Harmonization Challenges: Comparing FDA 21 CFR Part 11 and EU GMP Annex 11 Requirements for Audit Trail Review

Background: The pharmaceutical industry operates in an increasingly globalized environment where multinational companies must navigate divergent regulatory frameworks for computerized systems and electronic records. Audit trail review requirements represent a critical component of data integrity assurance, yet significant variations exist between major regulatory authorities.
Objective: This manuscript provides a comprehensive comparative analysis of audit trail review requirements under FDA 21 CFR Part 11 and EU GMP Annex 11, examines the challenges multinational pharmaceutical companies face in establishing unified Global Quality Systems (GQS), and proposes harmonization strategies.
Methods: A systematic review of regulatory guidance documents, industry publications, warning letters, and current literature was conducted. Additional regulatory frameworks from WHO, PIC/S, MHRA, TGA, and PMDA were analyzed to provide a global perspective.
Results: Fundamental differences exist in the scope, frequency, and depth of audit trail review requirements across regulatory jurisdictions. FDA 21 CFR Part 11 mandates comprehensive audit trails for creation, modification, and deletion of electronic records, while EU GMP Annex 11 focuses primarily on modification and deletion of GMP-relevant data. Regulatory interpretations of "regular review" vary significantly, creating implementation challenges for global organizations.
Conclusions: Achieving harmonization requires risk-based approaches, leveraging emerging technologies including artificial intelligence and machine learning, and implementing robust governance frameworks. The manuscript concludes with practical recommendations for establishing effective global audit trail review programs.