Advancing CMC in Accelerated Programs: Insights on the FDA’s CDRP Program

Whether developing a biologic or small molecule, establishing adequate chemistry, manufacturing, and controls (CMC) can present significant challenges, ranging from assay development and validation to impurity control, manufacturing scale-up, and generation of sufficient stability data. While these challenges are common across most development programs, they can become particularly difficult to manage when clinical timelines are accelerated. In these cases, sponsors face increased pressure to resolve complex technical issues quickly while still meeting the approval standards of the U.S. Food and Drug Administration (FDA).

Recognizing these challenges, the FDA launched the CMC Development and Readiness Pilot (CDRP) Program in 2023 as part of PDUFA VII commitments. Sponsors accepted into the pilot benefit from enhanced FDA engagement, including additional dedicated CMC-only meetings, product-specific CMC advice throughout development, and opportunities to apply science- and risk-based regulatory approaches. As of August 2025 (approximately halfway through the pilot), only 7 CBER and 12 CDER applications had been submitted. In comparison, during the same period, CDER received 173 requests for Breakthrough Therapy designation, and CBER received 48 requests. This disparity suggests the CDRP program remains underutilized, despite offering a meaningful opportunity for eligible sponsors to benefit from participation.

Benefits of Participation

For sponsors navigating accelerated timelines, the CDRP program offers meaningful support in aligning CMC development with regulatory expectations – reducing the likelihood of delays at critical milestones such as marketing application submission and review.

One of the most significant benefits is the ability to identify and mitigate knowledge gaps earlier in development. Sponsors participating in the program report that the increased communication, including unsolicited feedback and suggested discussion topics from FDA CMC reviewers, provided valuable insight and enabled more informed decision-making of CMC activities. Areas where this early engagement has proven particularly valuable include pre- and post-change product comparability, noncompendial excipient requirements, earlier establishment of control strategies, primary stability data requirements, and overcoming supply change challenges. Sponsors report that this feedback was critical to de-risking their CMC programs prior to Phase 3, when the cost and complexity of resolving such issues increases substantially.

This early alignment helps sponsors submit a more complete and robust CMC package, one that addresses potential application gaps proactively and can reduce the likelihood of information requests during application review. Minimizing the need for major post-submission amendments and contributes to a more efficient review process for both sponsors and the agency. Facility readiness is another area where participation pays clear dividends. Ensuring that manufacturing sites are inspection-ready at the time of application review is a well-recognized bottleneck for accelerated programs. Early alignment with FDA expectations for process validation, scale-up, and facility controls directly addresses this risk – helping sponsors avoid a late-stage obstacle that can otherwise derail even well-run programs.

Ultimately, these advantages translate to earlier patient access to transformative therapies, particularly for products addressing unmet medical needs. It is worth noting, however, that realizing these benefits requires meaningful investment: sponsors must be prepared to support frequent FDA interactions, rapidly address feedback, and advance CMC activities in parallel with ongoing clinical development. Strong cross-functional coordination and a clearly defined, executable CMC development plan are essential.

Overview of FDA CDRP program

Sponsors of products regulated by either Center for Biologics Evaluation and Research (CBER) or Center for Drug Evaluation and Research (CDER) are eligible to apply, provided they maintain an active commercial IND and have an accelerated clinical development timeline. For CBER-regulated products, the program must have Breakthrough Therapy, Fast Track or Regenerative Medicine Advance Therapy designation(s), although such designations are not required for CDER-regulated products. While CMC complexity is not a formal requirement, Sponsors developing more complex products may derive the greatest benefit from participation through increased engagement with FDA to help overcome complex technical challenges, such as developing an adequate potency assay for a biological product.

As part of the application process, Sponsors must submit a detailed CMC Development Plan outlining a forward-looking timeline that aligns CMC activities with the anticipated completion of clinical development. This plan should also identify anticipated CMC challenges and include key elements such as:

• Remaining CMC activities and associated timelines
• Product characterization and preliminary identification of critical quality attributes
• Status of drug substance and drug product manufacturing processes and control strategies
• Proposed commercial-scale manufacturing approach
• Process validation strategy
• Stability assessment plans for drug substance and drug product
• Identification of potential commercial manufacturing facilities
• Plans to ensure product availability at the time of approval

The program is limited in scope, with no more than nine proposals accepted on a rolling basis per fiscal year through 2027. An FDA strategy document further outlining the program is anticipated to be published in 2026.

Our Experience Supporting Sponsors in the CDRP Program

Our team brings deep expertise in CMC development and regulatory strategy, with direct experience supporting Sponsors navigating expedited development pathways, including participation in the CDRP program. We partner with Sponsors to develop comprehensive and realistic CMC Development Plans that meet FDA expectations while aligning with aggressive clinical timelines. This includes identifying critical development activities, defining risk-based prioritization strategies, and ensuring that all elements – from product characterization to commercial readiness – are cohesively integrated.

We also support preparation for and participation in FDA interactions, helping clients frame key questions, anticipate regulatory concerns, and effectively respond to FDA feedback. By proactively addressing potential challenges and translating FDA input into actionable development strategies, we help sponsors reduce risk, avoid delays, and strengthen their overall CMC package – positioning them for success within the CDRP program and beyond.