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Microbial Contamination Control in Parenteral Manufacturing : Drugs and the Pharmaceutical Sciences - Kevin L. Williams

Microbial Contamination Control in Parenteral Manufacturing

Drugs and the Pharmaceutical Sciences

Hardcover Published: 20th May 2004
ISBN: 9780824753207
Number Of Pages: 764

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This reference surveys emerging trends, concepts, and procedures used in the characterization and control of contaminants; the sterile production of traditional drugs and biologics; the design, construction, and validation of new parenteral facilities; and the monitoring of clean environments-vividly illustrating the routes by which products, processes, and manufacturing settings become contaminated through contact with the air, water, raw materials, and the actions of personnel, as well as the current methods necessary to successfully preclude contamination.

"will be welcomed by all involved in parenteral manufacturing.the value of this book is much more than as a guide to contamination control; it is the setting of each chapter within a wider and engaging context that makes this publication unique."-European Journal of Parenteral and Pharmaceutical Sciences be welcomed by all involved in parenteral manufacturing.the value of this book is much more than as a guide to contamination control; it is the setting of each chapter within a wider and engaging context that makes this publication unique."-European Journal of Parenteral and Pharmaceutical Sciences

Prefacep. iii
Contributorsp. xxv
Concepts and Foundations of Parenteral Manufacturing Contamination Control
Historical and Emerging Themes in Parenteral Manufacturing Contamination Controlp. 1
Introductionp. 1
The Birth of Microbiological Theoryp. 2
Historical Development and Regulation of Parenteral Dosage Formsp. 3
From Antibiotics to Biologicsp. 9
Changing Perspectives on Contaminantsp. 16
Emerging Approaches to Finding and Identifying Contaminantsp. 20
Microbial Contamination Hazard Analysis in Sterile Product Manufacturingp. 29
An Overview of the Evolution and Diversification of Microorganismsp. 29
A View of Microbes and Their Relationship to Sterile Drug Product Manufacturingp. 33
The Microbiological Function in Drug Product Manufacturingp. 36
Understanding Process Analysisp. 42
Microbial Contamination Hazard Analysis Step-by-Step--an Examplep. 48
Hazard Analysis Discussion and Conclusionp. 52
Overview of Modern Parenteral Products and Processesp. 59
Parenterals--General Introduction and Product Typesp. 59
Demands on Parenteral Products and Manufacturing Processesp. 60
Parenteral Manufacturing Processesp. 62
Area Design and Environment Controlp. 63
Fabrication of Batchp. 64
Sterility Assurance in Parenteral Manufacturingp. 64
Aseptic Processingp. 68
Recent Issues in Sterilization by Filtrationp. 75
Sterile Prefilled Syringes (PFS)--Manufacturing and Terminal Sterilization Perspectivesp. 75
Process Validation, Hazard Analysis and Critical Control Points (HACCP)p. 76
Continuous Processing of Parenteral Productsp. 78
Computer-Controlled Automation of Unit Processesp. 80
Processing of Biopharmaceutical Productsp. 80
Processing of Packaging Componentsp. 83
Future Trends in Parenteral Processingp. 86
The Role of USP in the Microbiological Assessment of Parenteral Manufacturingp. 91
Introductionp. 91
The USP Organizationp. 92
USP Legal Recognition and USP Relationship to FDAp. 93
Microbiological Assessment Continuump. 94
Sterility and Bioindicatorsp. 107
Introductionp. 107
Sterility Assurancep. 108
Resistance Performancep. 109
Selectionp. 112
Process Challenge Devicesp. 116
Regulatory Statusp. 117
Qualification of Biological Indicatorsp. 118
Applicationp. 119
Rapid Readout Biological Indicatorsp. 124
Conclusionp. 125
D-Value Calculationsp. 129
