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| Preface | |
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| The Author | |
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| Microbial Life and Ecology | |
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| An Overview of Microbial Life | |
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| Microbial Phylogeny | |
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| Microbial Taxonomy | |
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| Microbial Growth and Survival | |
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| Growth Curve | |
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| Temperature | |
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| Energy Sources | |
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| Oxygen | |
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| Bacteria | |
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| Cell Shape | |
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| Mycoplasma | |
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| Bacterial Growth and Reproduction | |
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| Cell Structures | |
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| The Phyla Gram-Positive Bacteria and Proteobacteria | |
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| Gram-Positive Bacteria | |
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| Proteobacteria | |
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| The Gram-Staining Method | |
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| KOH Test | |
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| Catalase Test | |
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| Fungi | |
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| Cell Structures | |
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| Fungal Growth and Reproduction | |
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| Molds | |
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| Yeasts | |
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| Microorganisms of Interest | |
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| Genus Staphylococcus | |
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| Staphylococcus aureus | |
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| Genus Pseudomonas | |
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| Pseudomonas aeruginosa | |
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| Genus Burkholderia | |
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| Burkholderia cepacia | |
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| Genus Ralstonia | |
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| Ralstonia pickettii | |
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| Genus Comamonas and Genus Stenotrophomonas | |
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| Family Enterobacteriaceae | |
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| Genus Escherichia | |
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| Escherichia coli | |
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| Genus Salmonella | |
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| Genus Shigella | |
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| Genus Serratia | |
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| Genus Klebsiella | |
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| Genus Bacillus | |
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| Bacillus subtilis | |
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| Bacillus cereus | |
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| Genus Clostridium | |
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| Clostridium perfringens | |
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| Clostridium sporogenes | |
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| Candida albicans | |
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| Zygosaccharomyces rouxii | |
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| Genus Aspergillus | |
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| Aspergillus niger | |
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| Genus Penicillium | |
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| References | |
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| Microbial Contamination and Control | |
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| Microbiological Contamination | |
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| Product Recalls | |
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| Nonsterile Products | |
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| Microbial Limit Standards | |
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| The Preservation of Pharmaceutical Products | |
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| Antimicrobial Activity and Efficacy | |
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| Types of Preservatives | |
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| Alcohols | |
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| Benzalkonium Chloride | |
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| Benzoic Acid and Salts | |
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| Boric Acid and Salts | |
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| Chlorhexidine | |
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| Cresol | |
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| Dowicil 200 | |
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| Mercurials | |
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| Parabens | |
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| Phenol | |
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| Sorbic Acid Salts | |
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| Microbiological Control | |
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| Risk Assessment | |
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| Objectionable Organisms | |
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| Sanitization and Disinfection Practices | |
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| Definitions and Types of Chemical Products | |
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| Factors in Choice and Use of Disinfectants | |
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| Rotation of Disinfectants | |
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| Qualification of Disinfectants | |
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| In Situ Testing | |
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| In Vitro Testing | |
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| Expiration Date for Disinfectant Solutions | |
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| Sanitizers Used for Equipment Cleaning | |
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| Neutralization and Microbial Recovery Studies | |
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| Requalification and Change Control | |
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| Conclusion | |
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| References | |
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| The USP Microbial Limit Tests | |
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| History of the Revision and Harmonization Process | |
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| USP Chapter <61> Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests | |
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| Sample Preparation | |
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| Total Aerobic Microbial Count | |
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| Total Combined Yeasts and Molds Count | |
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| Bioburden Tests | |
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| Two-Media Bioburden Test | |
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| One-Medium, Dual-Temperature Incubation Bioburden Test | |
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| TAMC and TYMC Tests via Plate-Count Methods | |
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| Pour-Plate Method | |
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| Spread-Plate Method | |
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| Incubation and Results Calculation | |
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| Test Controls | |
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| TAMC and TYMC Tests via Membrane Filtration Method | |
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| Test Controls | |
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| TAMC Test by the Multiple Tube Method | |
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| Procedure | |
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| Interpretation of the TAMC and TYMC Test Results | |
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| USP CHAPTER <62>: Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms | |
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| Sample Preparation for Direct Inoculation Tests | |
