[Congressional Bills 118th Congress]
[From the U.S. Government Publishing Office]
[S. 4426 Introduced in Senate (IS)]
<DOC>
118th CONGRESS
2d Session
S. 4426
To amend the Federal Food, Drug, and Cosmetic Act to establish a time-
limited conditional approval pathway, subject to specific obligations,
for certain drugs and biological products, and for other purposes.
_______________________________________________________________________
IN THE SENATE OF THE UNITED STATES
May 23, 2024
Mr. Braun (for himself, Mrs. Gillibrand, Mr. Cramer, Mr. Manchin, Mr.
Schmitt, Mr. Padilla, Mr. Vance, Mr. Booker, Mr. Hawley, Mr. Welch, 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 conditional approval pathway, subject to specific obligations,
for certain drugs and biological products, and for other purposes.
Be it enacted by the Senate and House of Representatives of the
United States of America in Congress assembled,
SECTION 1. SHORT TITLE.
This Act may be cited as the ``Promising Pathway Act 2.0''.
SEC. 2. CONDITIONAL APPROVAL OF NEW HUMAN DRUGS FOR INDIVIDUALS WITH
RARE, PROGRESSIVE, AND SERIOUS DISEASES.
(a) In General.--Subchapter A of chapter V of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 351 et seq.) is amended by adding at
the end of the following:
``SEC. 524C. CONDITIONAL APPROVAL OF HUMAN DRUGS FOR INDIVIDUALS WITH
RARE, PROGRESSIVE, AND SERIOUS DISEASES.
``(a) Conditional Approval; Priority Review; Other Designations.--
``(1) In general.--The sponsor of a drug may file with the
Secretary an application for conditional approval of an
eligible drug described in subsection (b). The Secretary shall
approve or deny such application in accordance with subsection
(c).
``(2) Priority review.--The Secretary shall give priority
review to an application for conditional approval of an
eligible drug described in subsection (b).
``(3) Other designations.--If a drug that is granted
conditional approval under this section is eligible for a
special designation by the Secretary under this Act, including
as a drug for a rare disease or condition under section 526,
all applicable benefits of such other designation shall be
available for use under such conditional approval, including
any tax credits and waiving of fees under chapter VII.
``(4) Other programs.--A sponsor of a drug seeking
conditional approval of such drug under this section may also
seek designation, exclusivity, or approval, as applicable, of
such drug under other applicable provisions of this Act or the
Public Health Service Act, subject to the requirements of such
provisions.
``(b) Eligibility.--
``(1) 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--
``(A) rapidly progressive, terminal, and has
substantial unmet medical need, as determined by the
Secretary; or
``(B) a rare disease or condition (as defined in
section 526(a)(2)) that results in a substantially
shortened lifespan, substantial reduction in quality of
life, or other substantial adverse health effects, as
determined by the Secretary.
``(2) 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 319F-
2(c)(2)(A)(ii) shall not be eligible for conditional approval
under this section.
``(c) Standard of Review for Conditional Approval.--
``(1) Requirements.--The Secretary shall only approve an
application for conditional approval of a drug under this
section if--
``(A) the Secretary determines that--
``(i)(I) evidence of safety for the drug
has been established by--
``(aa) the completion of a phase 1
clinical investigation of the drug (as
described in section 312.21 of title
21, Code of Federal Regulations (or
successor regulations)); or
``(bb) another demonstration of
safety, as determined appropriate by
the Secretary; and
``(II) evidence of effectiveness in
treating a given indication (which indication
is congruent with the eligibility requirements
of subsection (b)), as established by an
ongoing or completed phase 2 clinical
investigation of the drug (as described in
section 312.21 of title 21, Code of Federal
Regulations (or successor regulations)); or
``(ii) in the case of a drug that is
intended to treat a terminal pediatric rare
disease or condition (as defined in section
526(a)(2)) that does not predominately affect
adults--
``(I) evidence of safety for the
drug has been established in accordance
with clause (i)(I); and
``(II) the drug shows preliminary
evidence of clinical effectiveness
based upon studies in animal models;
and
``(B) the sponsor has provided a written
affirmation of the sponsor's intent to pursue under
section 505 of this Act or section 351 of the Public
Health Service Act approval of the drug, which
affirmation shall include a justification and a plan
for pursuing such approval.
