,,ii #aahth ,,congress #ast ,session ,s4 #aijf ,,in ,,the ,,senate ,,of ,,the ,,united ,,states ,june #h1 #bjbc,mr4 ,braun 7for himself1 ,mrs4 ,gillibrand1 ,mr4 ,wicker1 ,mr4 ,cramer1 and ,ms4 ,murkowski7 introduced the following bill2 which was read twice and referred to the ,committee on ,health1 ,education1 ,labor1 and ,pensions ,a ,,bill ,to amend the ,federal ,food1 ,drug1 and ,cosmetic ,act to establish a time-limited provisional approval pathway1 subject to specific obligations1 for certain drugs and biological products1 and for other purposes4 #a4 ,short title ,this ,act may be cited as the ,promising ,pathway ,act4 #b4 ,provisional approval of new human drugs 7a7 ,in general ,subchapter ,a of chapter ,v of the ,federal ,food1 ,drug1 and ,cosmetic ,act 7#ba ,u4,s4,c4 #cea et seq47 is amended by adding at the end of the following3 #ebd;,c4 ,provisional approval of new human drugs 7a7 ,priority review and evaluation of applications 7#a7 ,in general ,the ,secretary shall establish a priority review system to evaluate applications submitted under this section for provisional approval within #ij days of receipt of a completed application4 7#b7 ,other designations ,if a drug submitted for review under this section is eligible for a special designation by the ,secretary under this ,act1 including as a drug for a rare disease or condition under section #ebf1 all benefits of such other designation shall be available for use under provisional approval1 including any tax credits and waiving of fees under chapter ,,vii4 7b7 ,eligibility ,a drug may be eligible for provisional approval under this section if the ,secretary determines that the drug is intended for the treatment1 prevention1 or medical diagnosis of a serious or life-threatening disease or condition for which there is a reasonable likelihood that premature death will occur without early medical intervention for an individual contracting or being diagnosed with such disease or condition4 7c7 ,standard of review for provisional approval 7#a7 ,requirements ,an application for provisional approval under this section may be approved only if the ,secretary determines that-- 7,a7 there is substantial evidence of safety for the drug1 such that there is evidence consisting of adequate and well-controlled investigations1 including clinical investigations1 by experts qualified by scientific training and experience to evaluate the safety of the drug involved1 on the basis of which it could fairly and responsibly be concluded that the drug will have the effect it purports or is represented to have under the conditions of use prescribed1 recommended1 or suggested in the labeling or proposed labeling2 and 7,b7 there is relevant early evidence based on adequate and well-controlled investigations1 including early-stage clinical investigations1 to establish that-- 7i7 the drug provides a positive therapeutic outcome2 and 7ii7 the outcome of the drug is consistent with or greater than currently marketed on-label therapies1 with equal or fewer side effects1 if there are currently marketed on-label therapies4 7#b7 ,protocols ,the ,secretary shall promulgate rules that establish the appropriate protocols to enable rolling1 real-time1 mid-trial submission while preserving the integrity of the ongoing trial and without penalizing the sponsor for seeking provisional approval under this section4 7#c7 ,real world evidence ,the ,secretary shall allow the use of real world evidence 7as defined in section #eje;,f7b771 including real world data used to generate real world evidence1 to support an application for provisional approval under this section1 and to fulfill the follow-up requirements and support applications for approval under section #eje or section #cea of the ,public ,health ,service ,act1 as applicable4 7#d7 ,use of scientifically substantiated surrogates 7,a7 ,in general ,the sponsor of an application for provisional approval under this section may use scientifically substantiated surrogates to support such application4 7,b7 ,definition ,in subparagraph 7,a71 the term scientifically substantiated surrogates means surrogate endpoints to predict clinical benefit other than such endpoints previously validated by the ,secretary1 based on-- 7i7 epidemiologic1 therapeutic1 pathophysiologic1 or other evidence2 or 7ii7 an effect on a clinical endpoint other than survival or irreversible morbidity of interest4 7d7 ,transparency and patient monitoring requirements 7#a7 ,registries 7,a7 ,in general ,the sponsor of a drug provisionally approved under this section shall require that all patients who use such drug participate in an observational registry and consent to the sponsor's collection1 and submission to the registry1 of data related to the patient's use of such drug until such drug receives approval under section #eje or section #cea of the ,public ,health ,service ,act1 or the provisional approval is rescinded4 7,b7 ,requirements for registries ,an observational registry described in subparagraph 7,a7 may be run by a third party1 such as a government1 for profit1 or nonprofit organization1 and shall track all patients who use the provisionally approved drug4 7,c7 ,accessibility ,an observational registry described in subparagraph 7,a7 shall be easily accessible for-- 7i7 all patients who are participating in any registry related to a provisionally approved drug that allows for easy1 unrestricted 7or transparent7 access for such patients to their patient data and related information regarding their usage of the provisionally approved drug2 and 7ii7 approved researchers and medical professionals who may access data maintained