FDA's CMC Pilot Program Moves Forward

Washington, DC (Sept. 12)-The Office of New Drug Quality Assessment (ONDQA) in the Center for Drug Evaluation and Research (CDER) has approved one new drug application (NDA) under its CMC Pilot Program and has two more applications under review. The pilot was established last year to provide an opportunity for FDA and industry to explore strategies for including quality-by-design (QbD) principles and process analytical technology approaches in regulatory submissions, explained ONDQA deputy director Chi-wan Chen at the PDA-FDA Joint Regulatory Conference.

By working with companies on specific applications, FDA hopes to better define what constitutes a QbD-based submission and a science-based risk assessment. Two other pilot applications, including one supplement, are under review, and manufacturers have identified eight future submissions that will come into the agency during the next year and a half under the program. FDA plans to use the experience gained under the pilot to develop further guidance on QbD and its science- and risk-based approach to CMC review.

All pilot NDAs provide more scientific information on formulation and product development than typical applications in order to show a full understanding of the production process, Chen explained. Such relevant scientific information is useful to ONDQA in conducting a CMC review and in justifying future regulatory flexibility. This scientific information is included in an expanded Pharmaceutical Development section (P. 2 of the common technical document). A comprehensive Quality Overall Summary provides a broad overview of how this information is addressed in the document.

Regulatory flexibility is the expected reward for industry pilot participants. A manufacturer that demonstrates full knowledge and understanding of critical quality attributes, process development, and design space may be able to substitute in-process testing for end-product testing and report post-approval changes in an annual report. FDA may spell out such benefits in a “CMC regulatory agreement.” If the manufacturer defines critical quality attributes and design space for making planned changes, FDA may agree to future regulatory flexibility based on adherence to stated criteria. Such an agreement has been proposed in one application so far, explained Chen, and it is “being explored” by FDA officials.