Source: http://uscode.house.gov/view.xhtml?req=(title:21%20section:355-1%20edition:prelim)
Timestamp: 2019-04-24 14:49:03+00:00

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(A) The estimated size of the population likely to use the drug involved.
(B) The seriousness of the disease or condition that is to be treated with the drug.
(C) The expected benefit of the drug with respect to such disease or condition.
(D) The expected or actual duration of treatment with the drug.
(E) The seriousness of any known or potential adverse events that may be related to the drug and the background incidence of such events in the population likely to use the drug.
(F) Whether the drug is a new molecular entity.
If the Secretary has approved a covered application (including an application approved before the effective date of this section) and did not when approving the application require a risk evaluation and mitigation strategy under paragraph (1), the Secretary, in consultation with the offices described in paragraph (1), may subsequently require such a strategy for the drug involved (including when acting on a supplemental application seeking approval of a new indication for use of the drug) if the Secretary becomes aware of new safety information and makes a determination that such a strategy is necessary to ensure that the benefits of the drug outweigh the risks of the drug.
Not later than 120 days after the Secretary notifies the holder of an approved covered application that the Secretary has made a determination under subparagraph (A) with respect to the drug involved, or within such other reasonable time as the Secretary requires to protect the public health, the holder shall submit to the Secretary a proposed risk evaluation and mitigation strategy.
The applicability of this section to an application under section 355(j) of this title is subject to subsection (i).
Determinations by the Secretary under this subsection for a drug shall be made by individuals at or above the level of individuals empowered to approve a drug (such as division directors within the Center for Drug Evaluation and Research).
(E) any failure of expected pharmacological action of the drug, which may include reduced effectiveness under the conditions of use prescribed in the labeling of such drug, but which may not include reduced effectiveness that is in accordance with such labeling.
The term "covered application" means an application referred to in section 355(p)(1)(A) of this title.
(B) the effectiveness of the approved risk evaluation and mitigation strategy for the drug obtained since the last assessment of such strategy.
(B) based on appropriate medical judgment, may jeopardize the patient and may require a medical or surgical intervention to prevent an outcome described under subparagraph (A).
The term "serious risk" means a risk of a serious adverse drug experience.
(F) other scientific data deemed appropriate by the Secretary.
The term "responsible person" means the person submitting a covered application or the holder of the approved such application.
The term "unexpected serious risk" means a serious adverse drug experience that is not listed in the labeling of a drug, or that may be symptomatically and pathophysiologically related to an adverse drug experience identified in the labeling, but differs from such adverse drug experience because of greater severity, specificity, or prevalence.
(2) to the extent required by the Secretary, in consultation with the office responsible for reviewing the drug and the office responsible for postapproval safety with respect to the drug, include additional elements described in subsections (e) and (f).
(C) is eliminated after the 3-year period described in paragraph (1) if the Secretary determines that serious risks of the drug have been adequately identified and assessed and are being adequately managed.
The Secretary, in consultation with the offices described in subsection (c)(2), may under such subsection require that the risk evaluation and mitigation strategy for a drug include 1 or more of the additional elements described in this subsection if the Secretary makes the determination required with respect to each element involved.
(B) a patient package insert, if the Secretary determines that such insert may help mitigate a serious risk of the drug.
(D) disseminating information to health care providers about drug formulations or properties, including information about the limitations or patient care implications of such formulations or properties, and how such formulations or properties may be related to serious adverse drug events associated with use of the drug.
(B) the drug be dispensed to certain patients with a safe disposal packaging or safe disposal system for purposes of rendering drugs nonretrievable (as defined in section 1300.05 of title 21, Code of Federal Regulations (or any successor regulation)) if the Secretary determines that such safe disposal packaging or system may mitigate such serious risk and is sufficiently available.
(B) for a drug initially approved without elements to assure safe use, other elements under subsections (c), (d), and (e) are not sufficient to mitigate such serious risk.
(ii) be designed to be compatible with established distribution, procurement, and dispensing systems for drugs.
(F) each patient using the drug be enrolled in a registry.
(B) work to improve implementation of such elements by such persons.
(ii) modify elements under this subsection for 1 or more drugs as appropriate.
The mechanisms under section 360bbb of this title to provide for expanded access for patients with serious or life-threatening diseases or conditions may be used to provide access for patients with a serious or life-threatening disease or condition, the treatment of which is not an approved use for the drug, to a drug that is subject to elements to assure safe use under this subsection. The Secretary shall promulgate regulations for how a physician may provide the drug under the mechanisms of section 360bbb of this title.
