21 U.S.C. § 360bbb — Expanded access to unapproved thera-

Page 414 TITLE 21—FOOD AND DRUGS §§ 360aaa to 360aaa–6 division thereof from establishing a requirement with respect to emission of radiation from elec- tronic products procured for its own use if such requirement imposes a more restrictive stand- ard than that required to comply with the other- wise applicable Federal standard. (June 25, 1938, ch. 675, § 542, formerly act July 1, 1944, ch. 373, title III, § 542, formerly § 360F, as added Pub. L. 90–602, § 2(3), Oct. 18, 1968, 82 Stat. 1186; renumbered § 542 and amended Pub. L. 101–629, § 19(a)(1)(B), (2)(H), (3), (4), Nov. 28, 1990, 104 Stat. 4529, 4530; Pub. L. 103–80, § 4(a)(2), Aug. 13, 1993, 107 Stat. 779.) Editorial Notes CODIFICATION Section was classified to section 263n of Title 42, The Public Health and Welfare, prior to renumbering by Pub. L. 101–629. AMENDMENTS 1993—Pub. L. 103–80 amended directory language of Pub. L. 101–629, § 19(a)(4), which renumbered section 263n of Title 42, The Public Health and Welfare, as this section. 1990—Pub. L. 101–629, § 19(a)(1)(B), (2)(H), substituted ‘‘section 360kk’’ for ‘‘section 263f’’ and ‘‘this part’’ for ‘‘this subpart’’. Statutory Notes and Related Subsidiaries NONINTERFERENCE WITH OTHER FEDERAL AGENCIES Enactment of this section not to be construed to su- persede or limit the functions under any other provi- sion of law of any officer or agency of the United States, see section 4 of Pub. L. 90–602, set out as a note under section 360hh of this title. PART D—DISSEMINATION OF TREATMENT INFORMATION §§ 360aaa to 360aaa–6. Omitted Editorial Notes CODIFICATION Sections 360aaa to 360aaa–6 ceased to be effective pur- suant to section 401(e) of Pub. L. 105–115, set out as an Effective and Termination Dates note below. Section 360aaa, act June 25, 1938, ch. 675, § 551, as added Pub. L. 105–115, title IV, § 401(a), Nov. 21, 1997, 111 Stat. 2356, related to requirements for dissemination of treatment information on drugs or devices. Section 360aaa–1, act June 25, 1938, ch. 675, § 552, as added Pub. L. 105–115, title IV, § 401(a), Nov. 21, 1997, 111 Stat. 2358, related to information authorized to be dis- seminated under section 360aaa. Section 360aaa–2, act June 25, 1938, ch. 675, § 553, as added Pub. L. 105–115, title IV, § 401(a), Nov. 21, 1997, 111 Stat. 2359, related to establishment of list of articles and publications disseminated and list of providers that received articles and reference publications. Section 360aaa–3, act June 25, 1938, ch. 675, § 554, as added Pub. L. 105–115, title IV, § 401(a), Nov. 21, 1997, 111 Stat. 2359, related to requirement regarding submission of supplemental application for new use and an exemp- tion from that requirement. Section 360aaa–4, act June 25, 1938, ch. 675, § 555, as added Pub. L. 105–115, title IV, § 401(a), Nov. 21, 1997, 111 Stat. 2361, related to corrective actions and cessation of dissemination. Section 360aaa–5, act June 25, 1938, ch. 675, § 556, as added Pub. L. 105–115, title IV, § 401(a), Nov. 21, 1997, 111 Stat. 2362, related to definitions. Section 360aaa–6, act June 25, 1938, ch. 675, § 557, as added Pub. L. 105–115, title IV, § 401(a), Nov. 21, 1997, 111 Stat. 2363, related to rules of construction. Statutory Notes and Related Subsidiaries EFFECTIVE AND TERMINATION DATES Pub. L. 105–115, title IV, § 401(d), Nov. 21, 1997, 111 Stat. 2364, provided that: ‘‘The amendments made by this section [enacting this part and amending section 331 of this title] shall take effect 1 year after the date of enactment of this Act [Nov. 21, 1997], or upon the Secretary’s issuance of final regulations pursuant to subsection (c) [section 401(c) of Pub. L. 105–115 set out below] [Such regulations were issued effective Nov. 20, 1998. See 63 F.R. 64556.], whichever is sooner.’’ Pub. L. 105–115, title IV, § 401(e), Nov. 21, 1997, 111 Stat. 2364, provided that: ‘‘The amendments made by this section [enacting this part and amending section 331 of this title] cease to be effective September 30, 2006, or 7 years after the date on which the Secretary pro- mulgates the regulations described in subsection (c) [section 401(c) of Pub. L. 105–115 set out below] [Such regulations were issued effective Nov. 20, 1998. See 63 F.R. 64556.], whichever is later.’’ REGULATIONS Pub. L. 105–115, title IV, § 401(c), Nov. 21, 1997, 111 Stat. 2364, provided that: ‘‘Not later than 1 year after the date of enactment of this Act [Nov. 21, 1997], the Secretary of Health and Human Services shall promul- gate regulations to implement the amendments made by this section [enacting this part and amending sec- tion 331 of this title].’’ PART E—GENERAL PROVISIONS RELATING TO DRUGS AND DEVICES § 360bbb. Expanded access to unapproved thera- pies and diagnostics (a) Emergency situations The Secretary may, under appropriate condi- tions determined by the Secretary, authorize the shipment of investigational drugs or inves- tigational devices for the diagnosis, monitoring, or treatment of a serious disease or condition in emergency situations. (b) Individual patient access to investigational products intended for serious diseases Any person, acting through a physician li- censed in accordance with State law, may re- quest from a manufacturer or distributor, and any manufacturer or distributor may, after complying with the provisions of this sub- section, provide to such physician an investiga- tional drug or investigational device for the di- agnosis, monitoring, or treatment of a serious disease or condition if— (1) the licensed physician determines that the person has no comparable or satisfactory alternative therapy available to diagnose, monitor, or treat the disease or condition in- volved, and that the probable risk to the per- son from the investigational drug or investiga- tional device is not greater than the probable risk from the disease or condition; (2) the Secretary determines that there is sufficient evidence of safety and effectiveness to support the use of the investigational drug or investigational device in the case described in paragraph (1); (3) the Secretary determines that provision of the investigational drug or investigational device will not interfere with the initiation, conduct, or completion of clinical investiga- tions to support marketing approval; and (4) the sponsor, or clinical investigator, of the investigational drug or investigational de- Page 415 TITLE 21—FOOD AND DRUGS § 360bbb vice submits to the Secretary a clinical pro- tocol consistent with the provisions of section 355(i) or 360j(g) of this title, including any reg- ulations 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 pa- tients. (c) Treatment investigational new drug applica- tions and treatment investigational device exemptions Upon submission by a sponsor or a physician of a protocol intended to provide widespread ac- cess to an investigational drug or investiga- tional device for eligible patients (referred to in this subsection as an ‘‘expanded access pro- tocol’’), the Secretary shall permit such inves- tigational 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 dis- ease or condition; (2) there is no comparable or satisfactory al- ternative therapy available to diagnose, mon- itor, or treat that stage of disease or condition in the population of patients to which the in- vestigational drug or investigational device is intended to be administered; (3)(A) the investigational drug or investiga- tional device is under investigation in a con- trolled 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 in- vestigational 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 inter- fere with the enrollment of patients in ongo- ing 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-threat- ening diseases, the available scientific evi- dence, 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 ill- ness 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 pro- mulgated 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 appro- priate persons about the availability of an inves- tigational drug or investigational device under expanded access protocols submitted under this subsection. The information provided by the Secretary, in accordance with the preceding sen- tence, shall be the same type of information that is required by section 282(i)(3) of title 42. (d) Termination The Secretary may, at any time, with respect to a sponsor, physician, manufacturer, or dis- tributor described in this section, terminate ex- panded access provided under this section for an investigational drug or investigational device if the requirements under this section are no longer met. (e) Definitions In this section, the terms ‘‘investigational