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Pharmaceutical Microbiological Quality Assurance and Control: Practical Guide for Non-Sterile Manufacturing [Kõva köide]

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  • Formaat: Hardback, 592 pages, kõrgus x laius x paksus: 231x160x33 mm, kaal: 1043 g
  • Ilmumisaeg: 23-Jan-2020
  • Kirjastus: John Wiley & Sons Inc
  • ISBN-10: 1119356075
  • ISBN-13: 9781119356073
Teised raamatud teemal:
Pharmaceutical Microbiological Quality Assurance and Control: Practical Guide for Non-Sterile ManufacturingSuurem pilt
  • Formaat: Hardback, 592 pages, kõrgus x laius x paksus: 231x160x33 mm, kaal: 1043 g
  • Ilmumisaeg: 23-Jan-2020
  • Kirjastus: John Wiley & Sons Inc
  • ISBN-10: 1119356075
  • ISBN-13: 9781119356073
Teised raamatud teemal:
Püsilink: https://www.kriso.ee/db/9781119356073.html
Märksõnad:
This book provides a thorough and modern approach to controlling and monitoring microbial contaminations during the manufacturing of non-sterile pharmaceuticals. It covers state-of-the-art microbiology quality assurance and control (QA / QC) tests as well as risk mitigation strategies so that the reader can implement these methodologies in a facility or laboratory to meet microbiology current good manufacturing practices (cGMPs). Also, the authors discuss developments in microbiological testing technology. They share their long experience in practicing microbiological QA/QC in large multinational pharmaceutical companies and present real-life complex cases involving tough decision making.
Editors xix
List of Contributors
xxi
Preface xxvii
Foreword xxxiii
Acknowledgments xxxv
1 Microbiological Control Strategy
1(22)
David Roesti
Marcel Goverde
1.1 Introduction
1(1)
1.2 Overview of a Microbial Control Strategy Program
2(2)
1.3 Main Factors to Be Controlled
4(14)
1.3.1 Controlled Facilities
4(6)
1.3.2 Controlled Procedures
10(1)
1.3.3 Controlled Product Ingredients
10(2)
1.3.4 Controlled Utilities
12(1)
1.3.5 Controlled Equipment
13(2)
1.3.6 Controlled Formulation
15(3)
1.4 Conclusion
18(1)
Bibliography
18(5)
2 Microbial Contamination Risk Assessment in Non-sterile Drug Product Manufacturing and Risk Mitigation
23(34)
Tony Cundell
2.1 Introduction
24(1)
2.2 Regulatory, Compendia, and Industry Guidance
24(1)
2.3 Putting into Perspective the Microbiological Risk Associated with Non-sterile Products
25(4)
2.3.1 75000 Deaths Annually Caused by Infectious Diseases!
26(2)
2.3.2 Susceptibility of Different Patient Populations
28(1)
2.3.3 Frequency of Drug Product Recall
29(1)
2.4 Risk Assessment Tools
29(6)
2.4.1 Impact Matrix
30(1)
2.4.2 Failure Mode and Effects Analysis (FMEA)
31(1)
2.4.3 Hazard Analysis and Critical Control Points (HACCP)
31(1)
2.4.3.1 Application of HACPP to Tablet Manufacturing
32(3)
2.5 Organizational Risk Management Maturity
35(1)
2.6 Hierarchy of Risks
35(11)
2.6.1 Hierarchy of Risk by Pharmaceutical Ingredient
35(7)
2.6.2 Hierarchy of Risk by Dosage Form and Processing Steps
42(1)
2.6.2.1 Processing Steps
42(1)
2.6.2.2 Risk Associated with Different Processing Steps
43(2)
2.6.3 Hierarchy of Risk by Utility System
45(1)
2.7 Effect of Product Attributes
46(2)
2.7.1 What Are the Critical Quality Attributes for a Pharmaceutical Drug?
46(1)
2.7.2 Role of Formulation in Bioburden Control
46(1)
2.7.3 Hurdle Technology Concept
46(2)
2.7 A Concept of Hostility Level
48(1)
2.8 Emerging Manufacturing Technologies
48(4)
2.8.1 Jet Milling Micronization
48(2)
2.8.2 Hot Melt Extrusion
50(1)
2.8.3 Continuous Tablet Manufacturing
51(1)
2.9 A Case History
52(1)
2.10 Conclusions
53(1)
Bibliography
53(4)
3 Qualification of Microbiological Laboratory Personnel and Equipment
57(22)
Robert Schwarz
3.1 Introduction
57(1)
3.2 Reasons, Requirements, and Strategies for Qualification
58(10)
3.2.1 Qualification and Re-Qualification of Laboratory Personnel
58(2)
