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Table of Contents
1. INTRODUCTION 1.1 Objective
1.2 Regulatory Applicability 1.3 Scope
2. QUALITY MANAGEMENT 2.1 Principles
2.2 Responsibilities of the Quality Unit(s) 2.3 Responsibility for Production Activities 2.4 Internal Audits (Self Inspection) 2.5 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 Refuse
4.7 Sanitation and Maintenance
5. PROCESS EQUIPMENT 5.1 Design and Construction
5.2 Equipment Maintenance and Cleaning 5.3 Calibration
5.4 Computerized Systems
6. DOCUMENTATION AND RECORDS 6.1 Documentation System and Specifications 6.2 Equipment cleaning and Use Record
6.3 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials
6.4 Master Production Instructions (Master Production and Control Records)
6.5 Batch Production Records (Batch Production and Control Records)
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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 Batches of Intermediates or APIs 8.5 Contamination Control
9. PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES 9.1 General
9.2 Packaging Materials
9.3 Label Issuance and Control
9.4 Packaging and Labeling 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 Procedures 11.4 Certificates 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 Program
12.6 Periodic Review of Validated Systems 12.7 Cleaning Validation
12.8 Validation of Analytical Methods
13. CHANGE CONTROL
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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, Relabeling, 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
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Q7a
Q7a GMP Guidance for APIs
Q7aÔÁÏÒ©µÄGMPÖ¸ÄÏ
1. INTRODUCTION 1.1 Objective
This document is intended to provide guidance regarding good manufacturing practice (GMP) for the manufacturing of active pharmaceutical ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the quality and purity characteristics that they purport, or are represented, to possess.
In this guidance, the term manufacturing is defined to include all operations of receipt of materials, production, packaging, repackaging, labeling, relabeling, quality control, release, storage and distribution of APIs and the related controls. In this guidance, the term should identifies recommendations that, when followed, will ensure compliance with CGMPs. An alternative approach may be used if such approach satisfies the requirements of the applicable statues. For the purposes of this guidance, the terms current good manufacturing practices and good manufacturing practices are equivalent.
The guidance as a whole does not cover safety aspects for the personnel engaged in manufacturing, nor aspects related to protecting the environment. These controls are inherent responsibilities of the manufacturer and are governed by national laws.
This guidance is not intended to define registration and/or filing requirements or modify pharmacopoeial requirements. This guidance does not affect the ability of the responsible regulatory agency to establish specific registration/filing requirements regarding APIs within the context of marketing/manufacturing authorizations or drug applications. All commitments in registration/filing documents should be met.
1.2 Regulatory Applicability
Within the world community, materials may vary
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