Gmp Manual Table of contents

GMP Manual Contents

GMP Manual Contents 1

Pharmaceutical Quality System (PQS)

1.A

Preface

1.B

The road to a Ph Pharmaceutical Quality System

1.C 1.C.1 1.C.2

Introduction to the PQS General requirements Documentation

1.D 1.D.1 1.D.2 1.D.3 1.D.4

Main elements of a PQS Management responsibility Resource management Manufacturing operations Evaluation activities

1.D (1) 1.D (4) 1.D (7) 1.D (10)

1.E 1.E.1 1.E.2 1.E.3 1.E.4

Essentials of a PQS Principles of a process Process mapping Responsibilities Key Performance Indicators (KPIs)

1.E (1) 1.E (8) 1.E (25) 1.E (26)

1.F 1.F.1 1.F.2 1.F.3 1.F.4

Practical implementation of a PQS Assistance for implementation Organizational aspects Process of developing documents Document hierarchy

1.F (1) 1.F (3) 1.F (5) 1.F (7)

1.G

Structure of a PQS quality manual – example

1.H

Corr rre elation be between GM GMP re req quire rem ments (WHO) an and IS ISO 90 9001:2000

1.I

References

2

Personnel

2.A

Place of work and job descriptions

2.B 2.B.1 2.B.2

Requirements of the personnel Qualification requirements Health requirements GMP Manual (Up11) © Maas & Peither AG – GMP Publishing

1.C (1) 1.C (2)

2.B (1) 2.B (2)

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2.C 2.C.1 2.C.2 2.C.3 2.C.4 2.C.5 2.C.6 2.C.7 2.C.8

Training Purpose of training Responsibility for training Requirements profiles/learning objectives Training contents and target groups Training planning Carrying out Reviewing the training and the training system Documentation

2.D 2.D.1 2.D.2 2.D.3 2.D.4

Function owners subject to public law Qualified Person (QP) Head of Production Head of Quality Control Qualified Person in Accordance with Article 103 of Guideline 2001/83/EC Scientific Service in Charge of Information Medical sales representatives

2.D.5 2.D.6 s t n 3 e t n 3.A o 3.A.1 C

3.A.2 3.A.3 3.A.4 3.A.5 3.A.6 3.B 3.B.1 3.B.2 3.B.3 3.B. B.4 4

2.C (1) 2.C (1) 2.C (2) 2.C (3) 2.C (4) 2.C (4) 2.C (8) 2.C (11) 2.D (1) 2.D (12) 2.D (17) 2.D (21) 2.D (24) 2.D (26)

Premises Official Requirements Loca cattion, co con nnec ecttion to other ro roo oms Size, area, height Installation and supply of utilities Lighting, ventilation, air-conditioning Hygienic construction Room book and layout Material flow, personnel flow and layout Material flow Personnel flow Layout Design concepts in FDA’s Sterile Drug Produc uctts Produced by Aseptic Processing guideline

3.C 3.C.1 3.C.2 3.C.3 3.C.4 3.C.5 3.C.6 3.C.7

Room classes General GMP Requirements for Premises GMP Requirements for Cleanrooms: Air Cleanliness Grades Corresponding FDA Determinations GMP Requirements for Premises Room-specific Allocation of Air Cleanliness Stipulations Cleanliness Zoning Concepts Converting GMP Stipulations into Reality

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GMP Manual (Up11) © Maas & Peither AG – GMP Publishing

3.A (4) 3.A (5) 3.A (7) 3.A (7) 3.A (8) 3.A (8) 3.B (1) 3.B (4) 3.B (4) 3.B (5) 3.C (1) 3.C (1) 3.C (4) 3.C (6) 3.C (7) 3.C (9) 3.C (12)

GMP Manual Contents

3.D 3.D.1 3.D.2 3.D.3 3.D.4

Construction elements Walls Doors and windows Floors Ceilings

3.D (1) 3.D (6) 3.D (8) 3.D (10)

3.E 3.E.1 3.E.2 3.E.3 3.E.4

Barrier systems and isolators Protection concepts for maximized sterility assurance Pharmaceutical isolator technology Restricted access barrier systems (RABS te t echnology) Application options for RABS and isolators

3.E (1) 3.E (2) 3.E (8) 3.E (12)

3.F 3.F.1 3.F.2 3.F.3 3.F. 3. F.4 4 3.F.5

Building services Basic requirements for installation Heating Sanitary plumbing and sewage Elec El ectr tric ical al in inst stal alla lati tion onss in incl cl.. IT IT-m -man anag agem emen entt an and d co cont ntro roll sy syst stem emss Qualification

3.F (1) 3.F (3) 3.F (3) 3.F 3. F (3 (3)) 3.F (4)

3.G 3.G.1 3.G.2 3.G.3 3.G. G.4 4 3.G.5 3.G.6

Heating Ventilation Air Conditioning (HVAC) Introduction Room ventilation systems Filters Princi cip ples fo for the des desiign and pl planning of air air conditioning ventilation systems Design criteria for the ventilation of premises Maintenance of air ventilation systems

3.G (23) 3.G (26) 3.G (37)

3.H 3.H.1 3.H.2 3.H.3 3.H.4

Process Gases Quality Requirements Generation, Storage and Distribution System design Qualification and monitoring

3.H (2) 3.H (4) 3.H (5) 3.H (8)

3.I 3.I.1 3.I.2 3.I.3 3.I.4 3.I.5 3.I.6 3.I.7 3.I.8

Qualification of premises and air-conditioning systems Objectives of qualification Regulatory and normative fundamentals of qualification Project development and qualification Qualification Master Plan Qualification Plans and Qualification Reports Qualification checklists Requirements for measurement and test reports Requalification

3.I (1) 3.I (2) 3.I (3) 3.I (4) 3.I (5) 3.I (6) 3.I (29) 3.I (30)

3.J 3.J.1 3.J.2 3.J.3

Monitoring of HVAC systems Objectives of process monitoring Data management stipulations Air cleanliness and other room air data

3.J (1) 3.J (1) 3.J (3)


3.G (1) 3.G (3) 3.G (11)

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3.J.4 3.J.5 3.J.6

Risks of microbiological monitoring Alarm and action limits Operation and maintenance

3.K

References

4

Facilities and Equipment

4.A

Introduction

4.B 4.B.1 4.B.2 4.B.3

Mechanical components Construction and installation materials GMP-compliant design characteristics Electrical and pneumatic components

4.C

Control

4.D 4.D.1 4.D.2 s t 4.D.3

3.J (4) 3.J (4) 3.J (5)

4.B (1) 4.B (2) 4.B (3)

Facility concepts CIP (Cleaning in Place) Isolator technology Connected facilities

4.D (1) 4.D (2) 4.D (2)

4.E.3

Examples of facility qualification Design qualification Installation qualification Operational qualification

4.E (1) 4.E (5) 4.E (12)

4.F 4.F.1 4.F.2 4.F.3 4.F.4

Technical documentation Necessity Scope and content Administration of the technical documentation Log book