in the registry1 which access shall be for public health research and only in a de-identified1 aggregated manner4 7#b7 ,funding ,an observational registry under this subsection shall be maintained1 as applicable-- 7,a7 by the sponsor of the drug provisionally approved under this section that is the subject of the registry2 or 7,b7 by a third party1 such as a government1 for profit1 or nonprofit organization4 7#c7 ,sponsor requirements 7,a7 ,in general ,for any drug application provisionally approved under this section1 the ,secretary shall notify the sponsor of the exact data such sponsor is required to submit to an observational registry4 7,b7 ,annual review of the registry2 penalties ,the ,secretary shall conduct an annual review of observational registries established under this subsection4 ,if1 at such an annual review1 fewer than #ij percent of patients are participating in an observational registry with respect to a drug approved under this section1 the ,secretary shall issue to the sponsor of such drug a civil monetary penalty of not more than #ajj1jjj4 ,if a violation of this section is not corrected within the #cj-;day period following notification1 the sponsor shall1 in addition to any penalty under this subparagraph be subject to a civil monetary penalty of not more than #aj1jjj for each day of the violation after such period until the violation is corrected4 ,if application patient participation in an observational registry is not at or above #ij percent within #f months of issuance of such penalty1 the provisional approval shall be withdrawn4 7#d7 ,annual report to ,congress ,the ,secretary shall submit an annual report to ,congress on all drugs granted provisional approval under this section4 ,such report shall include-- 7,a7 the number of patients treated with each such drug1 and the number of patients tracked in an observational registry with respect to each such drug2 7,b7 a discussion of the minimum amount of data required in the registries1 including patient treatments and uses1 length of use1 side effects encountered1 relevant biomarkers or scientifically substantiated surrogates1 scan results1 cause of death and how long the patient lived1 and adverse drug effects2 7,c7 a list of all such drugs for which an application for approval under section #eje of this ,act or section #cea of the ,public ,health ,service ,act1 or an application for an extension of provisional approval under this section1 has been submitted2 and 7,d7 a list of all applications denied provisional approval under this section1 together with an explanation for the decisions to deny each such application4 7e7 ,withdrawal of provisional approval 7#a7 ,in general ,the ,secretary shall withdraw provisional approval under this section if there are a significant numbers of patients who experience serious adverse effects1 compared to the other currently marketed on-label therapies that are available for the applicable disease or condition4 7#b7 ,effect of withdrawal ,if a provisional approval is withdrawn under this subsection1 the sponsor may not make the drug available to any new patients1 but may be allowed to continue to make such drug available to patients who started taking the drug prior to the date of withdrawal1 for as long a period as dictated by patient need1 as determined by the ,secretary4 7f7 ,transparency ,any scientific1 medical1 academic1 or health care journal publishing an article explaining1 releasing1 conveying1 or announcing research findings which were funded by the ,department of ,health and ,human ,services shall be prohibited from publishing such research unless-- 7#a7 such article conveying research findings is made publicly available on the journal's internet website without a paywall or charge not later than #c months after the date on which such article was first provided to subscribers of such journal 7or first made available for purchase72 and 7#b7 the article's author or researcher or author's institution 7or1 in the case of multiple authors1 researchers1 or institutions1 all such authors1 researchers1 or institutions7 received less than #cj percent of funding for such research from the ,department of ,health and ,human ,services throughout the period of time the research was conducted4 7g7 ,informed ,consent ,prior to receiving a drug provisionally approved under this section1 the sponsor of the drug shall receive from each patient1 or the patient's representative1 informed consent1 through a signed informed consent form1 acknowledging that such patient understands that the drug did not undergo the usual process for approval of a drug by the ,food and ,drug ,administration1 and that such patient is willing to accept the risks involved in taking such drug4 7h7 ,postmarket controls and labeling 7#a7 ,,fda annual review of registry data ,the ,secretary shall annually review the data made available through the observational registries under subsection 7d7 and make a determination regarding whether the side effect profile of any drug provisionally approved under this section does not support the benefit provided1 or the data shows the benefit is less than the benefits offered through other1 fully approved drugs4 7#b7 ,labeling ,the sponsor of the provisionally approved drug shall ensure that all labeling and promotional materials for the drug bear the statement provisionally approved by the ,,fda pending a full demonstration of effectiveness under application number 7specifying the application number assigned by the ,secretary in place of the blank74 ,all promotional1 educational and marketing materials for provisionally approved products shall be