3.2.2 Equipment Qualification: Which Equipment Needs to Be Qualified in a Microbiological Laboratory?
60(1)
3.2.2.1 Equipment Classification According to ISPE
61(3)
3.2.2.2 Equipment Classification According to USP
64(1)
3.2.3 Equipment Qualification: How to Qualify Laboratory Equipment
65(3)
3.3 Critical Aspects of Microbiological Methods
68(4)
3.3.1 Antibiotic Susceptibility Testing (AST)
69(3)
3.4 Practical Examples for Qualification of Laboratory Personnel
72(4)
3.4.1 Titrations
72(1)
3.4.2 Verification of Spore Count on Biological Indicators
73(1)
3.4.3 Recovery Rate of Microbiological Swab Sampling
73(3)
Acknowledgments
76(1)
Bibliography
76(3)
4 Introduction to Culture Media in Pharmaceutical Microbiology for Non-sterile Products
79(26)
Marion Louis
Laurent Leblanc
Felix A. Montero Julian
4.1 Introduction
80(3)
4.2 Culture Media Challenges and Development
83(1)
4.3 Importance of Culture Media for Patient Safety
83(1)
4.4 Culture Media Are all Different
83(8)
4.4.1 Importance of Raw Materials
84(1)
4.4.1.1 Origins
84(1)
4.4.1.2 Selection
85(1)
4.4.1.3 Variability and Controls
85(2)
4.4.2 Manufacturing Process
87(1)
4.4.3 Development of Culture Media
87(1)
4.4.4 Stability Studies
88(1)
4.4.4.1 Thermal Shocks
89(2)
4.5 Innovation in Regard to Culture Media
91(1)
4.5.1 Objectionable Organisms Recall
91(1)
4.5.2 Increase Media Flexibility and Ease of Use
92(1)
4.6 Quality Controls
92(6)
4.6.1 Quality Release Test Performed by the Culture Media Manufacturer (External Provider or In-house Media Manufacturer)
92(3)
4.6.2 Quality Control Test Performed on Ready-to-Use Culture Media Purchased from External Manufacturers
95(1)
4.6.3 Importance of the Quality Control Strains
96(1)
4.6.4 Outsourcing Strategy and How to Perform an Audit at a Growth Media Partner
97(1)
4.6.4.1 Quality System
98(1)
4.6.4.2 Facilities and Equipment
98(1)
4.7 Culture Media Troubleshooting
98(5)
4.7.1 Temperature Storage Issues
99(1)
4.7.1.1 Storage Conditions Below 2 °C
99(1)
4.7.1.2 Exceptional Excursions of Temperature During Shelf Life
99(1)
4.7.2 Water Condensation and Excessive Moisture
100(1)
4.7.3 Fertility Issues
100(2)
4.7.4 Crystals in Xylose Lysine Deoxycholate (XLD) Culture Medium
102(1)
4.8 Conclusion
103(1)
Bibliography
103(2)
5 Microbiological Examination of Non-sterile Final Dosage Forms and Raw Material Including Acceptance Criteria and Testing Frequency
105(48)
David Roesti
5.1 Microbiological Acceptance Criteria
106(6)
5.1.1 Final Dosage Forms
106(4)
5.1.2 Raw Materials
110(1)
5.1.3 Internal Out of Expectation (OOE) Limits
111(1)
5.2 Testing Frequency
112(5)
5.2.1 Final Dosage Forms
112(1)
