(1) In the case of an application under subsection (b) with respect to a drug for which the Secretary provides notice to the sponsor that the Secretary intends to issue a scientific and medical evaluation and recommend controls under the Controlled Substances Act [21 U.S.C. 801 et seq.], approval of such application shall not take effect until the interim final rule controlling the drug is issued in accordance with section 201(j) of the Controlled Substances Act [21 U.S.C. 811(j)].
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(1) The sponsor of a contrast agent for which an application has been approved under this section may submit a supplement to the application seeking approval for a new use following the authorization of a premarket submission for an applicable medical imaging device for that use with the contrast agent pursuant to section 360j(p)(1) of this title.
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(B) review information and data submitted to the Secretary by the sponsor of an applicable medical imaging device pursuant to section 360e, 360(k), or 360c(f)(2) of this title so long as the sponsor of such applicable medical imaging device has provided to the sponsor of the contrast agent a right of reference.
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(1) Cell-based assays.
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(A) the sponsor’s goals for enrollment in such clinical study;
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(B) the sponsor’s rationale for such goals; and
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(C) an explanation of how the sponsor intends to meet such goals.
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(3) Computer modeling.
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(A) On the initiative of the Secretary or at the request of a sponsor, the Secretary may waive any requirement in paragraph (1), (2), or (3) if the Secretary determines that a waiver is necessary based on what is known or what can be determined about the prevalence or incidence of the disease or condition for which the new drug is under investigation (including in terms of the patient population that may use the drug), if conducting a clinical investigation in accordance with a diversity action plan would otherwise be impracticable, or if such waiver is necessary to protect public health during a public health emergency.
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(A) The Secretary may, after consultation with the sponsor of an application for an investigational new drug under section 355(i) of this title, the sponsor of an application for a new drug under section 355(b)(1) of this title, or the holder of an approved application for a drug under section 355(b)(1) of this title, issue to the sponsor or holder a written request for the conduct of pediatric studies for such drug. In issuing such request, the Secretary shall take into account adequate representation of children of ethnic and racial minorities. Such request to conduct pediatric studies shall be in writing and shall include a timeframe for such studies and a request to the sponsor or holder to propose pediatric labeling resulting from such studies. If a request under this subparagraph does not request studies in neonates, such request shall include a statement describing the rationale for not requesting studies in neonates.
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(4) Not later than 180 days after the submission of the reports of the studies, the Secretary shall accept or reject such reports and so notify the sponsor or holder. The Secretary’s only responsibility in accepting or rejecting the reports shall be to determine, within the 180-day period, whether the studies fairly respond to the written request, have been conducted in accordance with commonly accepted scientific principles and protocols, and have been reported in accordance with the requirements of the Secretary for filing.
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(A) If, on or after September 27, 2007, the Commissioner determines that the sponsor and the Commissioner have been unable to reach agreement on appropriate changes to the labeling for the drug that is the subject of the application, not later than 180 days after the date of submission of the application—(i) the Commissioner shall request that the sponsor of the application make any labeling change that the Commissioner determines to be appropriate; and(ii) if the sponsor of the application does not agree within 30 days after the Commissioner’s request to make a labeling change requested by the Commissioner, the Commissioner shall refer the matter to the Pediatric Advisory Committee.
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(i) the Commissioner shall request that the sponsor of the application make any labeling change that the Commissioner determines to be appropriate; and
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(ii) if the sponsor of the application does not agree within 30 days after the Commissioner’s request to make a labeling change requested by the Commissioner, the Commissioner shall refer the matter to the Pediatric Advisory Committee.
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(C) The Commissioner shall consider the recommendations of the Pediatric Advisory Committee and, if appropriate, not later than 30 days after receiving the recommendation, make a request to the sponsor of the application to make any labeling change that the Commissioner determines to be appropriate.
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(D) If the sponsor of the application, within 30 days after receiving a request under subparagraph (C), does not agree to make a labeling change requested by the Commissioner, the Commissioner may deem the drug that is the subject of the application to be misbranded.
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(2) Beginning on September 27, 2007, the Secretary shall include as a requirement of a written request that the sponsors of the studies that result in labeling changes that are reflected in the annual summary developed pursuant to subsection (f)(6)(F) distribute, at least annually (or more frequently if the Secretary determines that it would be beneficial to the public health), such information to physicians and other health care providers.
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(ii) If the deferral extension under this subparagraph is requested by the applicant, the applicant shall submit the deferral extension request containing the information described in this subparagraph not less than 90 days prior to the date that the deferral would expire. The Secretary shall respond to such request not later than 45 days after the receipt of such letter. If the Secretary grants such an extension, the specified date shall be the extended date. The sponsor of the required assessment under paragraph (1)(A) or reports on the investigation under paragraph (1)(B) shall not be issued a letter described in subsection (d) unless the specified or extended date of submission for such required studies has passed or if the request for an extension is pending. For a deferral that has expired prior to July 9, 2012, or that will expire prior to 270 days after July 9, 2012, a deferral extension shall be requested by an applicant not later than 180 days after July 9, 2012. The Secretary shall respond to any such request as soon as practicable, but not later than 1 year after July 9, 2012. Nothing in this clause shall prevent the Secretary from updating the status of a study or studies publicly if components of such study or studies are late or delayed.
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(1) The Secretary may (by order in the form of a letter) require the sponsor or holder of an approved application for a drug under section 355 of this title or the holder of a license for a biological product under section 262 of title 42 to submit by a specified date the assessments described in subsection (a)(2), if the Secretary finds that—(i) the drug or biological product is used for a substantial number of pediatric patients for the labeled indications; and(ii) adequate pediatric labeling could confer a benefit on pediatric patients;(B) there is reason to believe that the drug or biological product would represent a meaningful therapeutic benefit over existing therapies for pediatric patients for 1 or more of the claimed indications; or(C) the absence of adequate pediatric labeling could pose a risk to pediatric patients.
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(A) If, on or after September 27, 2007, the Commissioner determines that a sponsor and the Commissioner have been unable to reach agreement on appropriate changes to the labeling for the drug that is the subject of the application or supplement, not later than 180 days after the date of the submission of the application or supplement that receives a priority review or 330 days after the date of the submission of an application or supplement that receives a standard review—(i) the Commissioner shall request that the sponsor of the application make any labeling change that the Commissioner determines to be appropriate; and(ii) if the sponsor does not agree within 30 days after the Commissioner’s request to make a labeling change requested by the Commissioner, the Commissioner shall refer the matter to the Pediatric Advisory Committee.
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(i) the Commissioner shall request that the sponsor of the application make any labeling change that the Commissioner determines to be appropriate; and
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(ii) if the sponsor does not agree within 30 days after the Commissioner’s request to make a labeling change requested by the Commissioner, the Commissioner shall refer the matter to the Pediatric Advisory Committee.
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(C) The Commissioner shall consider the recommendations of the Pediatric Advisory Committee and, if appropriate, not later than 30 days after receiving the recommendation, make a request to the sponsor of the application or supplement to make any labeling changes that the Commissioner determines to be appropriate.
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(D) If the sponsor of the application or supplement, within 30 days after receiving a request under subparagraph (C), does not agree to make a labeling change requested by the Commissioner, the Commissioner may deem the drug that is the subject of the application or supplement to be misbranded.
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(2) Beginning on September 27, 2007, the Secretary shall require that the sponsors of the assessments that result in labeling changes that are reflected in the annual summary developed pursuant to subsection (f)(6)(H) distribute such information to physicians and other health care providers.
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(13) a list of sponsors of applications or holders of approved applications who received exclusivity under such section 355a of this title or such section 262(m) of title 42 after receiving a letter issued under such section 355c(d)(1) of this title for any drug or biological product before the studies referred to in such letter were completed and submitted;
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(17) a listing of penalties, settlements, or payments under section 353 of this title for failure to comply with requirements under such section 355c of this title, including, for each penalty, settlement, or payment, the name of the drug, the sponsor thereof, and the amount of the penalty, settlement, or payment imposed.
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(1) The manufacturer or sponsor of a drug may request the Secretary to designate a drug as a qualified infectious disease product at any time before the submission of an application under section 355(b) of this title or section 262(a) of title 42 for such drug. The Secretary shall, not later than 60 days after the submission of such a request, determine whether the drug is a qualified infectious disease product.
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(3) Notwithstanding any other provision of law, the Secretary shall promulgate regulations implementing this section only as described in paragraph (2), except that the Secretary may issue interim guidance for sponsors seeking designation under subsection (d) prior to the promulgation of such regulations.
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(i) make reasonable efforts to notify informally, not later than 2 business days before the issuance of the proposed order, the sponsors of drugs who have a listing in effect under section 360(j) of this title for the drugs or combination of drugs that will be subject to the administrative order;
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(III) afford sponsors or requestors of drugs that will be subject to such order the opportunity for formal dispute resolution up to the level of the Director of the Center for Drug Evaluation and Research, which initially must be requested within 45 calendar days of the issuance of the order, and, for subsequent levels of appeal, within 30 calendar days of the prior decision; and
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(i) In the case of a determination by the Secretary that a drug, class of drugs, or combination of drugs subject to this section poses an imminent hazard to the public health, the Secretary, after first making reasonable efforts to notify, not later than 48 hours before issuance of such order under this subparagraph, sponsors who have a listing in effect under section 360(j) of this title for such drug or combination of drugs—(I) may issue an interim final administrative order for such drug, class of drugs, or combination of drugs under paragraph (1), together with a detailed statement of the reasons for such order;(II) shall publish in the Federal Register a notice of availability of any such order; and(III) shall provide for a public comment period of at least 45 calendar days with respect to such interim final order.
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(I) make reasonable efforts to notify informally, not later than 48 hours before the issuance of the interim final order, the sponsors of drugs who have a listing in effect under section 360(j) of this title for such drug or combination of drugs;
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(iii) afford sponsors of such drugs that will be subject to such an order the opportunity for formal dispute resolution up to the level of the Director of the Center for Drug Evaluation and Research, which must initially be within 45 calendar days of the issuance of the order, and for subsequent levels of appeal, within 30 calendar days of the prior decision.
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(E) A sponsor of a drug subject to a final order issued under subparagraph (D) and that participated in each stage of formal dispute resolution under clause (iii) of such subparagraph may request a hearing on such order. The provisions of subparagraphs (A), (B), and (C) of paragraph (3), other than paragraph (3)(C)(v)(II), shall apply with respect to a hearing on such order in the same manner and to the same extent as such provisions apply with respect to a hearing on an administrative order issued under paragraph (2)(A)(iv).
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(A) A sponsor shall submit records requested by the Secretary relating to such a minor change under section 374(a)(4) of this title, within 15 business days of receiving such a request, or such longer period as the Secretary may provide.
