Hugo and Russell's Pharmaceutical Microbiology

Cover
Title Page
Copyright Page
Contents
Notes on Contributors
Preface to the First Edition
Prefaceto the Ninth Edition
About the Companion Website
Part 1 Introducing Pharmaceutical Microbiology
Chapter 1 Introduction to Pharmaceutical Microbiology
1.1 Pharmaceutical Microbiology: Microorganisms and Medicines
1.1.1 The Discipline of Pharmaceutical Microbiology
1.1.2 Microorganisms and Medicines
1.2 Scope and Content of the Book
Part 2 Biology of Microorganisms
Chapter 2 Fundamental Features of Microbiology
2.1 Introduction
2.1.1 Viruses, Viroids and Prions
2.1.2 Prokaryotes and Eukaryotes
2.2 Naming of Microorganisms
2.3 Microbial Metabolism
2.4 Microbial Cultivation
2.4.1 Culture Media
2.4.2 Cultivation Methods
2.4.3 Planktonic and Sessile (Biofilm) Growth
2.5 Enumeration of Microorganisms
2.6 Microbial Genetics
2.6.1 Bacteria
2.6.2 Eukaryotes
2.6.3 Genetic Variation and Gene Expression
2.7 Pharmaceutical Importance of the Major Categories of Microorganisms
2.8 Preservation of Microorganisms
Chapter 3 Bacteria
3.1 Introduction
3.1.1 Bacterial Diversity and Ubiquity
3.2 Bacterial Ultrastructure
3.2.1 Cell Size and Shape
3.2.2 Cellular Components
3.2.3 Cell Surface Components
3.3 Biofilms
3.4 Bacterial Sporulation
3.4.1 Endospore Structure
3.4.2 Endospore Formation
3.4.3 Endospore Germination
3.5 Bacterial Toxins
3.6 Bacterial Reproduction and Growth Kinetics
3.6.1 Multiplication and Division Cycle
3.6.2 Population Growth
3.6.3 Growth and Genetic Exchange
3.7 Environmental Factors that Influence Growth and Survival
3.7.1 Physicochemical Factors that Affect Growth and Survival of Bacteria
3.7.2 Nutrition and Growth
3.8 Detection, Identification and Characterisation of Organisms of Pharmaceutical and Medical Significance
3.8.1 Culture Techniques
3.8.2 Microscopy
3.8.3 Biochemical Testing and Rapid Identification
3.8.4 Molecular Approaches to Identification
3.8.5 Pharmaceutically and Medically Relevant Microorganisms
References
Further Reading
Chapter 4 Fungi
4.1 What Are Fungi?
4.2 Structure of the Fungal Cell
4.3 Medical Significance of Fungi
4.4 Antifungal Therapy
4.4.1 Polyene Antifungals
4.4.2 Azole Antifungals
4.4.3 Echinocandins
4.4.4 Synthetic Antifungal Agents
4.5 Medically Important Fungal Pathogens of Humans
4.5.1 Candida albicans
4.5.2 Aspergillus fumigatus
4.5.3 Histoplasma capsulatum
4.5.4 Cryptococcus neoformans
4.5.5 Dermatophytes
4.6 Emerging Fungal Pathogens
4.6.1 Saccharomyces cerevisiae
4.6.2 Non-albicans Candida Species
4.6.3 Penicillium marneffei
4.7 Antibiotic Production by Fungi
Further Reading
Chapter 5 Viruses and Other Acellular Infectious Agents: Characteristics and Control
5.1 Introduction
5.2 General Structure of Viruses
5.2.1 Viral Nucleic Acid
5.2.2 Viral Capsid
5.2.3 Viral Envelope
5.2.4 Viral Envelope-associated Proteins
5.3 Virus–Host Cell Interactions
5.3.1 Coronaviruses
5.3.2 Human Immunodeficiency Virus (HIV)
5.3.3 Oncogenic Viruses
5.4 Multiplication of Human Viruses
5.4.1 Attachment to the Host Cell
5.4.2 Penetration of the Viral Particle