``(2) Rolling, real-time review.--
``(A) In general.--If the Secretary determines,
after preliminary evaluation of data submitted by the
sponsor, that a drug may meet the standard for
conditional approval, 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 application,
which submission shall include--
``(i) a schedule for submission of
information necessary to make the application
complete; and
``(ii) a payment of any fee that may be
required under section 736.
``(B) Review.--The Secretary--
``(i) shall evaluate each application
submitted under subparagraph (A) to assess
whether such application is complete or ready
to be filed; and
``(ii) may commence review of portions of
such application for approval.
``(3) Use of real-world evidence.--
``(A) In general.--The Secretary shall allow the
use of real world evidence (as defined in section
505F(b)), including real world data used to generate
real world evidence, and of external sources of data,
including prospective or retrospective natural history
data, to support an application for conditional
approval under this section.
``(B) Data integrity requirements.--In using
evidence described in subparagraph (A) to support an
application for conditional approval under this
section, 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 2023 (or successor
guidance).
``(d) FDA Authority To Withdraw Conditional Approval.--
``(1) In general.--The Secretary may withdraw the
conditional approval of a drug under this section if--
``(A) after adequate review of appropriate safety
data, including data from an observational registry
established under subsection (g), the Secretary
determines that such data no longer supports
conditional approval;
``(B) the Secretary determines that the application
for conditional approval submitted under subsection
(a)(1) contained an untrue statement of material fact;
or
``(C) the Secretary determines that the drug is no
longer eligible under subsection (b).
``(2) FDA examination authority.--
``(A) In general.--For purposes determining whether
to withdraw the conditional approval of a drug under
paragraph (1), the Secretary may--
``(i) review any available clinical data
made available through clinical trials or an
observational registry under subsection (g),
applicable to such drug; and
``(ii) determine whether the sponsor of
such drug is in violation of a requirement
established under paragraph (3) or (4) of
section 505(o) or section 505-1 with respect to
the drug.
``(B) Transparency.--
``(i) In general.--The Secretary may
require drug sponsors and observational
registries under subsection (g) to submit the
data described in subparagraph (A) for the
purposes of the review under that subparagraph.
``(ii) Fines.--The Secretary may levy fines
on sponsors and observational registries that
do not comply with a request for data under
clause (i) within such reasonable timeframe as
is established by the Secretary.
``(3) Effect of withdrawal.--
``(A) Availability to new patients.--
``(i) In general.--If a conditional
approval is withdrawn under this subsection,
the sponsor may not make the drug available to
any new patients, but may continue to make such
drug available to patients who started taking
the drug prior to the date of withdrawal.
``(ii) Effect.--Nothing in this
subparagraph shall be construed to require--
``(I) a patient to continue taking
a conditionally approved drug if such
patient decides to stop taking such
drug; or
``(II) the sponsor to ensure such
drug continues to be manufactured after
the date of withdrawal.
``(B) 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 Secretary.
``(4) Withdrawal notice.--Upon determining to withdraw the
conditional approval of a drug under paragraph (1), the
Secretary shall submit written notice to the sponsor of such
drug and such withdrawal shall be effective on the date that is
14 days after the date of such submission of notice.
``(5) Appeals.--Not later than 180 days after the date of
enactment of the Promising Pathway Act 2.0, the Secretary, by
rule, shall establish a process by which a sponsor of a drug
for which conditional approval was withdrawn under paragraph
(1) may appeal such withdrawal.
``(6) Automatic withdrawal.--
``(A) 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 (f)(2) by the
deadline under that subsection, such conditional
approval shall automatically be withdrawn in accordance
with paragraph (3) on the date on which such
conditional approval expires.
``(B) Marketing requirement.--If any drug that
receives conditional approval under this section is not
brought to market within 1 year of the date on which
the conditional approval is granted, such conditional
approval, along with any benefits described in
subsection (a)(3), shall automatically be withdrawn in
accordance with paragraph (3) on such date.
``(C) No right to appeal; effect of automatic
withdrawal.--
``(i) In general.--A sponsor shall not have
the right to appeal an automatic withdrawal
under this paragraph.
``(ii) Effect.--The Secretary shall have no
means or power to prevent an automatic
withdrawal under this paragraph from occurring.
