[Federal Register Volume 88, Number 189 (Monday, October 2, 2023)]
[Notices]
[Pages 67763-67765]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-21235]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-N-3976]
Support for Clinical Trials Advancing Rare Disease Therapeutics
Pilot Program; Program Announcement
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration's (FDA or Agency) Center for
Biologics Evaluation and Research's (CBER) Office of Therapeutic
Products (OTP) and Center for Drug Evaluation and Research's (CDER)
Office of New Drugs are announcing the opportunity for a limited number
of development programs to participate in the Support for clinical
Trials Advancing Rare disease Therapeutics (START) Pilot Program, with
the goal of further accelerating the pace of development of certain
CBER- and CDER-regulated products (novel drug and biological products)
that are intended to treat a rare disease. Because each Center has
identified specific needs concerning regulated products for rare
diseases, the eligibility criteria for the pilot differ between CBER
and CDER. This pilot would augment the currently available formal
meetings between FDA and sponsors by addressing issues related to the
development of individual products through more rapid, ad-hoc
communication mechanisms. Sponsors, if selected for the pilot, would
receive more frequent advice related to such specific issues through
additional interactions to facilitate novel drug and biological product
program development and generate high quality and reliable data
intended to support a Biologics License Application (BLA) or New Drug
Application (NDA). This notice outlines the eligibility criteria, what
to submit in a request to participate in the pilot, selection criteria,
process, and FDA-Sponsor interactions expected to occur for programs
participating in the pilot.
DATES: From January 2, 2024, to March 1, 2024, FDA will accept requests
to participate in the START Pilot Program and select no more than three
participants from each Center (CBER and CDER). See the
``Participation'' section for eligibility criteria, instructions on how
to submit a request to participate, and information regarding the
selection process.
FOR FURTHER INFORMATION CONTACT: Andrew Harvan, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7268, Silver Spring, MD 20993-0002, 240-
402-7911; or Quyen Tran, Center for Drugs Evaluation and Research, Food
and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6301,
Silver Spring, MD 20993-0002, 301-796-2771.
For general questions about the START Pilot Program for CBER:
[email protected]. For general questions about the START
Pilot Program for CDER: [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
The purpose of the START Pilot Program is to further accelerate the
pace of development of novel drug and biological products that are
intended to address an unmet medical need as a treatment for a rare
disease. The pilot is designed to be milestone-driven (i.e., to
facilitate the progression of a development program to pivotal clinical
study stage or the pre-BLA or pre-NDA meeting stage) where product
development programs selected would benefit from enhanced
communications with FDA. Participation in the pilot will be considered
concluded when the development program has reached a significant
regulatory milestone such as initiation of the pivotal clinical study
stage or the pre-BLA or pre-NDA meeting stage as agreed upon with the
sponsor. Pilot participants will be selected based on demonstrated
development program readiness. The START Pilot Program is intended to
provide a mechanism for addressing clinical development issues that
otherwise would delay or prevent a promising novel drug or biological
product from progressing to the pivotal
[[Page 67764]]
clinical trial stage or pre-BLA/pre-NDA meeting stage.
The pilot would augment the currently available formal meetings
between FDA and sponsors (see FDA's draft guidance for industry
entitled ``Formal Meetings Between the FDA and Sponsors or Applicants
of PDUFA Products'' ((September 2023) (Ref. 1))) through more rapid,
ad-hoc communications with FDA by addressing issues with specific
programmatic needs for individual products. For example, these issues
can be related to clinical study design, choice of control group, fine-
tuning the choice of patient population, selecting appropriate
endpoints for efficacy trials to support marketing approval, selecting
statistical methodology, leveraging nonclinical information, or product
characterization. For eligible development programs sponsors and FDA
could benefit from such additional communication beyond the currently
available formal meeting mechanisms to address specific programmatic
needs that require in-depth discussions. The increased communication
between FDA review staff and sponsors is intended to facilitate program
development for specific products and to help generate high quality and
reliable data intended to support a BLA or NDA.
II. Participation
From January 2, 2024, to March 1, 2024, FDA will accept requests to
participate in the START Pilot Program and will initially select up to
three participants in each Center. Taking into consideration lessons
and sponsors' experiences from the initial iteration of this program, a
second iteration of the pilot may be conducted to include more
participants in the future. At a later date, FDA may also publish
another notice in the Federal Register to announce a second iteration
of the program.
Sponsors who are interested in participating in the START Pilot
Program should submit a request to participate as an amendment to their
Investigational New Drug (IND) application.
A. Eligibility Criteria
To be considered for the START Pilot Program, participants must
meet the following eligibility criteria:
1. Joint CBER and CDER Eligibility Criteria
IND has been submitted in or converted to Electronic
Common Technical Document (eCTD) format, unless the IND is of a type
granted a waiver from eCTD format (see FDA's guidance for industry
entitled ``Providing Regulatory Submissions in Electronic Format--
Certain Human Pharmaceutical Product Applications and Related
Submissions using the eCTD Specifications'' ((February 2020) (Ref. 2)))
and remains in active status.
Sponsor has demonstrated substantial effort to ensure that
that Chemistry, Manufacturing, and Controls (CMC) development aligns
with clinical development, for example, through documented control of
manufacturing and testing procedures to ensure clinical and CMC
development timeline are in alignment.