5.4.3 Uncoating of the Viral Particle
5.4.4 Replication of Viral Nucleic Acids and Translation of the Genome
5.4.5 Maturation or Assembly of Virions
5.4.6 Release of Virions into the Surrounding Environment
5.5 Cultivation of Human Viruses
5.5.1 Cell Culture
5.5.2 The Chick Embryo
5.5.3 Animal Inoculation
5.6 Viral Epidemics and Pandemics
5.7 Control of Viruses
5.7.1 Antiviral Chemotherapy
5.7.2 Vaccination
5.7.3 Viricidal Effects of Chemical and Physical Agents on Viruses
5.7.4 Control of Viruses in Pharmaceutical Products
5.8 Biotechnological Applications of Viruses
5.9 Bacterial Viruses
5.9.1 Overview
5.9.2 Bacteriophages and Their Products as Antibacterial Agents
5.9.3 Other Applications of Bacteriophages
5.10 Subviral Infectious Agents and Prions
Further Reading
Chapter 6 Protozoa
6.1 Introduction
6.1.1 Protozoa
6.1.2 Parasitism
6.1.3 Habitats
6.1.4 Physiology of Parasitic Protozoa
6.2 Blood and Tissue Parasites
6.2.1 Malaria
6.2.2 Trypanosomatids
6.2.3 Toxoplasma gondii
6.3 Intestinal Parasites
6.3.1 Giardia lamblia (syn. intestinalis, duodenalis)
6.3.2 Entamoeba histolytica
6.3.3 Cryptosporidium parvum
6.4 Trichomonas and Free-living Amoebae
6.4.1 Trichomonas Vaginalis
6.4.2 Free-living Opportunist Amoebae
6.5 Host Response to Infection
6.5.1 Immune Response
6.5.2 Immune Pathology
6.5.3 Immune Evasion
6.6 Detection of Parasites
6.6.1 Methods of Detection
6.6.2 Analysis of Samples
6.7 Control of Protozoan Parasites
6.7.1 Chemotherapy
6.7.2 Other Approaches to Control
Acknowledgement
References
Further Reading
Part 3 Pathogens and Host Response
Chapter 7 Principles of Microbial Pathogenicity and Epidemiology
7.1 Introduction
7.2 The Human Microbiome
7.3 Portals of Entry
7.3.1 Skin
7.3.2 Respiratory Tract
7.3.3 Intestinal Tract
7.3.4 Urogenital Tract
7.3.5 Conjunctiva
7.4 Consolidation
7.4.1 Nutrient Acquisition
7.4.2 Biofilms
7.4.3 Resistance to Host Defences
7.5 Manifestation of Disease
7.5.1 Non-invasive Pathogens
7.5.2 Partially Invasive Pathogens
7.5.3 Fully Invasive Pathogens
7.6 Damage to Tissues
7.6.1 Direct Damage
7.6.2 Indirect Damage
7.7 Recovery from Infection: the Exit of Microorganisms
7.8 Epidemiology of Infectious Disease
Further Reading
Chapter 8 Microbial Biofilms: Consequences for Health
8.1 Introduction
8.2 Biofilms
8.2.1 Biofilms in Nature and the Consequences for Health
8.2.2 Biofilms in the Food Industry
8.2.3 Biofilms in the Pharmaceutical Industry
8.2.4 Biofilms in Healthcare Facilities
8.2.5 Biofilms and Medical Devices
8.3 Tolerance of Biofilms to Antimicrobials
8.4 Mechanisms of Biofilm Tolerance
8.4.1 Biofilm Structure
8.4.2 Biofilm Physiology
8.4.3 Cellular Signalling and Biofilm Resistance
8.4.4 Plasticity of Biofilms
8.5 Treatment of Chronic Biofilm Infections
8.5.1 New Biofilm Assays
8.5.2 Better Use of Existing Antimicrobials
8.5.3 Next-generation Antimicrobials
Acknowledgements
References
Further Reading
Chapter 9 Immunology
9.1 Introduction
9.1.1 Historical Perspective and Scope of Immunology
9.1.2 Definitions and Outline Structure of the Immune System
9.1.3 Cells of the Immune System