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(C) If the sponsor fails to provide such additional information within a time prescribed by the Secretary, or if the Secretary determines that such additional information does not demonstrate that the change does not—(i) affect the safety or effectiveness of the drug; or(ii) materially affect the extent of absorption or other exposure to the active ingredient in comparison to a suitable reference product,the drug as modified is a new drug under section 321(p) of this title and shall be deemed to be misbranded under section 352(ee) of this title.
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(A) The Secretary shall issue one or more administrative orders specifying requirements for determining whether a minor change made by a sponsor pursuant to this subsection will affect the safety or effectiveness of a drug or materially affect the extent of absorption or other exposure to an active ingredient in the drug in comparison to a suitable reference product, together with guidance for applying those orders to specific dosage forms.
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(e) A sponsor who makes a change to a drug subject to this section shall submit updated drug listing information for the drug in accordance with section 360(j) of this title within 30 calendar days of the date when the drug is first commercially marketed, except that a sponsor who was the order requestor with respect to an order subject to subsection (b)(5)(C) (or a licensee, assignee, or successor in interest of such requestor) shall submit updated drug listing information on or before the date when the drug is first commercially marketed.
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(h) The Secretary shall establish procedures under which sponsors, requestors, or organizations nominated by sponsors or requestors to represent their interests in a proceeding may meet with appropriate officials of the Food and Drug Administration to obtain advice on the studies and other information necessary to support submissions under this section and other matters relevant to the regulation of nonprescription drugs and the development of new nonprescription drugs under this section.
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(i) The Secretary shall establish procedures to facilitate efficient participation by multiple sponsors or requestors in proceedings under this section, including provision for joint meetings with multiple sponsors or requestors or with organizations nominated by sponsors or requestors to represent their interests in a proceeding.
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(i) The responsible person may, after the sponsor is required to make a submission under subsection (a)(2) or (g), request in writing that a dispute about the strategy be reviewed by the Drug Safety Oversight Board under subsection (j), except that the determination of the Secretary to require a risk evaluation and mitigation strategy is not subject to review under this paragraph. The preceding sentence does not prohibit review under this paragraph of the particular elements of such a strategy.
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(1) The Secretary shall, at the request of the sponsor of a drug, expedite the development and review of such drug if the drug is intended, alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. (In this section, such a drug is referred to as a “breakthrough therapy”.)
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(2) The sponsor of a drug may request the Secretary to designate the drug as a breakthrough therapy. A request for the designation may be made concurrently with, or at any time after, the submission of an application for the investigation of the drug under section 355(i) of this title or section 351(a)(3) of the Public Health Service Act [42 U.S.C. 262(a)(3)].
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(1) The Secretary shall, at the request of the sponsor of a new drug, facilitate the development and expedite the review of such drug if it is intended, whether alone or in combination with one or more other drugs, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition, or if the Secretary designates the drug as a qualified infectious disease product under section 355f(d) of this title. (In this section, such a drug is referred to as a “fast track product”.)
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(2) The sponsor of a new drug may request the Secretary to designate the drug as a fast track product. A request for the designation may be made concurrently with, or at any time after, submission of an application for the investigation of the drug under section 355(i) of this title or section 351(a)(3) of the Public Health Service Act [42 U.S.C. 262(a)(3)].
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(i) the sponsor fails to conduct any required postapproval study of the product with due diligence, including with respect to conditions specified by the Secretary under paragraph (2)(C);
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(i) providing the sponsor with—(I) due notice;(II) an explanation for the proposed withdrawal;(III) an opportunity for a meeting with the Commissioner or the Commissioner’s designee; and(IV) an opportunity for written appeal to—(aa) the Commissioner; or(bb) a designee of the Commissioner who has not participated in the proposed withdrawal of approval (other than a meeting pursuant to subclause (III)) and is not subordinate of an individual (other than the Commissioner) who participated in such proposed withdrawal;
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(iv) convening and consulting an advisory committee on issues related to the proposed withdrawal, if requested by the sponsor and if no such advisory committee has previously advised the Secretary on such issues with respect to the withdrawal of the product prior to the sponsor’s request.
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(1) If the Secretary determines, after preliminary evaluation of clinical data submitted by the sponsor, that a fast track product may be effective, the Secretary shall evaluate for filing, and may commence review of portions of, an application for the approval of the product before the sponsor submits a complete application. The Secretary shall commence such review only if the applicant—(A) provides a schedule for submission of information necessary to make the application complete; and(B) pays any fee that may be required under section 379h of this title.
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(3) The sponsor of a drug may request the Secretary to designate the drug as a regenerative advanced therapy concurrently with, or at any time after, submission of an application for the investigation of the drug under section 355(i) of this title or section 351(a)(3) of the Public Health Service Act [42 U.S.C. 262(a)(3)].
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(5) The sponsor of a regenerative advanced therapy shall be eligible for the actions to expedite development and review of such therapy under subsection (a)(3)(B), including early interactions to discuss any potential surrogate or intermediate endpoint to be used to support the accelerated approval of an application for the product under subsection (c).
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(7) The sponsor of a regenerative advanced therapy that is granted accelerated approval and is subject to the postapproval requirements under subsection (c) may, as appropriate, fulfill such requirements, as the Secretary may require, through—(A) the submission of clinical evidence, clinical studies, patient registries, or other sources of real world evidence, such as electronic health records;(B) the collection of larger confirmatory data sets, as agreed upon pursuant to subsection (a)(3)(B); or(C) postapproval monitoring of all patients treated with such therapy prior to approval of the therapy.
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(4) A sponsor of a drug that seeks approval of a drug under this subsection may also seek designation or approval, as applicable, of such drug under other applicable sections or subsections of this chapter or the Public Health Service Act [42 U.S.C. 201 et seq.].
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(6) The Secretary shall provide prompt advice to the sponsor of a drug for which the sponsor seeks approval under this subsection to enable the sponsor to plan a development program to obtain the necessary data for such approval, and to conduct any additional studies that would be required to gain approval of such drug for use in a broader population.
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(1) A sponsor of a drug that has entered into an agreement with the Secretary to conduct a postmarketing study of a drug shall submit to the Secretary, within 1 year after the approval of such drug and annually thereafter until the study is completed or terminated, a report of the progress of the study or the reasons for the failure of the sponsor to conduct the study. The report shall be submitted in such form as is prescribed by the Secretary in regulations issued by the Secretary.
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(2) Notwithstanding paragraph (1), a sponsor of a drug approved pursuant to accelerated approval shall submit to the Secretary a report of the progress of any study required under section 356(c) of this title, including progress toward enrollment targets, milestones, and other information as required by the Secretary, not later than 180 days after the approval of such drug and not less frequently than every 180 days thereafter, until the study is completed or terminated. The Secretary shall promptly publish on the website of the Food and Drug Administration, in an easily searchable format, the information reported under this paragraph.
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(3) Any agreement entered into between the Secretary and a sponsor of a drug, prior to November 21, 1997, to conduct a postmarketing study of a drug shall be subject to the requirements of paragraph (1). An initial report for such an agreement shall be submitted within 6 months after the date of the issuance of the regulations under paragraph (1).
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(1) to identify the sponsor; and
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(1) that sponsors have entered into agreements to conduct; and
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(d) If a sponsor fails to complete an agreed upon study required by this section by its original or otherwise negotiated deadline, the Secretary shall publish a statement on the Internet site of the Food and Drug Administration stating that the study was not completed and, if the reasons for such failure to complete the study were not satisfactory to the Secretary, a statement that such reasons were not satisfactory to the Secretary.
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(e) With respect to studies of the type required under section 356(c)(2)(A) of this title or under section 314.510 or 601.41 of title 21, Code of Federal Regulations, as each of such sections was in effect on the day before the effective date of this subsection, the Secretary may require that a sponsor who, for reasons not satisfactory to the Secretary, fails to complete by its deadline a study under any of such sections of such type for a drug or biological product (including such a study conducted after such effective date) notify practitioners who prescribe such drug or biological product of the failure to complete such study and the questions of clinical benefit, and, where appropriate, questions of safety, that remain unanswered as a result of the failure to complete such study. Nothing in this subsection shall be construed as altering the requirements of the types of studies required under section 356(c)(2)(A) of this title or under section 314.510 or 601.41 of title 21, Code of Federal Regulations, as so in effect, or as prohibiting the Secretary from modifying such sections of title 21 of such Code to provide for studies in addition to those of such type.
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(a) Not later than 2 years after December 13, 2016, the Secretary, in consultation with the National Institute of Standards and Technology and stakeholders (including regenerative medicine and advanced therapies manufacturers and clinical trial sponsors, contract manufacturers, academic institutions, practicing clinicians, regenerative medicine and advanced therapies industry organizations, and standard setting organizations), shall facilitate an effort to coordinate and prioritize the development of standards and consensus definition of terms, through a public process, to support, through regulatory predictability, the development, evaluation, and review of regenerative medicine therapies and regenerative advanced therapies, including with respect to the manufacturing processes and controls of such products.
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(d) Not later than one year after the date of the approval of an application under section 355(j) of this title with respect to a drug for which the development and review is expedited under this section, the sponsor of such drug shall report to the Secretary on whether the drug has been marketed in interstate commerce since the date of such approval.
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(2) preliminary evidence submitted by the sponsor of the approved or licensed drug described in paragraph (1), or a sponsor that has been granted a right of reference to data submitted in the application for such drug, demonstrates that the platform technology has the potential to be incorporated in, or utilized by, more than one drug without an adverse effect on quality, manufacturing, or safety; and
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(4) The Secretary may revoke a designation made under paragraph (2), if the Secretary determines that the designated platform technology no longer meets the criteria described in subsection (b). The Secretary shall communicate the determination to revoke a designation to the requesting sponsor in writing, including a description of the rationale for such determination.
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(1) engaging in early interactions with the sponsor to discuss the use of the designated platform technology and what is known about such technology, including data previously submitted that is relevant to establishing, as applicable, safety or efficacy under section 355(b) of this title or safety, purity, or potency under section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)];
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(2) providing timely advice to, and interactive communication with, the sponsor regarding the development of the drug that proposes to use the designated platform technology to ensure that the development program designed to gather data necessary for approval or licensure is as efficient as practicable, which may include holding meetings with the sponsor and the review team throughout the development of the drug; and
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(f) The Secretary shall, consistent with applicable standards for approval, authorization, or licensure under this chapter and section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)], allow the sponsor of an application under section 355(b) of this title or section 351(a) of the Public Health Service Act or a request for emergency use authorization under section 360bbb–3 of this title, in order to support approval, licensure, or authorization, to reference or rely upon data and information within an application or request for a drug or biological product that incorporates or utilizes the same platform technology designated under subsection (d), provided that—(1) such data and information was submitted by the same sponsor, pursuant to the application for the drug with respect to which designation of the designated platform technology under subsection (d) was granted; or(2) the sponsor relying on such data and information received a right of reference to such data and information from the sponsor described in paragraph (1).
