GMP Regulations for Pharmaceutical Industry

Transcription

1 CONTENTS Foreword... (v) Preface... (vii) CHAPTER 1 GMP Regulations for Pharmaceutical Industry 1.1 Basic Requirements of GMP Organization Pillars in cgmp... 2 a. Management Responsibilities... 2 b. Resources... 2 c. Manufacturing Operations... 2 d. Evaluation Activities Six Quality System in GMP... 3 A. Pharmaceutical Quality Management System... 3 B. Production Management System... 3 a. Technical Measures... 4 b. Organizational Measures... 5 C. Facilities and Equipment Management System... 6 D. Laboratory Controls Management System... 6 E. Materials Management System... 7 F. Packaging and Labelling Management System Quality Culture and Pharmaceutical Industry... 9 CHAPTER 2 Good Laboratory Practices in Pharmaceutical Industry 2.1 Good Laboratory Practice Equipment Documentation in Good Laboratory Practice (ix)

2 2.3 Sampling in Good Laboratory Practice A. Approaches for sampling plans will be discussed for Testing in Good Laboratory Practice Laboratory Reagents, Solutions, Reference Standards and Culture Media in Good Laboratory Practice Glassware in Good Laboratory Practice On-going stability programme in Good Laboratory Practice Technical Transfer of Testing Methods in Good Laboratory Practice Measures in Good Laboratory Practice CHAPTER 3 Good Microbiology Practice in Pharmaceutical Industry 3.1 Premises, Layout and Zone Laboratory Environmental Monitoring Laboratory Equipment Personnel Media and Preparation A. Media procurement and Storage B. Media Preparation C. Media Incubation Time Reference Culture Sampling Laboratory Testing Disposal of Contaminated Waste Laboratory Data Management CHAPTER 4 Good Aseptic Practices in Pharmaceutical Industry 4.1 The Industry s Approach to Validation of Aseptic Manufacturing Cleanroom Classification Environmental Monitoring (x)

3 4.4 Methods of Microbiological Monitoring Microbial Identification Identification of Isolates Essential Elements of the Environmental Control and Facility Management Program Training for Aseptic Operations Process Simulating Testing Measure of Good Aseptic Practices CHAPTER 5 Good Clean Room Monitoring in Pharmaceutical Industry 5.1 Content of ISO : Sampling and Location Evaluations Sampling Sampling Procedure Sampling Instruments: LSAPC Light Scattering Airborne Particle Counter Recording and Evaluations of Airborne Particle Concentration ISO Class Number Test Reports and Interpretation of Results Out of Specifications CHAPTER 6 Good Engineering Practices in Pharmaceutical Industry 6.1 Good Engineering Practice Overview Key Concepts in Pharmaceutical Engineering Using Good Maintenance Practice in Good Engineering Spares Management in Good Engineering Practice Maintenance Qualification Cost Cutting becomes the Pharma Industry's Mantra Simplicity is the Ultimate Sophistication Measures in Good Engineering Practices (xi)

4 CHAPTER 7 Good Alarm Management Practices in Pharmaceutical Industry 7.1 Key aspects of Alarm Management Program Regulators Expectation of Alarm Management System A. FDA and Alarming B. ISA-18.2 Alarm System Management Lifecycle Element of a Good Alarm on Risk Assessment in Pharmaceutical Industry Categorization of Alarm Principle of Alarm Management System CHAPTER 8 Good Computer Validation System Practices in Pharmaceutical Industry 8.1 Computer Validation Master Plan Computer Qualification A. System Requirement Specifications (SRS) or User Requirement Specifications (URS) B. Design Qualification and Specifications C. Installation Qualification D. Operational Qualification E. Performance Qualification Validation Protocol/Report Validation of Hardware and Software CHAPTER 9 Good Distribution Practices Supply Chain Integrity in Pharmaceutical Industry 9.1 Key components of Good Distribution Practice A. Quality Management System B. Supplier Qualification C. Internal Audit D. Storage Management System (xii)

