Table of Contents
Book Cover
Title
Copyright
Contents
Preface
1 Introduction
MARKET SIZE
ISSUES AND CHALLENGES
Microbes and the Analytical Challenge
What Are We Really Trying to Detect?
Hazard Analysis and Risk Assessment
HOPES FOR THE FUTURE
REFERENCES
2 Historical Perspective on Methods Development
FOUNDATION OF THE FIELD OF MICROBIOLOGY
DEVELOPMENT OF THE CLASSICAL MICROBIOLOGICAL METHODS
DEVELOPMENT OF ADVANCED MICROBIOLOGICAL METHODS
THE SEARCH FOR RAPID MICROBIOLOGICAL METHODS
BIBLIOGRAPHY
3 Microbiological Methods of the Pharmacopoeia
MICROBIAL GROWTH IN PHARMACEUTICAL ENVIRONMENTS: STARVATION-SURVIVAL
BIOFILM FORMATION
INFLUENCE OF ENVIRONMENTAL CONDITIONS ON MICROBIAL SURVIVAL
CULTIVATION OF MICROORGANISMS ON SOLID AND LIQUID SUBSTRATES
Growth Curves
Lag Phase
Exponential Growth Phase
Stationary Phase
Reduction Phase
Influence of Media Composition, Temperature, and Incubation Time
Selective Media
Indicator Reactions
Influence of Antagonistic Agents on Recovery
Objectionable Microorganisms
Noncultivable Microorganisms
MICROBIOLOGICAL STANDARD METHODS OF THE PHARMACOPOEIA
Neutralization of Antimicrobial Activity and Validation of Recovery
Total Viable Count
Yeast and Mold Count
Specific Microorganisms
Test for Sterility
Antimicrobial Effectiveness Tests
Summary and Outlook
REFERENCES
4 Overview of Alternative Rapid Microbiological Technologies
INDUSTRIAL NEEDS AND REQUIREMENTS
Why Test?
RAPID METHODS AND THE DRUG DEVELOPMENT PROCESS
Cost
New Method Requirements
AVAILABLE TECHNOLOGIES
Sample Preparation
Media Preparation
Membrane Filtration
Specific Organism Isolation
Anaerobes
Immunological Methods
Electrical Methods
Impedance
Bioluminescence
Cytometry
MOLECULAR-BASED TECHNOLOGIES
IDENTIFICATION SYSTEMS
CONCLUSIONS
REFERENCES
5 Labor-Saving Devices and Automation of Traditional Methods
BLENDERS, STOMACHERS, AND PULSIFIERS
GRAVIMETRIC DILUTERS
COUNTING PROCEDURES
Hydrophobic Grid Membrane Filter
Petrifilm
Standard Plate Count
Coliform and Escherichia coli
Petrifilm E. coli O157:H7
Yeast and Mold
Redigel
Spiral Platers
Counting
Electronic Colony Counters
SOME VENERABLE, INEXPENSIVE, AND LABOR-SAVING METHODS
Loop-Tile Method
Agar Droplet Technique
Plate Loop
METHODS FOR SURFACE CONTAMINATION: AGAR CONTACT METHODS
RODAC Contact Plates
Agar Syringes and Agar Sausages
Dip Slides and Samplers
SPIRAL PLATING APPLICATIONS
MIC Testing
Mutagenicity Screening
REFERENCES
6 ATP Bioluminescence and Its Use in Pharmaceutical Microbiology
THE SCIENCE
THE PRODUCTS AVAILABLE
Pallchek
RapiScreen
MicroStar
THE FUTURE
SUMMARY
REFERENCES
7 Impedance
HISTORY OF DEVELOPMENT
IMPEDANCE THEORY
Direct Impedance
Indirect Impedance
Principle of Detection by Indirect Impedance
INFLUENCE OF ELECTRODES
PRINCIPLE FACTORS AFFECTING DETECTION TIME
INSTRUMENTS
Bactometer
BacTrac
Separate Registration of M-Value and E-value
Malthus
RABIT
PHARMACEUTICAL APPLICATIONS OF IMPEDANCE
Enumeration of Bacteria and Fungi
Testing for Biocidal Activity
Sterility Testing
Predictive Modeling of Growth
Detection of Pathogenic Organisms
Salmonella
Escherichia coli
Pseudomonas spp.
