APIC清洁验证指南（2021英文版）.docx

For Internal Use Only For Internal Use Only PAGE PAGE 10 ACTIVE PHARMACEUTICAL INGREDIENTS COMMITTEE (APIC) GUIDANCE ON ASPECTS OF CLEANING VALIDATION IN ACTIVE PHARMACEUTICAL INGREDIENT PLANTS Revision April 2019 (updated in February 2021) Table of Contents 1.0 FOREWORD 2.0 OBJECTIVE 3.0 SCOPE ACCEPTANCE CRITERIA Introduction Methods of Calculating Acceptance Criteria Acceptance criteria using health-based data 4.2.2 Acceptance criteria using a General Limit 4.2.3. Acceptance criteria for therapeutic macromolecules and peptides Swab Limits Rinse Limits Rationale for the use of different limits in pharmaceutical and chemical production LEVELS OF CLEANING Introduction Cleaning Levels Cleaning Verification/Validation 6.0 CONTROL OF CLEANING PROCESS BRACKETING AND WORST CASE RATING Introduction Bracketing Procedure Cleaning Procedures Investigations and Worst Case Rating Worst Case Rating DETERMINATION OF THE AMOUNT OF RESIDUE Introduction Validation Requirements Sampling Methods Analytical Methods 9.0 CLEANING VALIDATION PROTOCOL 9.1 Background 9.2 Purpose 9.3 Scope 9.4 Responsibility 9.5 Sampling Procedure 9.6 Testing procedure 9.7 Acceptance criteria 9.8 Training 9.9 Deviations 9.10 Revalidation 10.0 VALIDATION QUESTIONS 11.0 REFERENCES 12.0 GLOSSARY 13.0 COPYRIGHT AND DISCLAIMER 1.0 FOREWORD This guidance document was initially updated in 2014 by the APIC Cleaning Validation Task Force on behalf of the Active Pharmaceutical Ingredient Committee (APIC) of CEFIC. The current Task Force members are: Ilda Chasqueira, Hovione FarmaCiencia SA, Portugal Isabel Lopez Monje, Esteve, Spain Peter Mungenast, Merck KGaA, Germany Luc Vintioen, Ajinomoto Bio-Pharma Services, Belgium Sven Van Der Ven, Janssen, Belgium Florent Trouillet, Siegfried Evionnaz, Switzerland Simon Rieder, Siegfried AG, Switzerland Frank Stahlhut, Siegfried Minden, Germany Vartan Hamparsoumian, Seqens, France Sofia Riboira, Hovione FarmaCiencia SA, Portugal With support and review from: Annick Bonneure