Kim Benton on CMC Development and Readiness Pilot

In late October 2022, FDA announced a new program called the CMC Development and Readiness Pilot, or CDRP (see the Federal Register notice dated October 31, 2022). The purpose of the CDRP is to increase CMC-focused communication between FDA and sponsors “to accelerate CMC development and facilitate CMC readiness” for a biologics license application (BLA). FDA stated that CDRP will include “the use of science- and risk-based regulatory approaches.”

Participants selected for the CDRP will benefit from additional CMC-focused FDA interactions and input intended to accelerate CMC development. Applications to participate in the CDRP will be accepted starting April 1, 2023.  FDA intends to choose no more than nine proposals, with approximately 6 being CBER-regulated products and 3 CDER-regulated products.

With the rapid growth in cell and gene therapy and the unique CMC challenges encountered by both sponsors and CBER in CGT, our best guess is that the majority of the 6 participants chosen for CBER will be from the CGT space.

Let’s look at the benefits of the CDRP, the qualifications, the application process, and how FDA will consider the applications.

Benefits of CDRP:

FDA will provide product-specific CMC advice during product development via

• two additional CMC-focused Type B meetings
• a limited number of additional CMC-focused discussions, based on readiness and defined CMC milestones

Determining eligibility for CBER CDRP:

• Product is under an existing, active commercial IND
• The intended regulatory path is a licensure of a biological product under section 351(a) of the Public Health Service Act (PHS Act)
• Product has Breakthrough (BT) or Regenerative Medicine Advanced Therapy (RMAT) designation
• Clinical development has not yet reached phase 2 at the time of application to the pilot
• This criterion was set to allow an impact on CMC readiness by participation in the pilot. The FR notice estimated that the sponsor should be approximately 2 years from anticipated BLA submission for optimal benefit. FDA noted that exceptions may be considered, such as if clinical development is following an innovative trial design, or the product is intended to treat a rare disease.
• CMC-related information provided to the IND demonstrates the sponsor’s commitment to pursue a CMC development plan that aligns with the expedited clinical development program
• The sponsor agrees to allow public disclosure of certain information relevant to the CDRP
• Don’t panic! FDA stated that “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). Participants can expect that the disclosed information will be generalized to be used as “lessons learned” or case studies from the pilot. Last week at Dark Horse’s regulatory Lunch & Learn sessions at Advanced Therapies Week ‘23, yet another comment was made about how the field would benefit if sponsors would share information about their CMC challenges and approaches to solutions. We hope that sponsors’ potential concerns about disclosure do not prevent their application to participate in and reap the benefits from CDRP.  

Application process

Applications for the CDRP should be submitted in an amendment to the IND. We recommend clearly labeling the amendment, and including in the cover letter that this amendment is an application for/request to participate in the CMC Development and Readiness Pilot. You may also consider contacting the Regulatory Project Manager (RPM) assigned to the IND to make them aware of your submission of this amendment.

The Federal Register notice lists the required content for applications.

Selection criteria

FDA states that they intend to seek balance and diversity in product types, sponsors, and therapeutic indications to obtain a variety of relevant experience and learnings from the CDRP, and that selection criteria will include

• anticipated clinical benefits of facilitating earlier patient access to the product
• novelty of the product
• complexity of the product or its manufacturing process, including technology
• sponsor's overall manufacturing experience
• sponsor's experience with the particular product type, class, or the type of manufacturing process. (FDA may give additional consideration to less experienced sponsors.)

We expect the number of applications from CGT product sponsors to be high, and CBER will need to carefully consider the factors listed above to fairly select a balanced group of participants. Novel products for which sponsors have limited experience will have a higher chance of selection, along with products for rare diseases with no available treatments. FDA notes that INDs for combination products are eligible, but that products that require significant cross-Center interactions may be less likely to be selected for the pilot. This was an important clarification for FDA to include in the FR notice, because this is a CBER and CDER pilot under the PDUFA VII agreement, and CDRH was not given resources related to this pilot.

FDA plans to review of requests on a quarterly basis, and suggested this schedule may be altered depending on the volume of applications. 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 summary, we would describe the CDRP program as an excellent opportunity for sponsors to obtain the additional CMC-focused FDA interactions they have been seeking. We strongly encourage everyone who fits the eligibility criteria to consider applying. We at DHC are available to help clients evaluate whether their products meet the eligibility criteria and craft their CMC development plans to apply for the CDRP.