The Certified Pharmaceutical GMP Professional Handbook

Description

The Certified Pharmaceutical GMP Professional Handbook The Certified Pharmaceutical GMP Professional Handbook List of Figures and Tables Acronyms and Abbreviations Preface Acknowledgments Limit of Liability/Disclaimer of Warranty Part I: Regulatory Agency Governance Chapter 1: Global Regulatory Framework United States Federal Statutes Relevant to Pharmaceuticals The Administrative Procedure Act United States Federal Food, Drug, and Cosmetic Act United States Public Health Service Act The Virus-Serum-Toxin Act European Union’s Legal System Relevant to Pharmaceuticals Japan’s Legal System Relevant to Pharmaceuticals China’s Legal System Relevant to Pharmaceuticals India’s Legal System Relevant to Pharmaceuticals Chapter 2: Regulations and Guidances Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) Health Canada World Health Organization (WHO) International Conference on Harmonization European Medicines Agency (EMA) The United States Food and Drug Administration Therapeutic Goods Administration (TGA) United States Department of Agriculture (USDA) 9 CFR—Animals and Animal Products USDA Veterinary Service Memorandum No. 800.65 International Pharmaceutical Excipients Council Japanese Ministry of Health, Labour, and Welfare (MHLW) Chapter 3: Mutual Recognition Agreements Mutual Recognition Agreements MRAs Established by the European Union and Partner Countries Key Elements of Mutual Recognition Agreements Pharmaceutical Inspection Co-operation Scheme Chapter 4: Regulatory Inspections Inspection Authority Types of Inspections Sharing of Inspection Findings Inspections of Foreign Drug Manufacturers Reviewing Documents Validation Cultural Aspects Documentation of Violations of cGMPs Inspection Techniques Inspection Process of a U.S. Firm Chapter 5: Enforcement Actions Types of Enforcement Actions Notice of Observations/Violations FDA Untitled Letters Warning Letters Product Seizures Injunctions Loss of Marketing License Loss of Establishment License Debarment Voluntary Actions Chapter 6: Regulatory Agency Reporting Planned Changes Evaluating Post-Marketing Changes Technical Assessment Analytical Assessment Equivalence Assessment Adverse Effect Reporting Strategy Regulatory Reporting Requirements Planned Changes Unplanned Events Chapter 7: Site Master File (SMF), Validation Master Plan (VMP), Drug Master File (DMF), and Site Reference File (SRF) Site Master File Content of Site Master Files Validation Master Plan (VMP) and Master Validation Plan (MVP) Drug Master File Types of Drug Master Files Changes to Drug Master Files Preparing a Site Master File (SMF) Content of Site Master File Appendixes Part II: Quality Systems Chapter 8: Quality Management System Establishing a Quality Management System Quality Management System Principles Quality Management System Practices Audits, Reviews, and Assessments ICH Q10: Pharmaceutical Quality System ICH Q10 Objectives Enablers: Knowledge Management and Quality Risk Management Design and Content Considerations, Quality Manual Management Responsibility Management Commitment Quality Policy Quality Planning Resource Management Internal Communication Management Review Management of Outsourced Activities and Purchased Materials Management of Change in Product Ownership Continual Improvement of Process Performance and Product Quality Life Cycle Stage Goals Pharmaceutical Quality Management System Elements Continual Improvement of the Pharmaceutical Quality System Management Review Monitoring of Internal and External Factors Outcomes of Management Review and Monitoring Conclusion Chapter 9: Quality Unit (Site) Management Qualified Person Responsibilities of the Qualified Person Specific Requirements for the Qualified Person Certification of Batch Release Maintenance of a Quality Management System The Qualified Person and the Product Quality Review The Qualified Person and Reference and Retention Samples External Qualified Persons Delegation of Tasks/Absence of a Qualified Person Organizational Duties to Be Established by the Company of the Qualified Person Annex 16 to the EU Guide to GMP Certification and Batch Release Principle Introduction General Batch Testing and Release of Products Manufactured in the EC/EEA Batch Testing and Release of Products Imported from a Third Country General Location of Sampling for Testing in EC/EEA Batch Testing and Release of Products Imported from a Third Country with EC MRA Routine Duties of a Qualified Person Chapter 10: Risk Management General Quality Risk Management Process Risk Assessment Risk Control Risk Communication and Risk Review Risk Management Methodology Integration into Industry and Regulatory Operations Methods and Tools Basic Risk Management Facilitation Methods Failure Mode and Effects Analysis Failure