4.F (1) 4.F (2) 4.F (9) 4.F (12)

4.G 4.G.1 4.G.2 4.G.3 4.G.4

Calibration Definitions Procedure Documentation Administration of scheduled calibration dates/ times

4.G (1) 4.G (3) 4.G (4) 4.G (5)

4.H 4.H.1 4.H.2 4.H.3

Maintenance Types of maintenance GMP-conforming maintenance Systems for maintenance

4.H (2) 4.H (2) 4.H (3)

4.I 4.I.1 4.I.2 4.I.3 4.I.4

CIP (Cleaning in Place) Introduction CIP systems GMP-conforming design of CIP facilities Nozzle heads for container cleaning

4.I (1) 4.I (3) 4.I (6) 4.I (11)

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4.I.5 4.I.6

Measuring technology Realisation of cleaning systems

4.I (13) 4.I (15)

4.J 4.J.1 4.J.2 4.J.3 4.J.4 4.J.5 4.J.6 4.J.7 4.J.8 4.J.9 4.J.10 4.J.11

Containment (personnel protection) in solids handling Significance Definition of terms Containment grades of products Measurement of the residue limits (OEL) Example of containment facility planning Containment weak points Containment systems for filling and emptying drums Container systems Filter systems Sampling Containment on equipment

4.J (1) 4.J (3) 4.J (3) 4.J (6) 4.J (7) 4.J (15) 4.J (16) 4.J (23) 4.J (27) 4.J (28) 4.J (30)

4.K 4.K.1 4.K.2 4.K.3 4.K.4 4.K.5

Process control systems Definitions Features of process control systems How to use process control systems Carrying out a process control system project Qualification of process control systems

4.K (1) 4.K (2) 4.K (5) 4.K (6) 4.K (7)

4.L 4.L.1 4.L.2 4.L.3 4.L.4 4.L.5 4.L.6 4.L.7 4.L.8 4.L.9

Hygienic (sanitary) design when using solids Introduction Surfaces Material: stainless steel Connections Hoists and roller conveyors Pneumatic conveyor system Dosing systems Platforms and stands Clean room installations

4.L (1) 4.L (3) 4.L (6) 4.L (11) 4.L (22) 4.L (25) 4.L (26) 4.L (28) 4.L (31)

5

Pharmaceutical Water

5.A 5.A.1 5.A.2 5.A.3 5.A.4

Water types Potable water Purified water Highly purified water Water for injection

5.A (2) 5.A (3) 5.A (5) 5.A (7)

5.B 5.B.1 5.B.2 5.B.3

Generation of pharmaceutical water Purified water (PW) Water for injection (WFI) Purification of pharmaceutical water treatment systems

5.B (2) 5.B (11) 5.B (14)


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5.C 5.C.1 5.C.2 5.C.3 5.C.4 5.C.5 5.C.6 5.C.7

Distribution and storage of pharmaceutical water Loop Fixtures Measuring technique Formation of biofilms Rouging Buffering of ultra pure water Loop with subloops

5.C (1) 5.C (6) 5.C (7) 5.C (21) 5.C (23) 5.C (27) 5.C (29)

5.D 5.D.1 5.D.2 5.D.3 5.D.4 5.D.5 5.D.6 5.D.7 5.D.8

Qualification of water supplies Introduction Risk analysis Design qualification Installation qualification Operational qualification (OQ) Transfer to the user Process validation/performance qualification (PQ) Qualification report

5.D (1) 5.D (3) 5.D (8) 5.D (17) 5.D (28) 5.D (36) 5.D (42) 5.D (47)

5.E 5.E.1 5.E.2 5.E.3 5.E.4 5.E.5 5.E.6

Operation of water supplies Procedures to reduce microbial counts Maintenance of a water supply Calibration of measuring systems Change control Requalification Decommissioning/uninstalling

5.E (1) 5.E (4) 5.E (10) 5.E (11) 5.E (13) 5.E (14)

5.F 5.F.1 5.F.2 5.F.3 5.F.4

Pure steam systems Physical principles Quality requirements for pure steam Pure steam generation Pure steam distribution system

5.F (1) 5.F (3) 5.F (6) 5.F (10)

6

Qualification

6.A 6.A.1 6.A.2 6.A.3 6.A.4 6.A.5 6.A.6 6.A.7 6.A.8

Official requirements Legal aspects of qualification Documentation of the qualification Design Qualification (DQ) Installation Qualification (IQ) Operational Qualification (OQ) Performance Qualification (PQ) Qualification of established facilities Requalification

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6.A (1) 6.A (4) 6.A (5) 6.A (8) 6.A (9) 6.A (10) 6.A (11) 6.A (13)

GMP Manual Contents

6.B 6.B.1 6.B.2 6.B.3 6.B.4 6.B.5 6.B.6

Preparation of the qualification Commissioning Sequence Qualification team Responsibilities Qualification by external service providers Risk analysis

6.B (1) 6.B (5) 6.B (6) 6.B (6) 6.B (6) 6.B (10)

6.C 6.C.1 6.C.2 6.C.3 6.C.4 6.C.5

Qualification documentation Qualification master plan Qualification plan Qualification report Labeling of the qualification status SOP – “Qualification of facilities and equipment”

6.C (2) 6.C (3) 6.C (9) 6.C (10) 6.C (11)

6.D 6.D.1 6.D.2

Design qualification (DQ) User requirements (user specifications) Technical specification

6.D (3) 6.D (12)

6.E 6.E.1 6.E.2

Installation qualification (IQ) Examples of IQ plans Example: Fluid bed equipment

6.E (3) 6.E (22)

6.F 6.F.1 6.F.2

Operational qualification(OQ) Examples of OQ plans Example: Fluid bed dryer

6.F (3) 6.F (13)

6.G

Performance qualification (PQ)

6.H 6.H.1 6.H.2 6.H.3 6.H.4 6.H.5

Special cases of qualification Retrospective qualification Requalification Content of a review Maintenance of the qualified status Qualification of simple equipment

7

Process Validation

7.A 7.A.1 7.A.2 7.A.3 7.A.4 7.A.5

Official requirements Regulative aspects Principles of process validation Types of process validation Maintaining the validated status Documentation of process validation

7.B

Validation – a key element of quality assurance


6.H (1) 6.H (2) 6.H (3) 6.H (5) 6.H (7)

7.A (1) 7.A (11) 7.A (18) 7.A (23) 7.A (27)

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7.C 7.C.1 7.C.2 7.C.3

Process validation approaches Prospective validation Retrospective validation Concurrent validation

7.C (1) 7.C (3) 7.C (5)

7.D 7.D.1 7.D.2

Revalidation Time intervals for periodic revalidations Incidences requiring revalidation

7.D (2) 7.D (2)

7.E 7.E.1 7.E.2 7.E.3 7.E.4

Planning of process validation projects Responsibilities and task assignment Validation team Timing of validation Prerequisites for carrying out a validation project

7.E (1) 7.E (4) 7.E (6) 7.E (6)

