Microbial Limit and Bioburden Tests Validation Approaches and Global Requirements,Second Edition

Often called the "industry bible," Microbial Limit and Bioburden Tests: Validation Approaches and Global Requirements provides a practical guide to microbial limit methodologies. This new second edition has been substantially updated and expanded to include the most recent microbial limit tests and bioburden testing mandated by USP-NF. This comprehensive reference source reflects current industry standards, regulatory expectations, as well as the latest technical and scientific information. This edition also includes new chapters that provide complete coverage of biofilms, environmental monitoring, and microbial identification. The text also addresses new topics such as water testing.

In recent years, the field of pharmaceutical microbiology has experienced numerous technological advances, accompanied by the publication of new and harmonized compendial methods. It is therefore imperative for those who are responsible for monitoring the microbial quality of pharmaceutical/biopharmaceutical products to keep abreast of the latest changes. Microbial Limit and Bioburden Tests: Validation Approaches and Global Requirements guides readers through the various microbiological methods listed in the compendia with easy-to-follow diagrams and approaches to validations of such test methodologies. Includes New and Updated Material Now in its second edition, this work is the culmination of research and discussions with technical experts, as well as USP and FDA representatives on various topics of interest to the pharmaceutical microbiologist and those responsible for the microbial quality of products, materials, equipment, and manufacturing facilities. New in this edition is an entire chapter dedicated to the topic of biofilms and their impact on pharmaceutical and biopharmaceutical operations. The subject of rapid methods in microbiology has been expanded and includes a discussion on the validation of alternative microbiological methods and a case study on microbial identification in support of a product contamination investigation. Substantially updated and revised, this book assists readers in understanding the fundamental issues associated with pharmaceutical microbiology and provides them with tools to create effective microbial contamination control and microbial testing programs for the areas under their responsibility.

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

Lucia Clontz