21 U.S.C. § 360bbb–4 — Countermeasure development, review, and technical assistance

**(a) Definitions** In this section— (1) the term “countermeasure” means a qualified countermeasure, a security countermeasure, and a qualified pandemic or epidemic product; (2) the term “qualified countermeasure” has the meaning given such term in [section 247d–6a of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–6a&num=0&edition=prelim); (3) the term “security countermeasure” has the meaning given such term in [section 247d–6b of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–6b&num=0&edition=prelim); and (4) the term “qualified pandemic or epidemic product” means a product that meets the definition given such term in [section 247d–6d of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–6d&num=0&edition=prelim) and— (A) that has been identified by the Department of Health and Human Services or the Department of Defense as receiving funding directly related to addressing chemical, biological, radiological, or nuclear threats, including pandemic influenza; or (B) is included under this paragraph pursuant to a determination by the Secretary. **(b) General duties** In order to accelerate the development, stockpiling, approval, licensure, and clearance of qualified countermeasures, security countermeasures, and qualified pandemic or epidemic products, the Secretary, in consultation with the Assistant Secretary for Preparedness and Response, shall— (1) ensure the appropriate involvement of Food and Drug Administration personnel in interagency activities related to countermeasure advanced research and development, consistent with sections 247d–6, 247d–6a, 247d–6b, 247d–6d, 247d–7e, and 300hh–10 of title 42; (2) ensure the appropriate involvement and consultation of Food and Drug Administration personnel in any flexible manufacturing activities carried out under [section 247d–7e of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–7e&num=0&edition=prelim), including with respect to meeting regulatory requirements set forth in this chapter; (3) promote countermeasure expertise within the Food and Drug Administration by— (A) ensuring that Food and Drug Administration personnel involved in reviewing countermeasures for approval, licensure, or clearance are informed by the Assistant Secretary for Preparedness and Response on the material threat assessment conducted under [section 247d–6b of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–6b&num=0&edition=prelim) for the agent or agents for which the countermeasure under review is intended; (B) training Food and Drug Administration personnel regarding review of countermeasures for approval, licensure, or clearance; (C) holding public meetings at least twice annually to encourage the exchange of scientific ideas; and (D) establishing protocols to ensure that countermeasure reviewers have sufficient training or experience with countermeasures; (4) maintain teams, composed of Food and Drug Administration personnel with expertise on countermeasures, including specific countermeasures, populations with special clinical needs (including children and pregnant women that may use countermeasures, as applicable and appropriate), classes or groups of countermeasures, or other countermeasure-related technologies and capabilities, that shall— (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 (B) improve and advance the science relating to the development of new tools, standards, and approaches to assessing and evaluating countermeasures— (i) in order to inform the process for countermeasure approval, clearance, and licensure; and (ii) with respect to the development of countermeasures for populations with special clinical needs, including children and pregnant women, in order to meet the needs of such populations, as necessary and appropriate; and (5) establish within the Food and Drug Administration a team of experts on manufacturing and regulatory activities (including compliance with current Good Manufacturing Practice) to provide both off-site and on-site technical assistance to the manufacturers of qualified countermeasures (as defined in [section 247d–6a of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–6a&num=0&edition=prelim)), security countermeasures (as defined in [section 247d–6b of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–6b&num=0&edition=prelim)), or vaccines, at the request of such a manufacturer and at the discretion of the Secretary, if the Secretary determines that a shortage or potential shortage may occur in the United States in the supply of such vaccines or countermeasures and that the provision of such assistance would be beneficial in helping alleviate or avert such shortage. **(c) Final guidance on development of animal models** (1) **In general** — Not later than 1 year after March 13, 2013, the Secretary shall provide final guidance to industry regarding the development of animal models to support approval, clearance, or licensure of countermeasures referred to in subsection (a) when human efficacy studies are not ethical or feasible. (2) **Authority to extend deadline** — The Secretary may extend the deadline for providing final guidance under paragraph (1) by not more than 6 months upon submission by the Secretary of a report on the status of such guidance to the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor, and Pensions of the Senate. **(d) Development and animal modeling procedures** (1) **Availability of animal model meetings** — 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. (2) **Pediatric models** — To facilitate the development and selection of animal models that could translate to pediatric studies, any meeting conducted under paragraph (1) shall include discussion of animal models for pediatric populations, as appropriate. **(e) Review and approval of countermeasures** (1) **Material threat** — When evaluating an application or submission for approval, licensure, or clearance of a countermeasure, the Secretary shall take into account the material threat