Managing Non-Compliance Findings from PIC/S Member Inspections

Receiving a non-compliance finding from a PIC/S member inspection can be challenging, but with a structured and timely response, it also presents an opportunity to strengthen your quality system. As regulatory authorities rely increasingly on harmonized GMP frameworks under PIC/S, companies must be prepared to respond effectively to non-compliance findings from PIC/S inspections. This article outlines the classification of findings, best practices for CAPA planning, communication with regulators, and successful audit closure strategies.

Types of Non-Compliance Findings in PIC/S Inspections

• Critical: Observations posing an immediate risk to patient safety, product integrity, or data reliability
• Major: Significant deviations that may affect product quality or signal systemic GMP failure
• Other (Minor): Observations with limited or no direct impact on product quality, but indicative of gaps in GMP culture
• Each finding is linked to relevant clauses from the PIC/S GMP Guide or specific annexes such as Annex 1 or Annex 11

Initial Steps After Receiving an Inspection Report

1. Review and assess the full report with the cross-functional team (QA, QC, RA, Production)
2. Identify deficiencies and trace the cited systems, records, and processes
3. Start documentation of initial impact assessments for each observation
4. Assign a dedicated team to draft the CAPA response package
5. Notify leadership and regulatory affairs about potential product impact or reporting obligations

Timelines for Response Submission

• Critical Findings: CAPA response expected within 15 calendar days
• Major Findings: Typically due within 30 calendar days
• Minor/Other Findings: Often accepted within 60 calendar days
• Delays without justification may lead to regulatory escalation or import restrictions

Structuring an Effective CAPA Response

1. Observation Recap: Restate the regulatory authority’s exact wording
2. Root Cause Analysis (RCA):
   • Use structured tools (5 Whys, Fishbone/Ishikawa Diagram)
   • Document objective evidence, not assumptions
3. Corrective Action: Immediate fix to stop recurrence
4. Preventive Action: Systemic improvement to avoid future failures
5. Timelines and Owners: Each CAPA must include clear due dates and responsible persons
6. Effectiveness Check: Include verification plan and KPIs (e.g., recurrence trend analysis)

Examples of CAPA Responses to Common Findings

Data Integrity Violation (Annex 11)

• Root Cause: Inadequate access control and missing audit trail reviews
• CAPA: Implement password-protected logins, schedule regular QA audits of audit trails, and train users

Incomplete Stability Data (Chapter 6)

• Root Cause: Gaps in data migration during LIMS upgrade
• CAPA: Revalidate LIMS entries, update protocols per stability study guidelines, and retrain staff

Communication with the Inspecting PIC/S Authority

• Address all queries with factual, concise responses
• Use formal email or portal submission formats as required by the authority
• Request clarification only if needed, with specific references
• Maintain a communication tracker with timelines and correspondence logs

Best Practices for Documentation and Follow-Through

• Maintain a centralized CAPA file with:
  • Inspection report
  • CAPA response package
  • Supporting documents (e.g., revised SOPs, training logs, deviation forms)
  • Effectiveness checks and internal closure reports
• Link CAPA activities directly with document change controls and validation activities
• Use SOPs to guide CAPA escalation procedures

Audit Closure Process and Re-Inspection Triggers

• Closure occurs once:
  • CAPA is accepted by the authority
  • Effectiveness evidence is reviewed and approved
• Re-inspections may be triggered if:
  • CAPA is incomplete or ineffective
  • Product complaints continue
  • Multiple major/critical findings repeat
• Sites with repeated critical issues may be posted on public databases or face restrictions

How Findings Influence Regulatory and Business Outcomes

• Delayed CAPA may hold up marketing authorizations and site registrations
• Non-compliance can affect procurement eligibility (e.g., Global Fund, UNICEF)
• Inspection history influences frequency and scope of future audits
• Successful closure improves regulator trust and global credibility

Preventive Measures to Minimize Future Findings

1. Implement an annual GMP internal audit program using PIC/S templates
2. Track historical findings across multiple inspections for recurrence trends
3. Benchmark against industry best practices and update QMS accordingly
4. Establish a CAPA Effectiveness Review Board (QA-led)
5. Conduct unannounced mock audits simulating PIC/S format

Conclusion

Non-compliance findings from PIC/S inspections require timely, transparent, and technically sound responses. Pharmaceutical companies must treat inspection outcomes not as isolated events, but as opportunities to strengthen their GMP systems and global regulatory relationships. By implementing structured CAPA frameworks, engaging cross-functional expertise, and maintaining open communication with regulators, companies can transform inspection findings into catalysts for sustained quality excellence.