5 E. Environmental Condition Management F. Temperature Mapping G. Distribution Management System Counterfeit Supply Chain Integrity and Security Category of Supply Chain Integrity and Security CHAPTER 10 Good Data Management System in Pharmaceutical Industry 10.1 Regulatory Expectations When does Electronic Data become a CGMP Record? CIA or AIC Triangle The Data Governance System Designing Systems to Assure Data Quality and Integrity Triggers of Data Integrity Loss Data Integrity Metrics Measures of Good Data Management System CHAPTER 11 Quality Agreements in Pharmaceutical Industry 11.1 Elements of a Quality Agreement Activities in Quality Agreements CHAPTER 12 Change control Management and its Applications 12.1 Benefits of Change Control System ICH Q8 and ICH Q9 to Change Management in ICH Q Steps involved in Change Control Management E-Change Control System (xiii)

6 CHAPTER 13 Technology Transfer of Pharmaceutical Product 13.1 Different Types of Technology Transfer Technology Transfer Protocol and Report CHAPTER 14 Pharmaceutical Annual Product Quality Review 14.1 Importance of Annual Product Quality Review Contents of APQR Data Trend and Analyzation CHAPTER 15 Statistical Tools for Pharmaceutical Industry 15.1 Concept of Six Sigma and Lean Manufacturing Common Statistical Tools Pharmaceutical Industry can use to Meet Regulatory Requirements Other Statistical Tools used in Pharmaceutical Industry Qualitative and Quantitative Analysis A. Patterns and Trends Measures of Statistical Tools Analysis CHAPTER 16 Application of Different Quality Tools in Investigation of Non-Conformance Observations 16.1 Deviation Management A. Steps involved in Deviation Investigation B. Deviation Categorization Complaint A. Steps involved in Complaint Handling Recall A. Classification of Recall B. Recall Strategy C. Recall Communication D. Recall Status Reports E. Effectiveness Checks (xiv)

7 16.4 Out of Specification (OOS) A. Phase I: Laboratory Investigation B. Phase II: Full Scale Investigation a. Production Review b. Additional Laboratory Testing Field Alter Report (FAR) Out of Trend (OOT) Investigations Tools A. Root Cause Analysis (RCA) B. Corrective and Preventive Action (CAPA) C. Risk Management Program a. Quality Risk Management Tools Verification Program CHAPTER 17 New Approach to the Internal Audit from Traditional to Risk based Approach 17.1 Traditional Approach to IA Forecasting Approach to IA Benefits of QRM to IA Program IA Approach to Organization I. System based Approach A. Full Inspection Option B. Abbreviated Inspection Option II. Linked based -Process Approach III. Risk based approach for IA Program IV. Forensic Audit V. For-Cause-Audit Planning Audit Sampling Audit Tools Audit Evidence and Analysis Phase Audit CLOSE-OUT and FOLLOW-UP (xv)

8 CHAPTER 18 Quality by Design (QbD) Approach in the Product Life Cycle 18.1 Elements of QbD Steps involved in QbD Development Process The Principle Steps in QbD are QbD Documents Process Analytical Technology (PAT) Frame Work Use of PAT Tools in Continuous Manufacturing Process A. PAT Tools B. Risk-Based Approach C. Integrated Systems Approach D. Real Time Release E. Strategy for Implementation F. PAT Regulatory Approach Product Life Cycle A. Pharmaceutical Development B. Technology Transfer C. Commercial Manufacturing D. Product Discontinuation Definition CHAPTER 19 Process Validation in Pharmaceutical Industry 19.1 Approach of Process Validation A. Stage 1 Process Design B. Stage 2 Process Qualification C. Stage 3 Continued Process Verification D. Revalidation Content of Validation Protocol/Report (xvi)

9 CHAPTER 20 Cleaning Validation and Cross Contamination Approach on Risk MaPP Concept 20.1 Types of Cleaning A. Manual Cleaning B. Semi-Automated Processes Cleaning C. Automated Processes Cleaning Approach for Cleaning Validation Addition of New Product and Equipment to Validated Chain Equipment Hold Study Approaches Selection of Worst Case Product Cleaning Validation Protocol A. Indirect Sampling: Rinse Sampling B. Direct Sampling: Swab Sampling Quality Risk based Approach for Cleaning Validation European Union Expectation on Cross Contamination. 137 A. EU chapter 5 expectation B. EMA Selection & Reporting of the PDE Determination Strategy Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination Definitions CHAPTER 21 Pharmaceutical Water Generation and Distribution System and Regulatory Expectation 21.1 Design and Process Flow Steps involved in Pharmaceutical Water Preparations Possible Pretreatment Method for Pharmaceutical Water Preparation (xvii)