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(1) such data and information was submitted by the same sponsor, pursuant to the application for the drug with respect to which designation of the designated platform technology under subsection (d) was granted; or
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(2) the sponsor relying on such data and information received a right of reference to such data and information from the sponsor described in paragraph (1).
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(g) A sponsor of more than one application approved under section 355(b) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] for drugs that incorporate or utilize a designated platform technology may submit a single supplemental application for proposed changes to the designated platform technology that may be applicable to more than one such drug that incorporates or utilizes the same designated platform technology. Such supplemental application may cross-reference data and information submitted in other applications and may include one or more comparability protocols regarding how such changes to the platform technology would be made for each applicable drug or biological product.
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(1) The term “platform technology” means a well-understood and reproducible technology, which may include a nucleic acid sequence, molecular structure, mechanism of action, delivery method, vector, or a combination of any such technologies that the Secretary determines to be appropriate, that the sponsor demonstrates—(A) is incorporated in or utilized by a drug or biological product and is essential to the structure or function of such drug or biological product;
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(2) confer any new rights with respect to the permissibility of a sponsor of an application for a drug product or biological product referencing information contained in another application submitted by the holder of an approved application under section 355(c) of this title or of a license under section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)].
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(a) The Secretary of Health and Human Services may designate a priority countermeasure as a fast-track product pursuant to section 356 of this title or as a device granted review priority pursuant to section 360e(d)(5)1 of this title. Such a designation may be made prior to the submission of—(1) a request for designation by the sponsor or applicant; or(2) an application for the investigation of the drug under section 355(i) of this title or section 262(a)(3) of title 42.Nothing in this subsection shall be construed to prohibit a sponsor or applicant from declining such a designation.
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(1) a request for designation by the sponsor or applicant; or
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(a) The sponsor of a drug for a disease or condition which is rare in the States may request the Secretary to provide written recommendations for the non-clinical and clinical investigations which must be conducted with the drug before—(1) it may be approved for such disease or condition under section 355 of this title, or(2) if the drug is a biological product, it may be licensed for such disease or condition under section 262 of title 42.If the Secretary has reason to believe that a drug for which a request is made under this section is a drug for a disease or condition which is rare in the States, the Secretary shall provide the person making the request written recommendations for the non-clinical and clinical investigations which the Secretary believes, on the basis of information available to the Secretary at the time of the request under this section, would be necessary for approval of such drug for such disease or condition under section 355 of this title or licensing of such drug for such disease or condition under section 262 of title 42.
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(1) The sponsor of a drug intended to be designated as a qualified infectious disease product may request that the Secretary provide written recommendations for nonclinical and clinical investigations which the Secretary believes may be necessary to be conducted with the drug before such drug may be approved under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) for use in treating, detecting, preventing, or identifying a qualifying pathogen, as defined in section 505E of such Act [21 U.S.C. 355f].
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(j) To the extent consistent with the public health, the Secretary shall promulgate regulations for exempting from the operation of this section new animal drugs, and animal feeds bearing or containing new animal drugs, intended solely for investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of animal drugs. Such regulations may, in the discretion of the Secretary, among other conditions relating to the protection of the public health, provide for conditioning such exemption upon the establishment and maintenance of such records, and the making of such reports to the Secretary, by the manufacturer or the sponsor of the investigation of such article, of data (including but not limited to analytical reports by investigators) obtained as a result of such investigational use of such article, as the Secretary finds will enable him to evaluate the safety and effectiveness of such article in the event of the filing of an application pursuant to this section. Such regulations, among other things, shall set forth the conditions (if any) upon which animals treated with such articles, and any products of such animals (before or after slaughter), may be marketed for food use.
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(A) In the case of each new animal drug described in paragraph (1) that contains an antimicrobial active ingredient, the sponsor of the drug shall submit an annual report to the Secretary on the amount of each antimicrobial active ingredient in the drug that is sold or distributed for use in food-producing animals, including information on any distributor-labeled product.
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(i) the summary data shall be reported by antimicrobial class, and no class with fewer than 3 distinct sponsors of approved applications shall be independently reported; and
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(1) In the case of an application under subsection (b) with respect to a drug for which the Secretary provides notice to the sponsor that the Secretary intends to issue a scientific and medical evaluation and recommend controls under the Controlled Substances Act [21 U.S.C. 801 et seq.], approval of such application shall not take effect until the interim final rule controlling the drug is issued in accordance with section 201(j) of the Controlled Substances Act [21 U.S.C. 811(j)].
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(1) The manufacturer or the sponsor of a drug may request the Secretary to designate the drug as a drug for a rare disease or condition. A request for designation of a drug shall be made before the submission of an application under section 355(b) of this title for the drug, or the submission of an application for licensing of the drug under section 262 of title 42. If the Secretary finds that a drug for which a request is submitted under this subsection is being or will be investigated for a rare disease or condition and—(A) if an application for such drug is approved under section 355 of this title, or(B) if a license for such drug is issued under section 262 of title 42,the approval, certification, or license would be for use for such disease or condition, the Secretary shall designate the drug as a drug for such disease or condition. A request for a designation of a drug under this subsection shall contain the consent of the applicant to notice being given by the Secretary under subsection (b)1 respecting the designation of the drug.
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(2) if an application has not been approved for the drug under section 355(b) of this title or a license has not been issued for the drug under section 262 of title 42 and if preclinical investigations or investigations under section 355(i) of this title are being conducted with the drug, the manufacturer or sponsor of the drug will notify the Secretary of any decision to discontinue active pursuit of approval of an application under section 355(b) of this title or approval of a license under section 262 of title 42.
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(4) the sponsor, or clinical investigator, of the investigational drug or investigational device submits to the Secretary a clinical protocol consistent with the provisions of section 355(i) or 360j(g) of this title, including any regulations promulgated under section 355(i) or 360j(g) of this title, describing the use of the investigational drug or investigational device in a single patient or a small group of patients.
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(c) Upon submission by a sponsor or a physician of a protocol intended to provide widespread access to an investigational drug or investigational device for eligible patients (referred to in this subsection as an “expanded access protocol”), the Secretary shall permit such investigational drug or investigational device to be made available for expanded access under a treatment investigational new drug application or treatment investigational device exemption if the Secretary determines that—(1) under the treatment investigational new drug application or treatment investigational device exemption, the investigational drug or investigational device is intended for use in the diagnosis, monitoring, or treatment of a serious or immediately life-threatening disease or condition;(2) there is no comparable or satisfactory alternative therapy available to diagnose, monitor, or treat that stage of disease or condition in the population of patients to which the investigational drug or investigational device is intended to be administered;(A) the investigational drug or investigational device is under investigation in a controlled clinical trial for the use described in paragraph (1) under an investigational drug application in effect under section 355(i) of this title or investigational device exemption in effect under section 360j(g) of this title; or(B) all clinical trials necessary for approval of that use of the investigational drug or investigational device have been completed;(4) the sponsor of the controlled clinical trials is actively pursuing marketing approval of the investigational drug or investigational device for the use described in paragraph (1) with due diligence;(5) in the case of an investigational drug or investigational device described in paragraph (3)(A), the provision of the investigational drug or investigational device will not interfere with the enrollment of patients in ongoing clinical investigations under section 355(i) or 360j(g) of this title;(6) in the case of serious diseases, there is sufficient evidence of safety and effectiveness to support the use described in paragraph (1); and(7) in the case of immediately life-threatening diseases, the available scientific evidence, taken as a whole, provides a reasonable basis to conclude that the investigational drug or investigational device may be effective for its intended use and would not expose patients to an unreasonable and significant risk of illness or injury.A protocol submitted under this subsection shall be subject to the provisions of section 355(i) or 360j(g) of this title, including regulations promulgated under section 355(i) or 360j(g) of this title. The Secretary may inform national, State, and local medical associations and societies, voluntary health associations, and other appropriate persons about the availability of an investigational drug or investigational device under expanded access protocols submitted under this subsection. The information provided by the Secretary, in accordance with the preceding sentence, shall be the same type of information that is required by section 282(i)(3) of title 42.
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(4) the sponsor of the controlled clinical trials is actively pursuing marketing approval of the investigational drug or investigational device for the use described in paragraph (1) with due diligence;
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(d) The Secretary may, at any time, with respect to a sponsor, physician, manufacturer, or distributor described in this section, terminate expanded access provided under this section for an investigational drug or investigational device if the requirements under this section are no longer met.
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(b) Eligible investigational drugs provided to eligible patients in compliance with this section are exempt from sections 352(f), 353(b)(4), 355(a), and 355(i) of this title, section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)], and parts 50, 56, and 312 of title 21, Code of Federal Regulations (or any successor regulations), provided that the sponsor of such eligible investigational drug or any person who manufactures, distributes, prescribes, dispenses, introduces or delivers for introduction into interstate commerce, or provides to an eligible patient an eligible investigational drug pursuant to this section is in compliance with the applicable requirements set forth in sections 312.6, 312.7, and 312.8(d)(1) of title 21, Code of Federal Regulations (or any successor regulations) that apply to investigational drugs.
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(B) the sponsor requests use of such outcomes.
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(2) If the Secretary makes a determination under paragraph (1)(A), the Secretary shall provide written notice of such determination to the sponsor, including a public health justification for such determination, and such notice shall be made part of the administrative record. Such determination shall not be delegated below the director of the agency center that is charged with the premarket review of the eligible investigational drug.
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(1) The manufacturer or sponsor of an eligible investigational drug shall submit to the Secretary an annual summary of any use of such drug under this section. The summary shall include the number of doses supplied, the number of patients treated, the uses for which the drug was made available, and any known serious adverse events. The Secretary shall specify by regulation the deadline of submission of such annual summary and may amend section 312.33 of title 21, Code of Federal Regulations (or any successor regulations) to require the submission of such annual summary in conjunction with the annual report for an applicable investigational new drug application for such drug.
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If, regarding an obligation concerning drugs or devices under this Act or section 351 of the Public Health Service Act [42 U.S.C. 262], there is a scientific controversy between the Secretary and a person who is a sponsor, applicant, or manufacturer and no specific provision of the Act involved, including a regulation promulgated under such Act, provides a right of review of the matter in controversy, the Secretary shall, by regulation, establish a procedure under which such sponsor, applicant, or manufacturer may request a review of such controversy, including a review by an appropriate scientific advisory panel described in section 355(n) of this title or an advisory committee described in section 360e(g)(2)(B) of this title. Any such review shall take place in a timely manner. The Secretary shall promulgate such regulations within 1 year after November 21, 1997.
