[Federal Register Volume 87, Number 207 (Thursday, October 27, 2022)]
[Notices]
[Pages 65085-65088]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-23383]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-N-2480]


Rare Disease Endpoint Advancement Pilot Meeting Program

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The seventh iteration of the Prescription Drug User Fee 
Amendments (PDUFA VII) included as part of the FDA User Fee 
Reauthorization Act of 2022 highlights the goal of advancing and 
facilitating the development and timely approval of drugs and 
biological products for rare diseases, including rare diseases in 
children. The Food and Drug Administration (FDA or Agency) is 
announcing the Rare Disease Endpoint Advancement Pilot Meeting Program 
(RDEA Pilot Program) established under the seventh iteration of PDUFA 
that affords sponsors who are admitted into the RDEA Pilot Program 
additional engagement opportunities with the Agency to discuss efficacy 
endpoint development in rare disease drug and

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biological product development programs. Meetings under the program 
will be conducted by FDA's Center for Drug Evaluation and Research 
(CDER) or Center for Biologics Evaluation and Research (CBER) during 
fiscal years (FYs) 2023 to 2027. For each sponsor whose RDEA program 
proposal (RDEA proposal or proposal) is admitted into the program, up 
to four meetings that will provide an opportunity for medical product 
developers to discuss rare disease endpoint development will be held 
between the sponsor and CDER or CBER. To promote innovation and 
evolving science, novel endpoints developed through the RDEA Pilot 
Program may be presented by FDA (e.g., in a guidance or public workshop 
or on a public-facing website) as case studies, including novel 
endpoints for drugs that have not yet been approved or biological 
products that have not yet been licensed by FDA for a given indication.

DATES: The RDEA Pilot Program will proceed from October 1, 2022, 
through September 30, 2027. Sponsors may submit RDEA program proposals 
beginning July 1, 2023, through June 30, 2027. Submit either electronic 
or written comments about this program by December 27, 2022.

ADDRESSES: You may submit comments about the RDEA Pilot Program as 
follows. Please note that late, untimely filed comments will not be 
considered. The https://www.regulations.gov electronic filing system 
will accept comments until 11:59 p.m. Eastern Time December 27, 2022. 
Comments received by mail/hand delivery/courier (for written/paper 
submissions) will be considered timely if they are received on or 
before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked, and identified 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2022-N-2480 for ``Rare Disease Endpoint Advancement Pilot 
Program.'' Received comments, those filed in a timely manner (see 
ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday, 240-402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.

FOR FURTHER INFORMATION CONTACT: Mary Jo Salerno, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Silver Spring, MD 20993-0002, 240-402-0420, 
[email protected], with the subject line ``RDEA Pilot Meeting 
Program for CDER'' or Julienne Vaillancourt, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 7252, Silver Spring, MD 20993-0002, 301-
796-1827, [email protected], with the subject line ``RDEA Pilot 
Meeting Program for CBER.'' Additional information is available on the 
RDEA Pilot Program web page: https://www.fda.gov/drugs/development-resources/rare-disease-endpoint-advancement-pilot-program.

SUPPLEMENTARY INFORMATION:

I. Background

    In connection with the seventh iteration of PDUFA, FDA committed to 
conduct a pilot program to advance rare disease drug development 
programs by providing a mechanism for sponsors to collaborate with FDA 
throughout the efficacy endpoint development process (see ``PDUFA 
Reauthorization Performance Goals and Procedures Fiscal Years 2023 
Through 2027,'' section I.K.4.a, https://www.fda.gov/media/151712/download).
    FDA is announcing this pilot program to satisfy the above-mentioned 
commitment. The goals of the early meeting discussions granted under 
this program are to provide advice on how a proposed novel endpoint can 
be used in a specific rare disease drug development program and to 
promote innovation by allowing FDA to publicly present the proposed 
novel endpoints (or natural history studies in which the proposed 
endpoint is intended to be studied) considered through the program, 
including novel endpoints for drugs or biological products that have

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not yet been approved or licensed by FDA for a given indication. FDA 
has committed to accepting a limited number of qualified proposals for 
admission into the RDEA Pilot Program that increases after the first 
year of PDUFA VII. For FY 2023, sponsors may submit RDEA proposals 
beginning in the fourth quarter, and FDA will accept a maximum of one 
proposal. For FYs 2024 through 2027, FDA will accept up to one RDEA 
proposal per quarter with a maximum of three proposals per year.
    Complete RDEA proposals may be submitted throughout the quarter on 
a rolling basis; however, only those received by the quarterly closing 
date, which will be the last day of each quarter of the fiscal year 
(i.e., December 31, March 31, June 30, September 30), will be 
considered for selection in the following quarter. Within 60 days after 
the quarterly closing date, FDA will review the RDEA proposals, select 
a proposal to proceed to disclosure discussions, and notify sponsors of 
their proposal status. When FDA and the sponsor agree on the 
information that FDA may share publicly, FDA will notify the sponsor of 
admission into the program.
    Sponsors admitted to the RDEA Pilot Program may participate in up 
to four focused meetings with relevant FDA staff to discuss endpoint 
development. FDA's advice provided during and between RDEA meetings 
does not constitute a regulatory decision and is considered nonbinding. 
Being admitted into the RDEA Pilot Program and completing four RDEA 
meetings does not guarantee approval for a regulatory submission that 
includes efficacy endpoints discussed during RDEA meetings. Likewise, 
being denied admission into the RDEA Pilot Program does not mean that 
the proposed novel endpoint is unacceptable for regulatory decision 
making.
    After completion of four RDEA meetings, the sponsor can request 
additional input on their novel endpoint from FDA, as needed, through 
other formal meeting mechanisms, such as Type B, Type C, Type C 
Surrogate Endpoint, or Type D meetings. Sponsors that do not 
participate in the RDEA Pilot Program will have an opportunity to 
interact with the Agency through traditional channels.
    The listed eligibility and selection factors outlined in this 
notice reflect the current thinking at the time of publication. 
Information about the process for applying to and participating in the 
RDEA pilot meeting program will be communicated on the following web 
page: https://www.fda.gov/drugs/development-resources/rare-disease-endpoint-advancement-pilot-program.