9.2 The Innate Immune System
9.2.1 Innate Barriers at Epidermal and Mucosal Surfaces
9.2.2 Innate Defence Once Epidermal or Mucosal Barriers Have Been Compromised
9.2.2.1 Mononuclear Phagocytic Cells
9.3 The Humoral Adaptive Immune System
9.3.1 B-Lymphocyte Antigens
9.3.2 Basic Structure of Antibody Molecules
9.3.3 Clonal Selection and Expansion
9.3.4 Humoral Immune Effector Functions
9.4 Cell-mediated Adaptive Immune System
9.4.1 T-Lymphocyte Antigen Recognition and MHC Proteins
9.4.2 Processing of Proteins to Allow Peptide Presentation by MHC Molecules
9.4.3 More on T-lymphocyte Subpopulations
9.5 Some Clinical Perspectives
9.5.1 Transplantation Rejection
9.5.2 Hypersensitivity
9.5.3 Autoimmunity
9.5.4 Therapeutic Monoclonal Antibodies
9.5.5 Immunosuppressants
9.6 Summary
Dedication
Reference
Further Reading
Chapter 10 Vaccination and Immunisation
10.1 Introduction
10.2 Spread of Infection
10.2.1 Common-source Infections
10.2.2 Propagated-source Infections
10.3 Objectives of a Vaccine/Immunisation Programme
10.3.1 Disease Severity
10.3.2 Vaccine Effectiveness
10.3.3 Safety
10.3.4 Public Perception
10.3.5 Cost
10.3.6 Longevity of Immunity
10.4 Classes of Immunity
10.4.1 Passive Immunity
10.4.2 Active Immunity
10.5 Types of Vaccine
10.5.1 Live Vaccines
10.5.2 Inactivated (Killed) and Component Vaccines
10.5.3 DNA Vaccines
10.5.4 mRNA Vaccines
10.5.5 Viral Vector Vaccines
10.6 Routine Immunisation against Infectious Disease
10.6.1 Poliomyelitis Vaccination
10.6.2 Measles, Mumps and Rubella Vaccination
10.6.3 Tuberculosis
10.6.4 Diphtheria, Tetanus and Acellular Pertussis (DTaP) Immunisation
10.6.5 Immunisation against Bacteria Associated with Meningitis
10.6.6 Human Papillomavirus Vaccination
10.6.7 COVID-19 Vaccination
10.7 The UK Routine Childhood Immunisation Programme
10.8 Immunisation of the Over 65s and Other Risk Groups
Acknowledgements
Further Reading
Part 4 Prescribing Therapeutics and Infection Control
Chapter 11 Antibiotics and Synthetic Antimicrobial Agents: Their Properties and Uses
11.1 Antibiotic Development, Past and Present
11.1.1 Antibiotic Usage
11.2 β-Lactam Antibiotics
11.2.1 Penicillins
11.2.2 Cephalosporins
11.2.3 β-Lactamase Inhibitors
11.2.4 Carbapenems and Monobactams
11.2.5 Hypersensitivity
11.3 Tetracyclines
11.4 Macrolides
11.5 Sulphonamides and Trimethoprim
11.6 Quinolones
11.7 Aminoglycosides
11.8 Glycopeptides
11.9 Antitubercular Drugs
11.10 Newer Antibiotics for MRSA and Other Gram-positive Cocci Infections
11.11 Miscellaneous Antibacterial Antibiotics
11.11.1 Clindamycin
11.11.2 Fusidic Acid
11.11.3 Mupirocin
11.11.4 Colistin
11.11.5 Chloramphenicol
11.11.6 Metronidazole and Other Nitroimidazoles
11.11.7 Nitrofurantoin
11.12 Antifungal antibiotics
11.12.1 Azoles
11.12.2 Polyenes
11.12.3 Echinocandins
11.12.4 Other Antifungal Agents
11.13 Antiviral Drugs
11.13.1 Human Immunodeficiency Virus
11.13.2 Herpes and Cytomegalovirus Infections
11.13.3 Viral Hepatitis
11.13.4 Influenza and Respiratory Syncytial Virus
Acknowledgements
References
Further Reading
