Notice2023-19502
Chemistry, Manufacturing, and Controls Development and Readiness Pilot Program; Program Announcement
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Published
September 11, 2023
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA) is announcing the year two opportunity for a limited number of applicants to participate in a Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) program to facilitate the expedited CMC development of products under an investigational new drug application (IND), where warranted, based on the anticipated clinical benefit of earlier patient access to the products. FDA has implemented this pilot program to facilitate CMC readiness for selected Center for Biologics Evaluation and Research (CBER)- and Center for Drug Evaluation and Research (CDER)-regulated products with 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, such as those described in FDA guidance, as applicable. This notice outlines the eligibility criteria and process for submitting a request to participate in the pilot.
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<title>Federal Register, Volume 88 Issue 174 (Monday, September 11, 2023)</title>
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[Federal Register Volume 88, Number 174 (Monday, September 11, 2023)]
[Notices]
[Pages 62381-62383]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-19502]
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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) is announcing the year
two opportunity for a limited number of applicants to participate in a
Chemistry, Manufacturing, and Controls (CMC) Development and Readiness
Pilot (CDRP) program to facilitate the expedited CMC development of
products under an investigational new drug application (IND), where
warranted, based on the anticipated clinical benefit of earlier patient
access to the products. FDA has implemented this pilot program to
facilitate CMC readiness for selected Center for Biologics Evaluation
and Research (CBER)- and Center for Drug Evaluation and Research
(CDER)-regulated products with 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, such
as those described in FDA guidance, as applicable. This notice outlines
the eligibility criteria and process for submitting a request to
participate in the pilot.
DATES: Starting October 2, 2023, FDA will accept requests to
participate in 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 Anne Taylor, Center for Biologics Evaluation and Research,
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm.
7256, Silver Spring, MD 20993-0002, 240-402-5683.
For general questions about the CDRP Program for CBER:
<a href="/cdn-cgi/l/email-protection#3d545359484e494f44135f545251525a545e4e7d5b595c1355554e135a524b"><span class="__cf_email__" data-cfemail="01686f6574727573782f63686e6d6e66686272416765602f6969722f666e77">[email protected]</span></a>.
For general questions about the CDRP Program for CDER: <a href="/cdn-cgi/l/email-protection#690a0d0c1b440619184406191b06440a1b080d440007181c001b000c1a290f0d084701011a470e061f"><span class="__cf_email__" data-cfemail="bfdcdbdacd92d0cfce92d0cfcdd092dccddedb92d6d1cecad6cdd6daccffd9dbde91d7d7cc91d8d0c9">[email protected]</span></a>.
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
allowing streamlining of 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 conduct a CDRP to facilitate
the CMC development of selected products under INDs that have expedited
clinical development timeframes, based on the anticipated clinical
benefits of earlier patient access to the products. This includes
products with Breakthrough Therapy (BT), Fast Track (FT), and
Regenerative Medicine Advance Therapy (RMAT) designations. For sponsors
participating in the pilot, FDA will provide product-specific CMC
advice during product development, to include two additional CMC-
focused Type B meetings, as well as a limited number of additional CMC-
focused discussions, based on readiness and defined CMC milestones. 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 continuously accept requests to participate in the CDRP
program. FDA will select no more than nine proposals per fiscal year,
with
[[Page 62382]]
approximately two-thirds being CBER-regulated products and one-third
CDER-regulated products. Taking into consideration lessons learned from
the prior year, FDA will publish in the Federal Register a notice to
announce pilot programs for each of the remaining FYs of the CDRP
program. 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, lessons
learned through the pilot may be presented by FDA (e.g., in a public
workshop) as case studies, including when the product studied in the
pilot has not yet been approved by FDA. FDA intends to conduct a public
workshop and issue a strategy document focused on CMC aspects of
expedited development incorporating lessons from the CDRP. To be
eligible for the pilot, the sponsor and FDA will reach an agreement on
the information to be publicly disclosed. Generally, FDA does not
anticipate that the case studies will need to include information, such
as the sponsor's name or product information, that can specifically
identify a unique product.
Participation in the pilot program, including such agreement on
information disclosure, is voluntary and at the discretion of the
sponsor. Where feasible, 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
definitions of commercial INDs 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)(1)) 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, at the time of application to the pilot, the
IND clinical program has not yet reached the end of Phase 2 to allow
the pilot to have sufficient time to have an impact on CMC readiness
(e.g., 2 years from anticipated marketing application submission).