Control of Contaminants Via Facilities and Utilities
Biological Safety Cabinets and Isolators Used in Pharmaceutical Processingp. 139
Introductionp. 139
Design Considerationsp. 140
Common Lab Isolator Requirementsp. 150
Lab Isolators Used for Sterility Assurancep. 151
The Sterility Testp. 151
Isolator Room Requirementsp. 152
Biodecontamination Efficacyp. 152
Microbiological Monitoring of Sterility Testing Isolatorsp. 154
Isolator Cleaningp. 154
Conclusionp. 154
Developing a Process for Aseptic Facility Design and Validationp. 157
Introductionp. 157
Defining the Projectp. 157
Preliminary Project Teamp. 158
Deliverables for the Preconceptual Phasep. 158
Conceptual Designp. 160
Developing the Project Core Teamp. 160
Developing the Basis of Design or "BOD"p. 162
Leveraging the Effortp. 163
The Design Qualification Processp. 164
Example of an Approach to Design Qualificationp. 165
Preliminary Engineeringp. 166
The Project Functionp. 168
Pharmaceutical Water Systems: New Orientations in System Designp. 173
Introductionp. 173
Water Purity Standardsp. 174
Electronic Rinse Waterp. 175
Emphasis on Pretreatmentsp. 177
Source Watersp. 178
Pretreatmentsp. 179
Chlorine Removalp. 191
Chloramine Removalp. 195
Organic Entities, TOCp. 196
Endotoxinsp. 197
Ultrafiltrationp. 198
Principal Purificationsp. 198
Countercurrent Operationsp. 201
Reverse Osmosisp. 207
Storage Conditionsp. 213
Conclusionp. 213
Airborne Contamination Controlp. 215
Introductionp. 215
Cleanroom Design and Operationp. 217
Metrology and Test Methodsp. 224
Disinfection Practices in Parenteral Manufacturingp. 233
Introductionp. 233
Current Regulatory Environmentp. 234
Chemical Disinfectants--Activity, Mechanism of Action, Mechanism(s) of Resistancep. 236
Resistance to Disinfectantsp. 245
Spores and Disinfectantsp. 246
Prions and Disinfectantsp. 248
Reasons for Using a Disinfectantp. 249
What to Consider When Choosing a Disinfectantp. 249
Identifying the Number and Type of Microorganisms that Need to Be Controlledp. 250
Determining the Specificity of Microbial Action of Commercially Available Disinfectantsp. 250
Surface and Disinfectant Compatibilityp. 250
Safety and Precautionsp. 251
Physical and Environmental Factors that Influence Disinfectant Efficacyp. 251
Preparation of Disinfectant Solutionsp. 254
Quality Control of Disinfectantsp. 256
Methods for Validation of Disinfectant Efficacyp. 257
Application of Disinfectants for Contamination Controlp. 262
Developing and Implementing a Disinfection Programp. 266
Personnel Training and Demonstration of Competencyp. 273
Summaryp. 276
Manufacturing Process Control of Contaminants
Sterile Filtrationp. 283
Introductionp. 283
Types of Filtrationp. 284
Modus of Filtrationp. 293
Membrane Filter Materialsp. 297
Filter Constructions and Designp. 301
Filter Validationp. 315
Integrity Testingp. 324
Process Development of Alternative Sterilization Methodsp. 341
Introductionp. 341
Process Development-Generalp. 342
Physical Factors and Validationp. 345
Target Value for Sterilization Effectp. 354
Process-Influencing Factorsp. 379
Method of Cycle Development and Process Quantificationp. 403
Additional Studiesp. 414
Conclusionp. 415
Terminal Sterilization and Parametric Releasep. 419
Role and Significance of the Sterility Test in the Release of Sterile Pharmaceuticalsp. 419
Basic Considerations for Parametric Releasep. 427
History of Parametric Release and Present Positions of the Authoritiesp. 433
The Future of Parametric Releasep. 444
Raw Material Contamination Controlp. 449
Introductionp. 449
Raw Material Requirements for GMPp. 450
Incoming Inspection of Raw Materials Programp. 451
Qualification of Suppliersp. 454
Endotoxin: Worst-Case Parenteral Pyrogenp. 461
Introductionp. 461
Endotoxin Nomenclature and Classification as a Pyrogenp. 462
Structure Overviewp. 463
Why the Parenteral Focus on Endotoxin?p. 466
