バリデーション実施基準ガイド：第3版

D&MD' s Guide to Good Validation Practice, 3rd Edition is devoted to considering in greater detail the ways of complying with validation requirements at all stages of drug research, development and manufacture. The particular problems associated with the newer biopharmaceutical products are given special consideration. To complete this comprehensive guide to validation and its problems, full texts are provided of the major guidelines issued by National and International regulatory authorities, along with the relevant abstracts from the GLP, GMP, and GCP regulations. Other references include web sites for the retrieval of the text of regulations and guidelines, a list of useful publications, and of some well-known firms specializing in validation consulting.

Chapter 1: Executive Summary

Chapter 2: Introduction

• Validation in Research, Development, and Manufacturing
• The Regulatory Environment
• Types of Validation
• Corporate Implications of Non-compliance with GVP

Chapter 3: The Validation Master Plan

• Introduction
• Validation Master Plan Contents
• Responsibilities
• What is to be Validated?
  • Facilities
  • Systems
  • Processes
  • Analytical Methods
• Implementing the Plan
  • Design, Installation, and Operational Qualification
  • Performance Qualification and Validation
  • Documentation
• Change Control

Chapter 4: Facilities, Services, and Systems

• Facilities
  • Design and Construction
  • Utilities
• Validation of Special Systems
  • Water Systems: Purified and WFI
  • Sterilization Systems and Clean Steam Systems
  • Clean Rooms- Aseptic Work Areas
  • Computerized Systems

Chapter 5: Process Equipment and Pipe-work

• Introduction
• Design and DQ of Equipment and Piped Systems
• Installation, Operation, and Performance Qualification
• Validation of Cleaning Procedures
• Validation of Sterilization-In-Place Procedures

Chapter 6: Manufacturing Processes

• General Principles of Process Validation
• Guide to the Performance of Validations
• Special Processes- Validation Challenges
  • Glassware Washing Machines
  • Fermentor and Bioreactor Control
  • Chromatographic Separation
  • Transverse-flow Micro- and Ultrafiltration
  • Sterilizing Filtration
  • Virus Removal Processes
  • Aseptic Filling Operations
  • Lyophilizer (Freezedryer) Operation

Chapter 7: Analytical Methods for In-process and Final Quality Control

• Regulatory Requirements and Guidelines
• Qualification of Analytical Instruments and Equipment
• Test Method Validation
• Types of Analytical Procedures to be Validated
  • Test “Verification”, “Qualification” versus “Validation”
  • Physical and Chemical Analyses
  • Biological Assays

Chapter 8: Sample Checklists and Forms

• Check Lists for Plans and Protocols
• Equipment Qualification Report Forms

Chapter 9: References and Further Reading

• Access to Regulations on the Internet
• Validation and GMP Compliance Guidelines
  • U.S.A.
  • Canada
  • European Union
  • International Conference on Harmonization (ICH)
• Associations, Consultants and Publications

Chapter 10: Abstracts from International GLP/GMP/GCP Regulations

• Good Laboratory Practice
  • OECD PRINCIPLES OF GOOD LABORATORY PRACTICE*
  • (as revised in 1997)
  • USA Code of Federal Regulations
  • CANADA - “Guidelines for Good Manufacturing Practice”
  • JAPAN MHW Ordinance 16, March 123, 1999, Amended by MHW Ordinance #95, May 20, 2003

Chapter 11: Text of Key Validation Guidelines

• Process Validation Guidelines

• Exhibit 2.1 Definitions of “Process Validation”
• Exhibit 2.2 The Drug Development Cycle
• Exhibit 2.3 International "Practice" Regulations
• Exhibit 2.4 Regulations Specifically Concerning Validation
• Exhibit 2.5 Process Validation and the Product Development Cycle
• Exhibit 3.1 Typical “System Definition” Table for a VMP
• Exhibit 3.2 Derivation of Validation Plans/Protocols
• Exhibit 3.3 Validation Protocol Contents List
• Exhibit 4.1 Factors Determining User Requirements Specifications
• Exhibit 4.2 Standards for Pharmaceutical Water Grades
• Exhibit 4.3 Schematic of WFI System
• Exhibit 4.4 Clean Room Classes According to FS 209E
• Exhibit 4.5 EUDRA Clean Room Specifications
• Exhibit 4.6 ISO 14644-1 Standard
• Exhibit 4.7 EU Microbiological Monitoring of Clean Areas
• Exhibit 6.1 Validation and Product Development
• Exhibit 6.2 Process Validation Life Cycle
• Exhibit 6.3 Terminology of Process Validation
• Exhibit 6.4 Calculation of Process Capability
• Exhibit 6.5 Washer Qualification Plan
• Exhibit 6.6 Control of a Cell Culture Bioreactor
• Exhibit 6.7 Typical Flow/Pressure Graphs for TFF Membranes
• Exhibit 6.8 Parameters Affecting Sterilizing Filter Performance
• Exhibit 6.9 Viruses Commonly Used in Clearance Studies
• Exhibit 7.1 Basis of Questionnaire for Vendor Qualification
• Exhibit 7.2 The Characteristics of a Calibration Curve
• Exhibit 7.3 Parameters Applicable to Different Analytical Procedures
• Exhibit 7.4 Analytical Methods Applied to Biological Products
• Exhibit 7.5 Calculation of Intra-assay and Inter-assay Precision
• Exhibit 7.6 Three-dimensional Factorial Test Validation Plan
• Exhibit 11.1 FDA Guideline on General Principles of Process Validation
• Exhibit 11.2 EU European Commission
• Exhibit 11.3 ORA Compliance Policy Guide
• Exhibit 11.4 Guidance to 21CFR11
• Exhibit 11.5 FDA/ICH Analytical Method Validation Q2A & B
• Exhibit 11.6 FDA Bioanalytical Method Validation