Determining Root Cause in Sterility Failure Investigations

A practical investigation framework for tracing sterility failures through laboratory, manufacturing, environmental, and contamination-source evidence to establish a defensible root cause, determine the impact on affected batches, and support appropriate corrective actions.

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.

| WHY YOU SHOULD ATTEND

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.

| AREAS COVERED

• Phase I laboratory investigation and evidence required to establish laboratory error
• Phase II review of manufacturing, filling, environmental, personnel, equipment, utilities, and process factors
• Contamination-source evaluation using recovered organisms and supporting microbiological evidence
• Root cause determination using investigation data, 5 Why, Fishbone, interviews, records, and process review
• Investigation scope, affected-batch assessment, and considerations supporting batch disposition
• Documenting probable or definitive root cause, corrective actions, CAPA, and inconclusive investigations

| WHO SHOULD ATTEND

• Quality Assurance
• Quality Control
• QC Microbiology
• Sterility Assurance
• Manufacturing and Production
• Aseptic Processing and Filling Operations
• Validation
• Facilities and Engineering
• Regulatory Affairs
• Quality and Manufacturing Management

Course Director: Danielle DeLucy

Danielle DeLucy, has 15 years of pharmaceutical and biologics industry experience across Quality Management, Product Quality, Sterility Assurance, and QA oversight of filling and packaging operations. Her background as a Quality Control Pharmaceutical Microbiologist, combined with experience leading regulatory health inspections, directly supports the aseptic processing, contamination control, and media fill considerations addressed in this webinar.