No holder of an approved covered application shall use any element to assure safe use required by the Secretary under this subsection to block or delay approval of an application under section 355(b)(2) or (j) of this title or to prevent application of such element under subsection (i)(1)(B) to a drug that is the subject of an abbreviated new drug application.
After the approval of a risk evaluation and mitigation strategy under subsection (a), the responsible person involved may, subject to paragraph (2), submit to the Secretary an assessment of the approved strategy for the drug involved at any time.
(ii) minimize the burden on the health care delivery system of complying with the strategy.
An assessment under paragraph (1) or (2) of an approved risk evaluation and mitigation strategy for a drug shall include, with respect to each goal included in the strategy, an assessment of the extent to which the approved strategy, including each element of the strategy, is meeting the goal or whether 1 or more such goals or such elements should be modified.
After the approval of a risk evaluation and mitigation strategy by the Secretary, the responsible person may, at any time, submit to the Secretary a proposal to modify the approved strategy. Such proposal may propose the addition, modification, or removal of any goal or element of the approved strategy and shall include an adequate rationale to support such proposed addition, modification, or removal of any goal or element of the strategy.
The Secretary, in consultation with the offices described in subsection (c)(2), shall promptly review each proposed risk evaluation and mitigation strategy for a drug submitted under subsection (a) and each assessment of and proposed modification to an approved risk evaluation and mitigation strategy for a drug submitted under subsection (g), and, if necessary, promptly initiate discussions with the responsible person about such proposed strategy, assessment, or modification.
Unless the dispute resolution process described under paragraph (3) or (4) applies, and, except as provided in clause (ii) or clause (iii) below, the Secretary, in consultation with the offices described in subsection (c)(2), shall review and act on the proposed risk evaluation and mitigation strategy for a drug or any proposed modification to any required strategy within 180 days of receipt of the proposed strategy or modification.
The Secretary shall review and act on a proposed minor modification, as defined by the Secretary in guidance, within 60 days of receipt of such modification.
Not later than 60 days after the Secretary receives a proposed modification to an approved risk evaluation and mitigation strategy to conform the strategy to approved safety labeling changes, including safety labeling changes initiated by the responsible person in accordance with FDA regulatory requirements, or to a safety labeling change that the Secretary has directed the holder of the application to make pursuant to section 355(o)(4) of this title, the Secretary shall review and act on such proposed modification to the approved strategy.
The Secretary shall establish, through guidance, that responsible persons may implement certain modifications to an approved risk evaluation and mitigation strategy following notification to the Secretary.
An approved risk evaluation and mitigation strategy shall remain in effect until the Secretary acts, if the Secretary fails to act as provided under subparagraph (A).
Upon acting on a proposed risk evaluation and mitigation strategy or proposed modification to a risk evaluation and mitigation strategy under subparagraph (A), the Secretary shall make publicly available an action letter describing the actions taken by the Secretary under such subparagraph (A).
If a proposed risk evaluation and mitigation strategy is submitted under subsection (a)(1) in an application for initial approval of a drug and there is a dispute about the strategy, the responsible person shall use the major dispute resolution procedures as set forth in the letters described in section 101(c) of the Food and Drug Administration Amendments Act of 2007.
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.
Upon receipt of a request under clause (i), the Secretary shall schedule the dispute involved for review under subparagraph (B) and, not later than 5 business days of scheduling the dispute for review, shall publish by posting on the Internet or otherwise a notice that the dispute will be reviewed by the Drug Safety Oversight Board.
(ii) may convene a special meeting of the Drug Safety Oversight Board to review the matter more promptly, including to meet an action deadline on an application (including a supplemental application).
A request for review under subparagraph (A) shall not preclude further discussions to reach agreement on the risk evaluation and mitigation strategy, and such a request shall not preclude the use of administrative appeals within the Food and Drug Administration to reach agreement on the strategy, including appeals as described in the letters described in section 101(c) of the Food and Drug Administration Amendments Act of 2007 for procedural or scientific matters involving the review of human drug applications and supplemental applications that cannot be resolved at the divisional level. At the time a review has been scheduled under subparagraph (B) and notice of such review has been posted, the responsible person shall either withdraw the request under subparagraph (A) or terminate the use of such administrative appeals.