``(e) Labeling; Review of Materials.--
``(1) In general.--Sponsors may not make available to
patients a drug conditionally approved under this section,
unless--
``(A) all labeling and advertising of such drug
contains the statement `conditionally approved for a
limited population' in a prominent manner and adjacent
to, and not more prominent than--
``(i) the proprietary name of such drug, if
any; or
``(ii) if there is no proprietary name, the
established name of such drug, if any, as
defined in section 502(e)(3), or, in the case
of a drug that is a biological product, the
proper name, as defined by regulation; and
``(B) the prescribing information for the drug
required by section 201.57 of title 21, Code of Federal
Regulations (or any successor regulation) includes the
following statement: `This drug is conditionally
approved for use in a limited and specific population.
This drug has not received full approval by the Food
and Drug Administration. Conditional approval of this
drug may be withdrawn at short notice.'.
``(2) Submission.--Not later than 45 days before such
materials are distributed, all promotional, educational, and
marketing materials for such drug shall be submitted to the
Secretary for review.
``(3) Public list.--The Secretary shall maintain a list of
all drugs conditionally approved under this section on a
publicly accessible website. Such website shall briefly
describe what each conditionally approved drugs is and list the
1 or more diseases or conditions for which the drug is
indicated.
``(f) Renewal of Conditional Approval; Requirement To Bring Drug to
Market.--
``(1) Duration; renewals.--The conditional approval for a
drug under this section is effective for a 2-year period. The
sponsor may request renewal of such conditional approval for up
to 3 subsequent 2-year periods. Conditional approval with
respect to a drug shall not exceed a total of 8 years from the
initial date the drug was granted conditional approval.
``(2) Applications for renewal of conditional approval.--
``(A) In general.--Except as provided in
subparagraph (C), the sponsor of a drug seeking a
renewal of conditional approval for such drug under
this subsection shall submit to the Secretary, not
later than 180 days before the date on which such
conditional approval expires, an application that
contains the applicable information described in
paragraph (3) in a standardized format determined by
the Secretary.
``(B) Process for granting renewals.--Not later
than 180 days after the date of enactment of the
Promising Pathway Act 2.0, the Secretary, by rule,
shall establish the process for granting a renewal
under this subsection.
``(C) Exemption for small population diseases.--
``(i) In general.--The Secretary shall
exempt from the requirements of subparagraph
(A) and paragraph (3) 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 (as
defined in paragraph (3)(D)).
``(ii) Application for exemption.--Sponsors
may submit an application for exemption under
this subparagraph not later than 180 days
before the date on which the conditional
approval expires.
``(iii) Application process.--Not later
than 180 days after the date of enactment of
the Promising Pathway Act 2.0, the Secretary
shall establish a standardized application
process for purposes of this subparagraph.
``(iv) Deadline.--The Secretary shall
approve or deny an application under this
subparagraph before the date on which the
conditional approval expires.
``(v) Appeals.--Not later than 180 days
after the date of enactment of the Promising
Pathway Act 2.0, the Secretary shall establish
a process under which a sponsor my appeal a
denial of an application under this
subparagraph.
``(3) Additional preliminary evidence of effectiveness.--
The information described in this paragraph is the following:
``(A) For the first approval renewal.--With respect
to an application under paragraph (2) for the first
renewal of conditional approval for a drug under this
subsection, additional preliminary evidence of
effectiveness of the drug, as compared to the evidence
provided in the initial application for conditional
approval for the drug under subsection (c).
``(B) For the second approval renewal.--With
respect to an application under paragraph (2) for the
second renewal of conditional approval for a drug under
this subsection, additional preliminary evidence of
effectiveness of the drug, as compared to the evidence
provided in the renewal application described in
subparagraph (A).
``(C) For the final approval renewal.--With respect
to an application under paragraph (2) for the third
renewal of conditional approval for a drug under this
subsection, 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--
``(i) for patients who have benefitted from
such drug to retain access to such drug; and
``(ii) to generate additional preliminary
evidence of effectiveness for the purposes of
attaining approval under section 505 of this
Act or section 351 of the Public Health Service
Act.