posed by the chemical, biological, radiological, or nuclear agent or agents identified under [section 247d–6b of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–6b&num=0&edition=prelim) for which the countermeasure under review is intended. (2) **Review expertise** — When practicable and appropriate, teams of Food and Drug Administration personnel reviewing applications or submissions described under paragraph (1) shall include a reviewer with sufficient training or experience with countermeasures pursuant to the protocols established under subsection (b)(3)(D). **(f) Regulatory management plan** (1) **Definition** — In this subsection, the term “eligible countermeasure” means— (A) a security countermeasure with respect to which the Secretary has entered into a procurement contract under [section 247d–6b(c) of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–6b/c&num=0&edition=prelim); or (B) a countermeasure with respect to which the Biomedical Advanced Research and Development Authority has provided funding under [section 247d–7e of title 42](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section247d–7e&num=0&edition=prelim) for advanced research and development. (2) **Regulatory management plan process** — The Secretary, in consultation with the Assistant Secretary for Preparedness and Response and the Director of the Biomedical Advanced Research and Development Authority, shall establish a formal process for obtaining scientific feedback and interactions regarding the development and regulatory review of eligible countermeasures by facilitating the development of written regulatory management plans in accordance with this subsection. (3) **Publication** — The Secretary shall make available on the internet website of the Food and Drug Administration information regarding regulatory management plans, including— (A) the process by which an applicant may submit a request for a regulatory management plan; (B) the timeframe by which the Secretary is required to respond to such request; (C) the information required for the submission of such request; (D) a description of the types of development milestones and performance targets that could be discussed and included in such plans; and (E) contact information for beginning the regulatory management plan process. (4) **Submission of request and proposed plan by sponsor or applicant** (A) *In general* — 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. (B) *Timing of submission* — 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. (C) *Response by Secretary* — 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. (5) **Plan** — 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. (6) **Milestones and performance targets** — The developmental milestones described in paragraph (5)(A) and the performance targets and goals described in paragraph (5)(B) shall include— (A) feedback from the Secretary regarding the data required to support the approval, clearance, or licensure of the eligible countermeasure involved; (B) feedback from the Secretary regarding the data necessary to inform any authorization under [section 360bbb–3 of this title](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section360bbb-3&num=0&edition=prelim); (C) feedback from the Secretary regarding the data necessary to support the positioning and delivery of the eligible countermeasure, including to the Strategic National Stockpile; (D) feedback from the Secretary regarding the data necessary to support the submission of protocols for review under [section 355(b)(5)(B) of this title](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section355/b/5/B&num=0&edition=prelim); (E) feedback from the Secretary regarding any gaps in scientific knowledge that will need resolution prior to approval, licensure, or clearance of the eligible countermeasure and plans for conducting the necessary scientific research; (F) identification of the population for which the countermeasure sponsor or applicant seeks approval, licensure, or clearance and the population for which desired labeling would not be appropriate, if known; and (G) as necessary and appropriate, and to the extent practicable, a plan for demonstrating safety and effectiveness in pediatric populations, and for developing pediatric dosing, formulation, and administration with respect to the eligible countermeasure, provided that such plan would not delay authorization under [section 360bbb–3 of this title](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section360bbb-3&num=0&edition=prelim), approval, licensure, or clearance for adults. (7) **Prioritization** (A) *Plans for security countermeasures* — The Secretary shall establish regulatory management plans for all security countermeasures for which a request is submitted under paragraph (4)(A). (B) *Plans for other eligible countermeasures* — The Secretary shall determine whether resources are available to establish regulatory management plans for eligible countermeasures that are not security countermeasures. If resources are available to establish regulatory management plans for eligible countermeasures that are not security countermeasures, and if resources are not available to establish regulatory management plans for all eligible countermeasures for which requests have been submitted, the Director of the Biomedical Advanced Research and Development Authority, in consultation with the Commissioner, shall prioritize which eligible countermeasures may receive regulatory management plans. **(g) Annual report** Not later than 180 days after March 13, 2013, and annually thereafter, the Secretary shall make publicly available on the Web site of the Food and Drug Administration a report that details the countermeasure development and review activities of the Food and Drug Administration, including— (1) with respect to the development of new tools, standards, and approaches to assess and evaluate countermeasures— (A) the identification of the priorities of the Food and Drug Administration and the progress made on