At any time before a decision and order is issued under subparagraph (G), the Secretary (in consultation with the offices described in subsection (c)(2)) and the responsible person may reach an agreement on the risk evaluation and mitigation strategy through further discussion or administrative appeals, terminating the dispute resolution process, and the Secretary shall issue an action letter or order, as appropriate, that describes the strategy.
The Secretary shall ensure that the proceedings of any such meeting are recorded, transcribed, and made public within 90 days of the meeting. The Secretary shall redact the transcript to protect any trade secrets and other information that is exempted from disclosure under section 552 of title 5 or section 552a of title 5.
Not later than 5 days after any such meeting, the Drug Safety Oversight Board shall provide a written recommendation on resolving the dispute to the Secretary. Not later than 5 days after the Board provides such written recommendation to the Secretary, the Secretary shall make the recommendation available to the public.
(II) 7 days after receiving the recommendation of the Drug Safety Oversight Board.
With respect to an assessment of an approved risk evaluation and mitigation strategy under subsection (g)(1) or under any of subparagraphs (B) through (D) of subsection (g)(2), the Secretary shall issue an order, which shall be made public, that resolves the dispute not later than 7 days after receiving the recommendation of the Drug Safety Oversight Board.
An approved risk evaluation and mitigation strategy shall remain in effect until the Secretary acts, if the Secretary fails to act as provided for under subparagraph (G).
With respect to a proposal or assessment referred to in paragraph (1), the Secretary shall be considered to have met the action deadline for the action letter on the application if the responsible person requests the dispute resolution process described in this paragraph and if the Secretary has complied with the timing requirements of scheduling review by the Drug Safety Oversight Board, providing a written recommendation, and issuing an action letter under subparagraphs (B), (F), and (G), respectively.
No individual who is an employee of the Food and Drug Administration and who reviews a drug or who participated in an administrative appeal under subparagraph (C)(i) with respect to such drug may serve on the Drug Safety Oversight Board at a meeting under subparagraph (D) to review a dispute about the risk evaluation and mitigation strategy for such drug.
The Drug Safety Oversight Board may add members with relevant expertise from the Food and Drug Administration, including the Office of Pediatrics, the Office of Women's Health, or the Office of Rare Diseases, or from other Federal public health or health care agencies, for a meeting under subparagraph (D) of the Drug Safety Oversight Board.
(C) review a dispute under paragraph (3) or (4).
When a concern about a serious risk of a drug may be related to the pharmacological class of the drug, the Secretary, in consultation with the offices described in subsection (c)(2), may defer assessments of the approved risk evaluation and mitigation strategies for such drugs until the Secretary has convened 1 or more public meetings to consider possible responses to such concern.
(iii) give notice to the public of any public meetings to be convened under subparagraph (A), including a description of the deferral.
(iii) 1 or more workshops of scientific experts and other stakeholders.
(iii) after seeking such comment, issue an order addressing such regulatory action.
The Secretary, in consultation with the offices described in subsection (c)(2), may coordinate the timetable for submission of assessments under subsection (d), or a study or clinical trial under section 355(o)(3) of this title, with efforts to identify and assess the serious risks of such drug by the marketing authorities of other countries whose drug approval and risk management processes the Secretary deems comparable to the drug approval and risk management processes of the United States. If the Secretary takes action to coordinate such timetable, the Secretary shall give notice to the responsible person.
Use of the processes described in paragraphs (6) and (7) shall not be the sole source of delay of action on an application or a supplement to an application for a drug.
(A) A Medication Guide or patient package insert, if required under subsection (e) for the applicable listed drug.
(B) A packaging or disposal requirement, if required under subsection (e)(4) for the applicable listed drug.
(ii) an aspect of the elements to assure safe use for the applicable listed drug is claimed by a patent that has not expired or is a method or process that, as a trade secret, is entitled to protection, and the applicant for the abbreviated new drug application certifies that it has sought a license for use of an aspect of the elements to assure safe use for the applicable listed drug and that it was unable to obtain a license.
A certification under clause (ii) shall include a description of the efforts made by the applicant for the abbreviated new drug application to obtain a license. In a case described in clause (ii), the Secretary may seek to negotiate a voluntary agreement with the owner of the patent, method, or process for a license under which the applicant for such abbreviated new drug application may use an aspect of the elements to assure safe use, if required under subsection (f) for the applicable listed drug, that is claimed by a patent that has not expired or is a method or process that as a trade secret is entitled to protection.