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(5) If an authorization under this section with respect to an unapproved product or an unapproved use of an approved product has been in effect for more than 1 year, the Secretary shall provide in writing to the sponsor of such product an explanation of the scientific, regulatory, or other obstacles to approval, licensure, or clearance of such product or use, including specific actions to be taken by the Secretary and the sponsor to overcome such obstacles.
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(D) assigning a cross-disciplinary project lead for the review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor;
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(A) consult with countermeasure experts, including countermeasure sponsors and applicants, to identify and help resolve scientific issues related to the approval, licensure, or clearance of countermeasures, through workshops or public meetings; and
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(1) To facilitate the timely development of animal models and support the development, stockpiling, licensure, approval, and clearance of countermeasures, the Secretary shall, not later than 180 days after March 13, 2013, establish a procedure by which a sponsor or applicant that is developing a countermeasure for which human efficacy studies are not ethical or practicable, and that has an approved investigational new drug application or investigational device exemption, may request and receive—(A) a meeting to discuss proposed animal model development activities; and(B) a meeting prior to initiating pivotal animal studies.
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(A) A sponsor or applicant of an eligible countermeasure may initiate the process described under paragraph (2) upon submission of a written request to the Secretary. Such request shall include a proposed regulatory management plan.
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(B) A sponsor or applicant may submit a written request under subparagraph (A) after the eligible countermeasure has an investigational new drug or investigational device exemption in effect.
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(C) The Secretary shall direct the Food and Drug Administration, upon submission of a written request by a sponsor or applicant under subparagraph (A), to work with the sponsor or applicant to agree on a regulatory management plan within a reasonable time not to exceed 90 days. If the Secretary determines that no plan can be agreed upon, the Secretary shall provide to the sponsor or applicant, in writing, the scientific or regulatory rationale why such agreement cannot be reached.
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(5) The content of a regulatory management plan agreed to by the Secretary and a sponsor or applicant shall include—(A) an agreement between the Secretary and the sponsor or applicant regarding developmental milestones that will trigger responses by the Secretary as described in subparagraph (B);(B) performance targets and goals for timely and appropriate responses by the Secretary to the triggers described under subparagraph (A), including meetings between the Secretary and the sponsor or applicant, written feedback, decisions by the Secretary, and other activities carried out as part of the development and review process; and(C) an agreement on how the plan shall be modified, if needed.
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(A) an agreement between the Secretary and the sponsor or applicant regarding developmental milestones that will trigger responses by the Secretary as described in subparagraph (B);
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(B) performance targets and goals for timely and appropriate responses by the Secretary to the triggers described under subparagraph (A), including meetings between the Secretary and the sponsor or applicant, written feedback, decisions by the Secretary, and other activities carried out as part of the development and review process; and
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(A) sponsors of a countermeasure as defined in subsection (a); or
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(1) The Secretary may, at the request of the sponsor of a countermeasure, during a domestic, military, or public health emergency or material threat described in section 360bbb–3a(a)(1)(C) of this title, expedite the development and review of countermeasures that are intended to address such domestic, military, or public health emergency or material threat for approval, licensure, clearance, or authorization under this title or section 262 of title 42.
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(B) Expedited and increased engagement with sponsors regarding countermeasure development and manufacturing, including—(i) holding meetings with the sponsor and the review team and providing timely advice to, and interactive communication with, the sponsor regarding the development of the countermeasure to ensure that the development program to gather the nonclinical and clinical data necessary for approval, licensure, clearance, or authorization is as efficient as practicable;(ii) involving senior managers and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review;(iii) assigning a cross-disciplinary project lead for the review team to facilitate;(iv) taking steps to ensure that the design of the clinical trials is as efficient as practicable, when scientifically appropriate, such as by minimizing the number of patients exposed to a potentially less efficacious treatment; and(v) streamlining the review of approved, licensed, cleared, or authorized countermeasures to treat or prevent new or emerging threats, including the review of any changes to such countermeasures.
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(i) holding meetings with the sponsor and the review team and providing timely advice to, and interactive communication with, the sponsor regarding the development of the countermeasure to ensure that the development program to gather the nonclinical and clinical data necessary for approval, licensure, clearance, or authorization is as efficient as practicable;
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(3) Nothing in this subsection shall be construed to require the Secretary to grant, or take any other action related to, a request of a sponsor to expedite the development and review of a countermeasure for approval, licensure, clearance, or authorization under paragraph (1).
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(3) The term “priority review voucher” means a voucher issued by the Secretary to the sponsor of a material threat medical countermeasure application that entitles the holder of such voucher to priority review of a single human drug application submitted under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] after the date of approval of the material threat medical countermeasure application.
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(2) The sponsor of a material threat medical countermeasure application that receives a priority review voucher under this section may transfer (including by sale) the entitlement to such voucher to a sponsor of a human drug for which an application under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] will be submitted after the date of the approval of the material threat medical countermeasure application. There is no limit on the number of times a priority review voucher may be transferred before such voucher is used.
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(A) The sponsor of a human drug application shall notify the Secretary not later than 90 calendar days prior to submission of the human drug application that is the subject of a priority review voucher of an intent to submit the human drug application, including the date on which the sponsor intends to submit the application. Such notification shall be a legally binding commitment to pay for the user fee to be assessed in accordance with this section.
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(B) The sponsor of a human drug application that provides notification of the intent of such sponsor to use the voucher for the human drug application under subparagraph (A) may transfer the voucher after such notification is provided, if such sponsor has not yet submitted the human drug application described in the notification.
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(1) The Secretary shall establish a user fee program under which a sponsor of a human drug application that is the subject of a priority review voucher shall pay to the Secretary a fee determined under paragraph (2). Such fee shall be in addition to any fee required to be submitted by the sponsor under subchapter VII.
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(B) An application described under subparagraph (A) for which the sponsor requests the use of a priority review voucher shall be considered incomplete if the fee required by this subsection and all other applicable user fees are not paid in accordance with the Secretary’s procedures for paying such fees.
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(2) The Secretary approves a drug pursuant to an application submitted under section 355(b) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] for which the sponsor of the application used a priority review voucher issued under this section.
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(e) Nothing in this section precludes a sponsor who seeks a priority review voucher under this section from participating in any other incentive program, including under this chapter, except that no sponsor of a material threat medical countermeasure application may receive more than one priority review voucher issued under any section of this chapter with respect to such drug.
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(3) alter the authority of the Secretary under this Act [this chapter] or the Public Health Service Act [42 U.S.C. 201 et seq.] to determine the types of data or information previously submitted by a sponsor or any other person that may be incorporated by reference in an application, request, or notification for a drug, biological product, or device submitted under sections 355(i), 355(b), 355(j), 360b(b)(1), 360b(b)(2), 360b(j), 360bbb–3, 360ccc, 360j(g), 360e(c), 360c(f)(2), or 360(k) of this title, or subsection (a) or (k) of section 351 of the Public Health Service Act [42 U.S.C. 262], including a supplement or amendment to any such submission, and the requirements associated with such reference.
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(2) The Secretary shall not disclose confidential commercial or trade secret information to an expert consulted under this section without the written consent of the sponsor unless the expert is a special government employee (as defined under section 202 of title 18) or the disclosure is otherwise authorized by law.
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(B) the sponsor authorized such consultation.
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(b) If the Secretary finds under subsection (a) that the data from clinical investigations conducted outside the United States, including in the European Union, are inadequate for the purpose of making a determination on approval, clearance, or licensure of a drug, biological product, or device pursuant to an application submitted under this subchapter, the Secretary shall provide written notice to the sponsor of the application of such finding and include the rationale for such finding.
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(a) The Secretary shall, at the request of the sponsor intending to submit an application for approval of a new animal drug under section 360b(b)(1) of this title or an application for conditional approval of a new animal drug under section 360ccc of this title, expedite the development and review of such new animal drug if preliminary clinical evidence indicates that the new animal drug, alone or in combination with 1 or more other animal drugs, has the potential to prevent or treat a zoonotic disease in animals, including a vector borne-disease, that has the potential to cause serious adverse health consequences for, or serious or life-threatening diseases in, humans.
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(b) The sponsor of a new animal drug may request the Secretary to designate a new animal drug described in subsection (a) as a priority zoonotic animal drug. A request for the designation may be made concurrently with, or at any time after, the opening of an investigational new animal drug file under section 360b(j) of this title or the filing of an application under section 360b(b)(1) or 360ccc of this title.
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(B) providing timely advice to, and interactive communication with, the sponsor (which may include meetings with the sponsor and review team) regarding the development of the new animal drug to ensure that the development program to gather the nonclinical and clinical data necessary for approval is as efficient as practicable;
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(D) The Secretary shall provide an annual opportunity for patients, representatives of patients, and sponsors of medical devices that may be specifically the subject of a review by a classification panel to provide recommendations for individuals with appropriate expertise to fill voting member positions on classification panels.
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(i) Not later than the date that is one year after August 18, 2017, and at least once every 5 years thereafter, and as the Secretary otherwise determines appropriate, pursuant to this paragraph, the Secretary shall publish in the Federal Register a notice proposing a list of such accessories that the Secretary determines may be suitable for a distinct classification in class I and the proposed regulations for such classifications. In developing such list, the Secretary shall consider recommendations from sponsors of device submissions and other stakeholders for accessories to be included on such list. The notices shall provide for a period of not less than 60 calendar days for public comment. Within 180 days after the end of the comment period, the Secretary shall publish in the Federal Register a final action classifying such suitable accessories into class I.
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(k) For a device authorized for emergency use under section 360bbb–3 of this title for which, in accordance with section 360bbb–3(m) of this title, the Secretary has deemed a laboratory examination or procedure associated with such device to be in the category of examinations and procedures described in section 263a(d)(3) of title 42, the sponsor of such device may, when submitting a request for classification under subsection (f)(2), submit a single submission containing—(1) the information needed for such a request; and(2) sufficient information to enable the Secretary to determine whether such laboratory examination or procedure satisfies the criteria to be categorized under section 263a(d)(3) of title 42.
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(1) If a sponsor of a drug that is designated under section 360bb of this title and is otherwise the same, as determined by the Secretary, as an already approved or licensed drug is seeking exclusive approval or exclusive licensure described in subsection (a) for the same use or indication for which the already approved or licensed drug was approved or licensed, the Secretary shall require such sponsor, as a condition of such exclusive approval or licensure, to demonstrate that such drug is clinically superior to any already approved or licensed drug that is the same drug.
