Product and Process Verification and Validation
Domain 6 - Product and Process Verification and Validation
This domain tests the validation lifecycle for processes, methods, facilities, and computerised systems. Expect the FDA three-stage process validation model, qualification stages, and the difference between verification and validation.
Core rules
- The 2011 FDA process validation guidance defines three stages: Stage 1 process design, Stage 2 process qualification including PPQ, and Stage 3 continued process verification.
- PPQ is not "three batches" by regulation; the number and justification must be science-based, though three consecutive successful batches is the common expectation. PPQ must use production equipment, personnel, and procedures, and include worst-case or challenge conditions where relevant.
- Facility and equipment qualification: DQ, IQ, OQ, PQ. Process validation must not start before prerequisite qualification is complete.
- EU GMP Annex 15 covers prospective, concurrent, and retrospective validation, validation master plans, and cleaning validation. Annex 11 covers computerised systems; GAMP 5 (second edition, 2022) provides the risk-based framework.
- Verification confirms that a system or method meets its specified requirements; validation confirms it consistently produces the intended result in its intended use. Compendial methods require verification, not full revalidation, in a new laboratory. ICH Q2(R2) (2023) introduced a validation lifecycle and distinguishes validation from verification.
Worked example
A company installs a new tablet press and plans PPQ. IQ and OQ are complete; PQ runs are scheduled, but cleaning validation for the new product is unfinished. Correct sequence: complete cleaning validation or demonstrate the PPQ batches will not be released, complete operator training and SOP approval, run PPQ with predefined acceptance criteria and a statistical rationale, then enter Stage 3 with continued monitoring of weight variability and hardness. A PPQ performed before cleaning validation is a documentation gap that will surface at inspection.
Traps that cost marks
- Stating that exactly three PPQ batches are a regulatory requirement without justification.
- Starting PPQ before prerequisite qualification or before analytical methods are validated.
- Confusing verification (meets specification) with validation (fitness for intended use).
- Treating retrospective validation as a default rather than an exception.
- Omitting Stage 3 and assuming validation ends at PPQ.