,,ii #aahth ,,congress #b;d ,session ,s4 #ddbf ,,in ,,the ,,senate ,,of ,,the ,,united ,,states ,may #bc1 #bjbd,mr4 ,braun 7for himself1 ,mrs4 ,gillibrand1 ,mr4 ,cramer1 ,mr4 ,manchin1 ,mr4 ,schmitt1 ,mr4 ,padilla1 ,mr4 ,vance1 ,mr4 ,booker1 ,mr4 ,hawley1 ,mr4 ,welch1 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 conditional 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 ,act #b4j4 #b4 ,conditional approval of new human drugs for individuals with rare1 progressive1 and serious diseases 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 ,conditional approval of human drugs for individuals with rare1 progressive1 and serious diseases 7a7 ,conditional approval2 priority review2 other designations 7#a7 ,in general ,the sponsor of a drug may file with the ,secretary an application for conditional approval of an eligible drug described in subsection 7b74 ,the ,secretary shall approve or deny such application in accordance with subsection 7c74 7#b7 ,priority review ,the ,secretary shall give priority review to an application for conditional approval of an eligible drug described in subsection 7b74 7#c7 ,other designations ,if a drug that is granted conditional approval 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 applicable benefits of such other designation shall be available for use under such conditional approval1 including any tax credits and waiving of fees under chapter ,,vii4 7#d7 ,other programs ,a sponsor of a drug seeking conditional approval of such drug under this section may also seek designation1 exclusivity1 or approval1 as applicable1 of such drug under other applicable provisions of this ,act or the ,public ,health ,service ,act1 subject to the requirements of such provisions4 7b7 ,eligibility 7#a7 ,in general ,a drug may be eligible for conditional approval under this section if such drug is intended to treat a disease or condition that is-- 7,a7 rapidly progressive1 terminal1 and has substantial unmet medical need1 as determined by the ,secretary2 or 7,b7 a rare disease or condition 7as defined in section #ebf7;a77#b77 that results in a substantially shortened lifespan1 substantial reduction in quality of life1 or other substantial adverse health effects1 as determined by the ,secretary4 7#b7 ,exclusion from eligibility ,a drug that is intended to treat or respond to a material threat identified by the ,secretary of ,homeland ,security under section #cai;,f-#b7;c77#b77;,a77ii7 shall not be eligible for conditional approval under this section4 7c7 ,standard of review for conditional approval 7#a7 ,requirements ,the ,secretary shall only approve an application for conditional approval of a drug under this section if-- 7,a7 the ,secretary determines that-- 7i7 7,i7 evidence of safety for the drug has been established by-- 7aa7 the completion of a phase #a clinical investigation of the drug 7as described in section #cab4ba of title #ba1 ,code of ,federal ,regulations 7or successor regulations772 or 7bb7 another demonstration of safety1 as determined appropriate by the ,secretary2 and 7,,ii7 evidence of effectiveness in treating a given indication 7which indication is congruent with the eligibility requirements of subsection 7b771 as established by an ongoing or completed phase #b clinical investigation of the drug 7as described in section #cab4ba of title #ba1 ,code of ,federal ,regulations 7or successor regulations772 or 7ii7 in the case of a drug that is intended to treat a terminal pediatric rare disease or condition 7as defined in section #ebf7;a77#b77 that does not predominately affect adults-- 7,i7 evidence of safety for the drug has been established in accordance with clause 7i77,i72 and 7,,ii7 the drug shows preliminary evidence of clinical effectiveness based upon studies in animal models2 and 7,b7 the sponsor has provided a written affirmation of the sponsor's intent to pursue under section #eje of this ,act or section #cea of the ,public ,health ,service ,act approval of the drug1 which affirmation shall include a justification and a plan for pursuing such approval4 7#b7 ,rolling1 real-time review 7,a7 ,in general ,if the ,secretary determines1 after preliminary evaluation of data submitted by the sponsor1 that a drug may meet the standard for conditional approval1 the sponsor may submit portions of an application for conditional approval of a drug under this section for evaluation by the ,secretary before the sponsor submits a complete application1 which submission shall include-- 7i7 a schedule for submission of information necessary to make the application complete2 and 7ii7 a payment of any fee that may be required under section #gcf4 7,b7 ,review ,the ,secretary-- 7i7 shall evaluate each application submitted under subparagraph 7,a7 to assess whether such application is complete or ready to be filed2 and 7ii7 may commence review of portions of such application for approval4 7#c7 ,use of real-world evidence 7,a7 ,in general ,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 and of external sources of data1 including prospective or retrospective