Handbook of Investigation and Effective CAPA Systems, 3rd Edition

Worldwide regulatory agencies perform many inspections annually, and all too often investigation and CAPA system violations are at the top of the list of infractions. Life-sciences regulated companies (not only FDA-regulated ones) must ensure their investigation and CAPA systems look beyond the ‘usual suspects' to identify other quality issues in order to minimize risks (including safe ones) and reduce costs.Enhancements to this third edition include:A new section linking the investigation and CAPA programs with the overall quality culture of the companyFully updated, current versions of regulations including U.S. FDA, EU, ISO 9001, and ISO 13485Updated inspectional observations from the U.S. FDA and U.K. MHRAA revised investigation and CAPA processes chapter, which has an improved barrier analysis section, including detailed flowcharts describing the barrier analysis processNew charts and information related to the investigation of human errors; the human factor section includes information about training and competenceA new chapter devoted to analytical laboratory investigations, including a section covering the invalidation of testing resultsUpdated forms and examples of the different elements of the investigation and CAPA plan, including new case studies; a revised diagnostic tool used for investigating human errorJose(Pepe) Rodrguez-Perez, PhD, is president of Business Excellence Consulting, Inc., (BEC), a Puerto Rico-based, consulting, training, and remediation firm that focuses on the areas of regulatory compliance, FDA-regulatory training, and risk management. He is a biologist with a doctoral degree in biology from the University of Granada (Spain). Over his career, he has served as an educator, a technical services manager, and as a science advisor to the FDA. Cover Title page CIP data Contents List of Figures and Tables Preface to the Third Edition Acknowledgments Chapter 1. The Quality System and the Investigation and CAPA Element 1.1 THE QUALITY SYSTEM AND CAPA 1.2 INVESTIGATION AND CAPA RELATIONSHIP WITH OTHER QUALITY SUBSYSTEMS 1.3 NCR OR CAPA? INVESTIGATION PHASE VERSUS FIXING CAUSES 1.4 CORRECTIVE OR PREVENTIVE? 1.5 INVESTIGATION AND CAPA INVESTIGATION RELATIONSHIP WITH QUALITY CULTURE Chapter 2. Investigation and CAPA Requirements for the Life Sciences–Regulated Industry 2.1 FDA PHARMACEUTICAL CGMP 2.2 FDA MEDICAL DEVICES QSR 2.3 FDA QUALITY SYSTEM INSPECTION TECHNIQUE (QSIT) 2.4 FDA GUIDANCE: INVESTIGATING OUT-OF-SPECIFICATION (OOS) TEST RESULTS FORPHARMACEUTICAL PRODUCTION 2.5 FDA GUIDANCE: QUALITY SYSTEMS APPROACH TO PHARMACEUTICAL CURRENT GOOD MANUFACTURING PRACTICE REGULATIONS 2.6 EUROPEAN PHARMACEUTICAL GMP (EUDRALEX) VOLUME 4 2.7 HARMONIZATION PROCESSES: ICH AND GHTF/IMDRF 2.8 ICH Q10: PHARMACEUTICAL QUALITY SYSTEM 2.9 ISO 13485 AND NON-US MEDICAL DEVICE REGULATIONS 2.10 GHTF QUALITY MANAGEMENT SYSTEM—MEDICAL DEVICES—GUIDANCE ON CORRECTIVE ACTION AND PREVENTIVE ACTION AND RELATED QMS PROCESSES 2.11 COMPLAINT INVESTIGATIONS: REGULATORY EXPECTATIONS AND BEST PRACTICES 2.12 CURRENT OBSERVATIONS AND REGULATORY TRENDS FOR INVESTIGATIONS AND CAPA SYSTEMS Chapter 3. ISO 9001:2015: Nonconformance and CAPA Requirements Chapter 4. Effective Investigation and CAPA Processes: From Problem Detection to Effectiveness Check 4.1 PROBLEM DETECTION: DISCOVERING PROBLEMS 4.1.1 Sources of Data about Product and Quality Issues 4.1.2 Initial Impact Assessment 4.1.3 Process Trending 4.2 PROBLEM INVESTIGATION: DISCOVERING ROOT CAUSES 4.2.1 Symptoms, Causal Factors, and Root Causes 4.2.2 Fixing Symptoms: Corrections 4.2.3 Problem Description 4.2.4 Barrier Analysis 4.2.5 Root Cause Identification Processes and Tools 4.2.6 Root Cause Categories 4.3 CAPA PLAN: CORRECTIVE AND PREVENTIVE ACTIONS TO FIX ROOT CAUSES 4.3.1 Establish Effective Corrective and Preventive Actions 4.3.2 Validation and Verification Prior to Implementation 4.3.3 Implementation of Corrective