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(e) To assist sponsors in demonstrating clinical superiority as described in subsection (c), the Secretary—(1) upon the designation of any drug under section 360bb of this title, shall notify the sponsor of such drug in writing of the basis for the designation, including, as applicable, any plausible hypothesis offered by the sponsor and relied upon by the Secretary that the drug is clinically superior to a previously approved drug; and(2) upon granting exclusive approval or licensure under subsection (a) on the basis of a demonstration of clinical superiority as described in subsection (c), shall publish a summary of the clinical superiority findings.
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(1) upon the designation of any drug under section 360bb of this title, shall notify the sponsor of such drug in writing of the basis for the designation, including, as applicable, any plausible hypothesis offered by the sponsor and relied upon by the Secretary that the drug is clinically superior to a previously approved drug; and
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(A) In the case of an application under subsection (a) with respect to a drug for which the Secretary provides notice to the sponsor that the Secretary intends to issue a scientific and medical evaluation and recommend controls under the Controlled Substances Act [21 U.S.C. 801 et seq.], conditional approval of such application shall not take effect until the interim final rule controlling the drug is issued in accordance with section 201(j) of the Controlled Substances Act [21 U.S.C. 811(j)].
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(g) For purposes of indexing new animal drugs under this section, to the extent consistent with the public health, the Secretary shall promulgate regulations for exempting from the operation of section 360b of this title minor species new animal drugs and animal feeds bearing or containing new animal drugs intended solely for investigational use by experts qualified by scientific training and experience to investigate the safety and effectiveness of minor species animal drugs. Such regulations may, at the discretion of the Secretary, among other conditions relating to the protection of the public health, provide for conditioning such exemption upon the establishment and maintenance of such records, and the making of such reports to the Secretary, by the manufacturer or the sponsor of the investigation of such article, of data (including but not limited to analytical reports by investigators) obtained as a result of such investigational use of such article, as the Secretary finds will enable the Secretary to evaluate the safety and effectiveness of such article in the event of the filing of a request for an index listing pursuant to this section.
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(1) The manufacturer or the sponsor of a new animal drug for a minor use or use in a minor species may request that the Secretary declare that drug a “designated new animal drug”. A request for designation of a new animal drug shall be made before the submission of an application under section 360b(b) of this title or section 360ccc of this title for the new animal drug.
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(A) the sponsor of a new animal drug shall notify the Secretary of any decision to discontinue active pursuit of approval under section 360b or 360ccc of this title of an application for a designated new animal drug. The Secretary shall terminate the designation upon such notification;
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(C) the sponsor of an approved designated new animal drug shall notify the Secretary of any discontinuance of the manufacture of such new animal drug at least one year before discontinuance. The Secretary shall terminate the designation upon such notification; and
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If a drug is designated under section 360bb of this title as a drug for a rare disease or condition and if notice of a claimed exemption under section 355(i) of this title or regulations issued thereunder is filed for such drug, the Secretary shall encourage the sponsor of such drug to design protocols for clinical investigations of the drug which may be conducted under the exemption to permit the addition to the investigations of persons with the disease or condition who need the drug to treat the disease or condition and who cannot be satisfactorily treated by available alternative drugs.
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(B) The name and address of the sponsor.
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(c) A sponsor of a device may request that the Secretary designate such device for expedited development and priority review under this section. Any such request for designation may be made at any time prior to the submission of an application under section 360e(c) of this title, a notification under section 360(k) of this title, or a petition for classification under section 360c(f)(2) of this title.
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(G) provide for advisory committee input, as the Secretary determines appropriate (including in response to the request of the sponsor) for applications submitted under section 360e(c) of this title; and
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(2) In addition to the actions described in paragraph (1), for purposes of expediting the development and review of devices designated under subsection (d), the Secretary, in collaboration with the device sponsor, may, as appropriate—(A) coordinate with the sponsor regarding early agreement on a data development plan;(B) take steps to ensure that the design of clinical trials is as efficient and flexible as practicable, when scientifically appropriate;(C) facilitate, when scientifically appropriate, expedited and efficient development and review of the device through utilization of timely postmarket data collection with regard to application for approval under section 360e(c) of this title; and(D) agree in writing to clinical protocols that the Secretary will consider binding on the Secretary and the sponsor, subject to—(ii) a decision, made by the director of the office responsible for reviewing the device submission, that a substantial scientific issue essential to determining the safety or effectiveness of such device exists, provided that such decision is in writing, and is made only after the Secretary provides to the device sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant are present and at which the director documents the substantial scientific issue.
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(A) coordinate with the sponsor regarding early agreement on a data development plan;
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(D) agree in writing to clinical protocols that the Secretary will consider binding on the Secretary and the sponsor, subject to—(ii) a decision, made by the director of the office responsible for reviewing the device submission, that a substantial scientific issue essential to determining the safety or effectiveness of such device exists, provided that such decision is in writing, and is made only after the Secretary provides to the device sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant are present and at which the director documents the substantial scientific issue.
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(ii) a decision, made by the director of the office responsible for reviewing the device submission, that a substantial scientific issue essential to determining the safety or effectiveness of such device exists, provided that such decision is in writing, and is made only after the Secretary provides to the device sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant are present and at which the director documents the substantial scientific issue.
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(c) In making a determination of substantial equivalence pursuant to section 360c(i) of this title, the Secretary shall not compare a device to changed versions of a device implemented in accordance with an established predetermined change control plan as a predicate device. Only the version of the device cleared or approved, prior to changes made under the predetermined change control plan, may be used by a sponsor as a predicate device.
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(2) The term “priority review voucher” means a voucher issued by the Secretary to the sponsor of a rare pediatric disease product application that entitles the holder of such voucher to priority review of a single human drug application submitted under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] after the date of approval of the rare pediatric disease product application.
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(A) The sponsor of a rare pediatric disease product application that receives a priority review voucher under this section may transfer (including by sale) the entitlement to such voucher. There is no limit on the number of times a priority review voucher may be transferred before such voucher is used.
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(i) Beginning on the date that is 90 days after September 30, 2016, the sponsor of a rare pediatric disease product application that intends to request a priority review voucher under this section shall notify the Secretary of such intent upon submission of the rare pediatric disease product application that is the basis of the request for a priority review voucher.
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(ii) The sponsor of a rare pediatric disease product application that was submitted and that has not been approved as of September 30, 2016, shall be considered eligible for a priority review voucher, if—(aa) on or after the date that is 90 days after July 9, 2012; and(bb) on or before September 30, 2016; and(II) such application otherwise meets the criteria for a priority review voucher under this section.
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(i) The sponsor of a human drug application shall notify the Secretary not later than 90 days prior to submission of the human drug application that is the subject of a priority review voucher of an intent to submit the human drug application, including the date on which the sponsor intends to submit the application. Such notification shall be a legally binding commitment to pay the user fee to be assessed in accordance with this section.
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(ii) The sponsor of a human drug application that provides notification of the intent of such sponsor to use the voucher for the human drug application under clause (i) may transfer the voucher after such notification is provided, if such sponsor has not yet submitted the human drug application described in the notification.
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(1) The Secretary shall establish a user fee program under which a sponsor of a human drug application that is the subject of a priority review voucher shall pay to the Secretary a fee determined under paragraph (2). Such fee shall be in addition to any fee required to be submitted by the sponsor under subchapter VII.
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(B) An application described under subparagraph (A) for which the sponsor requests the use of a priority review voucher shall be considered incomplete if the fee required by this subsection and all other applicable user fees are not paid in accordance with the Secretary’s procedures for paying such fees.
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(2) The sponsor of an approved rare pediatric disease product shall submit a report to the Secretary not later than 5 years after the approval of the applicable rare pediatric disease product application. Such report shall provide the following information, with respect to each of the first 4 years after approval of such product:(A) The estimated population in the United States suffering from the rare pediatric disease.(B) The estimated demand in the United States for such rare pediatric disease product.(C) The actual amount of such rare pediatric disease product distributed in the United States.
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(B) The Secretary approves a drug pursuant to an application submitted under section 355(b) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] for which the sponsor of the application used a priority review voucher under this section.
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(2) If, after the last day of the 1-year period that begins on the date that the Secretary awards the third rare pediatric disease priority voucher under this section, a sponsor of an application submitted under section 355(b) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)] for a drug uses a priority review voucher under this section for such application, the Secretary shall submit to the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor, and Pensions of the Senate a document—(A) notifying such Committees of the use of such voucher; and(B) identifying the drug for which such priority review voucher is used.
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(g) Nothing in this section precludes a sponsor who seeks a priority review voucher under this section from participating in any other incentive program, including under this chapter, except that no sponsor of a rare pediatric disease product application may receive more than one priority review voucher issued under any section of this chapter with respect to the drug for which the application is made..3
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(B) A sponsor shall include in a request under section 360fff–1 of this title the information required under section 330.14 of title 21, Code of Federal Regulations (or any successor regulations) to meet the standard described in subparagraph (A)(ii).
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(B) At the time that a request is made under section 360fff–1 of this title, the sponsor of such request shall identify any information that such sponsor considers to be confidential information described in subparagraph (A).
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(1) In the case of a request under section 360fff–1 of this title that is determined to be eligible under subsection (a) for further review under this section and section 360fff–3 of this title, the Secretary shall, in notifying the public under subsection (a)(1)(C) of such eligibility determination, post the eligibility determination on the Internet website of the Food and Drug Administration, invite the sponsor of such request and any other interested party to submit comments, and provide a period of not less than 45 calendar days for comments in support of or otherwise relating to a GRASE determination, including published and unpublished data and other information related to the safety and efficacy of such request.
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(2) Not later than 60 calendar days after the submission of data and other information described in paragraph (1) by the sponsor, the Secretary shall determine whether the data and other information submitted by the sponsor under this section are sufficiently complete, including being formatted in a manner that enables the Secretary to determine the completeness of such data and information, to enable the Secretary to conduct a substantive review under section 360fff–3 of this title with respect to such request. Not later than 60 calendar days after the submission of data and other information described in paragraph (1) by the sponsor, if the Secretary determines—(A) that such data and other information are sufficiently complete, the Secretary shall—(i) issue a written notification to the sponsor of the determination to file such request, and make such notification publicly available; and(ii) file such request made under section 360fff–1 of this title; or(B) that such data and other information are not sufficiently complete, the Secretary shall issue a written notification to the sponsor of the determination to refuse to file the request, which shall include the reasons for the refusal, including why such data and other information are not sufficiently complete, and make such notification publicly available.
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(i) issue a written notification to the sponsor of the determination to file such request, and make such notification publicly available; and
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(B) that such data and other information are not sufficiently complete, the Secretary shall issue a written notification to the sponsor of the determination to refuse to file the request, which shall include the reasons for the refusal, including why such data and other information are not sufficiently complete, and make such notification publicly available.