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| Test for Absence of Escherichia coli | |
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| Test for Absence of Salmonella spp. | |
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| Test for Absence of Bile-Tolerant Gram-Negative Bacteria | |
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| Test for Absence of Pseudomonas aeruginosa | |
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| Test for Absence of Staphylococcus aureus | |
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| Test for Absence of Candida albicans | |
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| Test for Absence of Clostridia | |
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| Quantitative Test for Bile-Tolerant Gram-Negative Bacteria | |
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| Retesting | |
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| References | |
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| Pharmaceutical Waters | |
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| Types of Water for Pharmaceutical Purposes | |
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| Microbial Quality Attributes | |
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| Testing of Pharmaceutical Waters | |
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| Sampling Program | |
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| Sample Collection and Preservation | |
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| Bioburden Testing | |
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| Recovery Media | |
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| Coliform Testing | |
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| Identification of Waterborne Microorganisms | |
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| Establishing Alert and Action Levels | |
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| Validation of Water Systems | |
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| Microbial Control and Sanitization | |
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| References | |
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| Environmental Monitoring | |
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| Cleanroom Classification | |
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| Occupancy State | |
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| Routine EM Program | |
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| Testing Frequency and Sampling Sites | |
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| Setting Alert and Action Levels | |
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| Test Methods and Equipment | |
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| Surface Sampling for Viable Particles | |
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| Active Air Sampling for Viable Particles | |
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| Active Air Sampling for Nonviable Particles | |
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| Microbial Identification Program | |
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| Data Analysis | |
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| EM During Facility Validation Activities | |
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| Room Occupancy | |
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| EM of Isolators | |
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| Microbial Control in Cleanrooms | |
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| References | |
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| Bioburden Considerations in Equipment-Cleaning Validation | |
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| Biocontamination Control | |
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| Disposable and Single-Use Equipment | |
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| Equipment-Cleaning Methods | |
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| Validation of Cleaning Methods | |
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| Sampling Recovery Methods | |
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| Swabbing of Equipment | |
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| Rinsing of Equipment | |
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| Qualification of Sampling Methods | |
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| Recovery Study Using the Wet Method | |
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| Recovery Studies Using the Dry Method | |
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| Effects of Product and/or Cleaning Agent Residue on the Recovery of Microorganisms | |
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| Establishing Limits | |
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| Execution of Equipment-Cleaning Validation Protocol | |
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| Validation of Cleaned Equipment Hold Time | |
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| Validation of Dirty Equipment Hold Time | |
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| Ongoing Verification of Cleaning | |
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| Validation of Holding Time/Shipping Conditions | |
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| References | |
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| Method Validation and Media Suitability Testing | |
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| Suitability Test Design | |
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| Representative Challenge Organisms | |
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| Maintenance and Preparation of Test Organisms | |
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| Preparation of Working Cultures | |
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| Validation of Storage Period for Working Cultures | |
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| Recovery of Injured Organisms | |
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| Suitability Testing by Direct Inoculation/Plating Methods | |
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| Validation of Screening for Specified Microorganisms | |
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| Modifications to the Direct Inoculation Method | |
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| Validation of the TAMC and TYMC Tests | |
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| Approach 1 | |
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| Approach 2 | |
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| Modifications to the Plate Method | |
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| Suitability Testing for Membrane Filtration Methods | |
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| Validation of Screening for Specified Organisms | |
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| Validation of TAMC and TYMC | |
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| Modifications to the Membrane Filtration Method | |
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| Suitability of Microbiological Media | |
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| Growth Promotion Testing for Microbial Enumeration Media | |
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| Growth Promotion Testing for Selective Media | |
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| Validation of Rapid Microbiological Methods | |
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| The Validation Package | |
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| Validation Criteria | |
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| Validation of Quantitative Methods | |
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| Accuracy | |
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| Specificity | |
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| Precision | |
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| Limit of Quantitation | |
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| Linearity | |
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| Limit of Detection | |
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| Range | |
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| Ruggedness | |
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| Robustness | |
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| Validation of Qualitative Methods | |
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| Specificity | |
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| Limit of Detection | |
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| Ruggedness | |
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| Robustness | |
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| Accuracy and Precision | |
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| Validation of Automated Microbial Identification Methods | |
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| Accuracy | |