(C) shall inform the responsible person for the drug that is so approved if the risk evaluation and mitigation strategy for the applicable listed drug is modified.
There is established a Drug Safety Oversight Board.
(E) meet at least monthly to provide oversight and advice to the Secretary on the management of important drug safety issues.
(2) the identification of a material threat described in subparagraph (D) of section 360bbb–3(b)(1) of this title has been made pursuant to section 247d–6b of title 42.
For the effective date of this section, referred to in subsec. (a)(2)(A), see Effective Date note below.
Section 101(c) of the Food and Drug Administration Amendments Act of 2007, referred to in subsec. (h)(3), (4)(C)(i), is section 101(c) of Pub. L. 110–85, which is set out as a note under section 379g of this title.
2018-Subsec. (b)(1)(E). Pub. L. 115–271, §3041(a), substituted "of the drug, which may include reduced effectiveness under the conditions of use prescribed in the labeling of such drug, but which may not include reduced effectiveness that is in accordance with such labeling" for "of the drug".
Subsec. (e)(4). Pub. L. 115–271, §3032(a), added par. (4).
Subsec. (f)(2)(C)(iii). Pub. L. 115–271, §3032(b), added cl. (iii).
Subsec. (i)(1)(B), (C). Pub. L. 115–271, §3032(c)(1), added subpar. (B) and redesignated former subpar. (B) as (C).
Subsec. (i)(2)(B), (C). Pub. L. 115–271, §3032(c)(2), added subpar. (B) and redesignated former subpar. (B) as (C).
2017-Subsec. (e)(3)(B). Pub. L. 115–52, §606(1), struck out "; or" at end.
Subsec. (e)(3)(D). Pub. L. 115–52, §606(2), (3), added subpar. (D).
2016-Subsec. (f)(5). Pub. L. 114–255, §3075(c)(1), inserted "or other advisory committee" after "(or successor committee)" in introductory provisions.
Subsec. (f)(5)(B). Pub. L. 114–255, §3075(c)(2), substituted "periodically" for "at least annually," in introductory provisions.
Subsec. (h)(2)(A)(iii). Pub. L. 114–255, §3101(a)(2)(C)(i), substituted, in heading, "labeling" for "label" and in text, "approved safety labeling changes" for "approved safety label changes", "responsible person" for "sponsor", and "a safety labeling change" for "a safety label change".
Subsec. (h)(8). Pub. L. 114–255, §3101(a)(2)(C)(ii), struck out period after "(7)".
2013-Subsec. (f)(7). Pub. L. 113–5, §302(c)(1), struck out par. (7) which related to waiver of subsec. (f) requirements in public health emergencies.
Subsec. (k). Pub. L. 113–5, §302(c)(2), added subsec. (k).
2012-Subsec. (g)(1). Pub. L. 112–144, §1132(a)(1), struck out ", and propose a modification to," after "an assessment of".
Subsec. (g)(2). Pub. L. 112–144, §1132(a)(2)(A), in introductory provisions, struck out ", subject to paragraph (5)," after "shall" and ", and may propose a modification to," after "an assessment of".
"(ii) an element under subsection (f) should be modified or included in the strategy; or".
Subsec. (g)(2)(D). Pub. L. 112–144, §1132(a)(2)(C), struck out subpar. (D) which read as follows: "within 15 days when ordered by the Secretary, in consultation with the offices described in subsection (c)(2), if the Secretary determines that there may be a cause for action by the Secretary under section 355(e) of this title."
Subsec. (g)(3). Pub. L. 112–144, §1132(a)(3), substituted "for a drug shall include, with respect to each goal included in the strategy, an assessment of the extent to which the approved strategy, including each element of the strategy, is meeting the goal or whether 1 or more such goals or such elements should be modified." for "for a drug shall include-" and struck out subpars. (A) to (C) which related to assessment of elements to assure safe use, postapproval studies, and postapproval clinical trials.
"(B) adding, modifying, or removing an element to assure safe use under subsection (f)."
Subsec. (h). Pub. L. 112–144, §1132(b)(1), inserted "and modifications" after "review of assessments" in heading.
Subsec. (h)(1). Pub. L. 112–144, §1132(b)(2), inserted "and proposed modification to" after "under subsection (a) and each assessment of" and ", and, if necessary, promptly initiate discussions with the responsible person about such proposed strategy, assessment, or modification" after "subsection (g)".
