[Federal Register Volume 89, Number 184 (Monday, September 23, 2024)]
[Notices]
[Pages 77523-77526]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-21674]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-N-2396]


Chemistry, Manufacturing, and Controls Development and Readiness 
Pilot Program; Program Announcement

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
year three of the Chemistry, Manufacturing, and Controls (CMC) 
Development and Readiness Pilot (CDRP). This program facilitates the 
expedited CMC development of products under an investigational new drug 
application (IND) based on the anticipated clinical benefit of earlier 
patient access to the products. FDA has implemented this pilot program 
to assist with CMC readiness for products regulated by both the Center 
for Biologics Evaluation and Research (CBER) and the Center for Drug 
Evaluation and Research (CDER) that have accelerated clinical 
development timelines. To accelerate CMC development and facilitate CMC 
readiness, the pilot features increased communication between FDA and 
sponsors and explores the use of science- and risk-based regulatory 
approaches, as applicable. This notice outlines the eligibility 
criteria and process for submitting a request to participate in the 
pilot.

DATES: Starting October 1, 2024, FDA will accept requests to 
participate in year three of the CDRP program. See the 
``Participation'' section of this document for eligibility criteria, 
instructions on how to submit a request to participate, and selection 
criteria and process.

FOR FURTHER INFORMATION CONTACT: Tanya Clayton, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 4506, Silver Spring, MD 20993-0002, 301-
796-0871; or James Myers, Center for Biologics Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 
7301, Silver Spring, MD 20993-0002, 240-402-7911.
    For general questions about the CDRP Program for CBER: 
<a href="/cdn-cgi/l/email-protection#2940474d5c5a5d5b50074b404645464e404a5a694f4d480741415a074e465f"><span class="__cf_email__" data-cfemail="85ecebe1f0f6f1f7fcabe7eceae9eae2ece6f6c5e3e1e4abededf6abe2eaf3">[email protected]</span></a>.
    For general questions about the CDRP Program for CDER: <a href="/cdn-cgi/l/email-protection#3f5c5b5a4d12504f4e12504f4d50125c4d5e5b1256514e4a564d565a4c7f595b5e1157574c11585049"><span class="__cf_email__" data-cfemail="f291969780df9d8283df9d82809ddf91809396df9b9c83879b809b9781b2949693dc9a9a81dc959d84">[email protected]</span></a>.

[[Page 77524]]


SUPPLEMENTARY INFORMATION:

I. Background

    Development programs for CBER- and CDER-regulated drugs and 
biologics intended to diagnose, treat, or prevent a serious disease or 
condition where there is an unmet medical need may have accelerated 
clinical development timelines. Yet, marketing applications for 
products in expedited development programs still need to meet FDA's 
approval standards, including manufacturing facility compliance with 
current good manufacturing practice (CGMP). Products with accelerated 
clinical development activities may face challenges in expediting CMC 
development activities to align with the accelerated clinical 
timelines. Successfully expediting CMC readiness may require additional 
interactions with FDA during product development and, if applicable, 
warrant the use of science- and risk-based regulatory approaches to 
streamline CMC development activities so that clinical benefits of 
earlier patient access to these products can be realized.
    As described in the FDA Prescription Drug User Fee Act (PDUFA) VII 
Commitment Letter for fiscal years (FYs) 2023 Through 2027 (Ref. 1), 
FDA implemented the CDRP program to facilitate CMC readiness for 
selected CBER- and CDER-regulated products with accelerated clinical 
development timelines in FY 2023. To accelerate CMC development and 
facilitate CMC readiness, the pilot features increased communication 
between FDA and sponsors and explores the use of science- and risk-
based regulatory approaches, such as those described in the FDA 
guidance for industry entitled ``Expedited Programs for Serious 
Conditions--Drugs and Biologics'' (May 2014) (Ref. 2), as applicable.
    FDA (CBER and CDER) is continuing to administer the CDRP to 
facilitate the CMC development of selected products under INDs which 
have expedited clinical development timeframes, based on the 
anticipated clinical benefits of earlier patient access to the 
products. For sponsors participating in the pilot, FDA will provide 
product-specific CMC advice during product development, including two 
additional CMC-focused Type B meetings, as well as additional CMC-
focused discussions. To support these interactions, once a sponsor is 
admitted to the pilot, FDA will expand the IND quality assessment team 
so as to ensure it has representation from the full complement of 
relevant disciplines. The increased communication between FDA review 
staff and sponsors is intended to ensure a mutual understanding of 
approaches to completing CMC activities, including what information 
should be provided at the appropriate timepoint (i.e., at the time of 
new drug application (NDA) or biologics license application (BLA) 
submission, prior to the end of the review cycle, or post-approval) to 
ensure CMC readiness for a marketing application.