Chapter 12 Mechanisms of Action of Antibiotics and Synthetic Anti-infective Agents
12.1 Introduction
12.2 The Microbial Cell Wall
12.2.1 Peptidoglycan Biosynthesis in Bacteria and Its Inhibition
12.2.2 Mycolic acid and Arabinogalactan Biosynthesis in Mycobacteria
12.2.3 Echinocandins – Caspofungin, Anidulafungin and Micafungin
12.3 Protein Synthesis
12.3.1 Protein Synthesis and Its Selective Inhibition
12.3.2 Aminoglycoside–Aminocyclitol Antibiotics
12.3.3 Tetracyclines
12.3.4 Chloramphenicol
12.3.5 Macrolides and Azalides
12.3.6 Clindamycin
12.3.7 Streptogramins – Quinupristin and Dalfopristin
12.3.8 Oxazolidinones – Linezolid and Tedizolid Phosphate
12.3.9 Mupirocin
12.3.10 Fusidic Acid
12.3.11 Pleuromutilins – Retapamulin and Lefamulin
12.4 Chromosome Function and Replication
12.4.1 Basis for the Selective Inhibition of Chromosome Replication and Function
12.4.2 Fluoroquinolones
12.4.3 Nitroimidazoles (Metronidazole, Tinidazole) and Nitrofurans (Nitrofurantoin)
12.4.4 Semi-synthetic Rifamycins (Rifampicin, Rifabutin, Rifaximin, Rifapentine) and Fidaxomicin
12.4.5 5-Fluorocytosine
12.5 Folate Antagonists
12.5.1 Folate Metabolism in Microbial and Mammalian Cells
12.5.2 Sulphonamides
12.5.3 DHFR Inhibitors – Trimethoprim, Pyrimethamine, Proguanil and Trimetrexate
12.6 The Cytoplasmic Membrane
12.6.1 Composition and Susceptibility of Membranes to Selective Disruption
12.6.2 Polymyxins
12.6.3 Daptomycin
12.6.4 Polyenes
12.6.5 Imidazoles and Triazoles
12.6.6 Terbinafine and Amorolfine
Further Reading
Chapter 13 Bacterial Resistance to Antibiotics
13.1 Introduction
13.2 The Origins of Resistance
13.3 Mechanisms of Resistance
13.4 Resistance to β-Lactam Antibiotics
13.4.1 β-Lactamases
13.4.2 β-Lactamase Inhibitors
13.4.3 Altered Penicillin-binding Proteins and Methicillin-resistant Staphylococcus aureus
13.5 Resistance to Glycopeptide Antibiotics
13.5.1 MRSA and Reduced Glycopeptide Susceptibility
13.6 Resistance to Aminoglycoside Antibiotics
13.7 Resistance to Tetracycline Antibiotics
13.8 Resistance to Fluoroquinolone Antibiotics
13.9 Resistance to Macrolide, Lincosamide and Streptogramin Antibiotics
13.10 Resistance to Chloramphenicol
13.11 Resistance to Oxazolidinone Antibiotics
13.12 Resistance to Trimethoprim
13.13 Resistance to Mupirocin
13.14 Resistance to the Polymyxin Antibiotic Colistin (Polymyxin E)
13.15 Resistance to the Lipopeptide Antibiotic Daptomycin
13.16 Resistance to Antimycobacterial Therapy
13.17 Multiple Drug Resistance
13.17.1 R-Plasmids
13.17.2 Mobile Gene Cassettes and Integrons
13.17.3 Chromosomal Multiple Antibiotic Resistance (mar) Locus
13.17.4 Multidrug Efflux Pumps
13.18 Clinical Resistance, MICs, Breakpoints, Phenotypic Resistance and Outcome
13.19 Conclusion
Acknowledgement
References
Further Reading
Chapter 14 Clinical Uses of Antimicrobial Drugs
14.1 Introduction
14.2 Principles of Use of Antimicrobial Drugs
14.2.1 Susceptibility of Infecting Organisms
14.2.2 Host Factors
14.2.3 Pharmacological Factors
14.2.4 Drug Resistance
14.2.5 Drug Combinations
14.2.6 Adverse Reactions
14.2.7 Superinfection
14.2.8 Chemoprophylaxis
