Notice2024-21674
Chemistry, Manufacturing, and Controls Development and Readiness Pilot Program; Program Announcement
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Published
September 23, 2024
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
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.
Full Text
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<title>Federal Register, Volume 89 Issue 184 (Monday, September 23, 2024)</title>
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[Federal Register Volume 89, Number 184 (Monday, September 23, 2024)]
[Notices]
[Pages 77523-77526]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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 <a href="https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/research-investigational-new-drug-applications-what-you-need-know">https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/research-investigational-new-drug-applications-what-you-need-know</a>).
<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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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 <a href="https://www.fda.gov/media/151712/download">https://www.fda.gov/media/151712/download</a>.
2. FDA guidance for industry ``Expedited Programs for Serious
Conditions--Drugs and Biologics'' (May 2014): <a href="https://www.fda.gov/media/86377/download">https://www.fda.gov/media/86377/download</a>.
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): <a href="https://www.fda.gov/media/135373/download">https://www.fda.gov/media/135373/download</a>.
4. FDA guidance for industry ``Process Validation: General
Principles and Practices'' (Rev. 1) (January 2011): <a href="https://www.fda.gov/files/drugs/published/Process-Validation-General-Principles-and-Practices.pdf">https://www.fda.gov/files/drugs/published/Process-Validation-General-Principles-and-Practices.pdf</a>.
5. CDER MAPP 5015.13: ``Quality Assessment for Products in
Expedited Programs'' (December 2022): <a href="https://www.fda.gov/media/162786/download?attachment">https://www.fda.gov/media/162786/download?attachment</a>.
6. FDA draft guidance for industry ``Formal Meetings Between the
FDA and Sponsors or Applicants of PDUFA Products'' (Rev. 1) (September
2023): <a href="https://www.fda.gov/media/172311/download">https://www.fda.gov/media/172311/download</a>.
7. CDER MAPP 6025.6: ``Good Review Practice: Management of
Breakthrough Therapy-Designated Drugs and Biologics'' (Rev. 1)
(February 2024): <a href="https://www.fda.gov/media/89155/download">https://www.fda.gov/media/89155/download</a>.
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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