natural history data1 to support an application for conditional approval under this section4 7,b7 ,data integrity requirements ,in using evidence described in subparagraph 7,a7 to support an application for conditional approval under this section1 the sponsor shall consider the guidance of the ,food and ,drug ,administration entitled ,data ,standards for ,drug and ,biological ,product ,submissions ,containing ,real-,world ,data and dated ,december #bjbc 7or successor guidance74 7d7 ,,fda authority ,to withdraw conditional approval 7#a7 ,in general ,the ,secretary may withdraw the conditional approval of a drug under this section if-- 7,a7 after adequate review of appropriate safety data1 including data from an observational registry established under subsection 7g71 the ,secretary determines that such data no longer supports conditional approval2 7,b7 the ,secretary determines that the application for conditional approval submitted under subsection 7a77#a7 contained an untrue statement of material fact2 or 7,c7 the ,secretary determines that the drug is no longer eligible under subsection 7b74 7#b7 ,,fda examination authority 7,a7 ,in general ,for purposes determining whether to withdraw the conditional approval of a drug under paragraph 7#a71 the ,secretary may-- 7i7 review any available clinical data made available through clinical trials or an observational registry under subsection 7g71 applicable to such drug2 and 7ii7 determine whether the sponsor of such drug is in violation of a requirement established under paragraph 7#c7 or 7#d7 of section #eje7o7 or section #eje-a with respect to the drug4 7,b7 ,transparency 7i7 ,in general ,the ,secretary may require drug sponsors and observational registries under subsection 7g7 to submit the data described in subparagraph 7,a7 for the purposes of the review under that subparagraph4 7ii7 ,fines ,the ,secretary may levy fines on sponsors and observational registries that do not comply with a request for data under clause 7i7 within such reasonable timeframe as is established by the ,secretary4 7#c7 ,effect of withdrawal 7,a7 ,availability to new patients 7i7 ,in general ,if a conditional approval is withdrawn under this subsection1 the sponsor may not make the drug available to any new patients1 but may continue to make such drug available to patients who started taking the drug prior to the date of withdrawal4 7ii7 ,effect ,nothing in this subparagraph shall be construed to require-- 7,i7 a patient to continue taking a conditionally approved drug if such patient decides to stop taking such drug2 or 7,,ii7 the sponsor to ensure such drug continues to be manufactured after the date of withdrawal4 7,b7 ,civil monetary penalty ,any sponsor who makes available to new patients a drug for which conditional approval has been withdrawn under this subsection shall be subject to such civil monetary penalty as is determined by the ,secretary4 7#d7 ,withdrawal notice ,upon determining to withdraw the conditional approval of a drug under paragraph 7#a71 the ,secretary shall submit written notice to the sponsor of such drug and such withdrawal shall be effective on the date that is #ad days after the date of such submission of notice4 7#e7 ,appeals ,not later than #ahj days after the date of enactment of the ,promising ,pathway ,act #b4j1 the ,secretary1 by rule1 shall establish a process by which a sponsor of a drug for which conditional approval was withdrawn under paragraph 7#a7 may appeal such withdrawal4 7#f7 ,automatic withdrawal 7,a7 ,in general ,if the sponsor of a drug that receives conditional approval under this section does not submit an application for renewal of such conditional approval under subsection 7f77#b7 by the deadline under that subsection1 such conditional approval shall automatically be withdrawn in accordance with paragraph 7#c7 on the date on which such conditional approval expires4 7,b7 ,marketing requirement ,if any drug that receives conditional approval under this section is not brought to market within #a year of the date on which the conditional approval is granted1 such conditional approval1 along with any benefits described in subsection 7a77#c71 shall automatically be withdrawn in accordance with paragraph 7#c7 on such date4 7,c7 ,no right to appeal2 effect of automatic withdrawal 7i7 ,in general ,a sponsor shall not have the right to appeal an automatic withdrawal under this paragraph4 7ii7 ,effect ,the ,secretary shall have no means or power to prevent an automatic withdrawal under this paragraph from occurring4 7e7 ,labeling2 review of materials 7#a7 ,in general ,sponsors may not make available to patients a drug conditionally approved under this section1 unless-- 7,a7 all labeling and advertising of such drug contains the statement conditionally approved for a limited population in a prominent manner and adjacent to1 and not more prominent than-- 7i7 the proprietary name of such drug1 if any2 or 7ii7 if there is no proprietary name1 the established name of such drug1 if any1 as defined in section #ejb7;e77#c71 or1 in