Stage 3 Process Validation: Applying Continued Process Verification Expectations
This discussion paper proposes ideas for answering the questions “How is Stage 3 monitoring and testing following PPQ determined, as part of the lifecycle approach to PV?” “What is the impact of the lifecycle approach to monitoring and testing of existing/legacy products?” The purpose of this paper is to stimulate further discussion and suggest potential practical application. Approaches to providing answers, are proposed, but more experience in implementation of the lifecycle approach to PV is needed to finalize a consensus a position. Considerable input has already been received, considered, and/or incorporated. The author team is interested in hearing about other approaches that could be used, and lessons from use of the proposed approaches described in the discussion paper. The paper may be modified or expanded sometime in the future to reflect additional input.
Additional input in the following areas is sought:
- Examples of how the approaches described in this paper have been used or modified, especially for:
- Other types of drug product processes
- API processes
- Biopharma processes
- Revalidation of existing/legacy processes
- Other ideas about scope of CPV plan
- Other approaches to identifying parameters and critical quality attributes to be monitored at a heightened level in CPV
- Considerations for when enhanced monitoring is required/triggered
- Is maintenance of models for RTRt applications part of CPV?
- Application of statistically based release sampling and testing for existing (legacy) products
- Application of basic and advanced Statistical Process Control (SPC) and predictive modeling
Please direct all feedback to pvstage3@ispe.org. The authors would prefer that all input be focused primarily on the themes identified above.
Authors: Dafni Bika (BMS), Penny Butterell (Pfizer), Jennifer Walsh (BMS), Kurtis Epp (BioTechLogic), Joanne Barrick (Lilly)
1 Introduction
In January 2011, the FDA issued a Guidance for Industry on “Process Validation: General Principles and Practices” [1]. EMA has also issued a draft revision to the Guideline on Process Validation [2], which is circulated for public comment for completion by 31 October 2012. This document is intended to clarify how organizations can take advantage of opportunities arising from ICH Q8 [3], ICH Q9 [4], and ICH Q10 [5] and the possibility to use continuous process verification (which is differentiated from continued process verification used in the PV Guidance from the FDA [1]) in addition to, or instead of, traditional process verification. The PV Guidance from the FDA [1], which is the main focus of this document, describes a lifecycle approach to Process Validation that links product and process development, qualification of the commercial manufacturing process, and maintenance of the process in a state of control during routine commercial production. Process validation is defined as the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product thereby also assuring reliability of supply. The revised PV Guidance from the FDA [1] and the draft revision to the EMA PV Guidance [2] both emphasize that process validation should not be viewed as a one-off event. A lifecycle approach should be applied linking product and process development, qualification of the commercial manufacturing process, and maintenance of the process in a state of control during routine commercial production. The goals and typical activities of each Stage are summarized in the Table 1:
Read more by downloading Stage 3 Process Validation: Applying Continued Process Verification Expectations to New and Existing Products (Published August 2012).