Promising Pathway Act

II 118TH CONGRESS 1ST SESSION S. 1906 To amend the Federal Food, Drug, and Cosmetic Act to establish a time- limited provisional approval pathway, subject to specific obligations, for certain drugs and biological products, and for other purposes. IN THE SENATE OF THE UNITED STATES JUNE 8, 2023 Mr. BRAUN (for himself, Mrs. GILLIBRAND, Mr. WICKER, Mr. CRAMER, and Ms. MURKOWSKI) introduced the following bill; which was read twice and referred to the Committee on Health, Education, Labor, and Pensions A BILL To amend the Federal Food, Drug, and Cosmetic Act to establish a time-limited provisional approval pathway, subject to specific obligations, for certain drugs and bio- logical products, and for other purposes. Be it enacted by the Senate and House of Representa- 1 tives of the United States of America in Congress assembled, 2 SECTION 1. SHORT TITLE. 3 This Act may be cited as the ‘‘Promising Pathway 4 Act’’. 5 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00001 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 2 •S 1906 IS SEC. 2. PROVISIONAL APPROVAL OF NEW HUMAN DRUGS. 1 (a) IN GENERAL.—Subchapter A of chapter V of the 2 Federal Food, Drug, and Cosmetic Act (21 U.S.C. 351 3 et seq.) is amended by adding at the end of the following: 4 ‘‘SEC. 524C. PROVISIONAL APPROVAL OF NEW HUMAN 5 DRUGS. 6 ‘‘(a) PRIORITY REVIEW AND EVALUATION OF APPLI- 7 CATIONS.— 8 ‘‘(1) IN GENERAL.—The Secretary shall estab- 9 lish a priority review system to evaluate applications 10 submitted under this section for provisional approval 11 within 90 days of receipt of a completed application. 12 ‘‘(2) OTHER DESIGNATIONS.—If a drug sub- 13 mitted for review under this section is eligible for a 14 special designation by the Secretary under this Act, 15 including as a drug for a rare disease or condition 16 under section 526, all benefits of such other designa- 17 tion shall be available for use under provisional ap- 18 proval, including any tax credits and waiving of fees 19 under chapter VII. 20 ‘‘(b) ELIGIBILITY.—A drug may be eligible for provi- 21 sional approval under this section if the Secretary deter- 22 mines that the drug is intended for the treatment, preven- 23 tion, or medical diagnosis of a serious or life-threatening 24 disease or condition for which there is a reasonable likeli- 25 hood that premature death will occur without early med- 26 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00002 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 3 •S 1906 IS ical intervention for an individual contracting or being di- 1 agnosed with such disease or condition. 2 ‘‘(c) STANDARD OF REVIEW FOR PROVISIONAL AP- 3 PROVAL.— 4 ‘‘(1) REQUIREMENTS.—An application for pro- 5 visional approval under this section may be approved 6 only if the Secretary determines that— 7 ‘‘(A) there is substantial evidence of safety 8 for the drug, such that there is evidence con- 9 sisting of adequate and well-controlled inves- 10 tigations, including clinical investigations, by 11 experts qualified by scientific training and expe- 12 rience to evaluate the safety of the drug in- 13 volved, on the basis of which it could fairly and 14 responsibly be concluded that the drug will have 15 the effect it purports or is represented to have 16 under the conditions of use prescribed, rec- 17 ommended, or suggested in the labeling or pro- 18 posed labeling; and 19 ‘‘(B) there is relevant early evidence based 20 on adequate and well-controlled investigations, 21 including early-stage clinical investigations, to 22 establish that— 23 ‘‘(i) the drug provides a positive 24 therapeutic outcome; and 25 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00003 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 4 •S 1906 IS ‘‘(ii) the outcome of the drug is con- 1 sistent with or greater than currently mar- 2 keted on-label therapies, with equal or 3 fewer side effects, if there are currently 4 marketed on-label therapies. 5 ‘‘(2) PROTOCOLS.—The Secretary shall promul- 6 gate rules that establish the appropriate protocols to 7 enable rolling, real-time, mid-trial submission while 8 preserving the integrity of the ongoing trial and 9 without penalizing the sponsor for seeking provi- 10 sional approval under this section. 11 ‘‘(3) REAL WORLD EVIDENCE.—The Secretary 12 shall allow the use of real world evidence (as defined 13 in section 505F(b)), including real world data used 14 to generate real world evidence, to support an appli- 15 cation for provisional approval under this section, 16 and to fulfill the follow-up requirements and support 17 applications for approval under section 505 or sec- 18 tion 351 of the Public Health Service Act, as appli- 19 cable. 20 ‘‘(4) USE OF SCIENTIFICALLY SUBSTANTIATED 21 SURROGATES.— 22 ‘‘(A) IN GENERAL.