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(A) If the Secretary refuses to file a request made under section 360fff–1 of this title, the sponsor may—(i) within 30 calendar days of receipt of written notification of such refusal, request, in writing, a meeting with the Secretary regarding the filing determination; and(ii) submit additional data or other information.
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(i) If a sponsor seeks a meeting under subparagraph (A)(i), the Secretary shall convene the meeting within 30 calendar days of the request for such meeting.
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(II) the sponsor may submit additional data or other information; or
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(III) if the sponsor elects, within 120 calendar days, to have the Secretary file the request (with or without amendments to correct any purported deficiencies to the request)—(aa) the Secretary shall file the request over protest, not later than 30 calendar days after the sponsor makes such election;(bb) at the time of filing, the Secretary shall provide written notification of such filing to the sponsor; and(cc) the Secretary shall make such notification publicly available.
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(iii) The Secretary shall not require the sponsor to resubmit a copy of the request for purposes of filing a request filed over protest, as described in clause (ii)(III).
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(2) If the Secretary does not issue a proposed sunscreen order under paragraph (1)(B) within such 300-day period, the sponsor of such request may notify the Office of the Commissioner of such request and request review by the Office of the Commissioner. If such sponsor so notifies the Office of the Commissioner, the Commissioner shall, not later than 60 calendar days after the date of notification under this paragraph, issue a proposed sunscreen order with respect to such request.
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(4) A sponsor may request, in writing, a meeting with respect to a proposed sunscreen order issued under this subsection and described in subparagraph (B) or (C) of section 360fff(7) of this title, not later than 30 calendar days after the Secretary issues such order. The Secretary shall convene a meeting with such sponsor not later than 45 calendar days after such request for a meeting.
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(ii) in the case of a proposed sunscreen order described in subparagraph (C) of section 360fff(7) of this title, not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order; or
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(B) if the Secretary does not issue such final sunscreen order within such 90- or 210-calendar-day period, as applicable, the sponsor of such request may notify the Office of the Commissioner of such request and request review by the Office of the Commissioner.
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(5) If the Secretary does not issue a proposed sunscreen order under paragraph (4), or the Secretary does not publish a notification of the availability of a letter under paragraph (3), as applicable, the sponsor of such request may notify the Office of the Commissioner of such request and request review by the Office of the Commissioner. The Commissioner shall, not later than 60 calendar days after the date of notification under this paragraph, issue a proposed order with respect to such request.
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(A) A sponsor may request, in writing, a meeting with respect to a proposed sunscreen order issued under this subsection, including a letter deemed to be a proposed sunscreen order under paragraph (3), not later than 30 calendar days after the Secretary issues such order or the date upon which such feedback letter is deemed to be a proposed sunscreen order, as applicable. The Secretary shall convene a meeting with such sponsor not later than 45 calendar days after the date of such request for a meeting.
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(B) A sponsor may request one or more confidential meetings with respect to a proposed sunscreen order, including a letter deemed to be a proposed sunscreen order under paragraph (3), to discuss matters relating to data requirements to support a general recognition of safety and effectiveness involving confidential information and public information related to such proposed sunscreen order, as appropriate. The Secretary shall convene a confidential meeting with such sponsor in a reasonable time period. If a sponsor requests more than one confidential meeting for the same proposed sunscreen order, the Secretary may refuse to grant an additional confidential meeting request if the Secretary determines that such additional confidential meeting is not reasonably necessary for the sponsor to advance its proposed sunscreen order, or if the request for a confidential meeting fails to include sufficient information upon which to base a substantive discussion. The Secretary shall publish a post-meeting summary of each confidential meeting under this subparagraph that does not disclose confidential commercial information or trade secrets. This subparagraph does not authorize the disclosure of confidential commercial information or trade secrets subject to 552(b)(4)1 of title 5 or section 1905 of title 18.
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(I) if the Advisory Committee is not convened under paragraph (8), not later than 210 calendar days after the date on which the sponsor submits the additional information requested pursuant to such proposed sunscreen order, which shall include a rationale for not convening such Advisory Committee; or
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(II) if the Advisory Committee is convened under paragraph (8), not later than 270 calendar days after the date on which the sponsor submits such additional information; or
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(B) if the Secretary does not issue such final sunscreen order within such 90-, 210-, or 270-calendar-day period, as applicable, the sponsor of such request may notify the Office of the Commissioner about such request and request review by the Office of the Commissioner.
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(i) the format and content of information submitted by a sponsor in support of a request under section 360fff–1 of this title or a pending request;
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(A) If, prior to November 26, 2014, an application was submitted pursuant to section 330.14 of title 21, Code of Federal Regulations for a GRASE determination for a drug other than a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients and such drug was found to be eligible to be considered for inclusion in the over-the-counter drug monograph system pursuant to section 330.14 of title 21, Code of Federal Regulations, the sponsor of such application may request that the Secretary provide a framework under paragraph (2) for the review of such application.
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(B) A request for a framework for review of an application made under subparagraph (A) shall be made within 180 calendar days of November 26, 2014, and shall include the preference of such sponsor as to whether such application is reviewed by the Secretary in accordance with—(i) the processes and procedures set forth for pending requests under section 360fff–3(b) of this title, except that specific timelines shall be determined in accordance with other applicable requirements under this section;(ii) the processes and procedures set forth under part 330 of title 21, Code of Federal Regulations (or any successor regulations);(iii) an initial filing determination under the processes and procedures described in section 360fff–2(b) of this title and the processes and procedures set forth for pending requests under section 360fff–3(b) of this title, except that specific timelines shall be determined in accordance with other applicable requirements under this section; or(iv) an initial filing determination under the processes and procedures described in section 360fff–2(b) of this title and the processes and procedures set forth under part 330 of title 21, Code of Federal Regulations (or any successor regulations).
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(C) If a sponsor described in subparagraph (A) does not make such request within 180 calendar days of November 26, 2014, such application shall be reviewed by the Secretary in accordance with the timelines of the applicable regulations when such regulations are finalized under subsection (b).
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(2) Not later than 1 year after November 26, 2014, the Secretary shall provide, in writing, a framework to each sponsor that submitted a request under paragraph (1). Such framework shall set forth the various timelines, in calendar days, with respect to the processes and procedures for review under clauses (i), (ii), (iii), and (iv) of paragraph (1)(B) and—(A) such timelines shall account for the considerations under paragraph (5); and(B) the timelines for the various processes and procedures shall not be shorter than the timelines set forth for pending requests under sections 360fff–2(b) and 360fff–3(b) of this title, as applicable.
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(A) Not later than 60 calendar days after the Secretary provides a framework to a sponsor under paragraph (2), such sponsor may provide an election to the Secretary regarding the processes and procedures for review under clause (i), (ii), (iii), or (iv) of paragraph (1)(B). If such sponsor makes such election, the Secretary shall review the application that is the subject of such election pursuant to the processes and procedures elected by such sponsor and the applicable timelines in calendar days set forth under such framework, which the Secretary shall confirm in writing to the sponsor not later than the date upon which the Secretary provides a report under paragraph (4). If such sponsor does not make such election, such application shall be reviewed by the Secretary in accordance with the timelines of the applicable regulations when such regulations are finalized under subsection (b).
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(B) At any time during review of an application, the Secretary may review such application under different processes and procedures under clause (i), (ii), (iii), or (iv) of paragraph (1)(B) than the processes and procedures the sponsor elected in accordance with subparagraph (A), so long as the Secretary proposes, in writing, the change and the sponsor agrees, in writing, to such change.
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(C) If the sponsor elects to use the processes and procedures for review in accordance with clause (i) or (iii) of paragraph (1)(B), the Secretary may incorporate any resulting final order into a regulation addressing the conditions under which other drugs in the same therapeutic category are GRASE and not misbranded, including through direct final rulemaking, and the final order so incorporated shall cease to be effective on the effective date of the final regulation that addresses such drug.
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(i) reviewed and the decision times for each request, measured from the date of the original request for an eligibility determination submitted by the sponsor;
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(iv) for which a determination has not been made, and an explanation for the delay, a description of the current status of each such request, and the length of time each such request has been pending, measured from the date of original request for an eligibility determination by the sponsor;
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(iv) for which a determination has not been made, and an explanation for the delay, a description of the current status of each such request, and the length of time each such request has been pending, measured from the date of original request for an eligibility determination by the sponsor;
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(b) The Secretary may, consistent with applicable standards for approval under this chapter or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)], allow the sponsor of an application under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act for a genetically targeted drug or a variant protein targeted drug to rely upon data and information—(1) previously developed by the same sponsor (or another sponsor that has provided the sponsor with a contractual right of reference to such data and information); and(2) submitted by a sponsor described in paragraph (1) in support of one or more previously approved applications that were submitted under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act,for a drug that incorporates or utilizes the same or similar genetically targeted technology as the drug or drugs that are the subject of an application or applications described in paragraph (2) or for a variant protein targeted drug that is the same or incorporates or utilizes the same variant protein targeted drug, as the drug or drugs that are the subject of an application or applications described in paragraph (2).
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(2) submitted by a sponsor described in paragraph (1) in support of one or more previously approved applications that were submitted under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act,
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(2) confer any new rights, beyond those authorized under this chapter or the Public Health Service Act [42 U.S.C. 201 et seq.] prior to December 13, 2016, with respect to the permissibility of a sponsor referencing information contained in another application submitted under section 355(b)(1) of this title or section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)].
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(i) the sponsor of the investigation determines, on the basis of credible information (as defined by the Secretary) that the applicable conditions under subparagraph (A) are met; and
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(B) Any agreement regarding the parameters of an investigational plan (including a clinical protocol) that is reached between the Secretary and a sponsor or applicant shall be reduced to writing and made part of the administrative record by the Secretary. Any such agreement shall not be changed, except—(i) with the written agreement of the sponsor or applicant; or(ii) pursuant to a decision, made in accordance with subparagraph (C) by the director of the office in which the device involved is reviewed, that a substantial scientific issue essential to determining the safety or effectiveness of the device involved has been identified.
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(i) with the written agreement of the sponsor or applicant; or
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(C) A decision under subparagraph (B)(ii) by the director shall be in writing, and may be made only after the Secretary has provided to the sponsor or applicant an opportunity for a meeting at which the director and the sponsor or applicant are present and at which the director documents the scientific issue involved.
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(A) At any time, the Secretary may prohibit the sponsor of an investigation from conducting the investigation (referred to in this paragraph as a “clinical hold”) if the Secretary makes a determination described in subparagraph (B). The Secretary shall specify the basis for the clinical hold, including the specific information available to the Secretary which served as the basis for such clinical hold, and confirm such determination in writing.