5.2.1.1 Which Frequency to Set by Skip-lot Testing?
113(3)
5.2.2 Drug Substances and Excipients
116(1)
5.3 Procedure if Microbial Growth Occurs in Routine Testing
117(1)
5.4 Sampling
117(3)
5.5 Nutrient Medium Controls
120(5)
5.5.1 pH Value
121(1)
5.5.2 Absence of Microbial Contamination
121(1)
5.5.3 Growth Promotion Tests
121(4)
5.6 Test Method Overview
125(2)
5.7 Verification of the Suitability of the Method
127(15)
5.7.1 Sample Preparation
127(2)
5.7.2 Method Suitability for Microbial Enumeration Tests
129(1)
5.7.2.1 Membrane Filtration
129(2)
5.7.2.2 Plate Count Methods
131(3)
5.7.2.3 Most Probable Number Method
134(5)
5.7.3 Suitability of the Test Method for Absence of Specified Microorganisms
139(1)
5.7.4 Examples of Procedures in Case the Method Suitability Fails
140(2)
5.8 Microbiological Examination of Non-sterile Products
142(6)
5.8.1 Microbial Enumeration Tests: Membrane Filtration and Plate Count Methods
142(1)
5.8.1.1 Membrane Filtration
142(1)
5.8.1.2 Pour Plate Method
142(1)
5.8.1.3 Surface Spread Method
143(1)
5.8.1.4 Incubation
143(1)
5.8.1.5 Counting
143(2)
5.8.2 Microbial Enumeration Tests: MPN Method
145(1)
5.8.2.1 Enumeration by Means of Serial Dilutions (MPN Method)
145(1)
5.8.3 Test for Specified Microorganisms Procedure
145(3)
5.8.4 Method Transfer
148(1)
5.9 Elements to Consider for Raw Data Sheets
148(1)
Acknowledgments
149(1)
Bibliography
149(4)
6 Microbial Requirements and Testing of Primary Packaging
153(36)
Marcel Goverde
6.1 Introduction
154(7)
6.1.1 Definition of Primary Packaging
154(2)
6.1.2 Microflora in Packaging Materials
156(2)
6.1.3 Antimicrobial Packaging
158(3)
6.2 Guidelines and Literature
161(3)
6.3 Acceptance Criteria and Testing Frequency
164(6)
6.3.1 Examples of Acceptance Criteria
164(3)
6.3.2 Calculation Approach to Define Acceptance Criteria
167(2)
6.3.3 Comparison with Food Industry
169(1)
6.3.4 Testing Frequency
169(1)
6.4 Test Methods
170(4)
6.4.1 Membrane Filtration
172(1)
6.4.2 Pour-Plate Count
173(1)
6.4.3 Contact Plates and Swabs
173(1)
6.4.4 Test for Specified or Objectionable Microorganisms
174(1)
6.5 Suitability Test
174(3)
6.5.1 Suitability Test Approach for the Membrane Filtration Method
175(1)
6.5.2 Suitability Test for the Contact Plate Approach
176(1)
6.5.3 Pour-Plate Method and Specified Microorganisms
176(1)
6.6 OOS Procedure
177(1)
6.7 Examples of OOS or OOE Cases
178(6)
6.7.1 Example 1: OOE of a Metal Container (11) Used for API Storage
179(2)
6.7.2 Example 2: Possible OOS for a Foil Used for Inhalation Products
181(2)
6.7.3 Example 3: Contaminated Inhaler
183(1)
6.8 Conclusion
184(1)
Bibliography
185(4)
7 Utilities Design and Testing
189(42)
Tim Sandle
7.1 Introduction
190(1)
7.2 Defining, Developing, and Maintaining Utilities
191(7)
