[Federal Register Volume 87, Number 209 (Monday, October 31, 2022)]
[Notices]
[Pages 65596-65598]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-23575]


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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 
the 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 (IND) application, where 
warranted, based upon the anticipated clinical benefit of earlier 
patient access to the products. FDA is implementing 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 April 1, 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 20903-0002, 301-
796-0871; or Stephen Ripley, 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: 
[email protected].
    For general questions about the CDRP Program for CDER: [email protected].

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 is implementing the CDRP program to facilitate CMC readiness for 
selected CBER- and 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 the FDA guidance for industry 
entitled ``Expedited Programs for Serious Conditions--Drugs and 
Biologics'' (May 2014) (Ref. 2), as applicable.
    Starting in FY 2023, FDA (CBER and CDER) will conduct a CDRP to 
facilitate the CMC development of selected products under INDs which 
have expedited clinical development timeframes, based upon 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

    Starting April 1, 2023, FDA will accept requests to participate in 
the CDRP program and select no more than nine proposals, with 
approximately two thirds being CBER-regulated products and one third 
CDER-regulated products. Taking into consideration lessons from the 
prior year, FDA will publish in the Federal Register a notice to 
announce pilot programs for each of the 3 following fiscal years. 
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. 
Participation in the pilot program is voluntary and at the discretion 
of the sponsor. To be eligible for the pilot, the sponsor's written 
request should include the following statement:

    ``We, , acknowledge that certain information 
relevant to the CDRP may be publicly disclosed.''


[[Page 65597]]


    The general nature and extent of information that could be publicly 
shared will be discussed and agreed upon between the sponsor and FDA 
during the course of the pilot program, and, where feasible, FDA will 
notify a sponsor in advance when it plans to include some aspect of 
their program's experience 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
     Participant must have an active commercial IND (See the 
definitions of commercial INDs at: https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/research-investigational-new-drug-applications-what-you-need-know).
     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).
     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.
     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.
     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
     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 Tissues and Advanced Therapies/CBER 
or vaccines regulated by the Office of Vaccines Research and Review/
CBER.
     IND has a BT or RMAT designation.
3. CDER-Specific Eligibility Criteria
     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.
     IND has an expedited clinical timeframe warranted based 
upon 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:
     Available product characterization and preliminary 
identification of critical quality attributes.
     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.
     Identification of manufacturing facilities, including any 
contract facilities, along with the facilities' recent inspection 
history (including foreign regulatory inspections, where applicable).
     Plans for ensuring product availability for commercial 
launch.
     Drug substance and drug product stability assessment plan.
     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)).
    (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.

[[Page 65598]]

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 upon 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, as well as 
(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 have the ability 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 
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 29, 2014) (Ref. 7), CBER 
SOPP 8101: Regulatory Meetings with Sponsors and Applicants for Drugs 
and Biological Products (February 27, 2022) (Ref. 8), and CBER SOPP 
8212.3: Management of Breakthrough Therapy-Designated Products: Sponsor 
Interactions and Status Assessment Including Rescinding (February 3, 
2022) (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, this notice refers to 
previously approved collections of information. 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 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. 
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 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'' (February 
2020): https://www.fda.gov/media/135373/download.
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 (in clearance).
6. FDA guidance for industry ``Formal Meetings Between the FDA and 
Sponsors or Applicants of PDUFA Products'' (December 2017): https://www.fda.gov/media/109951/download.
7. CDER MAPP 6025.6: Good Review Practice: Management of 
Breakthrough Therapy-Designated Drugs and Biologics (July 2014).
8. CBER SOPP 8101: Regulatory Meetings with Sponsors and Applicants 
for Drugs and Biological Products (February 2022).
9. CBER SOPP 8212.3: Management of Breakthrough Therapy-Designated 
Products: Sponsor Interactions and Status Assessment Including 
Rescinding (February 2022).

    Dated: October 25, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-23575 Filed 10-28-22; 8:45 am]
BILLING CODE 4164-01-P