When does a process change require requalification?

Why

Replacing a pump with a different flow profile may alter shear exposure and process kinetics despite matching a nominal setpoint. Review change rationale, affected equipment qualification, critical parameters, product attributes, process history and regulatory commitments. Decide whether engineering tests, targeted requalification, PPQ activities or comparability studies are needed, with approval before implementation as appropriate.

For a therapeutic protein, ICH Q5E provides principles for evaluating quality comparability after process changes. Minor maintenance with documented equivalent performance may need less work, but no change should be automatically labeled trivial without review. After implementation, track routine process data to confirm the expected control.

Remember that the 2026 EU Annex 15 revision was a concept paper, not an effective replacement for current requirements.