PPQ

Process Performance Qualification

PPQ is the moment the commercial process is put on trial. The batches must be made at commercial scale, with the commercial equipment, the approved master batch record, and the operators who will actually run it — not a development team on a good day. Anything that makes the PPQ run unrepresentative undermines the conclusion it is meant to support.

The number of batches is a judgement you must justify, not a number you inherit. The old default of three has no basis in the current FDA guidance, which asks for a rationale grounded in process understanding, variability, and risk. A well-characterised, well-controlled process may justify fewer; a variable one or a legacy process with weak Stage 1 data will need more.

PPQ typically runs under a heightened sampling and testing plan — more points, more replicates than routine production — precisely because you are establishing, not confirming, that the process is reproducible. Product from successful PPQ batches can normally be released, provided the protocol was pre-approved and all acceptance criteria were met.

• —Commercial scale, commercial equipment, approved batch record, trained routine operators — or it does not represent the process.
• —Batch count is justified from process understanding and risk; three is a convention, not a requirement.
• —Heightened sampling and testing versus routine production, defined in a pre-approved protocol.
• —Failure is a signal about the process — investigate and fix the cause; do not simply run more batches until three pass.
• —Success does not end validation; it hands over to Stage 3 continued process verification.

FDA, Process Validation: General Principles and Practices (2011), Stage 2; EU GMP Annex 15 (2015) §5 Process Validation; ICH Q10 for the ongoing lifecycle linkage.