Validation master plan Validation matrix Example of a validation master plan Example for a validation matrix Example for a test plan

7.F (4) 7.F (6) 7.F (17) 7.F (24)

Risk analysis Finding out the adequate extent of validation Carrying out risk analysis

7.G (1) 7.G (1)

7.H 7.H.1 7.H.2

Validation protocol and report Elements of the validation protocol Content of a validation report

7.H (1) 7.H (9)

7.I 7.I.1 7.I.2 7.I.3 7.I.4

Quality by Design Process development Design space Statistical Design of Experiments (DoE) Multivariate Data Analysis (MVDA)

7.I (1) 7.I (3) 7.I (6) 7.I (9)

7.J 7.J.1 7.J.2 7.J.3 7.J.4 7.J.5 7.J.6

Process Analytical Technology (PAT) Process-analytical measurements Evaluation of the data Possible applications Implementations of PAT Advantages of PAT implementation PAT in the USA and Europe

7.J (1) 7.J (3) 7.J (4) 7.J (6) 7.J (6) 7.J (7)

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7.F 7.F.1 7.F.2 7.F.3 s 7.F.4

t n 7.G e t 7.G.1 n 7.G.2 o C

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8

Cleaning Validation

8.A

Official requirements

8.B 8.B.1 8.B.2 8.B.3

How to validate cleaning procedures Optimization of cleaning procedures Compilation of cleaning instructions Validating manual and automated cleaning procedures

8.C

Cleaning validation master plan

8.D 8.D.1 8.D.2

Establishing the scope of validation Bracketing: determination of critical substances 8.D (1) Matrixing: determination of equipment-specific validation protocols 8.D (5)

8.E 8.E.1 8.E.2 8.E.3

Acceptance criteria and limit calculation Calculation of active pharmaceutical ingredient residues Calculation of cleansing agent residues Determination of the microbial status

8.E (1) 8.E (10) 8.E (11)

8.F 8.F.1 8.F.2 8.F.3 8.F.4 8.F.5

Sampling procedures Swab test Rinse test Other procedures Selection of the appropriate sampling procedure Microbiological testing of surfaces

8.F (1) 8.F (4) 8.F (6) 8.F (7) 8.F (9)

8.G 8.G.1 8.G.2

Analytical procedures Requirements for method validation Selection of the appropriate analytical procedure

8.G (1) 8.G (6)

8.H 8.H.1 8.H.2 8.H.3

Documentation Validation protocol Validation report Other documents

8.H (1) 8.H (5) 8.H (7)

8.I 8.I.1 8.I.2 8.I.3 8.I.4 8.I.5

Maintenance of the validated status Changes and deviations Change control Revalidation New products and equipment Deviations

8.I (2) 8.I (3) 8.I (4) 8.I (9) 8.I (12)

8.J

Cleaning validation documentation (example)

8.K

References


8.B (1) 8.B (5) 8.B (8)

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9

Computer Validation

9.A 9.A.1 9.A.2

Introduction and basic terminology Introduction Basic terminology

9.A (1) 9.A (2)

9.B 9.B.1 9.B.2 9.B.3 9.B.4 9.B.5

Regulatory aspects Europe PIC/S USA Electronic signature / Electronic records GAMP® Good Automated Manufacturing Practice

9.B (1) 9.B (4) 9.B (4) 9.B (6) 9.B (8)

9.C 9.C.1 9.C.2 9.C.3 9.C.4

Life cycle of software and systems “V-Model” Software development Purchasing commercial of the shelf systems Configuration and customisation

9.C (2) 9.C (4) 9.C (6) 9.C (7)

9.D 9.D.1 9.D.2 9.D.3

Risk analysis and system classification GAMP® classification Risk indexes Risk management at the level of user requirements

9.D (1) 9.D (6) 9.D (14)

9.E 9.E.1 9.E.2 9.E.3 9.E.4 9.E.5 9.E.6 9.E.7 9.E.8

Validation of computerised systems Responsibility and organisation Validation plan Specifications (user requirements/technical specification) for hardware and software Unit, integration and acceptance tests Documentation for validation (validation plan and report) Data migration and start-up Examples Dealing with existing systems (legacy systems)

9.F 9.F.1 9.F.2 9.F.3 9.F.4 9.F.5 9.F.6 9.F.7 9.F.8 9.F.9

Operation of computerised systems System description User training Standard operating procedures (SOPs) Authorised access and security (virus protection) Data backup and archiving Contingency plans and data recovery Change management and error reporting Periodic review Retirement of computerised systems

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9.E (1) 9.E (4) 9.E (8) 9.E (11) 9.E (17) 9.E (18) 9.E (19) 9.E (34) 9.F (1) 9.F (1) 9.F (1) 9.F (2) 9.F (5) 9.F (7) 9.F (8) 9.F (10) 9.F (11)

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9.G 9.G.1 9.G.2 9.G.3

External service providers Relocation of activities (outsourcing, offshoring, nearshoring, backshoring) Service level agreement Auditing of suppliers and service providers

9.H

References

10

Considerations on Risk Management

10.A 10.A.1 10.A.2 10.A.3 10.A.4 10.A.5 10.A.6

Introduction and Principles Advantages of Risk Management Considerations on the Risk-Based Approach Regulatory Environment Objectives Science-Based Approach Summary

10.B 10.B.1 10.B.2 10.B.3 10.B.4 10.B.5 10.B.6 10.B.7 10.B.8 10.B.9 10.B.10 10.B.11 10.B.12

Basic Consideration on Implementing Risk Management Into a Process Areas of Hazards 10.B (1) Prerequisites 10.B (3) Use of Knowledge and Experience 10.B (5) Consideration on Manual Operations 10.B (5) Elements of Risk Management 10.B (6) Implementation of a Risk Management Process 10.B (7) Commitment of Management 10.B (7) Project Team 10.B (8) Analysis of Existing Risk Management Approaches 10.B (8) Standardization of Methods and Tools 10.B (9) Considerations on Risk Based Behavior 10.B (9) Additional Training Required? 10.B (10)

10.C 10.C.1 10.C.2 10.C.3 10.C.4 10.C.5 10.C.6

Details on Using Risk Management Principles as Behavior Application to the QM System The Team Assessment Criteria Procedure to Determine Conclusions Evaluation on Individual Topics (Detailed Evaluation) Using Risk Management Example on Process Validation

10.D

Methodologies to be Used to Facilitate Risk Management

10.E

Using Process Mapping

10.F 10.F.1 10.F.2

Using a Fishbone Diagram Create a Fish Bone Diagram Advantages and Disadvantages GMP Manual (Up11) © Maas & Peither AG – GMP Publishing

9.G (1) 9.G (2) 9.G (8)

10.A (2) 10.A (4) 10.A (7) 10.A (12) 10.A (13) 10.A (14)

10.C (1) 10.C (2) 10.C (3) 10.C (4) 10.C (4) 10.C (6)

10.F (2) 10.F (4)