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(C) Any written request to the Secretary from the sponsor of an investigation that a clinical hold be removed shall receive a decision, in writing and specifying the reasons therefor, within 30 days after receipt of such request. Any such request shall include sufficient information to support the removal of such clinical hold.
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(i) 1 The sponsor of a device for which submission of an application for an investigational device exemption is required shall submit to the Secretary in such application a diversity action plan for clinical studies of the device, in the form and manner specified in guidance issued by the Secretary.
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(ii) The sponsor of a device for which submission of an application for an investigational device exemption is not required, except for a device being studied as described in section 812.2(c) of title 21, Code of Federal Regulations (or successor regulations), shall develop a diversity action plan for any clinical study with respect to the device. Such diversity action plan shall be submitted to the Secretary in any premarket notification under section 360(k) of this title, request for classification under section 360c(f)(2) of this title, or application for premarket approval under section 360e of this title for such device.
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(i) the sponsor’s goals for enrollment in the clinical study;
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(ii) the sponsor’s rationale for such goals; and
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(iii) an explanation of how the sponsor intends to meet such goals.
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(i) On the initiative of the Secretary or at the request of a sponsor, the Secretary may waive any requirement in subparagraph (A) or (B) if the Secretary determines that a waiver is necessary based on what is known or can be determined about the prevalence or incidence of the disease or condition for which the device is under investigation (including in terms of the patient population that may use the device), if conducting a clinical investigation in accordance with a diversity action plan would otherwise be impracticable, or if such waiver is necessary to protect public health during a public health emergency.
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(B) review information and data provided to the Secretary by the sponsor of a contrast agent in an application submitted under section 355 of this title or section 262 of title 42, so long as the sponsor of such contrast agent has provided to the sponsor of the applicable medical imaging device that is the subject of such review a right of reference and the application is submitted in accordance with this subsection.
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(2) The term “priority review voucher” means a voucher issued by the Secretary to the sponsor of a tropical disease product application that entitles the holder of such voucher to priority review of a single human drug application submitted under section 355(b)(1) of this title or section 262 of title 42 after the date of approval of the tropical disease product application.
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(iii) that contains reports of one or more new clinical investigations (other than bioavailability studies) that are essential to the approval of the application and conducted or sponsored by the sponsor of such application; and
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(iv) that contains an attestation from the sponsor of the application that such reports were not submitted as part of an application for marketing approval or licensure by a regulatory authority in India, Brazil, Thailand, or any country that is a member of the Pharmaceutical Inspection Convention or the Pharmaceutical Inspection Cooperation Scheme prior to September 27, 2007.1
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(2) The sponsor of a tropical disease product that receives a priority review voucher under this section may transfer (including by sale) the entitlement to such voucher to a sponsor of a human drug for which an application under section 355(b)(1) of this title or section 262 of title 42 will be submitted after the date of the approval of the tropical disease product application. There is no limit on the number of times a priority review voucher may be transferred before such voucher is used.
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(4) The sponsor of a human drug application shall notify the Secretary not later than 90 days prior to submission of the human drug application that is the subject of a priority review voucher of an intent to submit the human drug application, including the date on which the sponsor intends to submit the application. Such notification shall be a legally binding commitment to pay for the user fee to be assessed in accordance with this section.
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(1) The Secretary shall establish a user fee program under which a sponsor of a human drug application that is the subject of a priority review voucher shall pay to the Secretary a fee determined under paragraph (2). Such fee shall be in addition to any fee required to be submitted by the sponsor under subchapter VII.
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(B) An application described under subparagraph (A) for which the sponsor requests the use of a priority review voucher shall be considered incomplete if the fee required by this subsection and all other applicable user fees are not paid in accordance with the Secretary’s procedures for paying such fees.
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(b) The sponsor of an application or submission described in subsection (a) shall—(1) submit to the Secretary a plan to monitor, identify, and address, as appropriate, in a reasonable time, postmarket cybersecurity vulnerabilities and exploits, including coordinated vulnerability disclosure and related procedures;(2) design, develop, and maintain processes and procedures to provide a reasonable assurance that the device and related systems are cybersecure, and make available postmarket updates and patches to the device and related systems to address—(A) on a reasonably justified regular cycle, known unacceptable vulnerabilities; and(B) as soon as possible out of cycle, critical vulnerabilities that could cause uncontrolled risks;(3) provide to the Secretary a software bill of materials, including commercial, open-source, and off-the-shelf software components; and
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(1) includes software validated, installed, or authorized by the sponsor as a device or in a device;
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(3) contains any such technological characteristics validated, installed, or authorized by the sponsor that could be vulnerable to cybersecurity threats.
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(I) the sponsor of an application or submission specified in subparagraph (E);
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(II) a person engaged in any activity described in clause (i) on behalf of such a sponsor, through a contract, grant, or other business arrangement with such sponsor;
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(2) The written agreement to provide information to the foreign government under this subsection shall include a commitment by the foreign government to protect information exchanged under this subsection from disclosure unless and until the sponsor gives written permission for disclosure or the Secretary makes a declaration of a public health emergency pursuant to section 247d of title 42 that is relevant to the information.
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(5) recruit meeting participants and hold or sponsor (in whole or in part) meetings as appropriate to further the goals and priorities established under paragraph (2);
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(2) the average total time to decision by the Secretary for applications for approval of a generic drug under section 355(j) of this title, amendments to such applications, and prior approval supplements with respect to such applications filed in the previous fiscal year, including the number of calendar days spent during the review by the Food and Drug Administration and the number of calendar days spent by the sponsor responding to a complete response letter;
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(B) A DTC advertisement that is required to be submitted to the Secretary prior to initial public dissemination is not subject to a fee under subparagraph (A) unless the sponsor designates the submission as a submission for advisory review.
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(11) The term “submission for advisory review” means an original submission of a direct-to-consumer television advertisement for which the sponsor voluntarily requests advisory comments before the advertisement is publicly disseminated.
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(v) For fiscal years 2023 and 2024, of the meeting requests from sponsors for which the Secretary has determined that a face-to-face meeting is appropriate, the number of face-to-face meetings requested by sponsors to be conducted in person (in such manner as the Secretary shall prescribe on the website of the Food and Drug Administration), and the number of such in-person meetings granted by the Secretary, with both such numbers disaggregated by the relevant agency center.
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(A) Each person—(i) who meets the definition of an animal drug sponsor within a fiscal year; and(ii) who, after September 1, 2003, had pending before the Secretary an animal drug application, a supplemental animal drug application, or an investigational animal drug submission,shall be assessed an annual sponsor fee as established under subsection (c).
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(E) the sponsor involved is a small business submitting its first animal drug application to the Secretary for review.
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(4) Fees under paragraphs (2), (3), and (4) of subsection (a) shall not apply with respect to any person who is the named applicant or sponsor of an animal drug application, supplemental animal drug application, or investigational animal drug submission if such application or submission involves the intentional genomic alteration of an animal that is intended to produce a drug, device, or biological product subject to fees under section 379h, 379j, 379j–42, or 379j–52 of this title.
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(A) Each person—(i) who meets the definition of a generic new animal drug sponsor within a fiscal year; and(ii) who, after September 1, 2008, had pending before the Secretary an abbreviated application, a supplemental abbreviated application, or an investigational submission,shall be assessed an annual generic new animal drug sponsor fee as established under subsection (c).
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(i) who meets the definition of a generic new animal drug sponsor within a fiscal year; and
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(C) Each generic new animal drug sponsor shall pay only 1 such fee each fiscal year, as follows:(i) 100 percent of the amount of the generic new animal drug sponsor fee published for that fiscal year under subsection (c) for an applicant with more than 6 approved abbreviated applications.(ii) 75 percent of the amount of the generic new animal drug sponsor fee published for that fiscal year under subsection (c) for an applicant with more than 1 and fewer than 7 approved abbreviated applications.(iii) 50 percent of the amount of the generic new animal drug sponsor fee published for that fiscal year under subsection (c) for an applicant with 1 or fewer approved abbreviated applications.
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(i) 100 percent of the amount of the generic new animal drug sponsor fee published for that fiscal year under subsection (c) for an applicant with more than 6 approved abbreviated applications.
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(ii) 75 percent of the amount of the generic new animal drug sponsor fee published for that fiscal year under subsection (c) for an applicant with more than 1 and fewer than 7 approved abbreviated applications.
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(iii) 50 percent of the amount of the generic new animal drug sponsor fee published for that fiscal year under subsection (c) for an applicant with 1 or fewer approved abbreviated applications.
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(ii) If a person makes a submission to the generic investigational new animal drug file to transfer that file to a different generic new animal drug sponsor, the person shall not be subject to a fee under subparagraph (A)(ii) for that submission.
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(C) 40 percent shall be derived from fees under subsection (a)(3) (relating to generic new animal drug sponsors).
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(B) generic new animal drug sponsor fees, and generic new animal drug product fees, based on the revenue amounts established under subsection (b) and the adjustments provided under this subsection; and
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(2) If the Secretary does not assess fees under subsection (a) during any portion of a fiscal year because of paragraph (1) and if at a later date in such fiscal year the Secretary may assess such fees, the Secretary may assess and collect such fees, without any modification in the rate, for abbreviated applications, generic new animal drug products, generic new animal drug sponsors, and generic investigational new animal drug files at any time in such fiscal year notwithstanding the provisions of subsection (a) relating to the date fees are to be paid.
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(7) The term “generic new animal drug sponsor” means either an applicant named in an abbreviated application for a generic new animal drug that has not been withdrawn by the applicant and for which approval has not been withdrawn by the Secretary, or a person who has submitted an investigational submission for a generic new animal drug that has not been terminated or otherwise rendered inactive by the Secretary.
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(8) The term “generic investigational new animal drug meeting request” means a request submitted by a generic new animal drug sponsor to meet with the Secretary to discuss an investigational submission for a generic new animal drug.
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(G) Meetings between the agency and the generic new animal drug sponsor.
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(ii) The condition specified in this clause is that the fee established under subsection (a)(2) has been paid within 20 calendar days of the Secretary providing the notification to the sponsor of the abbreviated new drug application or supplement of the failure of the owner of the Type II active pharmaceutical ingredient drug master file to pay the drug master file fee as specified in subparagraph (C).
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(i) If an abbreviated new drug application or supplement to an abbreviated new drug application references a Type II active pharmaceutical ingredient drug master file for which a fee under subsection (a)(2)(A) has not been paid by the applicable date under subsection (a)(2)(E), the Secretary shall notify the sponsor of the abbreviated new drug application or supplement of the failure of the owner of the Type II active pharmaceutical ingredient drug master file to pay the applicable fee.
