Insight

On 23 September 2026, PIC/S published the new version PE 009-18 of the PIC/S GMP Guide. This new PE 009-18 edition totals 400 pages, consisting of Part I (Basic GMP Requirements for Medicinal Products), Part II (GMP for Active Pharmaceutical Ingredients), and 20 Annexes, as listed below:

Part I — Basic Requirements for Medicinal Products

Chapter 1 — Pharmaceutical Quality System

• Principle
• Pharmaceutical Quality System
• Good Manufacturing Practices for Medicinal Products (GMP)
• Quality Control
• Product Quality Review
• Quality Risk Management

Chapter 2 — Personnel

• Principle
• General
• Key Personnel
• Training
• Personal Hygiene
• Consultants

Chapter 3 — Premises and Equipment

• Principle
• Premises
  • General
  • Production Area
  • Storage Area
  • Quality Control Area
  • Ancillary Area
• Equipment

Chapter 4 — Documentation

• Principle
• GMP Documentation Required (by Type)
• Generation and Control of Documentation
• Good Documentation Practices
• Retention of Documents
• Specifications
  • Specifications for Starting and Packaging Materials
  • Specifications for Intermediate and Bulk Products
  • Specifications for Finished Products
• Manufacturing Formula and Processing Instructions
• Packaging Instructions
• Batch Processing Records
• Batch Packaging Records
• Procedures and Records
  • Receipt
  • Sampling
  • Testing
  • Other

Chapter 5 — Production

• Principle
• General
• Prevention of Cross-Contamination in Production
• Validation
• Starting Materials
• Processing Operations — Intermediate and Bulk Products
• Packaging Materials
• Packaging Operations
• Finished Products
• Rejected, Recovered and Returned Materials
• Product Shortages due to Manufacturing Constraints

Chapter 6 — Quality Control

• Principle
• General
• Good Quality Control Laboratory Practice
• Documentation
• Sampling
• Testing
• On-Going Stability Programme
• Transfer of Analytical Methods

Chapter 7 — Contract Activities

• Principle
• General
• The Contract Giver
• The Contract Acceptor
• The Contract

Chapter 8 — Complaints and Product Recall

• Principle
• Personnel and Organisation
• Procedures for Handling and Investigation of Complaints (Including Possible Quality Defects)
• Investigation and Decision-Making
• Root Cause Analysis and Corrective and Preventive Actions
• Product Recalls and Other Potential Risk-Reducing Actions

Chapter 9 — Self-Inspection

• Principle

Part II — GMP for Active Pharmaceutical Ingredients (API)

1. Introduction

• 1.1 Purpose
• 1.2 Scope

2. Quality Management

• 2.1 Principles
• 2.2 Quality Risk Management
• 2.3 Responsibilities of the Quality Unit
• 2.4 Responsibilities for Production Activities
• 2.5 Internal Audits (Self-Inspection)
• 2.6 Product Quality Review

3. Personnel

• 3.1 Personnel Qualifications
• 3.2 Personnel Hygiene
• 3.3 Consultants

4. Buildings and Facilities

• 4.1 Design and Construction
• 4.2 Utilities
• 4.3 Water
• 4.4 Containment
• 4.5 Lighting
• 4.6 Sewage and Waste
• 4.7 Sanitation and Maintenance

5. Process Equipment

• 5.1 Design and Construction
• 5.2 Equipment Maintenance and Cleaning
• 5.3 Calibration
• 5.4 Computerised Systems

6. Documentation and Records

• 6.1 Documentation System and Specifications
• 6.2 Equipment Cleaning and Use Records
• 6.3 Records of Raw Materials, Intermediates, API Labelling and Packaging Materials
• 6.4 Master Production Instructions (Master Production and Control Records)
• 6.5 Batch Production Records (Batch Production and Control Records)
• 6.6 Laboratory Control Records
• 6.7 Batch Production Record Review

7. Materials Management

• 7.1 General Controls
• 7.2 Receipt and Quarantine
• 7.3 Sampling and Testing of Incoming Production Materials
• 7.4 Storage
• 7.5 Re-evaluation

8. Production and In-Process Controls

• 8.1 Production Operations
• 8.2 Time Limits
• 8.3 In-Process Sampling and Controls
• 8.4 Blending of Intermediates or API Batches
• 8.5 Contamination Control

9. Packaging and Labelling of APIs and Intermediates

• 9.1 General
• 9.2 Packaging Materials
• 9.3 Label Issuance and Control
• 9.4 Packaging and Labelling Operations

10. Storage and Distribution

• 10.1 Warehousing Procedures
• 10.2 Distribution Procedures

11. Laboratory Controls

• 11.1 General Controls
• 11.2 Testing of Intermediates and APIs
• 11.3 Validation of Analytical Methods (see Section 12)
• 11.4 Certificate of Analysis
• 11.5 Stability Monitoring of APIs
• 11.6 Expiry and Retest Dating
• 11.7 Reserve/Retention Samples

