GPhA Proposed Pathway for Quality by Design Dissolution Testing and Setting of Specifications for Generic Drugs

1. GPhA Proposed Pathway for Quality by Design Dissolution Testing and Setting of Specifications for Generic Drugs Presentation for the Advisory Committee for Pharmaceutical Science October 2005

2. cGMP’s for the 21st Century “Quality should be built into the product, and testing alone cannot be relied on to ensure product quality”* “Quality by design means designing and developing manufacturing processes during the product development stage to consistently ensure a predefined quality at the end of the manufacturing process”* *“Guidance for Industry Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations”

3. What is the Current State? • If USP dissolution method and acceptance criteria exist, generic applicants are required to utilize them. • For non-USP products, generic applicants are TYPICALLY required to use the method and specifications supplied by the Office of Generic Drugs (“OGD Method”). Mandating methods and specifications FOR DRUG PRODUCTS DOES NOT CONFORM WITH THE SPIRIT OF cGMP’s for the 21st century.

4. Potential Issues with the Current State • USP/OGD tests and acceptance criteria unilaterally imposed on generic applications • Generic formulations and manufacturing processes can differ from brand • To change compendia, USP requires FDA approval. To get FDA approval, must be listed in USP…Catch 22!

5. Potential Issues with the Current State • For non-USP products, generic applicants may request OGD method prior to submission (control document). • Increased number of correspondences with OGD (consumes resources) • No acceptance criteria (Q value) provided. • Need to “guess” acceptance criteria • Increased review cycles as DBE finds acceptance criteria deficient • POTENTIAL TO DELAY APPROVAL OF ANDAS

6. GPhA Supports Change “…moving to a regulatory process that encourages quality by design principles and dissolution methods and specifications that are based on product relevant characteristics is supported by members of the Generic Pharmaceutical Association.”* *“GPhA Proposed Pathway for Quality by Design Dissolution Testing and Setting of Specifications for Generic Drugs”

7. What is the Future State? For each formulation, methods and acceptance criteria are established based upon: • scientific evidence • consideration of critical attributes • design or type of formulation • Biopharmaceutics Classification System (BCS) • prior knowledge

8. Future State – Acceptance Criteria Considerations for determining acceptance criteria: • Monitor critical product attributes to ensure batch to batch consistency. • Can be conventional (Q values) or novel approaches developed internally or from scientific literature. • Can monitor overall variability (manufacturing and analytical)

10. Recommendations • GPhA recommends that FDA adopt a QbD approach for dissolution testing and setting of acceptance criteria for generic drugs - Dissolution tests and acceptance criteria for generic products may be different from RLD. • When using the QbD approach, the firm will detail justification of the tests and acceptance criteria in the development report.