Given the specific identified needs for the products regulated by
each Center for rare diseases, the following eligibility criteria
differ between CBER and CDER:
2. CBER-Specific Eligibility Criteria
Existing OTP-regulated IND for a cellular or gene therapy
under which the product is being developed toward a marketing
application.
Such product is intended to address an unmet medical need
as a treatment for a rare disease \1\ or serious condition, which is
likely to lead to significant disability or death within the first
decade of life.
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\1\ A rare disease or condition ``means any disease or condition
which affects less than 200,000 persons in the United States . . .''
(Section 526(a)(2) of the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 360bb(a)(2))). The START Pilot Program in CBER is not
intended to encompass all rare diseases, but only a subset of rare
diseases that are likely to lead to significant disability or death
within the first decade of life.
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3. CDER-Specific Eligibility Criteria
Such product is intended to treat rare neurodegenerative
conditions (including those of rare genetic metabolic etiology).
B. What To Submit in a Request To Participate in the START Pilot
To participate in the START Pilot Program, sponsors should submit a
written request as an amendment to the IND. The cover letter should (1)
state ``Request to participate in the START Pilot Program'', (2) note
whether there is a breakthrough therapy (BT) designation for the
product and for CBER-regulated products only--whether there is a BT
designation and/or regenerative medicine advanced therapy (RMAT)
designation, and (3) provide a point of contact.
The request should include the initial specific development
issue(s) for a given product for enhanced communication and a proposed
communication plan between the sponsor and review staff. In addition,
the following information should be provided:
1. Program development plan.
The plan should describe the current state of program development,
including any ongoing activities not already detailed in the IND.
CMC development plan and current status.
Nonclinical development plan and current status.
Clinical development plan and current status.
2. Any specific issue(s) (grouped by review disciplines) for which
the prospective applicants are seeking enhanced communications with FDA
review staff to facilitate program development, including, for example,
to ensure a mutual understanding of information needed to facilitate
initiating the pivotal clinical study or to the pre-BLA/pre-NDA meeting
stage.
3. The planned timeline for initiation of the clinical study(ies)
intended to provide the primary evidence of effectiveness to support a
marketing application or for a pre-BLA/pre-NDA meeting request.
4. The proposed communication plan for interactions between FDA
review staff and the sponsor, including the proposed timing (i.e.,
month and year) for the initial teleconference and format (e.g., email
or teleconference) of the subsequent communications on a scheduled and/
or as needed basis.
C. Selection Criteria and Process
FDA intends to select participant CBER and CDER INDs based on the
criteria outlined below. FDA will make its determination of
participants following the close of the application period. FDA intends
to issue a letter to notify each sponsor of FDA's decision on sponsor
requests to participate within 90 days of the application deadline.
For the initial selection of up to three INDs from each Center for
the START Pilot Program from eligible applicants, FDA intends to
consider factors such as: (1) potential clinical benefits of the
product, (2) whether resolution of the specific issues noted by the
sponsor in their request to participate in the pilot could be
facilitated through enhanced communication to improve efficiency of
program development, (3) whether there is an BT or RMAT designation for
the product, (4) whether CMC development timeline aligns with clinical
development plans, and (5) while INDs for combination products (21 CFR
3.2(e)(1)) may be eligible, products that require significant cross-
Center interactions (e.g., complex combination products) may be less
likely to be
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selected for the pilot. Overall, pilot participants will be selected
based on application readiness (e.g., sponsors who demonstrate having
the ability to move the program forward towards a marketing
application).
D. FDA-Sponsor Interactions During the START Pilot Program
If selected for the START Pilot Program, sponsors will receive
enhanced communications with FDA review staff. These enhanced
communications may vary between CBER and CDER but will include at a
minimum an initial meeting to review features of the pilot, discuss a
pathway intended to support a marketing application, and to discuss
specific issues for which a sponsor requests enhanced communication
with FDA. Additional communications will include ongoing interactions
via email or teleconference that take place on a scheduled and/or as
needed basis as agreed upon by the sponsor and FDA.
III. Paperwork Reduction Act of 1995
This notice refers to previously approved FDA collections of
information. These collections of information are subject to review by
the Office of Management and Budget (OMB) under the Paperwork Reduction
Act of 1995 (44 U.S.C. 3501-3521). The collections of information in 21
CFR part 312 have been approved under OMB control number 0910-0014 and
the collections of information in 21 CFR part 601 have been approved
under OMB control number 0910-0338.
IV. References
The following references are on display at the Dockets Management
Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852, 240-402-7500, and are available for viewing
by interested persons between 9 a.m. and 4 p.m., Monday through Friday;
they are also available electronically at https://www.regulations.gov.
FDA has verified the website addresses, as of the date this document
publishes in the Federal Register, but websites are subject to change
over time.
1. FDA Draft Guidance for Industry ``Formal Meetings Between the
FDA and Sponsors or Applicants of PDUFA Products'' (September 2023):
https://www.fda.gov/media/172311/download.
2. FDA Guidance for Industry ``Providing Regulatory Submissions in
Electronic Format--Certain Human Pharmaceutical Product Applications
and Related Submissions using the eCTD Specifications'' (February
2020): https://www.fda.gov/media/135373/download.
Dated: September 25, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-21235 Filed 9-29-23; 8:45 am]
BILLING CODE 4164-01-P