``(D) Definition.--In this paragraph, the term
`preliminary evidence of effectiveness' means--
``(i) clinical evidence generated by an
ongoing or completed clinical trial conducted
in accordance with section 11.22 of title 42,
Code of Federal Regulations (or successor
regulations);
``(ii) real-world evidence (as defined in
section 505F(b)); or
``(iii) evidence from an observational
registry under subsection (g).
``(4) 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 Secretary, in
conducting a review under subsection (d)(2), finds that the
evidence provided in such application under subparagraph (A) or
(B) of paragraph (3) was fraudulently manipulated by the
applicable observational registry and that such application
substantially relies on such data.
``(g) Observational Registries.--
``(1) Establishment.--
``(A) In general.--Subject to subparagraph (C), the
sponsor of a drug conditionally approved under this
section shall establish an observational registry, for
patients who are or will be treated with such drug,
that pertains to the disease or condition that the drug
is intended to treat.
``(B) Registries.--In establishing an observational
registry for a drug under subparagraph (A), the sponsor
may--
``(i) establish a new observational
registry;
``(ii) use an existing observational
registry that pertains to the disease or
condition such drug is intended to treat;
``(iii) combine 1 or more existing
observational registries that pertain to the
disease or condition such drug is intended to
treat with a new observational registry; or
``(iv) combine 2 or more existing
observational registries that pertain to the
disease or condition such drug is intended to
treat.
``(C) Approval of registry and right to appeal.--
Not later than 180 days after the date of enactment of
the Promising Pathway Act 2.0, the Secretary shall
establish--
``(i) a process to approve or deny the
establishment of an observational registry
under subparagraph (A); and
``(ii) a process for sponsors that received
such a denial to appeal the denial.
``(2) Requirement for patients to enroll in observational
registry.--
``(A) 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 (1).
``(B) Informed consent.--
``(i) In general.--Prior to enrolling in an
observational registry under subparagraph (A),
a patient shall provide informed consent in
accordance with clause (ii).
``(ii) Application of certain
requirements.--The requirements for informed
consent under part 50 of subchapter A of
chapter I of title 21, Code of Federal
Regulations (or successor regulations), shall
apply to enrollment an observational registry
under this paragraph.
``(3) Submission of patient data.--
``(A) 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 (1).
``(B) Submission standards.--Not later than 180
days after date of enactment of the Promising Pathway
Act 2.0, the Secretary shall establish data submission
standards for sponsors to comply with for purposes of
subparagraph (A) to ensure that registry data is
consistent and clinically informed.
``(4) Requirements for registries.--An observational
registry described in paragraph (1) for a drug conditionally
approved under this section may be operated by the sponsor of
such drug or, at the sponsor's discretion, a third party, for-
profit organization, or nonprofit organization.
``(5) Risk and benefit data.--
``(A) 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 (1).
``(B) Online portal.--The Secretary shall operate
an online portal on an existing website of the
Secretary for sponsors to submit data described in
subparagraph (A).
``(6) Accessibility.--
``(A) In general.--An observational registry
described in paragraph (1) shall--
``(i) not later than 30 days after receipt
of a request, provide patients (or their
designated representatives) with access to such
patient's personal registry information; and
``(ii) 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 treat.
``(B) Approved researchers and medical
professionals.--Not later than 180 days after the date
of enactment of the Promising Pathway Act 2.0, the
Secretary, by rule, shall establish a process for
approving researchers and medical professionals for
purposes of subparagraph (A)(ii).
``(7) 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 law, including
sections 505(o)(3), 505B, and 506.
``(h) Pursuit of a Different Indication.--
``(1) In general.--In the case of a drug conditionally
approved under this section for which such approval was
withdrawn under subsection (d), expired under subsection
(f)(1), or was denied for renewal under subsection (f)(4), not
later than 2 years after the date of withdrawal, expiration, or
denial, as applicable, the sponsor of such drug shall have the
opportunity to petition the Secretary to receive conditional
approval of such drug, in accordance with this section, for a
different indication.
``(2) Process.--Not later than 180 days after the date of
enactment of the Promising Pathway Act 2.0, the Secretary shall
establish a process for petitions under paragraph (1).