12. Validation

• 12.1 Validation Policy
• 12.2 Validation Documentation
• 12.3 Qualification
• 12.4 Approaches to Process Validation
• 12.5 Process Validation Programme
• 12.6 Periodic Review of Validated Systems
• 12.7 Cleaning Validation
• 12.8 Validation of Analytical Methods

13. Change Control

14. Rejection and Re-Use of Materials

• 14.1 Rejection
• 14.2 Reprocessing
• 14.3 Reworking
• 14.4 Recovery of Materials and Solvents
• 14.5 Returns

15. Complaints and Recalls

16. Contract Manufacturers (Including Laboratories)

17. Agents, Brokers, Traders, Distributors, Repackers and Relabellers

• 17.1 Applicability
• 17.2 Traceability of Distributed APIs and Intermediates
• 17.3 Quality Management
• 17.4 Repackaging, Relabelling and Holding of APIs and Intermediates
• 17.5 Stability
• 17.6 Transfer of Information
• 17.7 Handling of Complaints and Recalls
• 17.8 Handling of Returns

18. Specific Guidance for APIs Manufactured by Cell Culture/Fermentation

• 18.1 General
• 18.2 Cell Bank Maintenance and Record Keeping
• 18.3 Cell Culture/Fermentation
• 18.4 Harvesting, Isolation and Purification
• 18.5 Viral Removal/Inactivation Steps

19. APIs for Use in Clinical Trials

• 19.1 General
• 19.2 Quality
• 19.3 Equipment and Facilities
• 19.4 Control of Raw Materials
• 19.5 Production
• 19.6 Validation
• 19.7 Changes
• 19.8 Laboratory Controls
• 19.9 Documentation

20. Glossary

Annexes

Annex 1 — Manufacture of Sterile Medicinal Products

• Document Map
• Scope
• Principle
• Pharmaceutical Quality System (PQS)
• Premises
• Barrier Technologies
• Qualification of Cleanrooms and Clean Air Equipment
• Disinfection
• Equipment
• Utilities
  • Water Systems
  • Steam Used as a Direct Sterilising Agent
  • Gases and Vacuum Systems
  • Heating, Cooling and Hydraulic Systems
• Personnel
• Production and Specific Technologies
  • Terminally Sterilised Products
  • Aseptic Preparation and Processing
  • Finishing of Sterile Products
  • Sterilisation
    • Thermal Sterilisation
    • Moist Heat Sterilisation
    • Dry Heat Sterilisation
    • Radiation Sterilisation
    • Ethylene Oxide Sterilisation
    • Sterilisation by Filtration of Products Which Cannot Be Sterilised in Their Final Container
  • Form-Fill-Seal (FFS)
  • Blow-Fill-Seal (BFS)
  • Lyophilisation
  • Closed Systems
  • Single Use Systems (SUS)
• Environmental and Process Monitoring
  • General
  • Environmental and Process Monitoring
  • Environmental Monitoring — Total Particles
  • Environmental and Personnel Monitoring — Microbiological
  • Aseptic Process Simulation (APS, also known as Media Fill)
• Quality Control (QC)
• Glossary

Annex 2A — Manufacture of Advanced Therapy Medicinal Products (ATMPs) for Human Use

• Scope
• Principle
• Part A: General Guidance
  • Supplementary Provisions to PIC/S GMP Guide Part I
    • Chapter 1 — Pharmaceutical Quality System
    • Chapter 2 — Personnel
    • Chapter 3 — Premises and Equipment
    • Chapter 4 — Documentation
    • Chapter 5 — Production
    • Chapter 6 — Quality Control
    • Chapter 7 — Contract Activities
    • Chapter 8 — Complaints and Product Recall
• Part B: Specific Guidance for Specific Product Types
• Glossary Common to Annex 2A and 2B

Annex 2B — Manufacture of Biological Active Substances and Medicinal Products for Human Use

• Scope
• Principle
• Part A: General Guidance
  • Personnel
  • Premises and Equipment
  • Animals
  • Documentation
  • Production
    • Starting and Raw Materials
    • Seed Lot and Cell Bank System
    • Operating Principles
  • Quality Control
• Part B: Specific Guidance for Specific Product Types

Annex 3 — Manufacture of Radiopharmaceuticals

• Principle
• Introduction
• Quality Assurance
• Personnel
• Premises and Equipment
• Documentation
• Production
• Quality Control
• Reference and Retention Samples
• Distribution
• Glossary

Annex 4 — Manufacture of Veterinary Medicinal Products Other than Immunological Veterinary Medicinal Products

• Manufacture of Medicated Feed Premixes
• Manufacture of Ectoparasiticides
• Manufacture of Veterinary Medicinal Products Containing Penicillins
• Retention Samples
• Sterile Veterinary Medicinal Products

Annex 5 — Manufacture of Immunological Veterinary Medicinal Products

• Principle
• Personnel
• Premises
• Equipment
• Animals and Animal Houses
• Disinfection and Waste Disposal
• Production
• Starting Materials
• Quality Control

Annex 6 — Manufacture of Medicinal Gases

• Principle
• Manufacture of Active Pharmaceutical Ingredient (API) Gases
• Manufacture of Medicinal Gases
• Personnel
• Premises and Equipment
• Documentation
• Production
• Quality Control
• Transport of Packaged Gases
• Glossary