14.3 Clinical Use
14.3.1 Respiratory Tract Infections
14.3.2 Urinary Tract Infections
14.3.3 Gastrointestinal Infections
14.3.4 Skin and Soft Tissue Infections
14.3.5 Central Nervous System Infections
14.3.6 Fungal Infections
14.3.7 Medical device-associated Infections
14.4 Antibiotic Policies
14.4.1 Rationale
14.4.2 Types of Antibiotic Policies
Acknowledgements
References
Further Reading
Chapter 15 Antibiotic Prescribing and Antimicrobial Stewardship
15.1 The Need for Antimicrobial Stewardship
15.1.1 The Problem of Antibiotic Resistance
15.1.2 The Challenge of New Antibiotic Development
15.1.3 The Need for Alternative Approaches to Antibiotic Use
15.2 Antibiotic Consumption
15.2.1 Relationship between Antibiotic Consumption and Bacterial Resistance
15.2.2 Global Antibiotic Consumption
15.2.3 Non-prescription Access to Antibiotics
15.2.4 Non-human Antibiotic Use
15.3 Antimicrobial Stewardship Programmes
15.3.1 Definition and Aims of Antimicrobial Stewardship
15.3.2 Components of an ASP
15.3.3 ASP Interventions and their Evidence
15.3.4 Antimicrobial Stewardship in Primary and Community Care
15.3.5 ASPs and Infection Prevention and Control Strategies
15.3.6 The Experience of ASPs during a Pandemic
15.4 Monitoring Antimicrobial Stewardship Programmes
15.4.1 Electronic Surveillance of Antibiotic Use and Resistance
References
Further Reading
Chapter 16 Infection Prevention and Control: Healthcare-associated Infection
16.1 Introduction
16.2 Defining Healthcare-associated Infections
16.2.1 Surgical Site Infections
16.2.2 Bloodstream Infections
16.2.3 Urinary Tract Infections
16.2.4 Ventilator-associated Pneumonia
16.3 Microorganisms Implicated in Healthcare-associated Infection
16.3.1 Gram-positive Bacteria
16.3.2 Gram-negative Bacteria
16.3.3 Viruses
16.3.4 Clinically Relevant Fungi
16.4 Standard IPC Interventions for the Management and Prevention of HCAI
16.4.1 Standard Precautions
16.4.2 Hand Hygiene
16.4.3 Infection Precautions (Contact Precaution and Droplet Precautions)
16.4.4 Isolation Precautions
16.4.5 Cohorting
16.4.6 Cleaning and Disinfection
16.4.7 Active Surveillance
16.4.8 Clinical Protocol-driven Responses
16.4.9 Antimicrobial Stewardship
16.5 Impact of the Clinical Setting on Infection Prevention and Control
16.5.1 Outbreaks and IPC Interventions
16.6 Measuring Impact and Success
16.7 Professional Support for Infection Prevention and Control
References
Further Reading
Part 5 Contamination and Contamination Control
Chapter 17 Microbial Spoilage, Infection Risk and Contamination Control
17.1 Introduction
17.2 Spoilage: Chemical and Physicochemical Deterioration of Pharmaceuticals
17.2.1 Pharmaceutical Ingredients Susceptible to Microbial Attack
17.2.2 Observable Effects of Microbial Attack on Pharmaceutical Products
17.2.3 Factors Affecting Microbial Spoilage of Pharmaceutical Products
17.3 Hazard to Health
17.3.1 Microbial Toxins
17.4 Sources and Control of Contamination
17.4.1 In Manufacture
17.4.2 In Use
17.5 The Extent of Microbial Contamination
17.5.1 In Manufacture
17.5.2 In Use