and Preventive Actions 4.4 EFFECTIVENESS EVALUATION 4.4.1 Verifying That Solutions Worked 4.4.2 Training Effectiveness 4.5 MANAGEMENT OF THE INVESTIGATION AND CAPA SYSTEM 4.5.1 Investigation and CAPA System Structure 4.5.2 Investigation and CAPA Process Metrics and the FDA’s Quality Metrics Program 4.5.3 Risk Management and the Investigation and CAPA System 4.5.4 Management of External CAPA Chapter 5. Human Error Investigation and Reduction 5.1 ABOUT HUMAN ERROR: SOME STATISTICS 5.1.1. Data Integrity and Human Error 5.2 HUMAN ERROR AND THE HUMAN FACTOR 5.3 PSYCHOLOGY AND CLASSIFICATION OF HUMAN ERROR 5.4 HUMAN FACTORS 5.4.1 Compliance and Quality Culture 5.4.2 Workplace Involvement: Motivation and Attention 5.4.3 Adequate Supervision and Staffing 5.4.4 Procedures and Task Design 5.4.5 Training, Competence, and Performance 5.4.6 Examples of Human Factors in Process Operations 5.5 HOW ORGANIZATIONS DEAL WITH HUMAN ERRORS 5.6 INVESTIGATING HUMAN ERRORS 5.7 ROOT CAUSES RELATED TO HUMAN PERFORMANCE: PERSONAL FINDINGS WITHIN THE REGULATED INDUSTRY 5.8 HUMAN ERROR AND RETRAINING 5.9 WORKING FROM MEMORY 5.10 MULTITASKING AND HUMAN ERRORS 5.11 HOW TO REDUCE THE PROBABILITY OF HUMAN ERROR Chapter 6. Laboratory Investigations 6.1 INTRODUCTION TO QC LABORATORY INVESTIGATIONS AND CAPA 6.2 ANALYTICAL OOS INVESTIGATIONS 6.3 INVALIDATION OF TESTING RESULTS Chapter 7. The Biggest Opportunities of the Investigation/CAPA System and How to Fix Them 7.1 LACK OF INVESTIGATION PLAN 7.2 TIMELINESS 7.3 EVERYTHING IS AN ISOLATED EVENT 7.4 ROOT CAUSE NOT IDENTIFIED 7.5 ROOT CAUSES IDENTIFIED BUT NOT CORRECTED 7.6 CORRECTING THE SYMPTOM INSTEAD OF THE CAUSE 7.7 LACK OF INTERIM ACTIONS 7.8 LACK OF TRUE PREVENTIVE ACTIONS 7.9 LACK OF EFFECTIVENESS VERIFICATION OF THE ACTION TAKEN 7.10 MULTIPLE CAPA SYSTEMS WITHOUT CORRELATION 7.11 OVERUSE AND ABUSE OF HUMAN ERROR AND RETRAINING 7.12 FOCUSING MORE ON THE SOFTWARE THAN ON THE INVESTIGATION AND CAPA SYSTEM Chapter 8. Developing an Internal Investigation and CAPA Expert Certification 8.1 CONTENT OF THE CERTIFICATION 8.2 EVALUATING THE EFFECTIVENESS OF INVESTIGATION AND CAPA TRAINING EFFORTS Chapter 9. Documenting Investigation and CAPA: Forms and Examples 9.1 CONTENT OF THE INVESTIGATION REPORT 9.2 CONTENT OF THE CAPA PLAN 9.3 COMPLIANCE WRITING 9.4 FORMS 9.4.1 Investigation Report 9.4.2 Root Cause Analysis Checklist 9.4.3 Human Error Investigation 9.4.4 CAPA Plan 9.4.5 Investigation Report Assessment 9.4.6 CAPA Plan Assessment 9.5 EXAMPLES OF INVESTIGATION REPORTS 9.6 EXAMPLES OF CAPA PLANS 9.7 FINAL RECOMMENDATIONS Appendix A Acronyms Glossary References Index About the Author Worldwide regulatory agencies perform many inspections annually, and all too often investigation and CAPA system violations are at the top of the list of infractions. Life-sciences regulated companies (not only FDA-regulated ones) must ensure their investigation and CAPA systems look beyond the ‘usual suspects’ to identify other quality issues in order to minimize risks (including safe ones) and reduce costs. Enhancements to the third edition include: A new section linking the investigation and CAPA programs with the overall quality culture of the company • Fully updated, current versions of regulations including U.S. FDA, EU, ISO 9001, and ISO 13485 • Updated inspectional observations from the U.S. FDA and U.K. MHRA • A revised investigation and CAPA processes chapter, which has an improved barrier analysis section, including detailed flowcharts describing the barrier analysis process • New charts and information related to the investigation of human errors; the human factor section includes information about training and competence • A new chapter devoted to analytical laboratory investigations, including a section covering the invalidation of testing results • Updated forms and examples of the different elements of the investigation and CAPA plan, including new case studies; a revised diagnostic tool used for investigating human error