Contamination Control Philosophy in Parenteral Manufacturingp. 471
Developing an Endotoxin Control Strategy for Drug Substances/Excipientsp. 473
BET Standardizationp. 477
Origin and Importance of LALp. 482
LAL Discoveryp. 483
Hemolymph Coagulation in Limulus and Tachypleusp. 485
Prominent LAL Testsp. 487
Method Development and Validation--The Importance of a Good Testp. 492
Resolving Test Interferencesp. 500
Setting Endotoxin Specificationsp. 500
Depyrogenation Validationp. 503
Endotoxin Removal in Pharmaceutical Manufacturing Processesp. 512
The Future and Endotoxin Testingp. 513
The Whole Blood Pyrogen Testp. 518
Screening Active Pharmaceutical Ingredients and Excipients for Endotoxinp. 531
Overviewp. 531
Regulatory Documents for the BETp. 531
Endotoxin Alert Levels (EAL) for APIsp. 532
Synergistic Effect of Endotoxin with Other Pyrogensp. 533
Endotoxin Limits for Sterile Pharmacy Compoundingp. 535
Endotoxin Limits for Excipientsp. 537
Interference Testing for APIs and Excipientsp. 539
Viral and Prion Clearance Strategies for Biopharmaceutical Safetyp. 541
Biopharmaceutical Manufacturing: General Considerationsp. 541
Sources of Viral Contaminantsp. 543
Virus Detection Methodsp. 545
Regulatory Considerations: A Risk-Based Approachp. 547
How Much Viral Clearance is "Enough"?p. 548
Virus Clearance Methodsp. 549
Technical Aspects of Study Designp. 554
Considerations in Data Interpretation and Estimating Viral Clearancep. 557
Viral Clearance Validation Studies: Pitfalls and Cautionsp. 558
Prionsp. 559
Etiology of Prion Diseasesp. 561
Mode of Prion Transmissionp. 562
Prion Detection Methodsp. 564
Prion Clearance: A Risk-Based Approachp. 566
Process Clearance Evaluation: Considerations and Design Issuesp. 570
Considerations in Data Interpretation and Estimating Prion Clearancep. 572
Conclusionp. 572
Sampling, Monitoring, and Identifying Contaminants
Statistical Sampling Conceptsp. 585
Introductionp. 585
Poisson Probability Distributionp. 586
The Limit of Quantitationp. 589
Likelihood of Not Detecting an Organismp. 589
Hypergeometric Distributionp. 592
Lot-by-Lot Acceptance Sampling Attributesp. 594
Operating Characteristic Curvep. 595
Method of Designing a Sampling Planp. 596
Variable Type Sampling Plansp. 602
MIL Standard Plans for Variable Typep. 603
Common Types of Statisticsp. 605
Environmental Monitoringp. 609
Introductionp. 609
Microbiological Monitoringp. 610
Particulate Monitoring and Other Parametersp. 621
Overall Performance of Environmental Monitoringp. 622
Overall Quality Assessment of Environmental Monitoring Datap. 623
Prevention and Troubleshooting of Microbial Excursionsp. 625
Introductionp. 625
Facilities Designp. 626
Personnel Managementp. 628
Cleaning and Sanitization Programsp. 631
Conclusionp. 633
Simulation of Aseptic Manufacturep. 635
Introductionp. 635
Simulation: Its Purposep. 636
Placebosp. 638
Process Simulationp. 640
Microbiological Controlsp. 655
Incubation of Simulation Trialsp. 660
Applicationp. 663
Standard Methods of Microbial Identificationp. 677
Introductionp. 677
Biochemical Test-Based Identificationp. 678
Fatty Acid-Based Identificationp. 680
Factors to Consider in Choice of System for Identification of Bacteriap. 681
Conclusionp. 683
Rapid Methods of Microbial Identificationp. 685
Introductionp. 685
ATP Bioluminescencep. 686
Direct Viable Counts (DVC)p. 692
Flow Cytometryp. 693
Impedancep. 694
PCR Technologyp. 695
Immunoassaysp. 698
Criteria for Validating Rapid Methodsp. 702
Conclusionp. 704
Indexp. 709
Table of Contents provided by Rittenhouse. All Rights Reserved.

ISBN: 9780824753207
ISBN-10: 0824753208
Series: Drugs and the Pharmaceutical Sciences
Audience: Professional
Format: Hardcover
Language: English
Number Of Pages: 764
Published: 20th May 2004
Publisher: Taylor & Francis Inc
Country of Publication: US
Dimensions (cm): 22.86 x 15.88  x 3.81
Weight (kg): 1.12
Edition Number: 1