drug’’, ‘‘investigational device’’, ‘‘treatment in- vestigational new drug application’’, and ‘‘treat- ment investigational device exemption’’ shall have the meanings given the terms in regula- tions prescribed by the Secretary. (June 25, 1938, ch. 675, § 561, as added Pub. L. 105–115, title IV, § 402, Nov. 21, 1997, 111 Stat. 2365; amended Pub. L. 109–482, title I, § 102(f)(2), Jan. 15, 2007, 120 Stat. 3685.) Editorial Notes AMENDMENTS 2007—Subsec. (c). Pub. L. 109–482 substituted ‘‘section 282(i)(3)’’ for ‘‘section 282(j)(3)’’ in concluding provi- sions. Statutory Notes and Related Subsidiaries EFFECTIVE DATE OF 2007 AMENDMENT Amendment by Pub. L. 109–482 applicable only with respect to amounts appropriated for fiscal year 2007 or subsequent fiscal years, see section 109 of Pub. L. 109–482, set out as a note under section 281 of Title 42, The Public Health and Welfare. EFFECTIVE DATE Section effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of Pub. L. 105–115, set out as an Effective Date of 1997 Amendment note under section 321 of this title. INVESTIGATIONAL DRUGS Pub. L. 115–52, title VI, § 610(a), (b), Aug. 18, 2017, 131 Stat. 1051, 1053, provided that: ‘‘(a) PATIENT ACCESS TO INVESTIGATIONAL DRUGS.— ‘‘(1) PUBLIC MEETING.— ‘‘(A) IN GENERAL.—The Secretary of Health and Human Services (referred to in this section as the ‘Secretary’), acting through the Commissioner of Food and Drugs, in coordination with the Director of the National Institutes of Health, and in con- sultation with patients, health care providers, drug sponsors, bioethicists, and other stakeholders, shall, not later than 270 days after the date of en- actment of this Act [Aug. 18, 2007], convene a public meeting to discuss clinical trial inclusion and ex- clusion criteria to inform the guidance under para- graph (3). The Secretary shall inform the Comp- troller General of the United States of the date when the public meeting will take place. Page 416 TITLE 21—FOOD AND DRUGS § 360bbb–0 ‘‘(B) TOPICS.—The Secretary shall make available on the internet website of the Food and Drug Ad- ministration a report on the topics discussed at the meeting described in subparagraph (A) within 90 days of such meeting. Such topics shall include dis- cussion of— ‘‘(i) the rationale for, and potential barriers for patients created by, research clinical trial inclu- sion and exclusion criteria; ‘‘(ii) how appropriate patient populations can benefit from the results of trials that employ al- ternative designs; ‘‘(iii) barriers to participation in clinical trials, including— ‘‘(I) information regarding any potential risks and benefits of participation; ‘‘(II) regulatory, geographical, and socio- economic barriers; and ‘‘(III) the impact of exclusion criteria on the enrollment in clinical trials of particular popu- lations, including infants and children, preg- nant and lactating women, seniors, individuals with advanced disease, and individuals with co- morbid conditions; ‘‘(iv) clinical trial designs and methods, includ- ing expanded access trials, that increase enroll- ment of more diverse patient populations, when appropriate, while facilitating the collection of data to establish safe use and support substantial evidence of effectiveness, including data obtained from expanded access trials; and ‘‘(v) how changes to clinical trial inclusion and exclusion criteria may impact the complexity and length of clinical trials, the data necessary to demonstrate safety and effectiveness, and poten- tial approaches to mitigating those impacts. ‘‘(2) REPORT.—Not later than 1 year after the Sec- retary issues the report under paragraph (1)(B), the Comptroller General of the United States 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 on in- dividual access to investigational drugs through the expanded access program under section 561(b) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb(b)). The report shall include— ‘‘(A) a description of actions taken by manufac- turers and distributors under section 561A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb–0); ‘‘(B) consideration of whether Form FDA 3926 and the guidance documents titled ‘Expanded Access to Investigational Drugs for Treatment Use—Ques- tions and Answers’ and ‘Individual Patient Ex- panded Access Applications: Form FDA 3926’, issued by the Food and Drug Administration in June 2016, have