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10.G

Informal Use of Risk Management

10.H 10.H.1 10.H.2 10.H.3 10.H.4 10.H.5 10.H.6

Fault Tree Analysis (FTA) Basic Principles Objective: What a FTA Can Do and Where to Use It How to Run the Process of a FTA Prerequisites for an FTA Execution of an FTA Advantages and Disadvantages of an FTA

10.H (1) 10.H (1) 10.H (2) 10.H (2) 10.H (3) 10.H (5)

10.I 10.I.1 10.I.2 10.I.3 10.I.4 10.I.5

Failure Mode Effects Analysis (FMEA) Objectives and Areas of Application General Items on the FMEA Process Implementation of FMEA in a Project Advantages and Disadvantages of an FMEA Application Example of a Modified FMEA

10.I (2) 10.I (3) 10.I (18) 10.I (18) 10.I (23)

Hazard Analysis of Critical Control Points (HACCP) Prerequisite and Result to be Expected Advantages and Disadvantages Application Example

10.J (2) 10.J (8) 10.J (9)

10.J 10.J.1 s 10.J.2 t 10.J.3 n

e t 10.K n o C 11

Conclusion

Production

11.A 11.A.1 11.A.2 11.A.3

Sanitation Organisational prerequisites Sources of contamination Responsibilities and implementation

11.A (1) 11.A (2) 11.A (3)

11.B 11.B.1 11.B.2 11.B.3 11.B.4 11.B.5

Personnel hygiene Clothing Code of Conduct Hand disinfection Health requirements Training

11.B (1) 11.B (11) 11.B (14) 11.B (15) 11.B (16)

11.C 11.C.1 11.C.2 11.C.3

Production hygiene Sources of contamination Cleaning Disinfection

11.C (4) 11.C (11) 11.C (13)

11.D 11.D.1 11.D.2

Sanitation programme Organisation of room cleaning Documentation

11.D (1) 11.D (5)

11.E 11.E.1

Environmental monitoring General

11.E (1)

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11.E.2 11.E.3 11.E.4 11.E.5 11.E.6

Sampling plan Establishment of limits and frequencies Methods Investigation areas Evaluation

11.F

GMP in the production process

11.G 11.G.1 11.G.2 11.G.3 11.G.4

Weigh-in Legal requirements Weigh-in principles Weigh-in procedure Documentation

11.G (1) 11.G (3) 11.G (7) 11.G (11)

11.H 11.H.1 11.H.2 11.H.3 11.H.4

Identification Handling of labels Labelling of starting materials Labelling of equipment and containers Labelling of rooms

11.H (1) 11.H (2) 11.H (3) 11.H (7)

11.I 11.I.1 11.I.2 11.I.3 11.I.4

In-process control Objectives Organisation and responsibilities Carrying out Documentation and evaluation of data

11.I (2) 11.I (3) 11.I (4) 11.I (8)

11.J 11.J.1 11.J.2 11.J.3

Prevention of cross-contamination Causes of cross-contamination Measures to prevent cross-contamination Manufacture of critical products

11.J (1) 11.J (5) 11.J (6)

11.K 11.K.1 11.K.2 11.K.3 11.K.4 11.K.5 11.K.6 11.K.7 11.K.8

Deviations Definition Procedure Responsibilities Measures Failure investigation report Evaluation of measures SOP “deviations” – (example) Check-list for deviation handling

11.K (1) 11.K (2) 11.K (4) 11.K (4) 11.K (5) 11.K (7) 11.K (9) 11.K (14)

11.L 11.L.1 11.L.2 11.L.3 11.L.4 11.L.5

Reworking Definitions Procedure Rework / Reprocessing of rejected products Rework of returned products Rework of products that have not been rejected

11.L (1) 11.L (2) 11.L (4) 11.L (8) 11.L (8)


11.E (3) 11.E (4) 11.E (9) 11.E (11) 11.E (16)

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11.M 11.M.1 11.M.2 11.M.3 11.M.4 11.M.5 11.M.6 11.M.7 11.M.8 11.M.9

Warehouse and logistics Regulatory requirements Stock management system Responsibilities Personnel Storage areas Storage conditions Sanitation and pest control Material Flow Process Flow

11.M (1) 11.M (2) 11.M (6) 11.M (6) 11.M (7) 11.M (13) 11.M (16) 11.M (18) 11.M (22)

11.N 11.N.1 11.N.2 11.N.3 11.N.4 11.N.5

Transportation Requirements for logistic service providers Transportation challenges and monitoring devices Cool/Cold Chain Distribution Temperature Profiles Transportation Risks

11.N (2) 11.N (5) 11.N (9) 11.N (13) 11.N (18)

11.O

References

s t n 12 e t n 12.A o C 12.A.1

Sterile Production

12.A.2 12.A.3 12.A.4

Introduction Manufacturing products that can be sterilised in the final container Aseptic processing Production areas/premises Production equipment

12.A (2) 12.A (3) 12.A (4) 12.A (7)

12.B 12.B.1 12.B.2

Air Lock Concepts Personnel locks in the clean area Material locks

12.B (1) 12.B (7)

12.C 12.C.1 12.C.2 12.C.3 12.C.4

Manufacturing the solution Starting materials Solution batch Testing the bioburden Sterile filtration

12.C (1) 12.C (4) 12.C (8) 12.C (9)

12.D 12.D.1 12.D.2 12.D.3 12.D.4

Washing processes Stoppers Particulate impurities Glass containers (ampoules, bottles) Transport

12.D (1) 12.D (3) 12.D (5) 12.D (8)

12.E 12.E.1 12.E.2 12.E.3

Filling Filling equipment for solutions Process for filling LVP containers in cleanliness grade C Process for filling ampoules with solution in cleanliness grade A/B

12.E (1) 12.E (5) 12.E (8)

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12.E.4 12.E.5 12.E.6

Filling ampoules in cleanliness grade C and laminar flow Culture medium filling (Media Fill) Filling with powders

12.E (8) 12.E (8) 12.E (13)

12.F 12.F.1 12.F.2 12.F.3 12.F.4

Steam sterilisation Sterilisers Description of the procedure Qualification of a steam steriliser Validation of the steam sterilisation process

12.F (1) 12.F (2) 12.F (6) 12.F (11)

12.G 12.G.1 12.G.2 12.G.3 12.G.4 12.G.5 12.G.6 12.G.7

Microbiological monitoring Sources of contamination Room classification Monitoring program Sampling Sampling points Measure if levels are exceeded Organism identification

12.G (1) 12.G (2) 12.G (4) 12.G (17) 12.G (20) 12.G (22) 12.G (24)

12.H 12.H.1 12.H.2 12.H.3 12.H.4 12.H.5 12.H.6 12.H.7 12.H.8 12.H.9 12.H.10

Test for sterility Parametric release Sterility test Method description Number of samples Sample quantity Reading and evaluating Procedure in the event of culture medium turbidity Culture media Culture media controls Method validation

12.H (1) 12.H (3) 12.H (10) 12.H (11) 12.H (12) 12.H (12) 12.H (15) 12.H (16) 12.H (17) 12.H (18)