such priorities; and (B) the identification of scientific gaps that impede the development, approval, licensure, or clearance of countermeasures for populations with special clinical needs, including children and pregnant women, and the progress made on resolving these challenges; (2) with respect to countermeasures for which a regulatory management plan has been agreed upon under subsection (f), the extent to which the performance targets and goals set forth in subsection (f)(4)(B) and the regulatory management plan have been met, including, for each such countermeasure— (A) whether the regulatory management plan was completed within the required timeframe, and the length of time taken to complete such plan; (B) whether the Secretary adhered to the timely and appropriate response times set forth in such plan; and (C) explanations for any failure to meet such performance targets and goals; (3) the number of regulatory teams established pursuant to subsection (b)(4), the number of products, classes of products, or technologies assigned to each such team, and the number of, type of, and any progress made as a result of consultations carried out under subsection (b)(4)(A); (4) an estimate of resources obligated to countermeasure development and regulatory assessment, including— (A) Center-specific objectives and accomplishments; and (B) the number of full-time equivalent employees of the Food and Drug Administration who directly support the review of countermeasures; (5) the number of countermeasure applications and submissions submitted, the number of countermeasures approved, licensed, or cleared, the status of remaining submitted applications and submissions, and the number of each type of authorization issued pursuant to [section 360bbb–3 of this title](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section360bbb-3&num=0&edition=prelim); (6) the number of written requests for a regulatory management plan submitted under subsection (f)(3)(A), the number of regulatory management plans developed, and the number of such plans developed for security countermeasures; and (7) the number, type, and frequency of meetings between the Food and Drug Administration and— (A) sponsors of a countermeasure as defined in subsection (a); or (B) another agency engaged in development or management of portfolios for such countermeasures, including the Centers for Disease Control and Prevention, the Biomedical Advanced Research and Development Authority, the National Institutes of Health, and the appropriate agencies of the Department of Defense. **(h) Accelerating countermeasure development and review during an emergency** (1) **Acceleration of countermeasure development and review** — 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](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section360bbb–3a/a/1/C&num=0&edition=prelim), 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](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section262&num=0&edition=prelim). (2) **Actions** — The actions to expedite the development and review of a countermeasure under paragraph (1) may include the following: (A) Expedited review of submissions made by sponsors of countermeasures to the Food and Drug Administration, including rolling submissions of countermeasure applications and other submissions. (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. (C) Expedited issuance of guidance documents and publication of other regulatory information regarding countermeasure development and manufacturing. (D) Other steps to expedite the development and review of a countermeasure application submitted for approval, licensure, clearance, or authorization, as the Secretary determines appropriate. (3) **Limitation of effect** — 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). **(i) Third party evaluation of tests used during an emergency** (1) **In general** — For purposes of conducting evaluations regarding whether an in vitro diagnostic product (as defined in section 809.3 of title 21, Code of Federal Regulations (or any successor regulations)) for which a request for emergency use authorization is submitted under [section 360bbb–3 of this title](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section360bbb-3&num=0&edition=prelim) meets the criteria for issuance of such authorization, the Secretary may, as appropriate, consult with persons with appropriate expertise with respect to such evaluations or enter into cooperative agreements or contracts with such persons under which such persons conduct such evaluations and make such recommendations, including, as appropriate, evaluations and recommendations regarding the scope of authorization and conditions of authorization. (2) **Requirements regarding evaluations and recommendations** (A) *In general* — In evaluating and making recommendations to the Secretary regarding the validity, accuracy, and reliability of in vitro diagnostic products, as described in paragraph (1), a person shall consider and document whether the relevant criteria under subsection (c)(2) of [section 360bbb–3 of this title](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section360bbb-3&num=0&edition=prelim) for issuance of authorization under such section are met with respect to the in vitro diagnostic product. (B) *Written recommendations* — Recommendations made by a person under this subsection shall be submitted to the Secretary in writing, and shall include the reasons for such recommendation and other information that may be requested by the Secretary. (3) **Rule of construction** — Nothing in this subsection shall be construed to require the Secretary to consult with, or enter into cooperative agreements or contracts with, persons as described in paragraph (1) for purposes of authorizing an in vitro diagnostic product or otherwise affecting the emergency use authorization authorities under this section or [section 360bbb–3 of this title](https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title21-section360bbb-3&num=0&edition=prelim).