—The sponsor of an ap- 23 plication for provisional approval under this sec- 24 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00004 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 5 •S 1906 IS tion may use scientifically substantiated surro- 1 gates to support such application. 2 ‘‘(B) DEFINITION.—In subparagraph (A), 3 the term ‘scientifically substantiated surrogates’ 4 means surrogate endpoints to predict clinical 5 benefit other than such endpoints previously 6 validated by the Secretary, based on— 7 ‘‘(i) epidemiologic, therapeutic, patho- 8 physiologic, or other evidence; or 9 ‘‘(ii) an effect on a clinical endpoint 10 other than survival or irreversible mor- 11 bidity of interest. 12 ‘‘(d) TRANSPARENCY AND PATIENT MONITORING 13 REQUIREMENTS.— 14 ‘‘(1) REGISTRIES.— 15 ‘‘(A) IN GENERAL.—The sponsor of a drug 16 provisionally approved under this section shall 17 require that all patients who use such drug par- 18 ticipate in an observational registry and consent 19 to the sponsor’s collection, and submission to 20 the registry, of data related to the patient’s use 21 of such drug until such drug receives approval 22 under section 505 or section 351 of the Public 23 Health Service Act, or the provisional approval 24 is rescinded. 25 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00005 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 6 •S 1906 IS ‘‘(B) REQUIREMENTS FOR REGISTRIES.— 1 An observational registry described in subpara- 2 graph (A) may be run by a third party, such as 3 a government, for profit, or nonprofit organiza- 4 tion, and shall track all patients who use the 5 provisionally approved drug. 6 ‘‘(C) ACCESSIBILITY.—An observational 7 registry described in subparagraph (A) shall be 8 easily accessible for— 9 ‘‘(i) all patients who are participating 10 in any registry related to a provisionally 11 approved drug that allows for easy, unre- 12 stricted (or transparent) access for such 13 patients to their patient data and related 14 information regarding their usage of the 15 provisionally approved drug; and 16 ‘‘(ii) approved researchers and med- 17 ical professionals who may access data 18 maintained in the registry, which access 19 shall be for public health research and only 20 in a de-identified, aggregated manner. 21 ‘‘(2) FUNDING.—An observational registry 22 under this subsection shall be maintained, as appli- 23 cable— 24 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00006 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 7 •S 1906 IS ‘‘(A) by the sponsor of the drug provision- 1 ally approved under this section that is the sub- 2 ject of the registry; or 3 ‘‘(B) by a third party, such as a govern- 4 ment, for profit, or nonprofit organization. 5 ‘‘(3) SPONSOR REQUIREMENTS.— 6 ‘‘(A) IN GENERAL.—For any drug applica- 7 tion provisionally approved under this section, 8 the Secretary shall notify the sponsor of the 9 exact data such sponsor is required to submit 10 to an observational registry. 11 ‘‘(B) ANNUAL REVIEW OF THE REGISTRY; 12 PENALTIES.—The Secretary shall conduct an 13 annual review of observational registries estab- 14 lished under this subsection. If, at such an an- 15 nual review, fewer than 90 percent of patients 16 are participating in an observational registry 17 with respect to a drug approved under this sec- 18 tion, the Secretary shall issue to the sponsor of 19 such drug a civil monetary penalty of not more 20 than $100,000. If a violation of this section is 21 not corrected within the 30-day period following 22 notification, the sponsor shall, in addition to 23 any penalty under this subparagraph be subject 24 to a civil monetary penalty of not more than 25 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00007 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 8 •S 1906 IS $10,000 for each day of the violation after such 1 period until the violation is corrected. If appli- 2 cation patient participation in an observational 3 registry is not at or above 90 percent within 6 4 months of issuance of such penalty, the provi- 5 sional approval shall be withdrawn. 6 ‘‘(4) ANNUAL REPORT TO CONGRESS.—The 7 Secretary shall submit an annual report to Congress 8 on all drugs granted provisional approval under this 9 section. Such report shall include— 10 ‘‘(A) the number of patients treated with 11 each such drug, and the number of patients 12 tracked in an observational registry with re- 13 spect to each such drug; 14 ‘‘(B) a discussion of the minimum amount 15 of data required in the registries, including pa- 16 tient treatments and uses, length of use, side 17 effects encountered, relevant biomarkers or sci- 18 entifically substantiated surrogates, scan re- 19 sults, cause of death and how long the patient 20 lived, and adverse drug effects; 21 ‘‘(C) a list of all such drugs for which an 22 application for approval under section 505 of 23 this Act or section 351 of the Public Health 24 Service Act, or an application for an extension 25 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00008 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 9 •S 1906 IS of provisional approval under this section, has 1 been submitted; and 2 ‘‘(D) a list of all applications denied provi- 3 sional approval under this section, together with 4 an explanation for the decisions to deny each 5 such application. 