12.I 12.I.1 12.I.2 12.I.3

Testing for tightness and particles Testing for tightness Particle test Sequence of operation

12.I (1) 12.I (5) 12.I (12)

12.J 12.J.1 12.J.2 12.J.3

Freeze drying Description of the procedure Qualification of a freeze dryer Validation of the freeze drying process

12.J (1) 12.J (6) 12.J (9)

12.K 12.K.1 12.K.2 12.K.3 12.K.4

Dry Heat Sterilisation Description of the procedure Sterilisation kinetics Qualification of a sterilisation tunnel Validation of the sterilisation process

12.K (2) 12.K (3) 12.K (5) 12.K (8)


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13

Packaging

13.A 13.A.1 13.A.2 13.A.3 13.A.4 13.A.5

Packaging material Responsibilities Contents Materials Protection against counterfeit medicinal products Packaging material testing

13.A (2) 13.A (2) 13.A (2) 13.A (6) 13.A (7)

13.B 13.B.1 13.B.2 13.B.3 13.B.4 13.B.5 13.B.6 13.B.7 13.B.8 13.B.9 13.B.10 13.B.11 13.B.12 13.B.13

Packaging process Allocation of packaging material Line clearance Labelling Control functions Release for production In-process controls Cleaning primary containers Labelling Variable data Imprints Reconciliation Safety features Completion of a packaging process

13.B (2) 13.B (3) 13.B (6) 13.B (6) 13.B (8) 13.B (15) 13.B (21) 13.B (21) 13.B (22) 13.B (23) 13.B (24) 13.B (26) 13.B (26)

13.C 13.C.1 13.C.2 13.C.3 13.C.4 13.C.5

Qualification of a packaging line Master qualification plan Design qualification (DQ) Installation qualification (IQ) Operational qualification (OQ) Performance qualification (PQ)

13.C (2) 13.C (8) 13.C (24) 13.C (34) 13.C (46)

14

Laboratory Controls

14.A 14.A.1 14.A.2 14.A.3

Sampling Requirements Sampling plan (instructions) Notes for the sampling process

14.A (2) 14.A (3) 14.A (8)

14.B 14.B.1 14.B.2 14.B.3

Reagents Labeling Usage and stability Documentation

14.B (2) 14.B (2) 14.B (4)

14.C 14.C.1 14.C.2

Standards and reference substances Definition of different standards and their areas of use Handling, storage and stability

14.C (1) 14.C (5)

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14.D 14.D.1 14.D.2

Qualifying laboratory instruments Qualification protocols and reports System suitability test (SST)

14.D (2) 14.D (5)

14.E 14.E.1 14.E.2 14.E.3 14.E.4

Calibration in the lab Definitions Calibration instructions and record Examples Decision

14.E (1) 14.E (4) 14.E (5) 14.E (20)

14.F 14.F.1 14.F.2 14.F.3 14.F.4

Validation of analytical methods Principles Definitions of the parameters Documentation Revalidation

14.F (1) 14.F (3) 14.F (6) 14.F (6)

14.G 14.G.1 14.G.2 14.G.3 14.G.4 14.G.5 14.G.6

14.G.8 14.G.9

Stability testing ICH guidelines for stability tests Storage and storage conditions Analyses Reduction of the study design Stability testing in the marketing phase Defining the retest period for an active pharmaceutical ingredient and the shelf life for a drug product through evaluation of stability data (ICH Q1E) Decision tree for data evaluation for retest period or for APIs or drug products (excluding frozen products) Procedure for statistical analysis Examples of the statistical evaluation of stability data

14.G (40) 14.G (40) 14.G (42)

14.H 14.H.1 14.H.2 14.H.3 14.H.4 14.H.5

Out-of-specification results Significance Definitions FDA OOS Guidance Example for handling of an OOS result Trend tracking

14.H (1) 14.H (4) 14.H (4) 14.H (12) 14.H (13)

14.I 14.I.1 14.I.2

Raw data documentation Principles Single sheet documentation system

14.I (1) 14.I (3)

14.J 14.J.1

Batch release Certification by a Qualified Person and release in accordance with EC GMP Guidelines Responsibility for issuing the release Publication of release Release procedures in practice

14.J (4) 14.J (8) 14.J (9) 14.J (10)

14.G.7

14.J.2 14.J.3 14.J.4


14.G (2) 14.G (4) 14.G (13) 14.G (20) 14.G (24)

14.G (37)

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14.K 14.K.1 14.K.2 14.K.3 14.K.4

Microbiological testing Total microbial count Specified microorganisms Testing frequencies Miscellaneous tests

14.K (2) 14.K (24) 14.K (48) 14.K (52)

14.L 14.L.1 14.L.2 14.L.3 14.L.4 14.L.5 14.L.6 14.L.7 14.L.8 14.L.9

Pharmacopoeias Structure of Pharmacopoeias General considerations Development of Monographs European Pharmacopoeia (Ph Eur) British Pharmacopoeia (BP) United States Pharmacopeia (USP) Japanese Pharmacopoeia (JP) International Pharmacopoeia (Ph Int) Harmonization

14.L (1) 14.L (2) 14.L (3) 14.L (4) 14.L (7) 14.L (9) 14.L (11) 14.L (13) 14.L (14)

14.M

References

s t 15 n e t 15.A n 15.A.1 o C

Documentation

15.A.2 15.A.3 15.A.4 15.A.5

Official requirements GMP-requirements managed and reviewed according to German pharma business regulations Requirements of the EU GMP Guideline Requirements of the US GMP Regulations Formal requirements Management and revision documentation

15.A (1) 15.A (4) 15.A (8) 15.A (13) 15.A (17)

15.B 15.B.1 15.B.2 15.B.3

GMP-conforming documentation Handwritten entries Archiving Master-SOP – “GMP-conforming documentation”

15.B (1) 15.B (2) 15.B (3)

15.C 15.C.1 15.C.2 15.C.3 15.C.4 15.C.5

Batch documentation Manufacturing instructions/record Packaging instruction and batch packaging record Electronic batch recording Testing procedures and test protocol Batch record review

15.C (3) 15.C (26) 15.C (28) 15.C (31) 15.C (36)

15.D 15.D.1 15.D.2 15.D.3 15.D.4 15.D.5

Standard operating procedures (SOPs) Compilation Approval and implementation Training Usage Review

15.D (2) 15.D (7) 15.D (7) 15.D (8) 15.D (9)

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15.D.6 15.D.7 15.D.8 15.D.9 15.D.10

Changes Withdrawing an operating procedure Administration Archiving Example of an SOP “Compilation and administration of operating procedures”

15.D (9) 15.D (10) 15.D (10) 15.D (12) 15.D (13)

15.E 15.E.1 15.E.2

Site master file Introduction Design

15.E (1) 15.E (1)

15.F 15.F.1 15.F.2 15.F.3 15.F.4 15.F.5

Annual product review / Product quality review Documents required for an annual product review Annual product review report Collaboration with a contract manufacturer Example: annual product review Master-SOP for the annual product review