the case of a drug that is a biological product1 the proper name1 as defined by regulation2 and 7,b7 the prescribing information for the drug required by section #bja4eg of title #ba1 ,code of ,federal ,regulations 7or any successor regulation7 includes the following statement3 ,this drug is conditionally approved for use in a limited and specific population4 ,this drug has not received full approval by the ,food and ,drug ,administration4 ,conditional approval of this drug may be withdrawn at short notice44 7#b7 ,submission ,not later than #de days before such materials are distributed1 all promotional1 educational1 and marketing materials for such drug shall be submitted to the ,secretary for review4 7#c7 ,public list ,the ,secretary shall maintain a list of all drugs conditionally approved under this section on a publicly accessible website4 ,such website shall briefly describe what each conditionally approved drugs is and list the #a or more diseases or conditions for which the drug is indicated4 7f7 ,renewal of conditional approval2 requirement ,to bring drug to market 7#a7 ,duration2 renewals ,the conditional approval for a drug under this section is effective for a #b-year period4 ,the sponsor may request renewal of such conditional approval for up to #c subsequent #b-year periods4 ,conditional approval with respect to a drug shall not exceed a total of #h years from the initial date the drug was granted conditional approval4 7#b7 ,applications for renewal of conditional approval 7,a7 ,in general ,except as provided in subparagraph 7,c71 the sponsor of a drug seeking a renewal of conditional approval for such drug under this subsection shall submit to the ,secretary1 not later than #ahj days before the date on which such conditional approval expires1 an application that contains the applicable information described in paragraph 7#c7 in a standardized format determined by the ,secretary4 7,b7 ,process for granting renewals ,not later than #ahj days after the date of enactment of the ,promising ,pathway ,act #b4j1 the ,secretary1 by rule1 shall establish the process for granting a renewal under this subsection4 7,c7 ,exemption for small population diseases 7i7 ,in general ,the ,secretary shall exempt from the requirements of subparagraph 7,a7 and paragraph 7#c7 an application for a renewal of conditional approval for a drug under this subsection if the ,secretary determines that the population affected by the disease or condition that the drug is intended to treat does not support additional preliminary evidence of effectiveness 7as defined in paragraph 7#c77;,d774 7ii7 ,application for exemption ,sponsors may submit an application for exemption under this subparagraph not later than #ahj days before the date on which the conditional approval expires4 7iii7 ,application process ,not later than #ahj days after the date of enactment of the ,promising ,pathway ,act #b4j1 the ,secretary shall establish a standardized application process for purposes of this subparagraph4 7iv7 ,deadline ,the ,secretary shall approve or deny an application under this subparagraph before the date on which the conditional approval expires4 7v7 ,appeals ,not later than #ahj days after the date of enactment of the ,promising ,pathway ,act #b4j1 the ,secretary shall establish a process under which a sponsor my appeal a denial of an application under this subparagraph4 7#c7 ,additional preliminary evidence of effectiveness ,the information described in this paragraph is the following3 7,a7 ,for the first approval renewal ,with respect to an application under paragraph 7#b7 for the first renewal of conditional approval for a drug under this subsection1 additional preliminary evidence of effectiveness of the drug1 as compared to the evidence provided in the initial application for conditional approval for the drug under subsection 7c74 7,b7 ,for the second approval renewal ,with respect to an application under paragraph 7#b7 for the second renewal of conditional approval for a drug under this subsection1 additional preliminary evidence of effectiveness of the drug1 as compared to the evidence provided in the renewal application described in subparagraph 7,a74 7,c7 ,for the final approval renewal ,with respect to an application under paragraph 7#b7 for the third renewal of conditional approval for a drug under this subsection1 a written affirmation from the head of the drug's review division of the ,office of ,new ,drugs or the ,office of ,therapeutic ,products asserting that a third renewal is necessary-- 7i7 for patients who have benefitted from such drug to retain access to such drug2 and 7ii7 to generate additional preliminary evidence of effectiveness for the purposes of attaining approval under section #eje of this ,act or section #cea of the ,public ,health ,service ,act4 7,d7 ,definition ,in this paragraph1 the term preliminary evidence of effectiveness means-- 7i7 clinical evidence generated by an ongoing or completed clinical trial conducted in accordance with section #aa4bb of title #db1 ,code of ,federal ,regulations 7or successor regulations72 7ii7 real-world evidence 7as defined in section #eje;,f7b772 or 7iii7 evidence from an observational registry under subsection 7g74 7#d7 ,denial of renewal on the basis of data fraud ,the ,secretary may deny the application for renewal of conditional approval for a drug under this subsection if the ,secretary1 in conducting a review under subsection 7d77#b71 finds that the evidence provided in such application under subparagraph 7,a7 or 7,b7 of paragraph 7#c7 was fraudulently manipulated by the applicable observational registry and that such application substantially relies on such data4 7g7 ,observational registries 7#a7 ,establishment 7,a7 ,in general ,subject to subparagraph 7,c71 the sponsor of a drug conditionally approved under this section shall establish an observational registry1 for patients who are or will be treated with such drug1 that pertains to the disease or condition that the drug is intended to treat4 7,b7 ,registries ,in establishing an observational registry for a drug under subparagraph 7,a71 the sponsor may-- 7i7 establish a new observational registry2 7ii7 use an existing observational registry that pertains to the disease or condition such drug is intended to treat2 7iii7 combine #a or more existing observational registries that pertain to the disease or condition such drug is intended to treat with a new observational registry2 or 7iv7 combine #b or more existing observational registries that pertain to the disease or condition such drug is intended to treat4 7,c7 ,approval of registry and right to appeal ,not later than #ahj days after the date of enactment of the ,promising ,pathway ,act #b4j1 the ,secretary shall establish-- 7i7 a process to approve or deny the establishment of an observational registry under subparagraph 7,a72 and 7ii7 a process for sponsors that received such a denial to appeal the denial4 7#b7 ,requirement for patients to enroll in observational registry 7,a7 ,in general ,a drug conditionally approved under this section shall not be made available to a patient unless such patient is enrolled in the applicable observational registry described in paragraph 7#a74 7,b7 ,informed consent 7i7 ,in general ,prior to enrolling in an observational registry under subparagraph 7,a71 a patient shall provide informed consent in accordance with clause 7ii74 7ii7 ,application of certain requirements ,the requirements for informed consent under part #ej of subchapter ,a of chapter ,i of title #ba1 ,code of ,federal ,regulations 7or successor regulations71 shall apply to enrollment an observational registry under this paragraph4 7#c7 ,submission of patient data 7,a7 ,in general ,the sponsor of a drug conditionally approved under this section shall be responsible for obtaining and submitting patient data to the applicable observational registry described in paragraph 7#a74 7,b7 ,submission standards ,not later than #ahj days after date of enactment of the ,promising ,pathway ,act #b4j1 the ,secretary shall establish data submission standards for sponsors to comply with for purposes of subparagraph 7,a7 to ensure that registry data is consistent and clinically informed4 7#d7 ,requirements for registries ,an observational registry described in paragraph 7#a7 for a drug conditionally approved under this section may be operated by the sponsor of such drug or1 at the sponsor's discretion1 a third party1 for-profit organization1 or nonprofit organization4 7#e7 ,risk and benefit data 7,a7 ,in general ,the sponsor of a drug conditionally approved under this section shall submit relevant risk and benefit data to the applicable observational registry described in paragraph 7#a74 7,b7 ,online portal ,the ,secretary shall operate an online portal on an existing website of the ,secretary for sponsors to submit data described in subparagraph 7,a74 7#f7 ,accessibility 7,a7 ,in general ,an observational registry described in paragraph 7#a7 shall-- 7i7 not later than #cj days after receipt of a request1 provide patients 7or their designated representatives7 with access to such patient's personal registry information2 and 7ii7 provide approved researchers and medical professionals access to de-identified and aggregated data from the registry for the purposes of indication- and disease-specific and translational research into conditions and diseases relating to the disease or condition that the drug tracked by the observational registry is intended to treat4 7,b7 ,approved researchers and medical professionals ,not later than #ahj days after the date of enactment of the ,promising ,pathway ,act #b4j1 the ,secretary1 by rule1 shall establish a process for approving researchers and medical professionals for purposes of subparagraph 7,a77ii74 7#g7 ,effect ,nothing in this section shall be construed to modify or limit the ,secretary's authority to require for a drug conditionally approved under this section any type of postapproval study under any other provision of law1 including sections #eje7o77#c71 #eje;,b1 and #ejf4 7h7 ,pursuit of a different