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(ii) Any new generic drug submission submitted on or after October 1, 2012, that references such a facility shall not be received, within the meaning of section 355(j)(5)(A) of this title if the outstanding facility fee is not paid within 20 calendar days of the Secretary providing the notification to the sponsor of the failure of the owner of the facility to pay the facility fee under subsection (a)(4)(C).
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(i) If an abbreviated new drug application or supplement to an abbreviated new drug application submitted on or after October 1, 2012, references a facility for which a facility fee has not been paid by the applicable date under subsection (a)(4)(C), the Secretary shall notify the sponsor of the generic drug submission of the failure of the owner of the facility to pay the facility fee.
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(A) means an order issued by the Secretary to prohibit the sponsor of a clinical investigation from continuing the investigation if the Secretary determines that the investigation is intended to support a biosimilar biological product application and the sponsor has failed to pay any fee for the product required under subparagraph (A), (B), or (D) of section 379j–52(a)(1) of this title; and
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(II) the sponsor has failed to pay an initial or annual biosimilar biological product development fee for the product as required under subparagraph (A) or (B), or a reactivation fee as required under subparagraph (D).
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(iii) Notwithstanding section 355(i)(2) of this title, except in extraordinary circumstances, the Secretary shall prohibit the sponsor of a clinical investigation from continuing the investigation if—(I) the Secretary determines that the investigation is intended to support a biosimilar biological product application; and(II) the sponsor has failed to pay an initial or annual biosimilar biological product development fee for the product as required under subparagraph (A) or (B), or a reactivation fee for the product as required under subparagraph (D).
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(II) the sponsor has failed to pay an initial or annual biosimilar biological product development fee for the product as required under subparagraph (A) or (B), or a reactivation fee for the product as required under subparagraph (D).
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(5) enhancement of the interactions of the Centers with patients, sponsors, and the external biomedical community regarding the major disease area of focus of the Institute; and
Citations to §360fff(9)
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(2) With respect to sunscreen drugs subject to this section, the applicable requirements in terms of conformity with a final monograph, for purposes of paragraph (1)(A)(i), shall be the requirements specified in part 352 of title 21, Code of Federal Regulations, as published on May 21, 1999, beginning on page 27687 of volume 64 of the Federal Register, except that the applicable requirements governing effectiveness and labeling shall be those specified in section 201.327 of title 21, Code of Federal Regulations.
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(E) Except in the case of a request involving a drug described in section 360fff(9) of this title, as in effect on January 1, 2017, if the Secretary refuses to file a request under this paragraph, the requestor may not file such request over protest under paragraph (5)(A)(iii).
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Any person may submit a request to the Secretary for a determination of whether a nonprescription sunscreen active ingredient or a combination of nonprescription sunscreen active ingredients, for use under specified conditions, to be prescribed, recommended, or suggested in the labeling thereof (including dosage form, dosage strength, and route of administration) is GRASE and should be included in part 352 of title 21, Code of Federal Regulations (or any successor regulations) concerning nonprescription sunscreen.
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(i) is not included in part 352 of title 21, Code of Federal Regulations (or any successor regulations) concerning nonprescription sunscreen; and
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(A) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded, a sunscreen containing such ingredient or combination of ingredients shall be permitted to be introduced or delivered into interstate commerce for use under the conditions described in such final sunscreen order, in accordance with all requirements applicable to drugs not subject to section 353(b)(1) of this title, for so long as such final sunscreen order remains in effect.
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(B) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded, a sunscreen containing such ingredient or combination of ingredients shall not be introduced or delivered into interstate commerce, for use under the conditions described in such final sunscreen order, unless an application is approved pursuant to section 355 of this title with respect to a sunscreen containing such ingredient or combination of ingredients, or unless conditions are later established under which such ingredient or combination of ingredients is later determined to be GRASE and not misbranded under the over-the-counter drug monograph system.
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(1) A final sunscreen order shall have the effect of authorizing solely the order requestor (or the licensees, assignees, or successors in interest of such requestor with respect to the subject of such request and listed under paragraph (5)) for a period of 18 months, to market a sunscreen ingredient under this section incorporating changes described in paragraph (2) subject to the limitations under paragraph (4), beginning on the date the requestor (or any licensees, assignees, or successors in interest of such requestor with respect to the subject of such request and listed under paragraph (5)) may lawfully market such sunscreen ingredient pursuant to the order.
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(2) A change described in this paragraph is a change subject to an order specified in paragraph (1) that permits a sunscreen to contain an active sunscreen ingredient not previously incorporated in a marketed sunscreen listed in paragraph (3).
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(A) marketed in accordance with a final monograph for sunscreen drug products set forth at part 352 of title 21, Code of Federal Regulations (as published at 64 Fed. Reg. 27687); or(B) marketed in accordance with a final order issued under this section.
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(A) marketed in accordance with a final monograph for sunscreen drug products set forth at part 352 of title 21, Code of Federal Regulations (as published at 64 Fed. Reg. 27687); or
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(A) Not later than 1 year after November 26, 2014, the Secretary shall issue draft guidance on the implementation of, and compliance with, the requirements with respect to sunscreen under this part, including guidance on—(i) the format and content of information submitted by a sponsor in support of a request under section 360fff–1 of this title or a pending request;(ii) the data required to meet the safety and efficacy standard for determining whether a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded;(iii) the process by which a request under section 360fff–1 of this title or a pending request is withdrawn; and(iv) the process by which the Secretary will carry out section 360fff–3(c) of this title, including with respect to how the Secretary will address the total number of requests received under section 360fff–1 of this title and pending requests.
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(1) Nothing in this part shall be construed to affect the marketing of sunscreens that are marketed in interstate commerce on or before November 26, 2014, except as otherwise provided in this part.
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(2) Nothing in this part shall be construed to alter the authority of the Secretary with respect to prohibiting the marketing of a sunscreen that is not safe and effective or is misbranded, or with respect to imposing restrictions on the marketing of a sunscreen to ensure safety and effectiveness, except as otherwise provided in this part, including section 360fff–3(e) of this title.
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(3) Except as otherwise provided in section 360fff–6 of this title, nothing in this part shall be construed to affect the authority of the Secretary under this chapter or the Public Health Service Act (42 U.S.C. 201 et seq.) with respect to a drug other than a nonprescription sunscreen.
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(A) timely and efficient completion of evaluations of applications under section 330.14 of title 21, Code of Federal Regulations (or any successor regulations) for drugs other than sunscreens; and
Citations to §360fff(10)
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Any person may submit a request to the Secretary for a determination of whether a nonprescription sunscreen active ingredient or a combination of nonprescription sunscreen active ingredients, for use under specified conditions, to be prescribed, recommended, or suggested in the labeling thereof (including dosage form, dosage strength, and route of administration) is GRASE and should be included in part 352 of title 21, Code of Federal Regulations (or any successor regulations) concerning nonprescription sunscreen.
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(A) To be eligible for review under subsection (b) and section 360fff–3 of this title, a request shall be for a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients, for use under specified conditions, to be prescribed, recommended, or suggested in the labeling thereof, that—(i) is not included in part 352 of title 21, Code of Federal Regulations (or any successor regulations) concerning nonprescription sunscreen; and(ii) has been used to a material extent and for a material time under such conditions, as described in section 321(p)(2) of this title.
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(A) If a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is determined under paragraph (1)(A) to be eligible for further review, the Secretary shall make the request publicly available, with redactions for information that is treated as confidential under section 552(b) of title 5, section 1905 of title 18, or section 331(j) of this title.
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(A) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded, a sunscreen containing such ingredient or combination of ingredients shall be permitted to be introduced or delivered into interstate commerce for use under the conditions described in such final sunscreen order, in accordance with all requirements applicable to drugs not subject to section 353(b)(1) of this title, for so long as such final sunscreen order remains in effect.
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(B) Upon issuance of a final sunscreen order determining that a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded, a sunscreen containing such ingredient or combination of ingredients shall not be introduced or delivered into interstate commerce, for use under the conditions described in such final sunscreen order, unless an application is approved pursuant to section 355 of this title with respect to a sunscreen containing such ingredient or combination of ingredients, or unless conditions are later established under which such ingredient or combination of ingredients is later determined to be GRASE and not misbranded under the over-the-counter drug monograph system.
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(A) In the event that information relevant to a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients becomes available to the Secretary after issuance of a final sunscreen order, the Secretary may amend such final sunscreen order by issuing a new proposed sunscreen order under subsection (a)(1) and following the procedures set forth in this section.
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(ii) the data required to meet the safety and efficacy standard for determining whether a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded;
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(A) If, prior to November 26, 2014, an application was submitted pursuant to section 330.14 of title 21, Code of Federal Regulations for a GRASE determination for a drug other than a nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients and such drug was found to be eligible to be considered for inclusion in the over-the-counter drug monograph system pursuant to section 330.14 of title 21, Code of Federal Regulations, the sponsor of such application may request that the Secretary provide a framework under paragraph (2) for the review of such application.
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(1) Not later than 18 months after November 26, 2014, the Secretary shall issue proposed regulations establishing timelines for the review of applications for GRASE determinations for drugs other than nonprescription sunscreen active ingredients or combinations of nonprescription sunscreen active ingredients that are submitted to the Secretary after November 26, 2014, under section 330.14 of title 21, Code of Federal Regulations (or any successor regulations), and that are found to be eligible to be considered for inclusion in the over-the-counter drug monograph system pursuant to section 330.14 of title 21, Code of Federal Regulations (or any successor regulations), or that are subject to this subsection pursuant to paragraph (1) or (3) of subsection (a), as applicable, providing—(A) timely and efficient completion of evaluations of applications under section 330.14 of title 21, Code of Federal Regulations (or any successor regulations) for drugs other than sunscreens; and(B) timely and efficient completion of the review of the safety and effectiveness submissions pursuant to such applications, including establishing—(i) reasonable timelines, in calendar days, for the applicable proposed and final regulations for applications of various content, complexity, and format, and timelines for internal procedures related to such processes; and(ii) measurable metrics for tracking the extent to which the timelines set forth in the regulations are met.
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(ii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is GRASE and is not misbranded;
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(iii) resulting in a determination that the nonprescription sunscreen active ingredient or combination of nonprescription sunscreen active ingredients is not GRASE and is misbranded and the reasons for such determinations; and
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(ii) resulting in a determination that the nonprescription sunscreen active ingredient, combination of nonprescription sunscreen active ingredients, or other ingredient is GRASE and is not misbranded;
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(iii) resulting in a determination that the nonprescription sunscreen active ingredient, combination of nonprescription sunscreen active ingredients, or other ingredient is not GRASE and is misbranded and the reasons for such determinations; and
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(D) the progress of the Food and Drug Administration in allowing nonclinical testing alternatives to animal testing for the consideration of sunscreen active ingredients.