A Guide to CMC Development and Readiness Pilot (CDRP) Program

Drug development is often a long and risky venture, often taking 10-15 years of clinical trials before product approval. Accelerated clinical development opportunities don’t go through the traditional Phase 1 through Phase 3; rather, Phase 2 or combined Phase 2/ 3 trials can form the basis of a regulatory strategy.

The U.S. Food and Drug Administration’s (FDA) Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) program was launched to facilitate CMC development for therapies with compressed clinical development timelines based on the anticipated clinical benefits of earlier patient access to therapy.

Purpose of CDRP Program

The CDRP program aims to proactively address manufacturing bottlenecks to ensure a product is not held up from reaching patients due to incomplete CMC safety information required in the marketing application (505(b)(1) and 505(b)(2)).

It is critical to understand that a product’s accelerated clinical development does not reduce the CMC requirements for ensuring product safety and manufacturing consistency. It is important to CMC with clinical development to allow for a successful marketing application, and ensure the product reaches the patient population as soon as possible.

To assist in accelerated CMC development and in response to the industry’s requests, the FDA initiated this pilot program in April 2023, to promote earlier and more structured engagement between sponsors and the FDA on CMC development strategies to confidently scale up manufacturing capacity alongside clinical development. The pilot program will run while the Prescription Drug User Fee Act (PDUFA) VII is in effect until the end of the financial year (FY) 2027.

A maximum of nine participants a year are chosen for the pilot program. During a joint workshop held in September 2025, by FDA and the Duke-Margolis Institute for Health Policy, Dr. Vatsan (Associate Director for Policy in the Division of Cellular and Gene Therapies, OTAT in CBER/FDA) reported that the Center for Drug Evaluation and Research (CDER) received a total of 12 applications for the program, of which five were accepted. Meanwhile, the Center for Biologics Evaluation and Research (CBER) received a total of 7 applications and accepted four. Dr. Vatsan explained that the primary reason for rejecting applications was that they did not meet the minimum eligibility criteria.

In this article, I we will review the following topics:

• Eligibility and selection criteria
• Key considerations of the CDRP program
• How to prepare for a successful CDRP application

Eligibility and Selection Criteria

The application for the CDRP needs to address the following criteria:

• An active commercial investigational new drug (IND) application. In general, such programs should not have reached the end of Phase 2 at the time of application
• IND that has an expedited clinical timeframe warranted based on the anticipated clinical benefits of earlier patient access. This would include INDs for products with a Breakthrough (BTD), Fast-Track (FTD), and regenerative medicine advanced therapy (RMAT) designation. IND sponsors of other products that meet this criterion may also apply to the pilot, with their eligibility to be determined by FDA
• Combination products (21 CFR 3.2(e)(1)) are eligible; products that require significant cross-center interactions (i.e.,complex combination products) may be less likely to be selected for the pilot
• A plan to pursue a CMC development plan that aligns with the expedited clinical development program

Key Considerations for the CDRP Program

As sponsors evaluate applying for the CDRP program, a key consideration is the impact of the accelerated clinical timeframe on the CMC development timelines for their program. Dr. Vatsan advised sponsors not to underestimate the resources required to participate in the CDRP program.

One of the challenges in participating in the program stems from preparing for two to three CMC-focused FDA Type B meetings in one year, which requires significant time and resources, while also maintaining momentum for ongoing development and other regulatory and CMC activities. For small biotechs, the lack of resources or lack of experience may make this burden infeasible, requiring additional resources to be brought rapidly to the team.

While the focus of an FTD and BTD program is on clinical speed, the CDRP program focuses on manufacturing readiness to assist sponsors in overcoming significant risks related to manufacturing delays on their programs.

Common CMC challenges that require significant resources during accelerated product development include the following:

• Readiness of manufacturing facilities
• Manufacturing changes, technology transfer, and comparability protocols
• Potency assay development
• Process validation studies
• Stability studies
• Extractables and leachables testing and assessment

How to Prepare for a Successful CDRP Application

To focus pilot resources where they should be most useful and have an impact on the timelines with which CMC readiness is achieved, applicants should meet the eligibility criteria highlighted earlier in this article. Additionally, applicants to the pilot program should include a description of their CMC development plan in the Request to Participate.

The CMC plan should describe the current state of CMC development, including any ongoing activities not already included in the IND. A projected timeline for product development that aligns with the anticipated clinical development timeline should be included.

Applicants should include any additional CMC challenges that may require FDA’s input to facilitate FDA’s engagement regarding the type of supportive data and information that might be used to address these challenges.

The following table includes a list of publicly announced participants in the CDRP pilot program.

Summary

The CDRP program continues to evolve as lessons are learned, including previously unknown factors from past CMC development programs. With more comprehensive CMC development plans submitted, the Agency has more insight into potential showstoppers for the sponsor.

Although regulatory flexibility is present especially for accelerated products, the Agency’s expectation for a control strategy based on product and process understanding does not change. For CDER, The MAPP 5015.13 “Quality Assessment for Products in Expedited Programs” offers the FDA’s thinking and lists commonly proposed flexibility and basis for approaching them. The key point is that regulatory flexibility options will be determined on a case-by-case basis, considering modern pharmaceutical principles. Applicants need to present a clear CMC development plan with milestones and justifications.

ProductLife Group and its affiliate company, Halloran, leverage its regulatory CMC and strategy experience with accelerated programs and complex products to offer clients strategic advice and support in transforming CMC into successful filings and earlier market and patient access.

References

• Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP) Program https://www.fda.gov/drugs/pharmaceutical-quality-resources/chemistry-manufacturing-and-controls-development-and-readiness-pilot-cdrp-program
• https://healthpolicy.duke.edu/events/lessons-learned-chemistry-manufacturing-and-controls-cmc-development-and-readiness-pilot-0
• Quality Assessment for Products in Expedited Programs, MAPP 5015.13 Rev. 1
• https://www.regulatoryrapporteur.org/a-year-of-change-for-the-us-fda-an-update-on-notable-pilots-and-programmes/1020.article
• Industry suggests changes to FDA’s CMC readiness pilot | RAPS

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