However, in extenuating circumstances, requests for exceptions may be
considered, where the development programs would still benefit from the
pilot--examples of what could constitute such circumstances include:
[cir] Cases where the clinical development is following an
innovative trial design
[cir] The product is intended to treat a rare disease
<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''
under What To Submit in a Request To Participate in the Pilot 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 BT or RMAT 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
product under section 351(a) of the PHS Act.
<bullet> IND has an expedited clinical timeframe warranted based on
the anticipated clinical benefits of earlier patient access. This would
include INDs for products with a BT or FT designation; IND sponsors of
other products that meet this criterion may also apply to the pilot,
with their 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.
1. CMC Development Plan
To focus pilot resources where they should 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 description of their CMC development plan that
includes a timeline for CMC development aligned with when the clinical
development program is expected to be complete:
(1) The plan should describe the current state of CMC development,
including any ongoing activities not already included in the IND.
(2) The plan should include a projected timeline for product
development that aligns with the anticipated clinical development
timeline, showing the CMC tasks and activities intended to yield
complete CMC data and information to be included in the marketing
application. This part of the plan should cover the following CMC-
related areas:
<bullet> Available product characterization and preliminary
identification of critical quality attributes.
<bullet> Description of the current drug substance and drug product
manufacturing process and control strategy (including identification
and development of assays), and a description of and plan for the
proposed commercial scale manufacturing and control strategy, including
any necessary microbial control strategy.
<bullet> Identification of manufacturing facilities, including any
contract facilities, along with the facilities' recent inspection
history (including foreign regulatory inspections, where applicable).
<bullet> Plans for ensuring product availability for commercial
launch.
<bullet> Drug substance and drug product stability assessment plan.
<bullet> Overall plan for process validation (e.g., stage 1 and
stage 2 as described in FDA's guidance for industry entitled ``Process
Validation: General Principles and Practices'' (Ref. 4)).
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(3) Given the expedited clinical timeframe, mapping out a plan for
manufacturing readiness within the same overall timespan may reveal
potential challenges in accomplishing CMC activities within the
allotted time that is typically needed during CMC development to
prepare a marketing application that can support approval. The plan
should highlight these areas (exemplified in the bulleted list above,
and any additional CMC challenges that may require FDA input), to
facilitate FDA engagement regarding the types of supportive data and
information that might be used to address these challenges.
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)).
2. Proposed Plan and Timing for Meetings With FDA
The CMC Development Plan should include proposed timing (i.e.,
month and year) for the two additional CMC-specific Type B meetings
afforded by the pilot, as well as any other meetings and discussions
foreseen.
C. Selection Criteria and Process
FDA intends to select participant CBER and CDER INDs based on the
criteria outlined below. Review of requests is planned to occur
quarterly, or as needed, depending on the requests to participate in
the pilot that are received during the period. FDA intends to issue a
letter to notify each sponsor of FDA's decision on their request to
participate within 180 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, (4) sponsor's overall manufacturing experience, and (5)
sponsor's experience with the particular product type, class, or the
type of manufacturing process. FDA may give additional consideration to
less-experienced sponsors. Overall, FDA intends to seek balance and
diversity in product types, sponsors, 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 be able to discuss their
product development strategies and goals with FDA review staff during
predesignated Type B meetings and a limited number of additional CMC-
focused discussions. As part of the CMC readiness pilot, two dedicated
CMC meetings will be granted, and sponsors will have an opportunity for
followup discussions to address questions arising from the meeting or
meeting minutes, or if additional clarifications are needed.
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'' (December 2017) (Ref.
6), CDER MAPP 6025.6: Good Review Practice: Management of Breakthrough
Therapy-Designated Drugs and Biologics (July 2014) (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>.
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. 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'' (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'' (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: <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'' (December 2017):
<a href="https://www.fda.gov/media/109951/download">https://www.fda.gov/media/109951/download</a>.
7. CDER MAPP 6025.6: Good Review Practice: Management of
Breakthrough Therapy-Designated Drugs and Biologics (July 2014):
<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 6, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-19502 Filed 9-8-23; 8:45 am]
BILLING CODE 4164-01-P
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