10 21.4 Possible Purification Method for Pharmaceutical Water Preparation Qualification A. User Requirement Specification (URS) a. Process water b. Purified water/water for injection c. Pure steam B. Functional Design Specification (FDS) a. Process water b. Purified water/wfi c. Pure steam C. Design Specification (DS) a. Process Water b. Purified Water/WFI c. Pure Steam D. Performance Qualification for purified water / WFI/Pure Steam a. Phase 1 :Test period : 2 4 weeks b. Phase 2 : Test Period : 2 4 weeks c. Phase 3: Test Period: E. Validation Cycle of Qualification and Validation of Water System Component for Pharmaceutical Water System A. Pretreatment System a. Raw Water b. Chlorination c. Filtration d. Dechlorination e. Softener f. Hardness g. Oxidation Reduction Potential (ORP) h. Silt Density Indicator i. Microbial-Retentive Filtration (xviii)

11 B. Purification System a. Ion Exchange b. Mixed bed dimineralizers c. Reserve Osmosis d. Continuous Electro deionization (CEDI) or Electron De-ionization ( EDI) C. Storage and Distribution a. Storage Tanks b. Ultraviolet Light c. Distribution Systems d. Sanitization e. Total Organic Carbon (TOC) f. Conductivity g. Flow of distribution loop h. Pressure i. Microfiltration j. Ultrafilteration k. PureSteam Methods used for Preparation of Pharmaceutical Water Test Performed for Potable Water and its Recommended Limits Type of water is used in the Pharmaceutical Sterile Medicine Product as an Excipient as per EMEA/CVMP/115/01 Note for Guidance on Quality of Water for Pharmaceutical Use Type of water is used in the Pharmaceutical Non-Sterile Medicine Product as an Excipient as per EMEA/CVMP/115/01 Note for Guidance on Quality of Water for Pharmaceutical Use (xix)

12 21.11 Type of Water is used in the Manufacturer of Active Pharmaceutical Ingredients (APIs) as per EMEA/CVMP/115/01 Note for Guidance on Quality of Water for Pharmaceutical Use Type of Water is used for Cleaning/Rinsing of Equipment, Containers and Closure as per EMEA /CVMP/115/01 Note for Guidance on Quality of Water for Pharmaceutical Use Potable Water as per Reference ISPE Baseline Guide, Volume- 4 Water and Steam System, WHO TRS 929 WHO TRS A. Construction Requirement of Underground and Overage Storage Tank B. Control of Microbial load in Potable Water C. Dechlorination of Feed Water D. Procedure and limit of Hardness E. Procedure and limit of Oxidation Reduction Potential (ORP) F. Procedure and limit of Silt Density Indicator: G. Procedure for Microbial-Retentive Filters in Potable Water Line H. Potable Water Sampling and Testing Purified Water and WFI System as per ISPE Baseline Guide, Volume 4 Water and Steam System, WHO TRS 929 WHO TRS A. Design Requirement for Distribution of Purified Water and WFI System B. Storage Tank Design Requirement for Purified Water / WFI System C. Welding document Requirement during Design Qualification D. Flow velocity of Purified Water and WFI in Distribution Loop E. Conductivity Sensor (xx)

13 F. Pressure and Compound Gauge available in Purified Water and WFI System G. Sampling procedure is for Purified and Water for Injection as per USP Chapter <1231> H. Alert and Action levels defined for Purified and Water for Injection I. Continuous System Monitoring of Purified Water and Water for Injection System J. System Reviews of Purified Water and Water for Injection System Planned Preventive Maintenance Programme A. Potable/Purified/WFI/Pure Steam B. Alarm Management for Purified/WFI/Pure Steam. 165 C. RO Membrane Maintenance D. Ion Exchange Membrane Maintenance E. Continuous Electro deionization (CEDI) or Electron De-ionization (EDI) Maintenance F. Total Organic Carbon (TOC) G. Sanitization for Purified and Water for Injection System H. Ultra Violet lamp I. Cleaning Definition CHAPTER 22 Pharmaceutical Heating, Ventilation and Air Conditionings (HVAC) and Regulatory Expectations 22.1 Qualification A. Designed Qualification I. Aseptic Dosage Form Facility II. Check Points for Design Qualification for Aseptic and Biologics area III. Design Criteria for Solid /Semi Solids/Liquids/ Final API (xxi)

