All-in-one guide to monitoring and maintaining microbiological safety in the manufacturing of pharmaceuticals, diagnostics, and cosmetics
Addressing the full spectrum of microbiological quality control and quality assurance in pharmaceutical production, Pharmaceutical Microbiology covers methods and technologies required by regulatory authorities throughout the world, with all methods and protocols rated in terms of their compliance with current (2023) EU legislation.
Written by the former head of biological quality assurance for one of Europe’s biggest pharmaceutical and diagnostics companies, Pharmaceutical Microbiology covers sample topics including:
- General conditions for the operation of microbiological laboratories, calibration and qualification of devices, and type culture maintenance
- Industrial hygiene, ambient monitoring, quality control, process validation, microbiological water examination, and rapid microbiological methods
- Automation in the microbiology laboratory, quality assurance, identification of microorganisms, cleaning, sterilization, decontamination, and disposal, and contract testing
- Pharmacopoeial and non-pharmacopoeial methods for the identification and quantification of microorganisms, including cell culture and selected animal tests
Pharmaceutical Microbiology is an essential practice-oriented all-in-one reference for engineers, researchers, and professionals involved in setting up and running a microbiological quality control unit in the pharmaceuticals, diagnostics, and cosmetics industries.
Table of Contents:
Preface to the English Edition xvii
Preface to the First German Edition xix
List of Abbreviations xxi
Glossary xxvii
1 Introduction to Microbiology 1
1.1 Historical 1
1.2 Importance 2
1.3 World of Microorganisms 3
1.4 The Bacterial Cell 9
1.5 Taxonomy of Microorganisms 18
1.6 Medical Microbiology 22
References 26
Further Reading 27
2 General Conditions for the Operation of Microbiological Laboratories 29
2.1 Laws and Technical Regulations 29
2.2 Medical Care for Employees 33
2.3 Operating Description for Microbiological Laboratories 36
2.4 Establishment of Microbiological Laboratories 37
2.4.1 Required Devices/Equipment 37
2.5 Nutrient Media 39
2.6 Media Preparation 47
References 78
3 Calibration and Qualification of the Devices 81
3.1 Calibration Error 83
3.2 Calibration 83
3.3 Balance 84
3.4 pH Meter 85
3.5 Piston Pipettes 85
3.6 Stopwatch 86
3.7 Devices for Achieving Specific Temperatures 87
3.8 Clean Bench 90
3.9 Air Sampler 93
3.10 Particle Counter 95
3.11 Measuring Device for Determining the Water Activity 96
3.12 Photometer/Reader 96
3.13 Tube Reader for Endotoxin Determinations 98
3.14 Fluorescence Reader for Endotoxin Determinations 98
References 98
4 Stock Collection 101
4.1 Reference 101
4.2 Shipping 105
4.3 Storage 105
4.4 Cultivation 106
References 107
5 Industrial Hygiene 109
5.1 Hygiene 109
5.2 Microbiological Basics for Hygiene 112
5.3 Hygiene Measures 115
5.4 Sterilization, Disinfection, and Aseptic Production 127
5.5 Hygiene Protocol for Microbiological Laboratories 136
5.6 Pest Control 137
5.7 Hygiene Officer 140
5.8 Implementation of Hygiene Training Courses 140
References 143
6 Environmental Monitoring 145
6.1 Methods 145
6.2 Microbiological Monitoring in the Sterility Test Isolator 150
6.3 Physical Monitoring in Sterile Production 154
6.4 Physical Operation 155
6.5 Evaluation of the Microorganisms 158
6.6 Register of Microorganisms 159
References 170
Further Reading 172
7 Quality Control 173
7.1 Pharmacopeial Methods (Compendial Methods) 173
7.2 Non-Compendial Methods 214
7.3 Tests Using Animal Models 228
7.4 Cell Culture Methods 231
7.5 Validation of Pharmacopeial Methods 235
References 263
Further Reading 266
8 Process Validations 267
8.1 Media Fill 267
8.2 Depyrogenation 274
8.3 Validation of Sterilization with Dry Heat 276
8.4 Validation of Sterilization Using Moist Heat (Autoclave) 278
8.5 Validation of Sterile Filtration 279
8.6 Container Closure Integrity Test 282
8.7 Cleaning Validation 286
References 289
Further Reading 290
9 Microbiological Examination of Water 291
9.1 Sampling 293
9.2 Specimen Transport 294
9.3 Use of the Different Water Qualities (Table 9.6) 297
9.4 Purified Water 297
9.5 Highly Purified Water 301
9.6 Water for Injection 301
9.7 Water for Diluting Concentrated Hemodialysis Solutions 302
9.8 Water for the Preparation of Extracts 302
9.9 Drinking Water 303
9.10 Legionella 305
References 308
10 Rapid Microbiological Methods 309
10.1 Determination via ATP Content 309
10.2 Determination Via the Incorporation of Fluorescent Markers 313
10.3 Flow Cytometry 315
References 316
Further Reading 317
11 Automation in the Microbiology Laboratory 319
11.1 Automatic Dyeing Machines 319
11.2 Devices for Counting Colonies 320
11.3 Automatic Nutrient Media Filling Machine 320
11.4 Automation of the Endotoxin Test 321
References 322
12 Quality Assurance 323
12.1 Structure of an SOP System 323
12.2 Training 324
12.3 Audits and Inspections 326
12.4 Procedure for OOS and OOE Results 330
References 337
13 Microorganism Identification 339
13.1 Growth Curve 339
13.2 Generation Time 340
13.3 Preparation of Pure Cultures 340
13.4 Sensory and Macroscopic Characteristics 340
13.5 Microscopic Examination 341
13.6 Staining 347
13.7 Principle of the “Colored Row” 349
13.8 Immunological Procedures 351
13.9 Polymerase Chain Reaction 351
13.10 Gas Chromatography (FAME) 352
13.11 FT-IR Spectroscopy 352
13.12 Maldi-tof 353
References 353
14 Cleaning, Sterilization, Decontamination, and Disposal 355
14.1 Cleaning 355
14.2 Sterilization 355
14.3 Laboratory Cleaning and Disinfection 360
14.4 Disposal of Infectious Waste 362
14.5 Disinfection Measures in Case of Accidents 363
References 363
15 Contract Testing (Outsourcing) 365
References 366
Further Reading 366
16 Microbiological Networks 367
16.1 CPM 367
16.2 VAAM Expert Group Quality Management 367
16.3 Subcommittee Microbiology in the VfA 368
16.4 DGHM 368
References 369
17 Addresses 371
Literature 379
Index 389
About the Author :
Michael Rieth received his biology doctorate from the Institute of Microbiology University of Gottingen. He entered into the pharmaceutical industry in 1988. From 1999 to 2014 he was Head of Biological Quality Assurance at Merck KGaA, Darmstadt. He then worked in the field of Global Regulatory Affairs until his retirement in 2020. He has written four books, including Pharmaceutical Microbiology in the German language, which was awarded the Wallhausser Prize in 2013.