II. Participation

    FDA will accept requests to participate in the CDRP program 
continuously throughout the fiscal year. FDA will select no more than 
nine proposals per fiscal year, with approximately two-thirds being 
CBER-regulated products and one-third CDER-regulated products. FDA will 
renew the CDRP program each fiscal year and announce the opening of the 
pilot program in the Federal Register for the remainder of this PDUFA 
VII period (until the end of FY 2027). However, once enrolled in the 
pilot a participating firm will continue to be enrolled in the program 
until their marketing application is filed. Sponsors who are interested 
in participating in the pilot program should submit a request to 
participate in the pilot as an amendment to their IND. The cover letter 
should state ``Request to Participate in the CMC Development and 
Readiness Pilot.''
    To promote innovation and understanding in this area, FDA will hold 
a public workshop and issue a strategy document focused on CMC aspects 
of expedited development incorporating lessons from the CDRP. At the 
workshop, sponsors may be asked to present lessons learned from the 
pilot. FDA may also present summary lessons and case studies. 
Generally, FDA does not anticipate that the case studies will need to 
include information, such as the sponsor's name, that can identify a 
unique product or product-specific manufacturing process information. 
Case studies will focus on FDA-sponsor interactions and problem 
solving, and address scientific and technical issues only in general 
terms. However, as described in the FDA PDUFA VII Commitment Letter for 
FYs 2023 Through 2027, to be eligible for the pilot, the sponsor must 
reach agreement with FDA on the information that could be publicly 
disclosed. FDA will notify a sponsor in advance when it plans to 
include some aspect of their experience in the program in a public 
discussion (e.g., a slide presentation, a white paper).

A. Eligibility Criteria

    To be considered for the pilot program, participants must meet the 
following eligibility criteria:
1. Joint CBER and CDER Eligibility Criteria
    <bullet> Participant must have an active commercial IND (see the 
definition of commercial IND at https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/research-investigational-new-drug-applications-what-you-need-know).
    <bullet> 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 as per 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. 3).
    <bullet> INDs for combination products (21 CFR 3.2(e)) are 
eligible; products that require significant cross-Center interactions 
(e.g., complex combination products) may be less likely to be selected 
for the pilot.
    <bullet> In general, there should be enough time remaining before 
submission of the marketing application to allow the pilot to have an 
impact on CMC readiness.
    <bullet> CMC-related information is provided to demonstrate a 
commitment to pursue a CMC development plan that aligns with the 
expedited clinical development program (see ``CMC Development Plan'' in 
section II.B of this document for details).
    Due to the differences in product complexity between CBER- and 
CDER-regulated products, the following eligibility and selection 
criteria differ between the Centers.
2. CBER-Specific Eligibility Criteria
    <bullet> IND is an existing, CBER-regulated IND intended for 
submission as an application for licensure of a biological product 
under section 351(a) of the Public Health Service Act (PHS Act) (42 
U.S.C. 262(a)) for cellular therapies, gene therapies, and other 
products regulated by the Office of Therapeutic Products/CBER or 
vaccines regulated by the Office of Vaccines Research and Review/CBER.
    <bullet> IND has a Breakthrough Therapy (BT) or Regenerative 
Medicine Advance Therapy designation.
3. CDER-Specific Eligibility Criteria
    <bullet> IND is an existing, CDER-regulated IND for a product 
intended for submission as an application for: (1) approval of a new 
drug submitted under section 505(b) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 355(b)), or (2) licensure of a biological

[[Page 77525]]

product under section 351(a) of the PHS Act.
    <bullet> IND has an expedited clinical timeframe warranted based on 
anticipated clinical benefits of earlier patient access. This would 
include INDs with BT or Fast Track designations as well as other INDs 
that meet this criterion, with eligibility to be determined by FDA.