Staphylococcus aureus
Clostridia
MISCELLANEOUS APPLICATIONS IN DRUG DEVELOPMENT
CONCLUSION
REFERENCES
8 Traditional and Automated Rapid Methods for Species Identification and Typing
GENOTYPING
Restriction Endonuclease Analysis
Plasmid Typing
Ribotyping
PFGE Typing
PCR-Based Typing Systems
Identification with Primers and Probes
CHEMOTAXONOMY
Mass Spectrometry and Pyrolysis
Pyrolysis MS
Reproducibility
Fourier Transform Infrared Spectroscopy
Gas Chromatography and the Microbial Identification System
Microbial Identification System
ELECTROPHORETIC PROTEIN TYPING
CONCLUSION
REFERENCES
9 Techniques for Detection of Specific Organisms and Potential for DNA-Based Technologies
CURRENT ESTABLISHED METHODS FOR SPECIFIC ORGANISM DETECTION
Immunological Detection Systems
Alternative Approaches and Combined Technologies
DNA-BASED TECHNOLOGIES
Why Use Nucleic Acids to Detect Microorganisms?
How Are Nucleic Acids Used in Assays and What Are the New Technologies?
Recognition of the target by the probe
Amplification of the target sequence
Detection of the assay signal
Amplification of the assay signal
WHY AREN’T MORE NUCLEIC ACID ASSAYS BEING USED?
CONCLUSION
REFERENCES
10 Alternative Technologies for Sterility Testing
ALTERNATE TECHNOLOGIES: CLINICAL ORIGINS
BACTEC® System
ESP® Detection System
BacT/Alert®
ALTERNATE TECHNOLOGIES: NONCLINICAL ORIGINS
Bactometer®
ScanRDI®
The Electronic Nose
REGULATORY ACCEPTANCE AND THE FUTURE FOR STERILITY TESTING
REFERENCES
11 Limulus Endotoxin Test
DISCOVERY
Comparison of Blood Coagulation in Limulus and Mammals
Preparation of Limulus Amebocyte Lysate
EARLY REGULATORY INTEREST IN AN ALTERNATIVE TO THE RABBIT PYROGEN TEST
FDA’s Experience with Bacterial Endotoxin
Licensing the LAL Test
LAL Licensed Manufacturers
COMMERCIALIZATION
Evolution of the Test Methodology
Current Technology and Automation
INDUSTRY ACCEPTANCE
Replacement of the Pyrogen (Rabbit) Test
Sensitivity, Reproducibility, Sample Interference
Non-Endotoxin Pyrogens
False Positives
FDA GUIDELINES
The Guideline
Legal Effect
USP BACTERIAL ENDOTOXIN TEST AND RELATED MONOGRAPHS
Reference Standard and Control Standard Endotoxin
Preparatory Testing
Test for Confirmation of Labeled LAL Reagent Sensitivity
Inhibition or Enhancement Test
Maximum Valid Dilution
Test Procedure
Preparations
Procedure
Calculation and Interpretation
Geometric Mean Calculation
Endotoxin Content Calculation
Interpretation
EUROPEAN AND JAPANESE PHARMACOPOEIA ACCEPTANCE OF THE LAL TEST
International Standard
METHODOLOGY
Gel-Clot Assay
Turbidimetric Assay
Chromogenic Assay
AUTOMATION
RESEARCH AND CLINICAL APPLICATIONS
LAL as a Research Tool
FUTURE OF THE ASSAY
REFERENCES
12 A Practical Guide to Validation
WHAT IS VALIDATION?
BACKGROUND
START AT THE BEGINNING
SPECIFICATION QUALIFICATION (SQ)
VALIDATION PLAN
DESIGN QUALIFICATION (DQ)
INSTALLATION QUALIFICATION (IQ)
OPERATION QUALIFICATION (OQ)
PERFORMANCE QUALIFICATION (PQ)
STANDARD OPERATING PROCEDURES (SOPs)
VALIDATION SUMMARY
IMPLEMENTATION
PERIODIC REVIEW
MULTIPLE SITE VALIDATION
AMENDMENTS TO PRODUCT MARKETING AUTHORIZATIONS
CONCLUSION
REFERENCES
13 Regulatory Recognition and Acceptance
OBJECTIVES
BRIEF HISTORY OF REGULATION DEVELOPMENT
REGULATORY CONCERNS
REGULATORY ACCEPTANCE
SUMMARY AND CONCLUSIONS
REFERENCES
14 New Technologies for Microbiological Assays
IMMUNOLOGICAL TESTS
Signal Amplification
Bioluminescent and chemiluminescent labels and detection schemes
Immuno-PCR and DNA labels
Background
Formats
Capture and enrichment
Biosensors
Homogeneous assays
CELL COMPONENTS
MICROCHIPS
Cell Analysis Chips
Microarrays
INSTRUMENTAL TECHNIQUES
Gas Chromatography-Mass Spectrometry
Atomic Force Microscopy and Optical Tweezers
Single Molecule Assays
CONCLUSIONS
REFERENCES
Afterword
ADVANCES IN TECHNOLOGY
ACCEPTABILITY
ATTITUDE
REFERENCES
Contributors
Index
