
[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