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| Precision | |
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| Robustness | |
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| Ruggedness | |
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| Final Thoughts | |
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| Points to Consider | |
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| References | |
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| Microbiological Quality of Pharmaceutical and Biopharmaceutical Products and Raw Materials | |
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| Microbiological Testing | |
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| Raw Materials | |
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| Biopharmaceutical Products | |
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| Nonsterile Finished Drug Products | |
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| USP Chapter <1111> | |
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| Testing Frequency | |
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| Stability Testing | |
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| Water Activity | |
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| Measuring Water Activity | |
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| The Chilled-Mirror/Dew Point Method | |
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| Capacity Sensors | |
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| Pharmaceutical Applications for Water Activity | |
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| International Harmonization | |
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| Looking Ahead | |
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| References | |
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| Rapid Testing and Alternative Methods in Microbiology | |
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| Rapid Method Technology Platforms | |
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| Impedance/Conductance Technology | |
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| Gas Consumption or Generation | |
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| ATP Bioluminescence | |
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| The Celsis ATP Bioluminescence Systems | |
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| Automated Biochemical Assays | |
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| The VITEK System | |
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| The Biolog Systems | |
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| Fatty Acid Analysis Using Gas Chromatography | |
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| The MIDI System | |
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| Enzyme-Linked Immunosorbent Assay (ELISA) | |
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| The VIDAS | |
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| Analysis of Biomolecules Using Mass Spectrometry | |
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| Polymerase Chain Reaction (PCR) | |
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| Detection of Microbial Contamination Using PCR Technology | |
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| Pulse-Field Gel Electrophoresis (PFGE) | |
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| Riboprinting | |
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| The Riboprinter | |
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| Fluorescent Labeling Assays | |
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| Scan RDI Microbial Detection | |
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| D-Count | |
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| Biosensors and Microarrays | |
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| Laboratory-on-a-Chip Technology | |
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| Barriers to Implementation | |
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| Regulatory Climate | |
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| Future Trends | |
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| Case Study: Genotypically Similar Staphylococci | |
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| Contaminant Isolate and Environmental Sampling | |
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| Ribosomal Gene Sequencing | |
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| Phenotypic Analysis | |
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| Genetic Subtyping-PFGE | |
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| Results and Reporting | |
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| References | |
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| Biofilms | |
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| Biofilm Definition | |
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| Biofilm Structure | |
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| The Biology of Biofilms | |
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| Biofilm Formation | |
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| Quorum Sensing | |
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| Cell Adhesion | |
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| Smooth versus Rough Surfaces | |
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| Hydrophobic versus Hydrophilic Surfaces | |
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| Electrostatic Charge Properties | |
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| Low-Shear versus High-Shear Environments | |
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| Biofilm Dispersion | |
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| Biofilm Resistance and Phenotypes | |
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| Pharmaceutical Production Equipment and Materials Prone to Biofilm Formation | |
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| Water Systems | |
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| Production Equipment | |
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| Ultrafiltration/Diafiltration (UF/DF) Systems | |
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| Chromatography Systems | |
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| Miscellaneous Parts and Materials | |
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| Biofilm Control and Prevention | |
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| Heat Treatment | |
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| Chemical Treatment | |
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| Prevention of Biofilms | |
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| Methods for Detection and Recovery of Biofilm Organisms | |
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| Qualification of Chemical Sanitization Using Biofilm Cells | |
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| Types of Biofilm Reactors | |
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| Choosing a Biofilm Reactor | |
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| Testing Sanitizers Using the CDC Biofilm Reactor | |
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| Setting up the Biofilm Reactor | |
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| Exposure of Biofilm to Disinfectant Solution | |
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| Harvesting Biofilm Cells | |
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| Sanitizer/Disinfectant Efficacy Evaluation | |
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| Method Qualification and Test Controls | |
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| Testing Sanitizers Using a Static Biofilm Reactor | |
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| Industrial Significance of Biofilms | |
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| The Future in Biofilm Research | |
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| References | |
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| Handling Aberrant and Out-of-Specification Microbial Data | |
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| Historical Overview of Investigating OOS Results | |
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| Out-of-Specification (OOS) Result | |
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| Laboratory Investigations | |
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| Conducting the Investigation | |
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| Retesting and Resampling | |
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| Testing for Outliers | |
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| Repeat Testing | |
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| Concluding the Investigation | |
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| Product Lot Disposition | |
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| OOS Investigations and FDA Citations | |
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| References | |
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| Index | |