reviewed and approved by the ,secretary before such materials are distributed4 7#c7 ,rescission of provisional approval ,if the ,secretary determines that the side effect profile of any drug included in such observational registries does not support the benefit provided by such drug1 or that the data shows that the benefit is less than the benefits offered through other1 drugs approved under section #eje of this ,act or section #cea of the ,public ,health ,service ,act1 the ,secretary shall rescind such provisional approval4 7i7 ,duration of provisional approval2 requirement ,to bring drug to market 7#a7 ,duration2 renewals ,the provisional approval for a drug under this section is effective for a #b-year period4 ,the sponsor may request renewal for provisional approval status for up to #c subsequent #b-year periods4 ,provisional approval status with respect to a drug shall not exceed a total of #h years from the initial date the sponsor was awarded provisional approval status4 7#b7 ,marketing requirement ,if any drug that receives provisional approval under this section is not brought to market within #ahj days of the provisional approval1 such provisional approval shall be rescinded4 7j7 ,limitation on liability ,with respect to any claim under ,state law alleging that a drug sold or otherwise made available pursuant to a grant of provisional approval under this section is unsafe or ineffective1 no liability in a cause of action shall lie against a sponsor or manufacturer1 unless the relevant conduct constitutes reckless or willful misconduct1 gross negligence1 or an intentional tort under any applicable ,state law4 7k7 ,right ,to petition an advisory committee for approval 7#a7 ,in general ,the sponsor of a drug granted provisional approval pursuant to this section may request1 at any time after provisional approval is granted under this section1 a meeting with the appropriate advisory committee 7or advisory committees7 to present safety and efficacy data for the purposes of receiving a recommendation from such an advisory committee for approval under section #eje of this ,act or section #cea of the ,public ,health ,service ,act of the provisionally approved drug4 ,such a requested meeting shall be granted not later than #ij days after a request is made4 ,nothing in this paragraph shall be construed to alter the processes and timeframes for recommendation for approval by such an advisory committee of the provisionally approved drug or for approval of the provisionally approved drug under section #eje of this ,act or section #cea of the ,public ,health ,service ,act4 7#b7 ,waiver of adequate and well-controlled study requirements 7,a7 ,in general ,in considering whether to recommend a drug that was provisionally approved under this section for approval under section #eje1 the ,director of the ,center for ,drug ,evaluation and ,research shall consider the option to waive requirements for adequate and well-controlled studies in accordance with the process described in section #cad4abf7;c7 of title #ba1 ,code of ,federal ,regulations 7or successor regulations74 7,b7 ,biological products ,in considering whether to recommend a biological product that was provisionally approved under this section for licensure under section #cea of the ,public ,health ,service ,act1 the ,director of the ,center for ,biologics ,evaluation and ,research may1 and shall consider the option to1 waive requirements1 as applicable1 for adequate and well-controlled studies for such biological product in accordance with the process described in section #cad4abf7;c7 of title #ba1 ,code of ,federal ,regulations 7or successor regulations74 4 7b7 ,conforming amendment ,section #eje7;a7 of the ,federal ,food1 ,drug1 and ,cosmetic ,act 7#ba ,u4,s4,c4 #cee7;a77 is amended by inserting 1 or there is in effect a provisional approval under section #ebd;,c with respect to such drug before the period4 7c7 ,reimbursement 7#a7 ,private health insurers ,section #bgai;,a of the ,public ,health ,service ,act 7#db ,u4,s4,c4 #cjj;gg-#ai;a7 is amended by adding at the end the following3 7f7 ,treatment of certain drugs ,a group health plan or health insurance issuer of group or individual health insurance coverage shall not deny coverage of any drug provisionally approved under section #ebd;,c of the ,federal ,food1 ,drug1 and ,cosmetic ,act on the basis of such drug being experimental4 ,in determining coverage under the applicable plan or coverage1 a group health plan or health insurance issuer shall treat a drug provisionally approved under such section in the same manner as such plan or coverage would treat a drug approved under section #eje of the ,federal ,food1 ,drug1 and ,cosmetic ,act or section #cea of this ,act4 ,nothing in this subsection shall be construed to require a group health plan or health insurance issuer to cover any specific drug provisionally approved under such section #ebd;,c4 4 7#b7 ,federal health care programs ,the requirement under subsection 7f7 of section #bgai;,a of the ,public ,health ,service ,act 7as added by paragraph 7#a77 shall apply with respect to coverage determinations under a ,federal health care program 7as defined in section #aabh;,b7f7 of the ,social ,security ,act 7#db ,u4,s4,c4 #acbj;a-#g;b7f777 in the same manner such requirement applies under such subsection 7f74 7#c7 ,conforming amendment ,section #aibg7k77#b77;,a77i7 of the ,social ,security ,act 7#db ,u4,s4,c4 #acifr-#h7k77#b77;,a77i77 is amended-- 7,a7 by striking or which and inserting 1 which2 and 7,b7 by inserting 1 or which is provisionally approved under section #ebd;,c of such ,act before the semicolon4