Mode, Effects, and Criticality Analysis Fault Tree Analysis Hazard Analysis and Critical Control Points Hazard Operability Analysis Preliminary Hazard Analysis Risk Ranking and Filtering Supporting Quality and Statistical Tools Chapter 11: Training and Personnel Qualifications Job-Specific Training Good Manufacturing Practices Training Training Effectiveness Employee Qualifications Documentation of Training Employee Proficiency Chapter 12: Change Control and Management Chapter 13: Investigations and Corrective and Preventive Action (CAPA) CAPA Process General Considerations for CAPA CFR 211.192 Production Record Review FDA 21 CFR 820.100 Corrective and Preventive Action FDA Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations FDA Guide to Inspections of Quality Systems Chapter 14: Audits and Self-Inspections Audit Types First-Party Audits Audit Process Written Procedure Audit Schedule Qualified, Independent Auditors Analyze Audit Results to Assess Conformance to Requirements Documentation of Findings and Corrective Actions Management Responsibility for Implementation of Corrective Actions Verification of Corrective Actions Chapter 15: Documents and Records Management Documentation Hierarchy Documents and Records Good Documentation Practices Master Documents Executed Documents GMP Records Training Records Facility Records Material Receipts Batch Records Log Books Complaint Records Records Management Record Retention Litigation Concerns Chapter 16: Product Quality Complaints and Adverse Event Reports Importance of Post-Market Surveillance and Reporting Building an Effective Complaint Management System Adverse Event Reporting—FAERS Differences between Complaints and Adverse Events Keys to Compliance Chapter 17: Product Trend Requirements Regulations Annual Product Reviews General Requirements Data Elements Product Quality Reviews General Requirements Data Elements Mandated by EU Regulations Additional Considerations Chapter 18: Supplier and Contractor Quality Management Requirements for Materials and Services On-Site Audit Quality System Survey Change Control Trending Supplier Certification Supply Chain Considerations Registration, Evaluation, Authorization, and Restriction of Chemicals (REACh) Restriction of Hazardous Substances (RoHS) Conflict Minerals Animal Tissue Counterfeit Medicine and Medicinal Components Part III: Laboratory Systems Chapter 19: Compendia (US, Europe, and Japan) Analytical Tests Chapter 20: Laboratory Investigations of Atypical Results Regulatory Guidance Analytical Error Conducting an OOS Investigation Analytical OOS Investigations Full-Scale OOS Investigation Production Review Reporting Testing Results Concluding the Investigation Interpretation of Investigation Results Microbiology OOS Investigations Standard Operating Procedures and Protocol Identification (Speciation) of the Organism Record of Laboratory Tests and Deviations Monitoring of Production Area Environment Monitoring Personnel (Laboratory and Production) Product Bioburden Production Record Review Manufacturing History (Including Media Fills Where Applicable) API Source Excipients Satellite Facilities Contract Laboratories Case Study Objectionable Microorganisms Absolute Number of Organisms Seen The Characteristics of the Microorganism Product Characteristics Route of Administration Patient Population Chapter 21: Instrument Management Chapter 22: Specifications Development of Specifications Criteria for Establishing Specifications Raw Material Specifications Drug Substances Inactive Ingredients (Excipients) Intermediates Packaging Components Finished Drug Product Finished Product Specifications Acceptance Limits for Excipients Additional Considerations Specification Revision Chapter 23: Laboratory Record-Keeping and Data Requirements Significant Digits and Rounding Rules for Significant Digits/Figures Maintaining Significant Digits in Calculations Rounding with Significant Figures Chapter 24: Laboratory Handling Controls Incoming Material Receipt, Inspection, and Sampling Samples for Products Manufactured In-House Stability Samples Reagents or Solutions Calibration and Laboratory Standards Sample Storage Reagents or Solutions Analytical Standards Chapter 25: Stability Programs Types of Stability Studies Product Development Stability Commercial Support Stability Change Management Stability Execution of Stability Studies Conditions Time Points Packaging Configurations Accelerating Studies Chapter 26: Reserve Samples and Retains Part IV: Infrastructure: Facilities, Utilities, Equipment Chapter 27: Facilities Introduction Design and Construction Features (21 CFR 211.42) Lighting (21 CFR 211.44) Ventilation, Air Filtration, Air Heating and Cooling (21 CFR 211.46) Plumbing (21 CFR 211.48) Sewage and Refuse (21 CFR 211.50) Washing and Toilet Facilities (21 CFR 211.52) Sanitation (21 CFR 211.56) Maintenance (21 CFR 211.58) Chapter 28: Cleanrooms Specific ISO Sections Related to Cleanrooms ISO 14644-2:2000 ISO 14644-1:1999 ISO 14644-2:2000 ISO 14644-3:2005 ISO 14644-4:2001 ISO 14644-5:2004 ISO 14644-6:2007 ISO 14644-7:2004 ISO 14644-8:2013 ISO 14644-9:2012 ISO 14698-1:2003 ISO 14698-2:2003 Cleanroom Operation Cleanroom Personnel Gowning and Hygiene Glove Donning Techniques Sources of Contamination Gowning Recommendations Chapter 29: Utilities Chapter 30: Equipment Design Materials of Construction Lubricants Equipment Layout Equipment Cleaning Validation GMP of Cleaning Validation and Analytical Methods Cleaning Validation and Sampling, Rinsing, Rinse Samples, and Detergents Establishment of Cleaning Validation Limits Documentation Equipment Cleaning Maintenance Equipment Change Control Chapter 31: Qualification and Validation Introduction Validation Master Plan (VMP) and Master Validation Plan (MVP) Design Qualification Commissioning and Qualification Installation Qualification Operational Qualification Performance Qualification Process Validation Validation Life Cycle Chapter 32: Maintenance and Metrology Systems Measurement Systems Analysis (MSA) or Test Method Validation (TMV) Chapter 33: General Cleaning, Sanitization, and Pest Control Washing Facilities and Cleaning Procedures Sanitization Procedures Literature Efficacy of Various Sanitizers Pest Control Chapter 34: Automated or Computerized Systems System Life Cycle Validation and Qualification Regulatory References Open and Closed Systems Change Management Testing Changes Chapter 35: Societal Security—Business Continuity Management Systems An Overview of ISO 22301:2012 The PDCA Approach Brief Overview of Key Clauses of ISO 22301:2012 Business Continuity Standard Clause 4: Context of the Organization Clause 5: Leadership Clause 6: Planning Clause 7: Support Clause 8: Operation Clause 9: Performance Evaluation Clause 10: Improvement Part V: Materials Management and Supply Chain Chapter 36: Receipt of Materials Incoming Inspection Identification and Labeling of Starting Materials API GMP for Receipt of Materials Chapter 37: Sampling Processes General Sampling Requirements Sampling Facilities, Utensils, and Equipment Sample Containers and Labeling Training of Personnel Sampling of Starting Materials for API Manufacturing Sampling of Packaging Materials Chapter 38: Material Storage, Identification, and Rotation Material Storage Material Identification Stock Rotation and Control Control of Obsolete and Outdated Materials and Products Chapter 39: Shipping and Distribution Chapter 40: Traceability and Sourcing Traceability Raw Materials and Components Product Manufacturing and Packaging Finished Dosage Form Distribution Records Biological Agents Pharmaceutical Supply Chain Chapter 41: Salvaged/Returned Goods and Destruction Returned Drug Products Salvaged Drug Products Disposal of Drug Products Part VI: Sterile and Nonsterile Manufacturing Systems Chapter 42: Master Batch and Completed Batch Records Issuance Yield Critical Step Verification Processing Instructions Hold Times Completed Batch Records Review and Disposition of PBR Chapter 43: Production Operations General Process Validation Application Factors Human Drugs Nonsterile Manufacturing and Manufacturing of Liquids, Creams, and Ointments Sanitization and Protection Gowning Requirements Sanitization and Hygiene Chapter 44: In-Process Controls 21 CFR 211.110 and Eudralex Volume 4 21 CFR 211.110(b) Appropriate Written Procedures 21 CFR 211.110(c) In-Process Material Testing 21 CFR 211.110(d) Rejected In-Process Materials FDA Guidance—Powder Blends and Finished Dosage Units Time Limits Microbiological Contamination Contamination Control 21 CFR 211.115 Reprocessing Combination Products Biotechnology Products Viral Clearance Inactivation Manufacturing and Aseptic Processing Lyophilization Chapter 45: Dispensing and Weighing Controls Weighing Equipment Dispensing Utensils Staging Areas Weigh Room Weighing Process Audit Chapter 46: Requirements for Critical Unit Processes Hazard Analysis and Critical Control Points (HACCP) Hazard Analysis Critical Control Point Identification Establishment of Critical Limits Monitoring Procedures Corrective Actions Record Keeping Verification Procedures Good Manufacturing Practices Chapter 47: Contamination and Cross-Contamination Introduction Warning Letter Citations Causes of Contamination and Cross-Contamination Methods for Preventing Contamination and Cross-Contamination Equipment Cleaning Equipment-Related Parameters Residue Removal Cleaning Agents Cleaning Processes Process Variables Proper Identification and Labeling Line Clearance Summary Chapter 48: Reprocessed and Reworked Materials Reprocessing Reworking Part VII: Filling, Packaging, Labeling Chapter 49: Filling Operations and Controls