Annex 7 — Manufacture of Herbal Medicinal Products

• Principle
• Premises
  • Storage Areas
  • Production Areas
• Equipment
• Documentation
  • Specifications for Starting Materials
  • Processing Instructions
• Quality Control

Annex 8 — Sampling of Starting and Packaging Materials

• Principle
• Personnel
• Starting Materials
• Packaging Materials

Annex 9 — Manufacture of Liquids, Creams and Ointments

• Principle
• Premises and Equipment
• Production

Annex 10 — Manufacture of Pressurised Metered-Dose Aerosol Preparations for Inhalation

• Principle
• General
• Premises and Equipment
• Production and Quality Control

Annex 11 — Computerised Systems

• Principle
• General
• Risk Management
• Personnel
• Suppliers and Service Providers
• Project Phase
• Validation
• Operational Phase
  • Data
  • Accuracy Checks
  • Data Storage
  • Printouts
  • Audit Trails
  • Change and Configuration Management
  • Periodic Evaluation
  • Security
  • Incident Management
  • Electronic Signatures
  • Batch Release
  • Business Continuity
  • Archiving
• Glossary

Annex 12 — Use of Ionising Radiation in the Manufacture of Medicinal Products

• Introduction
• Responsibilities
• Dosimetry
• Validation of the Process
• Commissioning of the Plant
  • General
  • Gamma Irradiation Plant
  • Electron Beam Irradiation Plant
• Premises
• Processing
  • Gamma Irradiation Plant
  • Electron Beam Irradiation Plant
• Documentation
• Microbiological Monitoring

Annex 13 — Manufacture of Investigational Medicinal Products

• Introduction
• Scope
• Pharmaceutical Quality System
• Personnel
• Premises and Equipment
• Documentation
• Production
• Quality Control
• Release of Batches
• Contracted Operations
• Complaints
• Recalls and Returns
• Glossary

Annex 14 — Manufacture of Medicinal Products Derived from Human Blood or Plasma

• Glossary
• Scope
• Principle
• Quality Management
• Traceability and Post-Collection Measures
• Premises and Equipment
• Production
• Quality Control
• Release of Intermediate and Finished Products
• Retention of Plasma Pool Samples
• Disposal of Waste
• Annexure

Annex 15 — Qualification and Validation

• Principle
• General
• Organisation and Planning of Qualification and Validation
• Documentation, Including Validation Master Plan (VMP)
• Qualification Stages for Equipment, Facilities and Systems
• Re-Qualification
• Process Validation
• Qualification of Transportation
• Validation of Packaging
• Qualification of Utilities
• Validation of Test Methods
• Cleaning Validation
• Change Control
• Glossary

Annex 16 — Qualified Person and Batch Release

• Scope
• Principles
• The Certification (Assessment and Release) Process
• GMP Assessment Relying on Third Parties (e.g. Audits)
• Handling of Unexpected Deviations
• Release of Batches
• Glossary
• Appendix I
• Appendix II

Annex 17 — Real-Time Release Testing and Parametric Release

• Principle
• Scope
• Real-Time Release Testing (RTRT)
• Parametric Release and Sterilisation
• Glossary

Annex 18 — GMP Guide for Active Pharmaceutical Ingredients (Incorporated into Part II)

Annex 19 — Reference and Retention Samples (Revised in This Version, PE 009-18)

• Scope
• Principle
• Duration of Storage
• Quantities of Reference and Retention Samples
• Storage Conditions
• Written Agreements
• Reference Samples — Key Points
• Retention Samples — Key Points
• Reference and Retention Samples for Parallel Imported/Parallel Distributed Products
• Reference and Retention Samples in the Case of Closure of a Manufacturer

Annex 20 — Quality Risk Management

• Foreword and Scope of Application
• Introduction
• Scope
• Principles of Quality Risk Management
• General Quality Risk Management Process
• Responsibilities
• Initiating a Quality Risk Management Process
• Risk Assessment
• Risk Control
• Risk Communication
• Risk Review
• Risk Management Methodology
• Integration of Quality Risk Management into Industry and Regulatory Operations
• Definitions
• References
• Appendix I: Risk Management Methods and Tools
  • Basic Risk Management Facilitation Methods
  • Failure Mode Effects Analysis (FMEA)
    • Potential Areas of Use
  • Failure Mode, Effects and Criticality Analysis (FMECA)
  • Fault Tree Analysis (FTA)
  • Hazard Analysis and Critical Control Points (HACCP)
  • Hazard Operability Analysis (HAZOP)
  • Preliminary Hazard Analysis (PHA)
  • Risk Ranking and Filtering
  • Supporting Statistical Tools
• Appendix II: Potential Applications of Quality Risk Management
  • As Part of Integrated Quality Management
  • As Part of Regulatory Operations
  • As Part of Development
  • For Facilities, Equipment and Utilities
  • As Part of Materials Management
  • As Part of Production
  • As Part of Laboratory Control and Stability Studies
  • As Part of Packaging and Labelling
• Glossary