17.6 Factors Determining the Outcome of a Medicament-borne Infection
17.6.1 Type and Degree of Microbial Contamination
17.6.2 Route of Administration
17.6.3 Resistance of the Patient
17.7 Preservation of Medicines Using Antimicrobial Agents: Basic Principles
17.7.1 Introduction
17.7.2 Effect of Preservative Concentration, Temperature and Size of Inoculum
17.7.3 Factors Affecting the ‘Availability’ of Preservatives
17.8 Quality Assurance and the Control of Microbial Risk in Medicines
17.8.1 Introduction
17.8.2 Quality Assurance in Formulation Design and Development
17.8.3 Good Pharmaceutical Manufacturing Practice
17.8.4 Quality Control Procedures
17.8.5 Post-market Surveillance
17.9 Overview
References
Further Reading
Chapter 18 Chemical Disinfectants, Antiseptics and Preservatives
18.1 Introduction
18.1.1 European Union Regulation
18.1.2 Definitions
18.1.3 Economic Aspects
18.2 Factors Affecting Choice of Antimicrobial Agent
18.2.1 Properties of the Chemical Agent
18.2.2 Microbiological Challenge
18.2.3 Intended Application
18.2.4 Environmental Factors
18.2.5 Toxicity of the Agent
18.3 Types of Compound
18.3.1 Acids and Esters
18.3.2 Alcohols
18.3.3 Aldehydes
18.3.4 Biguanides
18.3.5 Halogens
18.3.6 Heavy Metals
18.3.7 Hydrogen Peroxide and Peroxygen Compounds
18.3.8 Phenols
18.3.9 Surface-active Agents
18.3.10 Other Antimicrobials
18.3.11 Antimicrobial Combinations and Systems
18.4 Disinfection Policies
References
Further Reading
Chapter 19 Laboratory Evaluation of Antimicrobial Agents
19.1 Introduction
19.1.1 Definitions
19.2 Factors Affecting the Antimicrobial Activity of Disinfectants
19.2.1 Innate (Natural) Resistance of Microorganisms
19.2.2 Microbial Density
19.2.3 Disinfectant Concentration and Exposure Time
19.2.4 Physical and Chemical Factors
19.2.5 Presence of Extraneous Organic Material
19.3 Evaluation of Liquid Disinfectants
19.3.1 General
19.3.2 Antibacterial Disinfectant Efficacy Tests
19.3.3 Other Microbe Disinfectant Tests
19.4 Evaluation of Solid Disinfectants
19.5 Evaluation of Air Disinfectants
19.6 Evaluation of Preservatives
19.7 Rapid Evaluation Procedures
19.8 Evaluation of Potential Chemotherapeutic Antimicrobials
19.8.1 Tests for Bacteriostatic Activity
19.8.2 Tests for Bactericidal Activity
19.8.3 Tests for Fungistatic and Fungicidal Activities
19.8.4 Evaluation of Possible Synergistic Antimicrobial Combinations
19.9 Tests for Biofilm Susceptibility
19.9.1 Synergy Biofilm Assays
Acknowledgement
References
Further Reading
Chapter 20 Microbicides: Mode of Action and Resistance
20.1 Introduction
20.2 Mechanisms of Interaction
20.3 Antimicrobial Effects
20.4 Mechanisms of Action
20.4.1 Oxidation Reactions
20.4.2 Cross-linking Reactions
20.4.3 Coagulation
20.4.4 Disruption of Functional Structures
20.5 Enhancing Activity
20.6 Mechanisms of Resistance to Microbicides
20.6.1 General Mechanisms
20.6.2 Induction of Resistance
20.6.3 Dissemination of Resistance
20.6.4 Bacterial Endospores
20.6.5 Bacterial Biofilms
20.6.6 Misuse and Abuse of Microbicides
20.7 Viricidal Activity of Microbicides
20.8 Microbicides and Protozoa