``(i) Transition to Other Forms of Approval.--
``(1) In general.--A drug that receives conditional
approval under this section may be granted approval under
section 505 of this Act or section 351 of the Public Health
Service Act during the period in which such conditional
approval is in effect. Effective on the date on which approval
for such drug is granted under section 505 of this Act or
section 351 of the Public Health Service Act, such conditional
approval shall be automatically withdrawn in accordance with
subsection (d)(3).
``(2) Consideration of certain evidence.--In determining
whether to approve under section 505 of this Act or section 351
of the Public Health Service Act a drug that has received
conditional approval under this section, the Secretary may
consider evidence from the observational registry for the drug
under subsection (g).
``(j) Informed Consent.--
``(1) In general.--Prior to being prescribed a drug
conditionally approved under this section, a patient shall
provide informed consent in accordance with paragraph (2).
``(2) Application of certain requirements.--The
requirements for informed consent under part 50 of subchapter A
of chapter I of title 21, Code of Federal Regulations (or
successor regulations), shall apply to drugs conditionally
approved under this section.
``(3) Observational registries.--An observational registry
established for a drug in accordance with subsection (g) may
obtain, and maintain records of, informed consent of a patient
on behalf of the drug sponsor, in accordance with paragraph
(2).
``(4) Common rule.--Drugs conditionally approved under this
section shall comply with subpart A of part 46 of title 45,
Code of Federal Regulations (commonly known as the `Common
Rule') (or successor regulations), if applicable.
``(k) 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 section, no liability shall lie against
a sponsor or manufacturer of the drug, or any health care provider who
prescribes or administers the drug, absent intentional wrongdoing.
``(l) Report to Congress.--
``(1) In general.--Not later than 2 years after the date of
enactment of the Promising Pathway Act 2.0, and once every 2
years thereafter, the Secretary, in collaboration with drug
sponsors, shall submit a report to Congress on all drugs
granted conditional approval under this section. Such report
shall include--
``(A) an estimated number of patients treated with
each such drug, and the number of patients tracked in
an observational registry under subsection (g) with
respect to each such drug, if applicable;
``(B) a discussion, at an aggregate level , of the
types and amounts of data obtained through
observational registries under subsection (g), such as
patient treatments and uses, length of use, side
effects encountered, relevant biomarkers, scan results,
cause of death and how long the patient lived, and
adverse drug effects;
``(C) a list of all such drugs for which an
application for approval under this section, or an
application for an extension of conditional approval
under this section, has been submitted; and
``(D) the number of all applications granted and
denied conditional approval under this section.
``(2) Sponsor participation.--Not later than 180 days
before the date on which the Secretary submits a report under
paragraph (1), the sponsor of a drug conditionally approved
under this section shall provide to the Secretary the
information described in subparagraphs (A) and (B) of paragraph
(1), as applicable.
``(3) Notice authority.--The Secretary may notify sponsors
of drugs conditionally approved under this section and
observational registries under subsection (g) as necessary to
complete a report under paragraph (1).''.
(b) Conforming Amendment.--Section 505(a) of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 355(a)) is amended by inserting ``,
or there is in effect a conditional approval under section 524C with
respect to such drug'' before the period.
(c) Reimbursement.--
(1) Private health insurers.--Section 2719A of the Public
Health Service Act (42 U.S.C. 300gg-19a) is amended by adding
at the end the following:
``(f) Coverage of Certain Drugs.--A group health plan or health
insurance issuer offering group or individual health insurance coverage
shall provide coverage for, and shall not impose any cost sharing
requirements for, drugs conditionally approved under section 524C of
the Federal Food, Drug, and Cosmetic Act for patients who have the
disease or condition the drug is intended to treat.''.
(2) Federal health care programs.--The requirement under
subsection (f) of section 2719A of the Public Health Service
Act (as added by paragraph (1)) shall apply with respect to
coverage determinations under a Federal health care program (as
defined in section 1128B(f) of the Social Security Act (42
U.S.C. 1320a-7b(f))) in the same manner such requirement
applies under such subsection (f).
(3) Conforming amendment.--Section 1927(k)(2)(A)(i) of the
Social Security Act (42 U.S.C. 1396r-8(k)(2)(A)(i)) is
amended--
(A) by striking ``or which'' and inserting ``,
which''; and
(B) by inserting ``, or which is conditionally
approved under section 524C of such Act'' before the
semicolon.
<all>