B. What To Submit in a Request To Participate in the Pilot

    To participate in the CDRP, sponsors should submit a written 
request as an amendment to the IND. In addition to providing a point of 
contact and noting any expedited program designations the IND has 
received to date, the request should include the following information.
CMC Development Plan
    To focus pilot resources where they will be most useful and have an 
impact on the timeliness with which CMC readiness is achieved, 
prospective applicants to the pilot program should include in their 
Request to Participate a brief description of their CMC development 
plan, with a prospective timeline for CMC development that would align 
with when the clinical development program is expected to be complete:
    <bullet> The plan should list the remaining CMC tasks and 
activities anticipated to be necessary, with estimated timeframes. This 
part of the plan should cover the following CMC-related areas:
    [cir] Currently available product characterization and preliminary 
identification of critical quality attributes.
    [cir] Summary of the current drug substance and drug product 
manufacturing process and control strategy (including assays, noting 
any that are still under development).
    [cir] A brief description of the proposed commercial scale 
manufacturing and control strategy, including any necessary microbial 
control strategy--focusing on important differences from clinical 
scale.
    [cir] Identification of potential commercial manufacturing 
facilities, including any contract facilities, or, at least, the type 
(in house, contract manufacturing organization) of facilities 
anticipated.
    [cir] Plans for ensuring product availability at approval.
    [cir] Drug substance and drug product stability assessment plan.
    [cir] Strategy for process validation (see FDA's guidance for 
industry entitled ``Process Validation: General Principles and 
Practices'' (Ref. 4)).
    <bullet> Given the expedited clinical timeframe, mapping out a plan 
for manufacturing readiness within the same overall timespan may reveal 
potential challenges in accomplishing CMC readiness. The plan should 
highlight any anticipated CMC challenges--whether related to the 
bullets above or otherwise. This will facilitate FDA engagement and 
collaboration. Participants in the pilot should plan to discuss these 
challenges with FDA during the pilot. For CDER-regulated products, see 
MAPP 5015.13, ``Quality Assessment for Products in Expedited Programs'' 
(Ref. 5).
    <bullet> The CMC Development Plan should include proposed timing 
(i.e., month and year) for the first CMC-specific Type B meeting 
afforded by the pilot.

C. Selection Criteria and Process

    FDA intends to select CBER and CDER INDs based on the criteria 
outlined below. Requests will be acknowledged and reviewed when 
received. FDA intends to issue a Proceed to Disclosure Agreement 
letter, if selected into the pilot, or deny letter within 90 days of 
receipt.
    In selecting INDs for the pilot program, FDA intends to consider 
factors such as: (1) anticipated clinical benefits of facilitating 
earlier patient access to the product, (2) novelty of the product, (3) 
complexity of the product or its manufacturing process, including 
technology, and (4) anticipated CMC challenges. Overall, FDA intends to 
seek balance and diversity in product types and therapeutic indications 
to obtain a variety of relevant experience and learnings from the 
pilot.