Subsec. (h)(2). Pub. L. 112–144, §1132(b)(3), (4), redesignated par. (3) as (2) and struck out former par. (2). Prior to amendment, text of par. (2) read as follows: "The Secretary, in consultation with the offices described in subsection (c)(2), shall initiate discussions with the responsible person for purposes of this subsection to determine a strategy not later than 60 days after any such assessment is submitted or, in the case of an assessment submitted under subsection (g)(2)(D), not later than 30 days after such assessment is submitted."
Subsec. (h)(2)(A). Pub. L. 112–144, §1132(b)(5)(A), amended subpar. (A) generally. Prior to amendment, subpar. (A) related to Secretary's description of any required risk evaluation and mitigation strategy for a drug as part of the action letter on the application or in an order.
Subsec. (h)(2)(C). Pub. L. 112–144, §1132(b)(5)(B), amended subpar. (C) generally. Prior to amendment, text read as follows: "Any action letter described in subparagraph (A)(i) or order described in subparagraph (A)(ii) shall be made publicly available."
Subsec. (h)(3), (4). Pub. L. 112–144, §1132(b)(4), redesignated pars. (4) and (5) as (3) and (4), respectively. Former par. (3) redesignated (2).
Subsec. (h)(4)(A)(i). Pub. L. 112–144, §1132(b)(6)(A), substituted "The responsible" for "Not earlier than 15 days, and not later than 35 days, after discussions under paragraph (2) have begun, the responsible" and inserted ", after the sponsor is required to make a submission under subsection (a)(2) or (g)," before "request in writing".
"(ii) has complied with the timing requirements of scheduling review by the Drug Safety Oversight Board, providing a written recommendation, and issuing an action letter under subparagraphs (B), (F), and (G), respectively."
Subsec. (h)(5). Pub. L. 112–144, §1132(b)(4), (7), redesignated par. (6) as (5) and substituted "subparagraph (B) or (C)" for "any of subparagraphs (B) through (D)" in subpar. (A) and "paragraph (3) or (4)" for "paragraph (4) or (5)" in subpar. (C). Former par. (5) redesignated (4).
Subsec. (h)(6), (7). Pub. L. 112–144, §1132(b)(4), redesignated pars. (7) and (8) as (6) and (7), respectively. Former par. (6) redesignated (5).
Subsec. (h)(8), (9). Pub. L. 112–144, §1132(b)(4), (8), redesignated par. (9) as (8) and substituted "paragraphs (6) and (7)." for "paragraphs (7) and (8)". Former par. (8) redesignated (7).
Section effective 180 days after Sept. 27, 2007, see section 909 of Pub. L. 110–85, set out as an Effective Date of 2007 Amendment note under section 331 of this title.
"(a) Guidelines.-The Commissioner of Food and Drugs shall develop evidence-based opioid analgesic prescribing guidelines for the indication-specific treatment of acute pain only for the relevant therapeutic areas where such guidelines do not exist.
"(3) provide for a notice and comment period consistent with section 701(h) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 371(h)) for the submission of comments by the public.
"(c) Report.-Not later than 1 year after the date of enactment of this Act [Oct. 24, 2018], or, if earlier, at the time the guidelines under subsection (a) are finalized, the Commissioner of Food and Drugs 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, and post on the public website of the Food and Drug Administration, a report on how the Food and Drug Administration will utilize the guidelines under subsection (a) to protect the public health and a description of the public health need with respect to each such indication-specific treatment guideline.
"(2) submit to the committees specified in subsection (c) and post on the public website of the Food and Drug Administration an updated report under such subsection.
"(2) are not intended to be used for the purposes of restricting, limiting, delaying, or denying coverage for, or access to, a prescription issued for a legitimate medical purpose by an individual practitioner acting in the usual course of professional practice."
"(2) how often participation in such programs is necessary."
Pub. L. 112–144, title XI, §1132(c), July 9, 2012, 126 Stat. 1122 , provided that: "Not later than 1 year after the date of enactment of this Act [July 9, 2012], the Secretary of Health and Human Services shall issue guidance that, for purposes of section 505–1(h)(2)(A) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355–1(h)(2)(A)), describes the types of modifications to approved risk evaluation and mitigation strategies that shall be considered to be minor modifications of such strategies."
2 So in original. Probably should be "single, shared system,".

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