20.9 Microbicides and Fungi
20.10 Inactivation of Prions
20.11 Conclusion
References
Further Reading
Chapter 21 Sterilisation Procedures and Sterility Assurance
21.1 Introduction
21.2 Sensitivity of Microorganisms
21.2.1 Survivor Curves
21.2.2 Expressions of Resistance
21.2.3 Sterility Assurance
21.3 Sterilisation Methods
21.4 Heat Sterilisation
21.4.1 Sterilisation Processes
21.4.2 Moist Heat Sterilisation
21.4.3 Dry Heat Sterilisation
21.5 Gaseous Sterilisation
21.5.1 Ethylene Oxide
21.5.2 Formaldehyde
21.5.3 Peroxygen Compounds
21.6 Radiation Sterilisation
21.6.1 Steriliser Design and Operation
21.7 Filtration Sterilisation
21.7.1 Filtration Sterilisation of Liquids
21.7.2 Filtration Sterilisation of Gases
21.8 Newer Sterilisation Technologies
21.8.1 High-intensity Light
21.8.2 Low-temperature Plasma
21.9 Sterilisation Control and Sterility Assurance
21.10 Bioburden Determinations
21.11 Environmental Monitoring
21.12 Validation and In-process Monitoring of Sterilisation Procedures
21.12.1 Physical Indicators
21.12.2 Chemical Indicators
21.12.3 Biological Indicators
21.13 Sterility Testing
21.13.1 Sterility Testing Methods
21.13.2 Antimicrobial Agents
21.13.3 Positive Controls
21.13.4 Specific Cases
21.13.5 Sampling
21.13.6 Retests
21.13.7 The Role of Sterility Testing
References
Further Reading
Part 6 Pharmaceutical Production
Chapter 22 Sterile Pharmaceutical Products and Principles of Good Manufacturing Practice
22.1 Introduction
22.2 Defining Sterility
22.3 Sterilisation Methods
22.3.1 Factors Affecting Sterilisation
22.4 Demonstrating Sterility
22.5 Types of Sterile Product
22.5.1 Injections
22.5.2 Non-injectable Sterile Fluids
22.5.3 Ophthalmic Preparations
22.5.4 Dressings
22.5.5 Implants
22.5.6 Absorbable Haemostats
22.5.7 Surgical Ligatures and Sutures
22.5.8 Instruments and Equipment
22.5.9 General Considerations
22.6 Good Manufacturing Practices for Sterile Products
22.6.1 Regulatory Framework
22.6.2 In-process Controls and Quality Control (QC)
22.7 Sterility Assurance and the Manufacture of Sterile Products
22.8 Terminal Sterilisation and Aseptic Processing
22.9 Cleanrooms and Facility Design
22.9.1 Design of Premises
22.9.2 Internal Surfaces, Fittings and Floors
22.9.3 Services
22.9.4 Air Supply
22.10 Operating Principles for Aseptic Processing
22.10.1 Sterile Filtration
22.10.2 Managing Aseptic Assembly, Connections and Interventions
22.10.3 Transfer of Materials into and out of Aseptic Processing Areas
22.11 Minimising Human Intervention
22.11.1 Blow–Fill–Seal Technology
22.11.2 Restricted Access Barrier Systems
22.11.3 Isolators
22.11.4 Single-use Sterile Disposable Technology
22.12 Personnel
22.13 Media Simulation Trials
22.14 Quality Risk Management
22.15 Environmental Monitoring
22.16 Release of Sterile Products
22.16.1 Assessments of Sterility
22.16.2 Assessments of Pyrogenicity
22.16.3 Visible Particulates
22.17 Summary
Acknowledgements
Reference
Further Reading
Chapter 23 The Manufacture and Quality Control of Immunological Products
23.1 Introduction
23.2 Vaccines
23.2.1 Types of Vaccines