D. FDA-Sponsor Interactions During the Pilot

    During this CDRP program, sponsors will have the ability to discuss 
their product development strategies and goals with FDA review staff 
during the two dedicated Type B meetings, as well as in additional CMC-
focused discussions. Besides additional interactions and collaboration 
with FDA, for those INDs in the pilot, FDA will assemble a team to 
support the CMC development and readiness of the IND, e.g., 
participating in the meetings and other discussions under the pilot.
    In preparation for a meeting, sponsors should submit written 
questions along with a background information package clearly marked as 
a ``PDUFA VII CDRP meeting'' as part of the cover letter to enable FDA 
review staff to address the questions. The briefing package should be 
submitted to the corresponding IND. Meetings associated with the pilot 
should be requested by sponsors. For additional information on meetings 
and other communications between the sponsors and FDA, see the FDA 
draft guidance for industry entitled ``Formal Meetings Between the FDA 
and Sponsors or Applicants of PDUFA Products'' (September 2023) (Ref. 
6), CDER MAPP 6025.6: ``Good Review Practice: Management of 
Breakthrough Therapy-Designated Drugs and Biologics'' (Rev. 1) 
(February 2024) (Ref. 7), CBER ``SOPP 8101.1: Regulatory Meetings With 
Sponsors and Applicants for Drugs and Biological Products'' (March 
2023) (Ref. 8), and CBER ``SOPP 8212: Breakthrough Therapy Products--
Designation and Management'' (August 2023) (Ref. 9).

III. Paperwork Reduction Act of 1995

    Collections of information from fewer than 10 respondents within 
any 12-month period are not subject to the Paperwork Reduction Act of 
1995 (PRA) (5 CFR 1320.3(c)(4)). To the extent this information 
collection involves 10 or more respondents within any 12-month period, 
the collections of information are subject to the PRA. These 
collections of information are subject to review by the Office of 
Management and Budget (OMB) under the PRA (44 U.S.C. 3501-3521). The 
collections of information for NDAs, formal meetings with sponsors and 
applicants for PDUFA products, and the PDUFA VII Commitment Letter have 
been approved under OMB control number 0910-0001. The collections of 
information for INDs have been approved under OMB control number 0910-
0014. The collections of information for BLAs have been approved under 
OMB control number 0910-0338. The collections of information pertaining 
to CGMP requirements have been approved under OMB control number 0910-
0139. The collections of information pertaining to expedited programs 
for serious conditions for drugs and biologics and breakthrough 
therapy-designation for drugs and biologics have been approved under 
OMB control number 0910-0765.

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. 
Although FDA verified the website addresses in this document, please 
note that websites are subject to change over time.

[[Page 77526]]

    1. ``PDUFA Reauthorization Performance Goals and Procedures Fiscal 
Years 2023 Through 2027'' at https://www.fda.gov/media/151712/download.
    2. FDA guidance for industry ``Expedited Programs for Serious 
Conditions--Drugs and Biologics'' (May 2014): https://www.fda.gov/media/86377/download.
    3. FDA guidance for industry ``Providing Regulatory Submissions in 
Electronic Format--Certain Human Pharmaceutical Product Applications 
and Related Submissions Using the eCTD Specifications'' (Rev. 7) 
(February 2020): https://www.fda.gov/media/135373/download.
    4. FDA guidance for industry ``Process Validation: General 
Principles and Practices'' (Rev. 1) (January 2011): https://www.fda.gov/files/drugs/published/Process-Validation-General-Principles-and-Practices.pdf.
    5. CDER MAPP 5015.13: ``Quality Assessment for Products in 
Expedited Programs'' (December 2022): https://www.fda.gov/media/162786/download?attachment.
    6. FDA draft guidance for industry ``Formal Meetings Between the 
FDA and Sponsors or Applicants of PDUFA Products'' (Rev. 1) (September 
2023): https://www.fda.gov/media/172311/download.
    7. CDER MAPP 6025.6: ``Good Review Practice: Management of 
Breakthrough Therapy-Designated Drugs and Biologics'' (Rev. 1) 
(February 2024): https://www.fda.gov/media/89155/download.
    8. CBER ``SOPP 8101.1: Regulatory Meetings With Sponsors and 
Applicants for Drugs and Biological Products'' (March 2023).
    9. CBER ``SOPP 8212: Breakthrough Therapy Products--Designation and 
Management'' (August 2023).

    Dated: September 17, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-21674 Filed 9-20-24; 8:45 am]
BILLING CODE 4164-01-P


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