Materials Control Filling Assembly Procedures Filling Equipment Controls Contamination Controls Staged Materials Status Labeling Chapter 50: Environmental Monitoring Nonviable Particle Monitoring Contact Plates Swab Monitoring Settle Plates Active (Viable) Air Monitoring Chapter 51: In-Process and Finished Goods Inspections Inspection Methodologies Visual Inspection Seal Quality Inspection (Airborne Ultrasound) Nondestructive Leak Testing (Vacuum Decay) Bubble Emission Testing Blister Package Inspection and Container Leak Testing Burst Testing Creep Testing Dye Penetration Freeze-Dried Product Leak Testing Automated Vision Inspection Systems Qualification and Calibration Chapter 52: Product Inspection Manual Visual Inspection Training Qualification Chapter 53: Packaging Operations and Controls Content Protection Types of Plastics Used for Pharmaceutical Packaging Types of Glass Used for Pharmaceutical Packaging Packaging Operation Controls The Packaging Line Chapter 54: Labeling Operations and Controls Label Receipt Labeling Issuance to Manufacturing Label Quality and Label Operations Expiration Dating Artwork Development and Controls Printing Process Vendor Proof Gang Printing Roll Label Splicing Off-Line Printing Secure Storage of Labeling Destruction of Labeling Control of Graphical Files and Printing Plates Examples of FDA Warning Letters Other Examples of FDA Warning Letters Chapter 55: Filling and Packaging Records Regulations and Guidance Documents Filling and Packaging Records Production, Process Control, and Laboratory Record Review Part VIII: Product Development and Technology Transfer Chapter 56: Quality by Design Concepts Quality by Design Critical Process Parameter Critical Quality Attributes Design Space Validation Principles with Quality by Design Process Analytical Technology Tools Multivariate Tools Process Analytical Technology Process Control Tools Control Charts Continuous Improvement and Knowledge Management Tools Chapter 57: Phase-Appropriate GMP Requirements Clinical Trials Observational Studies Participating in a Clinical Study Informed Consent Institutional Review Boards Combination Products Investigational Products Change Control Chapter 58: Raw Materials, Packaging, and Infrastructure for Product Development Chapter 59: New Product Development Studies and Reports Chapter 60: Scale-up and Transfer Activities Development and Validation Reports Technology Transfer Types Process Development and Characterization Studies Process Ranging Studies Process Capability Studies In-Process Control Studies Hold-Time Studies Physico-Mechanical Simulations and Shipping Studies Appendix A: At-a-Glance Comparisons Appendix B: 21 CFR 211 Pharmaceuticals GMP Overview Subpart A—General Provisions Subpart B—Organization and Personnel Subpart C—Buildings and Facilities Subpart D—Equipment Subpart E—Control of Components and Drug Product Containers and Closures Subpart F—Production and Process Controls Subpart G—Packaging and Labeling Control Subpart H—Holding and Distribution Subpart I—Laboratory Controls Subpart J—Records and Reports Subpart K—Returned and Salvaged Drug Products Appendix C: 21 CFR 820 Medical Device GMP Overview Subpart A—General Provisions Subpart B—Quality System Requirements Subpart C—Design Controls Subpart D—Document Controls Subpart E—Purchasing Controls Subpart F—Identification and Traceability Subpart G—Production and Process Controls Subpart H—Acceptance Activities Subpart I—Nonconforming Product Subpart J—Corrective and Preventive Action Subpart K—Labeling and Packaging Control Subpart L—Handling, Storage, Distribution, and Installation Subpart M—Records Subpart N—Servicing Subpart O—Statistical Techniques Appendix D: Body of Knowledge—Pharmaceutical GMP Professional Certification (CPGP) Levels of Cognition Based on Bloom’s Taxonomy—Revised (2001) Remember Understand Apply Analyze Evaluate Create Glossary References and Suggested Reading Publications Australian Guidelines European and Other National Guidelines European Directives European Pharmacopeia FDA Guidances Container and Closure Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products FDA Guide to Inspections Biotechnology Computer Issues Devices Drugs Miscellaneous Health Canada Guidelines International Conference on Harmonization Guideliness Quality Guidelines Safety Guidelines Efficacy Guidelines Multidisciplinary Guidelines International Society for Pharmaceutical Engineering Guidelines International Organization for Standardization (ISO) Documents Japan Parenteral Drug Association Technical Reports Pharmaceutical Inspection Convention/ Co-operation Scheme (PIC/S) United States Code of Federal Regulations 9 CFR United States Code of Federal Regulations 21 CFR United States Code of Federal Regulations 40 CFR United States Pharmacopeia World Health Organization