23.2.2 The Seed Lot System
23.2.3 Production of the Bacteria and the Cellular Components of Bacterial Vaccines
23.2.4 Fermentation
23.2.5 Production of the Viruses and the Components of Viral Vaccines
23.2.6 Blending
23.2.7 Filling and Drying
23.2.8 Quality Control
23.3 In Vivo Diagnostics
23.3.1 Preparation
23.3.2 Quality Control
23.4 Immune Sera
23.4.1 Preparation
23.4.2 Quality Control
23.5 Human Immunoglobulins
23.5.1 Source Material
23.5.2 Fractionation
23.5.3 Quality Control
23.6 Monoclonal Antibodies
23.6.1 Preparation
23.6.2 Quality Control
23.7 Acknowledgements
References
Further Reading
Chapter 24 Recombinant DNA Technology
24.1 Introduction: Biotechnology in the Pharmaceutical Sciences
24.2 Enabling Techniques
24.2.1 Cutting and Joining DNA Molecules
24.2.2 Cloning Vectors
24.2.3 Introduction of Vector into Hosts
24.2.4 Construction of Genomic Libraries
24.2.5 Screening of Genomic Libraries
24.2.6 Optimising Expression of Recombinant Genes
24.2.7 Amplifying DNA: the Polymerase Chain Reaction
24.2.8 Genome Editing Using CRISPR–Cas9 Endonuclease
24.3 Biotechnology in the Pharmaceutical Industry
24.3.1 Recombinant Human Insulin
24.3.2 Recombinant Somatostatin
24.3.3 Recombinant Somatotropin
24.3.4 Recombinant Hepatitis B Vaccine
24.3.5 Recombinant Influenza and Coronavirus Vaccines
24.3.6 Production of Recombinant Antibiotics
24.4 New Diagnostics Using Recombinant DNA Technology
24.4.1 Diagnosis of Infectious Diseases
24.4.2 Diagnosis of Genetic Disorders
Further Reading
Part 7 Current Trends and New Directions
Chapter 25 The Wider Contribution of Microbiology to the Pharmaceutical Sciences
25.1 Introduction
25.1.1 Early Treatment of Human Disease
25.1.2 Present-day Exploitation
25.2 Pharmaceuticals Produced by Microorganisms
25.2.1 Dextrans
25.2.2 Vitamins, Amino Acids and Organic Acids
25.2.3 Iron-chelating Agents
25.2.4 Enzymes
25.3 Applications of Microorganisms in the Partial Synthesis of Pharmaceuticals
25.3.1 Production of Antibiotics
25.3.2 Steroid Biotransformations
25.3.3 Chiral Inversion
25.4 Applications of Microorganisms in the Discovery of Pharmaceuticals
25.4.1 Phage Display
25.5 Use of Microorganisms and Their Products in Assays
25.5.1 Antibiotic Bioassays
25.5.2 Vitamin and Amino Acid Bioassays
25.5.3 Phenylketonuria Testing
25.5.4 Carcinogen and Mutagen Testing
25.5.5 Use of Microbial Enzymes in Sterility Testing
25.5.6 Immobilised Enzyme Technology
25.6 Use of Microorganisms as Models of Mammalian Drug Metabolism
25.7 Microorganisms as Therapy
25.7.1 Bacteriophages
25.7.2 Probiotics
25.7.3 Toxins
25.8 Insecticides
25.9 Bioterrorism
25.10 Concluding Remarks
Further Reading
Chapter 26 Alternative Strategies to Antibiotics: Priorities for Development
26.1 Introduction
26.2 Bacteriophage Therapy
26.3 Bacteriophage Lysins
26.4 Vaccines and Immunotherapies
26.4.1 Vaccines for Bacterial Infections
26.4.2 Immunotherapies
26.5 Probiotics
26.5.1 Gastrointestinal Conditions
26.5.2 Recurrent Vaginitis
26.6 Antimicrobial Peptides
26.7 Conclusion
Acknowledgements
References
Further Reading
Index
EULA