indication 7#a7 ,in general ,in the case of a drug conditionally approved under this section for which such approval was withdrawn under subsection 7d71 expired under subsection 7f77#a71 or was denied for renewal under subsection 7f77#d71 not later than #b years after the date of withdrawal1 expiration1 or denial1 as applicable1 the sponsor of such drug shall have the opportunity to petition the ,secretary to receive conditional approval of such drug1 in accordance with this section1 for a different indication4 7#b7 ,process ,not later than #ahj days after the date of enactment of the ,promising ,pathway ,act #b4j1 the ,secretary shall establish a process for petitions under paragraph 7#a74 7i7 ,transition to other forms of approval 7#a7 ,in general ,a drug that receives conditional approval under this section may be granted approval under section #eje of this ,act or section #cea of the ,public ,health ,service ,act during the period in which such conditional approval is in effect4 ,effective on the date on which approval for such drug is granted under section #eje of this ,act or section #cea of the ,public ,health ,service ,act1 such conditional approval shall be automatically withdrawn in accordance with subsection 7d77#c74 7#b7 ,consideration of certain evidence ,in determining whether to approve under section #eje of this ,act or section #cea of the ,public ,health ,service ,act a drug that has received conditional approval under this section1 the ,secretary may consider evidence from the observational registry for the drug under subsection 7g74 7j7 ,informed consent 7#a7 ,in general ,prior to being prescribed a drug conditionally approved under this section1 a patient shall provide informed consent in accordance with paragraph 7#b74 7#b7 ,application of certain requirements ,the requirements for informed consent under part #ej of subchapter ,a of chapter ,i of title #ba1 ,code of ,federal ,regulations 7or successor regulations71 shall apply to drugs conditionally approved under this section4 7#c7 ,observational registries ,an observational registry established for a drug in accordance with subsection 7g7 may obtain1 and maintain records of1 informed consent of a patient on behalf of the drug sponsor1 in accordance with paragraph 7#b74 7#d7 ,common rule ,drugs conditionally approved under this section shall comply with subpart ,a of part #df of title #de1 ,code of ,federal ,regulations 7commonly known as the ,common ,rule7 7or successor regulations71 if applicable4 7k7 ,limitation on liability ,with respect to any claim under ,state law relating to a drug made available pursuant to a grant of conditional approval under this section1 no liability shall lie against a sponsor or manufacturer of the drug1 or any health care provider who prescribes or administers the drug1 absent intentional wrongdoing4 7l7 ,report to ,congress 7#a7 ,in general ,not later than #b years after the date of enactment of the ,promising ,pathway ,act #b4j1 and once every #b years thereafter1 the ,secretary1 in collaboration with drug sponsors1 shall submit a report to ,congress on all drugs granted conditional approval under this section4 ,such report shall include-- 7,a7 an estimated number of patients treated with each such drug1 and the number of patients tracked in an observational registry under subsection 7g7 with respect to each such drug1 if applicable2 7,b7 a discussion1 at an aggregate level 1 of the types and amounts of data obtained through observational registries under subsection 7g71 such as patient treatments and uses1 length of use1 side effects encountered1 relevant biomarkers1 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 this section1 or an application for an extension of conditional approval under this section1 has been submitted2 and 7,d7 the number of all applications granted and denied conditional approval under this section4 7#b7 ,sponsor participation ,not later than #ahj days before the date on which the ,secretary submits a report under paragraph 7#a71 the sponsor of a drug conditionally approved under this section shall provide to the ,secretary the information described in subparagraphs 7,a7 and 7,b7 of paragraph 7#a71 as applicable4 7#c7 ,notice authority ,the ,secretary may notify sponsors of drugs conditionally approved under this section and observational registries under subsection 7g7 as necessary to complete a report under paragraph 7#a74 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 conditional 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 ,coverage of certain drugs ,a group health plan or health insurance issuer offering group or individual health insurance coverage shall provide coverage for1 and shall not impose any cost sharing requirements for1 drugs conditionally approved under section #ebd;,c of the ,federal ,food1 ,drug1 and ,cosmetic ,act for patients who have the disease or condition the drug is intended to treat4 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 conditionally approved under section #ebd;,c of such ,act before the semicolon4