[Federal Register Volume 88, Number 174 (Monday, September 11, 2023)]
[Notices]
[Pages 62381-62383]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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 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)(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)).

[[Page 62383]]

    (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 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: 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'' (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): 
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 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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