A new FDA pilot provides FDA meeting opportunities for expedited drug program sponsors on expanded manufacturing issues. Hogan Lovells | So Good News



FDA-regulated drug and biologic development programs include diagnostics; Breakthrough Therapy, where there is an unmet medical need for the serious disease or condition it is intended to treat or prevent; Accelerate clinical development timelines, including designation for Fast Track and Regenerative Medicine Advance Therapy. (RMAT) programs. However, marketing applications for products in these programs are still required to meet FDA approval standards, including current good manufacturing practice (CGMP) and manufacturing compliance. Products with accelerated clinical development activities may face challenges in expediting CMC development activities to accommodate accelerated clinical timelines. Successfully expediting CMC readiness may require additional interactions with the FDA during product development, if applicable. Ensures the use of science and risk-based regulatory approaches to facilitate CMC development activities; Only then can the clinical benefits of early patient access to these products be realized. understood

Because of the accelerated review timeframes for drug and biologic plans aimed at addressing unmet medical needs for serious conditions, CMC and GMP issues often become rate-limiting factors for response completion letters and FDA prohibitions. From important advances in public health and the approval of urgently needed medicines for patients; CMC and GMP challenges are particularly important for complex biological products. To some extent, the Breakthrough and RMAT programs are intended to address these challenges, but additional interaction and support from FDA and industry has recognized the need for FDA to address CMC and GMP issues early in the review cycle for applications related to early resolution. Express plan setting(s).

In response to these concerns and as described in the Prescription User Fee Act (PDUFA) VII Commitment Letter; FDA is implementing this testing program to facilitate CMC readiness for select Centers for Biologics Evaluation and Research (CBER) and Centers for Drug Evaluation and Research. (CDER): Regulated products with accelerated clinical development schedules. For sponsors participating in the pilot, FDA will provide product-specific CMC advice during product development; To include more CMC-focused Type B meetings based on readiness and defined CMC milestones; A limited number of additional CMC-focused discussions will also be included. .

Who is eligible for the program?

CDRP pilot program participants must have an active commercial IND clinical program that has not yet reached the end of Phase 2 to impact CMC readiness;For example, 2 years from the submission of the estimated marketing application). However, In expanding situations, Development programs can consider requests for exceptions that still benefit the tester.

In selecting INDs for the pilot program, FDA intends to consider the following factors.

(1) the anticipated benefits of making the product available to patients earlier;

(2) product novelty;

(iii) the complex product or technology in its manufacturing process;

(4) in addition to the overall manufacturing experience of the sponsor;

(5) type of product; Class or type of production work and experience of sponsor.

FDA may give additional consideration to less experienced sponsors.

What should be included in a request to participate?

Applicants to the pilot program should indicate in their “Request to Participate” as an amendment to their IND:

(1) Current status of CMC development, including current activities not yet included in the IND.

(2) A projected schedule for product development consistent with the expected clinical development schedule showing the CMC functions and activities intended to fully generate CMC data and information to be included in the marketing application. This part of the plan should cover the following CMC areas:

  • Preliminary identification of available product characteristics and critical quality attributes.
  • A description and plan for the proposed commercial scale production and control strategy, including the current pharmaceutical and pharmaceutical manufacturing process and control strategy (including identification and assay development) and the required microbial control strategy.
  • Identification of manufacturing facilities along with recent inspection record of facilities (including foreign regulatory inspection, where applicable).
  • Plans to ensure product availability for commercial launch.
  • Drug and Drug Product Stability Evaluation Program.
  • Overall plan for process validation.

(3) potential challenges to accomplishing CMC tasks within the allotted time typically required during CMC development.

The CMC development plan should include additional CMC-specific Type B meetings provided by the pilot, as well as proposed time for other meetings and anticipated discussions.

The next step

Beginning April 1, 2023, FDA will accept requests to participate in the CDRP program. The first year of the pilot was limited to nine applications (six designated for CBER products), but the FDA will continue the program for another three years, and the number of participants for these years has not yet been disclosed. During this CDRP program, Sponsors can discuss their product development strategies and goals with FDA review staff during pre-defined Type B meetings, and there will be a limited number of additional CMC-focused discussions. The FDA also said it may hold a public workshop and issue a strategy paper incorporating lessons learned from the CDRP. In addition, CDER/OPQ will adopt a new Policies and Procedures Manual (MAPP 5015.13) effective December 7, 2022. CDER will provide additional details on how the pilot program will be supported, implemented, and used. Regulatory compliance under 21 CFR 314.105(c). As stated in the PDUFA VII Commitment Letter; April 30 No later than 2026, the FDA will issue a strategy document outlining guidance and process documents for the agency’s plans to incorporate learnings from the pilot and related experiences with accelerated clinical development timelines.

On a related note, CBER’s Office of Tissue and Advanced Therapies (OTAT) has announced a virtual town hall meeting on December 7, 2022, to answer stakeholder questions about CMC issues related to cell therapy, including tissue engineered medical products regulated by OTAT.


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