505(b)(2) CMC Role in Clinical Submission

Since the 505(b)(2) clinical submission process is still in its ~first decade with FDA, a question often asked by pharma is "How does CMC (chemistry, manufacturing and controls) play a role in the clinical development program for a 505(b)(2) clinical submission"?

During the 505(b)(2) drug clinical development process, pharma often will change the formulation, components or API (Active Pharmaceutical Ingredient). The impact of any of these changes must be evaluated for impact on the safety, efficacy and tolerance of the proposed drug product. A review of the evolution of the formulation and the data supporting the comparability of the different formulation(s) form the basis for the "Pharmaceutical Development" section of the CTD ( Common Technical Document) clinical submission. A CMC "bridging" study can accomplish these goals.

All sections of the CTD are important, however, CMC is one of the most important and the data must be quality controlled from formulation to formulation, lot to lot, batch to batch, change to change. CMC is the foundation of the drug product.

Include:

• a review of the implications of changes during the clinical development process
• incorporate comparability protocols at the right point in the program
• provide a coherent and approvable pharmaceutical clinical development summary for the proposed drug product.