15.F (4) 15.F (6) 15.F (8) 15.F (9) 15.F (14)

16

Research and Development

16.A

General conditions and legal requirements

16.B 16.B.1 16.B.2 16.B.3 16.B.4 16.B.5 16.B.6 16.B.7

Development phases and GMP requirements Formulation development Analytical development Manufacturing and testing of stability samples Packaging development Process development Cleaning verification and validation Process optimization: Basic principles for process validation Up scaling to pilot plant and production scale Handover to other manufacturing sites

16.B.8 16.B.9 16.C 16.C.1 16.C.2 16.C.3 16.D 16.D.1 16.D.2 16.D.3 16.D.4 16.D.5 16.D.6

Interfaces to GLP and GCP GLP –Good Laboratory Practice GCP –Good Clinical Practice Interfaces between the areas regulated by GMP and those regulated by GCP Manufacture and control of clinical samples Prerequisites for the approval of clinical investigations Manufacturing of clinical samples and comparator drugs Packaging and labeling Control and release of investigational medicinal products Storage and shipment of investigational drugs Returns, recalls and destruction of clinical samples


16.B (4) 16.B (7) 16.B (11) 16.B (14) 16.B (16) 16.B (19) 16.B (22) 16.B (25) 16.B (27) 16.C (1) 16.C (5) 16.C (10) 16.D (1) 16.D (2) 16.D (6) 16.D (11) 16.D (14) 16.D (15)

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s t n e t n o C

16.E

Documentation and recording of changes during development

16.F

Development report

17

Contractors and Suppliers

17.A 17.A.1 17.A.2 17.A.3 17.A.4 17.A.5 17.A.6 17.A.7 17.A.8

Contract manufacture Reasons for contract manufacture Procedure for assigning manufacturing contracts Duties of the contract giver Duties of the contract acceptor Contract manufacturer agreement Audits of contract manufacturers SOP for assigning manufacturing contracts Framework contract for contract manufacture and quality control

17.A (1) 17.A (3) 17.A (9) 17.A (12) 17.A (17) 17.A (21) 17.A (30) 17.A (36)

17.B 17.B.1 17.B.2 17.B.3 17.B.4 17.B.5 17.B.6

Contract Analysis Introduction Legal background Selection of an external testing laboratory Liability limitation contract Certificate of Analysis Transfer of the test to the contract laboratory

17.B (1) 17.B (2) 17.B (3) 17.B (5) 17.B (14) 17.B (15)

17.C 17.C.1 17.C.2 17.C.3 17.C.4 17.C.5 17.C.6 17.C.7 17.C.8 17.C.9

Suppliers Introduction Definitions Quality systems Records Contracts and quality agreements Supplier review and controls Supplier audits Re-evaluation of Suppliers GMP Manual Cross References to Suppliers

17.C (1) 17.C (4) 17.C (5) 17.C (14) 17.C (17) 17.C (19) 17.C (21) 17.C (26) 17.C (28)

17.D

References

18

Inspections

18.A

Principles

18.B 18.B.1 18.B.2 18.B.3 18.B.4

Inspection procedures System-based Product-based Procedure-based Area-based

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18.B (1) 18.B (2) 18.B (2) 18.B (3)

GMP Manual Contents

18.C 18.C.1 18.C.2

Inspectors Technical qualification requirements Personal requirements

18.C (1) 18.C (3)

18.D 18.D.1 18.D.2 18.D.3 18.D.4

Organization of inspections Inspection planning Inspection preparation Carrying out the inspections Evaluation and documentation

18.D (1) 18.D (3) 18.D (4) 18.D (8)

18.E 18.E.1 18.E.2 18.E.3 18.E.4 18.E.5

Self-inspection Purpose of self-inspection Carrying out the self-inspection Self-inspection documentation Errors and remedial action Follow-up activities

18.E (1) 18.E (1) 18.E (3) 18.E (9) 18.E (11)

18.F 18.F.1 18.F.2 18.F.3

Inspection of contract manufacturers Purpose of the inspection of contract manufacturer Carrying out inspections of contract manufacturer Handling of changes and deviations

18.F (1) 18.F (1) 18.F (3)

18.G 18.G.1 18.G.2

Inspection of suppliers Purpose of the supplier inspection Carrying out the supplier inspection

18.G (1) 18.G (2)

18.H

Questionnaire for preparing GMP-inspections

18.I

References

19

Quality Unit

19.A

General This chapter will be part of a later update.

19.B 19.B.1 19.B.2 19.B.3 19.B.4 19.B.5

The “Qualified Person” according to Directive 2001/83/EC Introduction Legal background of the European “Qualified Person” regulations Qualification and experience Duties and responsibilities Qualified Person and Pharmaceutical Quality Systems

19.B (1) 19.B (2) 19.B (5) 19.B (8) 19.B (26)

19.C 19.C.1 19.C.2 19.C.3

Change control Principles of change control Introduction and operation of change control programs Documentation

19.C (1) 19.C (4) 19.C (9)

19.D

References


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20

Continual Improvement

20.A

Preface

20.B 20.B.1 20.B.2 20.B.3 20.B.4 20.B.5 20.B.6 20.B.7

Six Sigma Definition What it is / what it does / how it works Goals/Objectives/Benefits Implementation Tools Variations Examples

20.B (1) 20.B (1) 20.B (19) 20.B (21) 20.B (24) 20.B (25) 20.B (26)

20.C 20.C.1 20.C.2 20.C.3 20.C.4 20.C.5 s t 20.C.6 n 20.C.7

Statistical Process Control (SPC) Definition What it is /what it does / how it works Goals/Objectives/Benefits Implementation Tools Variations Examples

20.C (1) 20.C (1) 20.C (32) 20.C (33) 20.C (36) 20.C (36) 20.C (36)

20.D.3 20.D.4 20.D.5 20.D.6

Process Analytical Technology (PAT) Definition The Role of PAT in Pharmaceutical Manufacturing Regulatory Perspective and Guidances PAT instrumentation Application of PAT in a GMP environment Examples of PAT Applications

20.D (1) 20.D (1) 20.D (5) 20.D (11) 20.D (13) 20.D (19)

20.E

References

21

Active and Inactive Ingredients

21.A 21.A.1 21.A.2 21.A.3 21.A.4 21.A.5 21.A.6 21.A.7 21.A.8 21.A.9 21.A.10 21.A.11 21.A.12

GMP for Active Pharmaceutical Ingredients (APIs) Introduction Quality management Personnel Buildings and facilities Process equipment Documentation and records Materials management Production and in-process controls Packaging and identification labelling of APIs and intermediates Storage and distribution Laboratory controls Validation

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e t 20.D n o 20.D.1 C 20.D.2

21.A (1) 21.A (6) 21.A (13) 21.A (15) 21.A (21) 21.A (25) 21.A (33) 21.A (36) 21.A (43) 21.A (47) 21.A (49) 21.A (55)