6 ‘‘(e) WITHDRAWAL OF PROVISIONAL APPROVAL.— 7 ‘‘(1) IN GENERAL.—The Secretary shall with- 8 draw provisional approval under this section if there 9 are a significant numbers of patients who experience 10 serious adverse effects, compared to the other cur- 11 rently marketed on-label therapies that are available 12 for the applicable disease or condition. 13 ‘‘(2) EFFECT OF WITHDRAWAL.—If a provi- 14 sional approval is withdrawn under this subsection, 15 the sponsor may not make the drug available to any 16 new patients, but may be allowed to continue to 17 make such drug available to patients who started 18 taking the drug prior to the date of withdrawal, for 19 as long a period as dictated by patient need, as de- 20 termined by the Secretary. 21 ‘‘(f) TRANSPARENCY.—Any scientific, medical, aca- 22 demic, or health care journal publishing an article explain- 23 ing, releasing, conveying, or announcing research findings 24 which were funded by the Department of Health and 25 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00009 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 10 •S 1906 IS Human Services shall be prohibited from publishing such 1 research unless— 2 ‘‘(1) such article conveying research findings is 3 made publicly available on the journal’s internet 4 website without a paywall or charge not later than 5 3 months after the date on which such article was 6 first provided to subscribers of such journal (or first 7 made available for purchase); and 8 ‘‘(2) the article’s author or researcher or au- 9 thor’s institution (or, in the case of multiple authors, 10 researchers, or institutions, all such authors, re- 11 searchers, or institutions) received less than 30 per- 12 cent of funding for such research from the Depart- 13 ment of Health and Human Services throughout the 14 period of time the research was conducted. 15 ‘‘(g) INFORMED CONSENT.—Prior to receiving a drug 16 provisionally approved under this section, the sponsor of 17 the drug shall receive from each patient, or the patient’s 18 representative, informed consent, through a signed in- 19 formed consent form, acknowledging that such patient un- 20 derstands that the drug did not undergo the usual process 21 for approval of a drug by the Food and Drug Administra- 22 tion, and that such patient is willing to accept the risks 23 involved in taking such drug. 24 ‘‘(h) POSTMARKET CONTROLS AND LABELING.— 25 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00010 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 11 •S 1906 IS ‘‘(1) FDA ANNUAL REVIEW OF REGISTRY 1 DATA.—The Secretary shall annually review the data 2 made available through the observational registries 3 under subsection (d) and make a determination re- 4 garding whether the side effect profile of any drug 5 provisionally approved under this section does not 6 support the benefit provided, or the data shows the 7 benefit is less than the benefits offered through 8 other, fully approved drugs. 9 ‘‘(2) LABELING.—The sponsor of the provision- 10 ally approved drug shall ensure that all labeling and 11 promotional materials for the drug bear the state- 12 ment ‘provisionally approved by the FDA pending a 13 full demonstration of effectiveness under application 14 number llllll’ (specifying the application 15 number assigned by the Secretary in place of the 16 blank). All promotional, educational and marketing 17 materials for provisionally approved products shall 18 be reviewed and approved by the Secretary before 19 such materials are distributed. 20 ‘‘(3) RESCISSION OF PROVISIONAL AP- 21 PROVAL.—If the Secretary determines that the side 22 effect profile of any drug included in such observa- 23 tional registries does not support the benefit pro- 24 vided by such drug, or that the data shows that the 25 VerDate Sep 11 2014 05:08 Jul 01, 2023 Jkt 039200 PO 00000 Frm 00011 Fmt 6652 Sfmt 6201 E:\BILLS\S1906.IS S1906 kjohnson on DSK79L0C42PROD with BILLS 12 •S 1906 IS benefit is less than the benefits offered through 1 other, drugs approved under section 505 of this Act 2 or section 351 of the Public Health Service Act, the 3 Secretary shall rescind such provisional approval. 4 ‘‘(i) DURATION OF PROVISIONAL APPROVAL; RE- 5 QUIREM [Text truncated for display. Full text available on Congress.gov.]