reduced application burden with respect to in- dividuals and physicians seeking access to inves- tigational new drugs pursuant to section 561(b) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb) and improved clarity for patients, physicians, and drug manufacturers about such process; ‘‘(C) consideration of whether the guidance or regulations issued to implement section 561 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb) have improved access for individual pa- tients to investigational drugs who do not qualify for clinical trials of such investigational drugs, and what barriers to such access remain; ‘‘(D) an assessment of methods patients and health care providers use to engage with the Food and Drug Administration or drug sponsors on ex- panded access; and ‘‘(E) an analysis of the Secretary’s report under paragraph (1)(B). ‘‘(3) GUIDANCE.— ‘‘(A) IN GENERAL.—Not later than 1 year after the publication of the report under paragraph (1)(B), the Secretary, acting through the Commissioner of Food and Drugs, shall issue one or more draft guid- ances regarding eligibility criteria for clinical trials. Not later than 1 year after the public com- ment period on each such draft guidance ends, the Secretary shall issue a revised draft guidance or final guidance. ‘‘(B) CONTENTS.—The guidance documents de- scribed in subparagraph (A) shall address methodo- logical approaches that a manufacturer or sponsor of an investigation of a new drug may take to— ‘‘(i) broaden eligibility criteria for clinical trials and expanded access trials, especially with respect to drugs for the treatment of serious and life-threatening conditions or diseases for which there is an unmet medical need; ‘‘(ii) develop eligibility criteria for, and in- crease trial recruitment to, clinical trials so that enrollment in such trials more accurately reflects the patients most likely to receive the drug, as applicable and as appropriate, while establishing safe use and supporting findings of substantial evidence of effectiveness; and ‘‘(iii) use the criteria described in clauses (i) and (ii) in a manner that is appropriate for drugs intended for the treatment of rare diseases or conditions. ‘‘(b) IMPROVING INSTITUTIONAL REVIEW BOARD REVIEW OF SINGLE PATIENT EXPANDED ACCESS PROTOCOL.—Not later than 1 year after the date of enactment of this Act [Aug. 18, 2017], the Secretary, acting through the Commissioner of Food and Drugs, shall issue guidance or regulations, or revise existing guidance or regula- tions, to streamline the institutional review board re- view of individual patient expanded access protocols submitted under [section] 561(b) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb(b)). To facili- tate the use of expanded access protocols, any guidance or regulations so issued or revised may include a de- scription of the process for any person acting through a physician licensed in accordance with State law to request that an institutional review board chair (or designated member of the institutional review board) review a single patient expanded access protocol sub- mitted under such section 561(b) for a drug. The Sec- retary shall update any relevant forms associated with individual patient expanded access requests under such section 561(b) as necessary.’’ § 360bbb–0. Expanded access policy required for investigational drugs (a) In general The manufacturer or distributor of one or more investigational drugs for the diagnosis, monitoring, or treatment of one or more serious diseases or conditions shall make available the policy of the manufacturer or distributor on evaluating and responding to requests submitted under section 360bbb(b) of this title for provision of such a drug. (b) Public availability of expanded access policy The policies under subsection (a) shall be made public and readily available, such as by posting such policies on a publicly available Internet website. Such policies may be generally applicable to all investigational drugs of such manufacturer or distributor. (c) Content of policy A policy described in subsection (a) shall in- clude— (1) contact information for the manufacturer or distributor to facilitate communication about requests described in subsection (a); (2) procedures for making such requests; (3) the general criteria the manufacturer or distributor will use to evaluate such requests