14 IV. Design Criteria for Potent Solid/Semi Solids/ Liquids/ Final API Form V. Design Acceptance Criteria VI. Check Points for Design Qualification Solid / Semi Solids/Liquids/ Final API (Potent and Non Potent) A. Installation Qualification B. Operational Qualification C. Performance Qualification Regular Check Points of HVAC System Definition CHAPTER 23 Manufacturing Execution System (MES) in Pharmaceutical Industry 23.1 Overview of REPAC Model Overview of Three-Layer-Model Overview of Standards ISA S /02/03 for MES Systematic Planning Approach to MES Implementation in 14 Stages MES Functions Implementation Strategy CHAPTER 24 Pharmaceutical Drug Master File I. Submissions to Drug Master Files II. Types of Drug Master File and its Contents III. General Information and Suggestions IV. Format, Assembly, and Delivery V. Drug Master File submissions and correspondence should be addressed as follows VI. Authorization to refer to a Drug Master File VII. Processing and Reviewing Policies VIII. Holder Obligations (xxii)

15 IX. Major Reorganization of a Drug Master File X. Closure of a Drug Master File XI. Submission Process of Drug Product CHAPTER 25 Common Technical Document in Regulatory Filing 25.1 Organization of the Common Technical Document Module 1: Administrative Information and Prescribing Information Module 2: Common Technical Document Summaries Module 3: Quality Module 4: Nonclinical Study Reports Module 5: Clinical Study Reports Electronic Common Technical Document CHAPTER 26 European Union Marketing Authorization A. Mutual Recognition Procedure (MRP) a. Steps involved in the mutual recognition procedure b. Flow chart for the Mutual Recognition Procedure B. Decentralized Procedure a. Steps involved in the Decentralised procedure b. Flow Chart of the Decentralised Procedure C. Numbering System for the Procedures for Mutual Recognition and Decentralised Procedure D. Centralised authorisation procedure a. Flow Chart of the Centralised Procedure CHAPTER 27 Site Master File 27.1 Content of Site Master File A. General Information on the Manufacturer (xxiii)

16 B. Quality Management system of the Manufacturer C. Personnel D. Premises and Equipment E. Documentation F. Production G. Quality Control (QC) H. Distribution, Complaints, Product Defects and Recalls I. Self-inspections Appendix CHAPTER 28 Standard Operating Procedure (SOP) 28.1 Writing Styles SOP Process SOP Review and Approval Frequency of Revisions and Reviews Checklists Document Control SOP Document Tracking and Archival SOP General Format Definitions CHAPTER 29 Quality Manual I. Contents of the Quality Manual II. Topics that should be covered in the final section on Quality Policies for Specific Regulation Elements CHAPTER 30 Human Error Reduction: Pharma Industry Challenge 30.1 How Do Industry and Regulatory Expectations and Approaches Differ? (xxiv)

17 30.2 Understanding, Investigation & Tackling of Human Error Power of 5-WHY Human Error and Retraining What Can Be Done for Human Error? Measure of Human Error CHAPTER 31 Regulatory Inspections: Face Challenges through Proactive Measures 31.1 Regulatory Expectations? Current Regulatory Audits Looking Regulators Looks at Audit Trail Assessments An Approach to Managing Regulatory Risks and Achieving Compliance Measures of Regulatory Inspections CHAPTER 32 Pharmaceutical GMP: Past, Present, and Future A Review 32.1 Current Expectations for Pharmaceutical Quality Systems A Quality Culture That Leads to Sustainable Compliance Quality Culture Building Knowledge, Effective Monitoring & Control Systems Global Supply Chain and Vendor Qualification Bundling GMP Enforcement with Other Violations Quality Systems Change Control: New FDA Expectations for Equipment Changes References (xxv)