GMP Manual Contents

21.A.13 21.A.14 21.A.15 21.A.16 21.A.17 21.A.18 21.A.19

Change Control Rejection and re-use of materials Complaints and Recalls Contract manufacturers, including laboratories Agents, brokers, traders, distributors, repackers, and relabellers Specific guidance for APIs manufactured by cell culture/fermentation APIs for use in clinical trials

21.A (59) 21.A (63) 21.A (70) 21.A (70) 21.A (72)

21.B 21.B.1 21.B.2 21.B.3 21.B.4

GMP for APIs – considerations on special topics Materials management Production and maintenance Re-use and recovery of materials Interaction with brokers

21.B (1) 21.B (9) 21.B (23) 21.B (32)

21.C 21.C.1 21.C.2 21.C.3 21.C.4 21.C.5 21.C.6 21.C.7

Excipients Introduction Regulatory aspects and guidance documents Safety, toxicological, and precedence of use issues Compendial monographs Excipient Master Files and other filings Applicability of ICH guidance to excipients Other aspects critical to the marketing of excipients

21.C (1) 21.C (6) 21.C (36) 21.C (39) 21.C (45) 21.C (48) 21.C (50)

21.D

References

22

Biologics

21.A (75) 21.A (81)

This chapter is left empty in order to facilitate later additions.

23

Medical Devices

23.A 23.A.1 23.A.2 23.A.3 23.A.4

Introduction Definition Types of medical devices Regulatory background Process approach to a Quality Management System

23.A (2) 23.A (3) 23.A (5) 23.A (10)

23.B 23.B.1 23.B.2 23.B.3 23.B.4 23.B.5 23.B.6

Quality Management System (QMS) Management responsibility Quality manual Quality policy Quality planning Management review Audits

23.B (1) 23.B (4) 23.B (5) 23.B (6) 23.B (7) 23.B (10)

23.C 23.C.1 23.C.2

Personnel General Training

23.C (1) 23.C (2) GMP Manual (Up11) © Maas & Peither AG – GMP Publishing

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s t n e t n o C

23.C.3 23.C.4

Health, hygiene, practices, and clothing Consultants and contractors

23.C (3) 23.C (4)

23.D 23.D.1 23.D.2 23.D.3 23.D.4 23.D.5 23.D.6 23.D.7 23.D.8 23.D.9 23.D.10

Design control General Design planning Design input Design output Design review Design verification Design validation / Clinical evaluation Design transfer Design changes Design history file

23.D (1) 23.D (4) 23.D (5) 23.D (9) 23.D (10) 23.D (12) 23.D (15) 23.D (17) 23.D (18) 23.D (20)

23.E

Human factors

23.F

Statistical techniques

23.G

Risk management

23.H 23.H.1 23.H.2

Document and record control Control of documents Control of records

23.H (1) 23.H (4)

23.I 23.I.1 23.I.2 23.I.3 23.I.4 23.I.5

Production and process controls Manufacturing materials Automated processes Sterile products Changes Material acceptance procedures

23.I (2) 23.I (2) 23.I (3) 23.I (4) 23.I (4)

23.J 23.J.1 23.J.2

Identification and traceability Identification Traceability

23.J (1) 23.J (1)

23.K 23.K.1 23.K.2 23.K.3

Buildings, facilities, and equipment Buildings and facilities Environment Equipment

23.K (1) 23.K (2) 23.K (3)

23.L

Validation

23.M 23.M.1 23.M.2

Purchasing/supplier control Purchase orders Quality agreements

23.M (3) 23.M (3)

23.N 23.N.1 23.N.2

Packaging and labeling Packaging Manufacturer’s information

23.N (1) 23.N (1)

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GMP Manual Contents

23.O 23.O.1 23.O.2 23.O.3 23.O.4 23.O.5

Handling, storage, distribution, installation and servicing Handling Storage Distribution Installation Servicing

23.O (1) 23.O (2) 23.O (2) 23.O (3) 23.O (3)

23.P 23.P.1 23.P.2 23.P.3 23.P.4

Nonconformance, Corrective Action and Preventive Action Definitions CAPA System Nonconforming product Advisory notice, device correction or product recall

23.P (1) 23.P (1) 23.P (5) 23.P (5)

23.Q 23.Q.1 23.Q.2

Customer complaints Complaint evaluation Complaint investigation

23.Q (2) 23.Q (2)

23.R

Combination products

23.S

References

s t n e t n o C


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GMP Manual Contents

A

Information

A.1

Empty Chapter

A.2

Empty Chapter

A.3

List of Abbreviations

A.4

Glossary

A.5

Adress-Register

A.6

References

B

Japanese Regulations

B.1

MHW Ministerial Ordinance No. 2,1961: Regulations for Buildings and Facilities of Pharmacies, etc.

B.2

MHLW Ministerial Ordinance No. 136,2004 : Standards for Quality Assurance for Drugs, Quasi-drugs, Cosmetics and Medical Devices

s t n e B.3 t n o C

MHLW Ministerial Ordinance No. 179, 2004: Standards for Manufacturing Control and Quality Control for Drugs and Quasi-drugs

C

EU Directives and Guidelines

C.1

EU GMP Guide: Introduction

C.2

Commission Directive 2003/94/EC

C.3

Commission Directive 91/412/EEC

C.4

Part I Basic Requirements for Medicinal Products

C.4.1

Chapter 1: Quality Management

C.4.2

Chapter 2: Personnel

C.4.3

Chapter 3: Premises and Equipment

C.4.4

Chapter 4: Documentation

C.4.5

Chapter 5: Production

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GMP Manual Contents

C.4.6

Chapter 6: Quality Control

C.4.7

Chapter 7: Contract Manufacture and Analysis

C.4.8

Chapter 8: Complaints and Product Recall

C.4.9

Chapter 9: Self Inspection

C.5

Part II Basic Requirements for Active Substances used as Starting Materials

C.6.1

Annex 1 Manufacture of Sterile Medicinal Products

C.6.2

Annex 2 Manufacture of Biological Medicinal Products for Human Use

C.6.3

Annex 3 Manufacture of Radiopharmaceuticals

C.6.4

Annex 4 Manufacture of Veterinary Medicinal Products other than Immunological Veterinary Medicinal Products

C.6.5

Annex 5 Manufacture of Immunological Veterinary Medicinal Products

C.6.6

Annex 6 Manufacture of Medicinal Gases

C.6.7

Annex 7 Manufacture of Herbal Medicinal Products

C.6.8

Annex 8 Sampling of Starting and Packaging Materials

C.6.9

Annex 9 Manufacture of Liquids, Creams and Ointments

C.6.10

Annex 10 Manufacture of Pressurised Metered Dose Aerosol Preparations for Inhalation

