Determining Root Cause in Sterility Failure Investigations

A positive sterility result immediately raises a difficult question: did contamination occur during laboratory testing, or does the result indicate a genuine product or manufacturing failure? Answering that requires more than reviewing the test itself. Investigators must examine laboratory controls and practices, manufacturing and filling conditions, environmental data, personnel, equipment, utilities, materials, process history, and other evidence that could explain the contamination.

The investigation becomes more difficult when several plausible causes exist or the evidence does not establish one definitive source. This session examines how to move from possible causes to an evidence-supported conclusion, including contamination-source evaluation, root cause analysis, investigation scope, affected-batch assessment, documentation, and CAPA. It also addresses when evidence may support invalidating a sterility result and when inconclusive findings cannot justify that conclusion.

A Finding Is Not Yet a Root Cause

A laboratory anomaly, environmental observation, or recovered organism may point investigators in a direction without establishing what actually caused the failure. Sterility investigations need evidence that connects the finding to the event, supports the stated root cause, and withstands scrutiny of the resulting batch decision.

Follow the Investigation as the Evidence Develops

The session progresses from the initial laboratory investigation into manufacturing, filling, and environmental review, then examines contamination-source evidence and root cause tools. It concludes with investigation findings, affected-batch impact, test invalidation considerations, documentation, CAPA, and the decisions required when a definitive root cause cannot be established.

Code: FDB2996