II. General, Eligibility, and Disclosure Information for the RDEA Pilot 
Program

A. General Information

    The RDEA Pilot Program will be jointly administered by the 
following Centers:
     CDER: CDER's Rare Diseases Team, in the Office of New 
Drugs, Division of Rare Diseases and Medical Genetics, which is the 
point of contact for RDEA Pilot Program communications for CDER 
products.
     CBER: CBER's Rare Disease Liaison, in the Office of the 
Director, Policy Staff, which is the point of contact for RDEA Pilot 
Program communications for CBER products.

B. Eligibility and Selection Information

    To be eligible for the RDEA Pilot Program:
     The associated development program should be active and 
address a rare disease, with an active investigational new drug 
application (IND) or pre-IND for the rare disease.
    [cir] Sponsors that do not yet have an active development program 
but have, or are initiating, a natural history study where the proposed 
endpoint is intended to be studied are also eligible to apply.
    [cir] FDA may also consider accepting a proposal for a development 
program for a common disease that includes innovative or novel endpoint 
elements, including the specific endpoint and/or the methodology being 
developed if there is sufficient justification that the proposal could 
be applicable to a rare disease.
     The proposed endpoint is a novel efficacy endpoint 
intended to establish substantial evidence of effectiveness for a rare 
disease treatment. An endpoint is considered novel if it has never been 
used to support drug approval or if it has been substantially modified 
from previous use to support drug approval.
    Preference will be given to proposals:
     That have the potential to impact drug development more 
broadly, such as one that uses a novel approach to develop an efficacy 
endpoint or an endpoint that could potentially be relevant to other 
diseases.
     That collectively reflect a range of different types of 
endpoints.
     That have novel approaches for collecting additional 
clinical data in the premarket stage to advance validation of the 
endpoint for a surrogate endpoint proposal. If the sponsor is proposing 
to develop a surrogate endpoint as part of a rare disease application, 
participation in a prior Type C Surrogate Endpoint meeting is 
encouraged.

C. Disclosure

    To promote innovation in this area, novel efficacy endpoints 
developed through the RDEA Pilot Program may be presented by FDA (e.g., 
in a guidance, at public workshops and conferences, or on FDA's 
website) as case studies, including while the drug studied in the trial 
has not yet been approved by FDA. Accordingly, before FDA grants the 
initial meeting under the program, FDA and the sponsor must agree on 
the information that FDA may include in these public case studies. The 
specific information to be disclosed will depend on the content of each 
novel efficacy endpoint and associated natural history study if 
applicable. FDA intends to focus on information that is beneficial to 
advancing efficacy endpoint development for drugs that treat rare 
diseases and those elements relevant to understanding the novel 
efficacy endpoint and its potential use in a clinical trial intended to 
support regulatory approval.
    Sponsors wishing to participate in the program should identify 
aspects of the proposed novel endpoint and associated natural history, 
if applicable, that they consider nondisclosable and provide a 
rationale for withholding the information. Participation in the 
program, including any agreement on information disclosure, will be 
voluntary and at the discretion of the sponsor. Sponsors that do not 
wish to make such disclosures may seek regulatory input through other 
existing channels.

IV. Paperwork Reduction Act of 1995

    While this notice contains no collection of information, it does 
refer to previously approved FDA collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521) is not required 
for this notice. The previously approved collections of information are 
subject to review by OMB under the PRA. The collections of information 
in 21 CFR part 312 for INDs and clinical trials have been approved 
under OMB control number 0910-0014. The collections of information in 
21 CFR part 601 for biologic new drug applications (NDAs) have been 
approved under OMB control number 0910-0338. The collections of 
information in 21 CFR part 314 for the submission of NDAs and for 
requesting meetings with FDA about drug development programs have been

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approved under OMB control number 0910-0001. The collections of 
information relating to rare disease drug and biological product 
development programs have been approved under OMB control number 0910-
0765.

    Dated: October 21, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-23383 Filed 10-26-22; 8:45 am]
BILLING CODE 4164-01-P