C.6.11

Annex 11 Computerised Systems

C.6.12

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


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s t n e t n o C

GMP Manual Contents

C.6.13

Annex 13 Investigational Medicinal Products

C.6.14

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

C.6.15

Annex 15 Qualification and Validation

C.6.16

Annex 16 Certification by a Qualified Person and Batch Release

C.6.17

Annex 17 Parametric Release

C.6.18

Annex 18 Good Manufacturing Practice for Active Pharmaceutical Ingredients

C.6.19

Annex 19 Reference and Retention Samples

s C.6.20 t n e t C.7 n o C.8 C

Annex 20 Quality Risk Management Glossary Part III

C.8.1

Explanatory Notes on the preparation of a Site Master File

C.9

Note For Guidance on Quality of Water for Pharmaceutical Use

C.10

Compilation of Community Procedures on Inspections and Exchange of Information

D

USA: CFR and FDA Guidelines

D.1

Code of Federal Regulations

D.2

Guidance for Industry Process Validation: General Principles and Practices

D.3

Guide to Inspections of High Purity Water Systems

D.4

Guide to Inspections of Validation of Cleaning Processes

D.5

Guide to inspections of oral solid dosage forms pre/post approval issues for development and validation

D.6

Guide to Inspections of Validation Documentation

D.7

Guide to Inspections: Computerized Systems in Drug Establishments (2/83)

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D.8

Guide to Inspections of Pharmaceutical Quality Control Laboratories

D.9

Guidance for Industry: Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production

D.10

Guidance for Industry Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice

D.11

Guidance for Industry PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance

D.12

Guidance for Industry Part 11, Electronic Records; Electronic Signatures – Scope and Application

D.13

21 CFR Part 820 – Quality System Regulation

D.14

Guidance for Industry Quality Systems Approach to Pharmaceutical CGMP Regulations

D.15

Guidance for Industry cGMP for Phase 1 Investigational Drugs

D.16

Federal Food, Drug, and Cosmetic Act (FD&C Act)

D.17

Pre-Approval Inspections

E

ICH-Guidelines

E.1.A

ICH Q1A(R2): Stability Testing of New Drug Substances and Products

E.1.B

ICH Q1B: Stability Testing: Photostability Testing of New Drug Substances and Products

E.1.C

ICH Q1C: Stability Testing for New Dosage Forms

E.1.D

ICH Q1D: Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products

E.1.E

ICH Q1E: Evaluation of Stability Data

E.2

ICH Q2(R1): Validation of Analytical Procedures: Text and Methodology


s t n e t n o C

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E.3.A

ICH Q3A(R2): Impurities in New Drug Substances

E.3.B

ICH Q3B(R2): Impurities in New Drug Products

E.3.C

ICH Q3C(R5): Impurities: Guideline for Residual Solvents

E.4

ICH Q4: Pharmacopoeias

E.4.A

ICH Q4A: Pharmacopoeial Harmonisation

E.4.B

ICH Q4B: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions

E.4.B.1

ICH Q4B Annex 1: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Residue on Ignition/Sulphated Ash – General Chapter

s t n e t n E.4.B.2 o C

ICH Q4B Annex 2: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Test for Extractable Volume of Parenteral Preparations – General Chapter

E.4.B.3

ICH Q4B Annex 3: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Test for Particulate Contamination: Sub-Visible Particles – General Chapter

E.4.B.4.1

ICH Q4B Annex 4A: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions Microbiological Examination of Non-Sterile Products: Microbial Enumerations Tests – General Chapter

E.4.B.4.2

ICH Q4B Annex 4B : Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Microbiological Examination of Non-Sterile Products: Test for Specified Micro-Organisms – General Chapter

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E.4.B.4.3

ICH Q4B Annex 4C: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Microbiological Examination of Non-Sterile Products: Acceptance Criteria For Pharmaceutical Preparations and Substances for Pharmaceutical Use – General Chapter

E.4.B.5

ICH Q4B Annex 5: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Disintegration Test – General Chapter

E.4.B.6

ICH Q4B Annex 6: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Uniformity of Dosage Units – General Chapter

E.4.B.7

ICH Q4B Annex 7: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Dissolution Test – General Chapter

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E.4.B.8

ICH Q4B Annex 8: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Sterility Test – General Chapter

E.4.B.9

ICH Q4B Annex 9: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Tablet Friability – General Chapter

E.4.B.10

ICH Q4B Annex 10: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Polyacrylamide Gel Electrophoresis – General Chapter

E.5.A

ICH Q5A(R1): Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin

E.5.B

ICH Q5B: Quality of Biotechnological Products: Analysis of the Expression Construct in Cells Used for Production of R-DNA Derived Protein Products

E.5.C

ICH Q5C: Quality of Biotechnological Products: Stability Testing of Biotechnological/ Biological Products


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E.5.D

ICH Q5D: Derivation and Characterisation of Cell Substrates used for Production of Biotechnological/Biological Products

E.5.E

ICH Q5E: Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Process

E.6.A

ICH Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances

E.6.B

ICH Q6B: Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products

E.7

ICH Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

E.7.1

“How to do” Document – Interpretation of the ICH Q7a Guide

s t n E.8 e t n o E.9 C

ICH Q8 (R2): Pharmaceutical Development ICH Q9: Quality Risk Management

E.10

ICH Q10: Pharmaceutical Quality System

E.10.1

Quality Implementation Working Group on Q8, Q9 and Q10 Questions & Answers

F

PIC/S Guidelines

F.1

PIC/S PI 006-3: Recommendations on Validation Master Plan Installation and Operational Qualification Non-Sterile Process Validation Cleaning Validation

F.2

PIC/S PI 007-5: Recommendation on the Validation of Aseptic Processes

F.3

PIC/S PI 011-3: Good Practices for Computerised Systems in Regulated “GXP” Environments

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F.4

PIC/S PI 023-2: Aide-mémoire Inspection of Pharmaceutical Quality Control Laboratories

F.5

PIC/S PE 008-4: Explanatory notes for pharmaceutical manufacturers on the preparation of a Site Master File

F.6

PIC/S PI 009-3: Aide-mémoire Inspection of Utilities

F.7

PIC/S PI 028-1: Aide-mémoire GMP Inspection Related to Packaging

F.8

PIC/S PI 032-2: Recommendation GMP Annex 1 Revision 2008, Interpretation of Most Important Changes for the Manufacture of Sterile Medicinal Products

G

GMP of other Regions This chapter is supplied on CD-ROM and online (www.gmp-manual.com ) only.

G.1

WHO Guidelines

G.1.1

Quality assurance of pharmaceuticals

G.1.1.1

1. WHO good manufacturing practices: main principles for pharmaceutical products

G.1.1.2

2. WHO good manufacturing practices: starting materials

G.1.1.3

3. WHO good manufacturing practices: specific pharmaceutical products

G.1.1.4

4. Inspection

G.1.1.5

5. Hazard and risk analysis in pharmaceutical products

G.1.1.6

6. Sampling operations

G.1.2

Guide to good storage practices for pharmaceuticals

G.1.3

Annex 5 WHO good distribution practices for pharmaceutical products

G.2

Canada Good Manufacturing Practices (GMP) Guidelines – 2009 Edition (GUI-0001)


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Gmp Manual Table of contents

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