医薬品の安全性試験実施基準ガイド：第3版

D&MD' s Guide to Good Laboratory Practice, 3rd Edition examines the GLP regulations in the United States and other countries in detail, and gives firm guidelines for compliance, using as a basis the GLP requirements published in the U.S.A Code of Federal Regulations, Title 21, Part 58, 2006 Edition (21CFR58). The guidelines laid down by other countries, especially members of the European Community, are based upon guidelines developed by the Organization for Economic Development (OECD) in 1980. Guidelines on safety testing and analytical methods issued by the International Conference on Harmonization (ICH) are also reviewed. Special attention is paid to the documentation and the preparations for internal and external inspections and audits.

Chapter 1: Executive Summary

Chapter 2: Introduction

• The Assurance of Quality in Drug Research, Development, and Pre-Clinical Testing
• Good Laboratory Practice and the Transfer of Technology
• The Cost of GLP Non-compliance

Chapter 3: International Regulations Governing GLP

• Chronology and Current Regulations
  • United States of America
  • Europe
  • Canada
  • Japan
• Comparison of the Regulations

Chapter 4: Critical Compliance Issues

• Organization and Personnel (Subpart B, 58.29- 35)
  • Matrix Organization
  • Personnel Qualifications, Training, and Behavior (see 58.29 & 58.31)
  • Management Responsibilities (See 58.31)
  • Specific Appointments: The Study Director (see 58.33)
  • The Quality Assurance Unit (see 58.35)
  • Facilities (Subpart C, 58.41 - 51)
    • Containment Issues
  • Animal Unit Design
  • Equipment (Subpart D, 58.61- 63) (OECD: “Apparatus“)
• Testing Facilities Operation (Subpart E 58.81 - 90)
  • Standard Operating Procedures ( 58.81)
  • Guide to SOP Writing
  • Reagents and Solutions ( 58.83)
  • Animal Care (58.90)
  • Test and Control Articles (Subpart F, 58.105- 113) (OECD: “Test & Reference Items“)
• Protocol for and Conduct of a Study (Subpart G, 58.120- 130)
  • The Study Protocol ( 58.120) (OECD “Study Plan“)
  • Conduct of the Study ( 58.130)
  • Recording of Data
  • Electronic Data Management
• Records and Reports (Subpart J, 58.185- 195)
  • The Final Report of the Study ( 58.185)
  • Archiving the Data ( 58.190)
  • Retention of Archived Records and Specimens ( 58.195)
  • Form of Retained Records ( 58.195 g)
  • Transfer of Records ( 58.195h)
• Conclusions

Chapter 5: Submitting Pre-clinical Study Findings in Clinical Trial Applications

• IND Contents According to FDA
• The ICH Common Technical Document
  • Nonclinical Summaries and Tables
  • Order of Presentation of Information within Sections
  • Module 4- Nonclinical Data

Chapter 6: GLP Inspections and Study Audits

• What Are Inspections and Audits?
  • Establishment Inspections
  • Key Inspection Points
  • Study Audits
  • Establishment Inspection Report (EIR)
  • Deviations which are not required to be notified by FDA 483 are:
• How to Survive Inspections and Audits
  • Before- Preparing for the Inspection
  • During- Inspection Days
  • After- Dealing with the Report
  • How Others Fared- Excerpts from Form 483

Chapter 7: Conclusions

Chapter 8: References and Further Reading

• Access to Regulatory Documents
• Useful Publications
  • Associations and Information Web Sites
  • GLP Consultants

Chapter 9: Appendices

• GLP Inspection Forms
• Texts of GLP Regulations
• Endnotes
• Japan Ordinance 21 & PAB 424, 1997

• Exhibit 2.1 What is Quality Assurance?
• Exhibit 2.2 The Stages in Drug Development
• Exhibit 3.1 Member Nations of OECD
• Exhibit 3.2 OECD Documents Concerning GLP and Compliance Monitoring
• Exhibit 3.3 Comparison of Contents of GLP Regulations
• Exhibit 3.4 Definitions of Major Terms
• Exhibit 4.1 Matrix Management Chart
• Exhibit 4.2 Sample Ground Rules for Laboratory Operation
• Exhibit 4.3 Section of a Study Schedule GANTT Chart (“On Target“ Software)
• Exhibit 4.4 Certificate of Analysis
• Exhibit 4.5 Suggested Layout for the Master SOP Manual
• Exhibit 4.6 Study Monitoring Record
• Exhibit 4.7 Critical Factors in Facility Compliance
• Exhibit 4.8 Biohazard Laminar-Flow Cabinet, Class II Type B1
• Exhibit 4.9 Animal Unit Layout
• Exhibit 4.10 Typical Equipment Maintenance Record
• Exhibit 4.11 Minimum List of SOPs Required (according to 21CFR58.81)
• Exhibit 4.12 Templates for SOP
• Exhibit 4.13 Solution Label
• Exhibit 4.14 Animal Cage Label
• Exhibit 4.15 Sample Container Label
• Exhibit 4.16 Sample Storage Box Label
• Exhibit 4.17 Label for Specimen Container
• Exhibit 4.18 Retention Times for Archived Materials
• Exhibit 4.19 Other Records to be Maintained
• Exhibit 5.1 Contents of the CTD
• Exhibit 5.2 TOC of Section 2.6
• Exhibit 5.3 Example of Pharmacology Summary Table
• Exhibit 5.4 Example of a Specific Pharmacokinetics Table
• Exhibit 5.5 Example of a Toxicology Summary Table
• Exhibit 5.6 Example of a Toxicokinetics Summary Graph
• Exhibit 5.7 Table of Contents of Module 4
• Exhibit 6.1 Inspection Request Form