Quality risk-management review
Draft guidance questions and concerns
There are some remaining questions despite the thoroughness of the draft guidance. Below are a few key issues.
- What is required for final PQ approval? The final guidance should include clarification on what constitutes validation. This clarification is critical because the common practice of using three batches to verify validation no longer applies (3).
- In the case of a PAT strategy, will the approach to process qualification be different from other process designs? The final guidance needs to include more specifics with regard to what degree of PAT is required to positively impact validation and approvals (3). This clarification is especially important because often, the more PAT involved, the more investment and validation required.
- Industry needs to have a sense of which statistical methods and levels of sampling FDA recommends. Reference to specific documents and testing level(s) may suffice (3).
- The final guidance should discuss the impact of the new guidance on existing products and processes and how to integrate them into the new approach (3).
- The final guidance should discuss potential impact on current and future new drug and abbreviated new drug applications (NDAs and ANDAs) and their site of manufacture. For example, is there an expected date to have the new process validation requirements implemented in applications? For NDAs, additional time may be needed and patents may be affected. For ANDAs, shouldn't companies be required to demonstrate equivalency of control as the innovator process?
- Finally, there is a concern that product development information could become available though freedom of information, thus revealing data that have significant confidential information about the process. How will this be handled?
Warren Charlton is a consultant at WHC Bio Pharma Technical Services, PO Box 20309, Greenville, NC 27858, tel. 252.327.4733, fax 252.756.4733, firstname.lastname@example.org
3. J. Agalloco et al., "FDA's Guidance for Industry: Process Validation: General Principles and Practices," presented at PDA, Jan. 14, 2009.
4. FDA, Draft Guidance for Industry—Process Validation: General Principles and Practices (Rockville, MD, Nov. 2008).
5. W. Charlton, T. Ingallinera, and D. Shive, "Validation of Clinical Manufacturing," and Validation Chapter, in Validation of Pharmaceutical Process, J. Agalloco and F. Carleton, eds. (Informa Healthcare, New York, 3rd ed., 2008), pp. 542–544.
6. Bausch & Stroebel Risk Analysis System.