7.2.1 What Are Utilities?
191(1)
7.2.2 Good Design Principles
192(3)
7.2.3 Validation Master Plan
195(1)
7.2.4 Qualification of Utilities
195(1)
7.2.5 Upgrading, Reconstructing, and Renovating Utilities
196(1)
7.2.6 Outsourcing
197(1)
7.3 Review of Critical Utilities
198(28)
7.3.1 Compressed Air and Gases
198(1)
7.3.1.1 Compressed Gas Standards
199(1)
7.3.1.2 Microbial Survival in Compressed Gases
200(1)
7.3.1.3 Microbiological Requirements
201(2)
7.3.1.4 Sampling
203(1)
7.3.1.5 Instrumentation for Sampling
204(1)
7.3.1.6 Culture Medium Used and Incubation Conditions
205(3)
7.3.1.7 Reporting Requirements
208(1)
7.3.1.8 Bacterial Endotoxin and Compressed Gases
208(1)
7.3.2 Cleanrooms and Controlled Environments
208(1)
7.3.2.1 Heating, Ventilation, and Air Conditioning (HVAC)
208(2)
7.3.2.2 Validation
210(1)
7.3.2.3 Monitoring and Control
210(1)
7.3.2.4 Environmental Monitoring to Show Environmental Control
211(1)
7.3.2.5 Energy Efficiency
212(1)
7.3.3 Water Systems
212(1)
7.3.3.1 Types of Water
213(1)
7.3.3.2 Good Water System Design
214(2)
7.3.3.3 Microbial Control of Water
216(2)
7.3.3.4 Monitoring Water
218(3)
7.3.4 RMMs in Monitoring
221(1)
7.3.5 Clean Steam
221(1)
7.3.6 Clean Equipment, Sanitization, and Cleaning Validation
222(4)
7.4 Conclusion
226(1)
Bibliography
227(4)
8 Microbiological Environmental Monitoring
231(34)
Alexandra Stark
8.1 Introduction
232(1)
8.2 Microbiological Control Strategy
233(1)
8.3 Cleanliness Zoning Concept for Non-sterile Products
233(1)
8.4 Microbiological Environmental Monitoring Strategy
234(1)
8.5 Microbiological Environmental Monitoring Methods
235(3)
8.5.1 Microbiological Monitoring of Air
235(1)
8.5.1.1 Active Air Monitoring
235(1)
8.5.1.2 Settle Plate
236(1)
8.5.2 Microbiological Monitoring of Surfaces
236(1)
8.5.2.1 Contact Samples
236(1)
8.5.2.2 Swab Samples
237(1)
8.5.2.3 Rinse Samples
237(1)
8.5.3 Microbiological Monitoring of Detergents and Disinfectants
237(1)
8.6 Method Validations and Suitability Tests for Microbiological Environmental Monitoring
238(6)
8.6.1 Choice and Validation of Nutrient Media
238(2)
8.6.2 Incubation Temperature and Incubation Period
240(1)
8.6.3 Experimental Studies to Evaluate the Impact of the Applied Testing Method Toward Microbial Recovery
241(1)
8.6.4 Recovery Rate
242(1)
8.6.5 Sample Hold Time
243(1)
8.7 Initial Validation of Cleanrooms and Production Equipment
244(2)
8.7.1 Initial Validation of Cleanrooms
244(1)
8.7.2 Initial Validation of Production Equipment
245(1)
8.8 Definition of a Microbiological Environmental Routine Monitoring Program
246(7)
8.8.1 Definition of Microbiological Control Levels
246(2)
8.8.2 Definition of Monitoring Frequencies
248(1)
8.8.3 Definition of Sampling Locations
249(1)
8.8.4 Measures if Microbiological Control Levels Are Exceeded
250(2)
8.8.5 Trending of Results
252(1)
8.8.5.1 Trending Areas and Periods
252(1)
8.8.5.2 Trending of Identified Isolates
252(1)
8.8.5.3 Adverse Microbiological Trend
252(1)
8.9 Microbiological Environmental Monitoring: Examples for Users
253(8)
8.9.1 Example for the Definition of Sampling Locations for a Production Area
253(2)
8.9.2 Examples for Deviation Handling
255(1)
8.9.2.1 Example No. 1: Equipment-Surface Monitoring with Exceeded Action Level
256(3)
8.9.2.2 Example No 2: Cleanroom Surface Monitoring with Exceeded Action Level
259(2)
8.10 Conclusion
261(1)
Bibliography
262(3)
9 Identification of Microorganisms
265(64)
Christine E. Farrance
9.1 Introduction
266(2)
9.2 History and Challenges of Bacterial Taxonomy and Classification
268(8)
9.2.1 Definition of Strains
269(1)
9.2.2 Evolution of a Phylogenetic Marker
270(2)
9.2.3 Setting a New Starting Point
272(1)
9.2.4 The Contemporary View of Microbial Taxonomy
273(1)
9.2.5 Limits of Resolution
274(2)
9.2.6 Summary: The Whole Picture
276(1)
9.3 History and Challenges of Fungal Taxonomy and Classification
276(3)
9.3.1 Identification of Fungi Using the rRNA Region
278(1)
9.4 Current Identification Technologies
279(27)
9.4.1 Considerations of the Different Systems
280(2)
9.4.2 Challenges with Nomenclature and Reference Data
282(1)
9.4.3 Considerations for Using an In-house System or a Contract Testing Lab
283(1)
9.4.4 Phenotypic Systems
284(1)
9.4.4.1 Biochemical Approaches
284(1)
9.4.4.2 Fatty Acid Approach
285(1)
9.4.4.3 Summary of Phenotypic Identification Systems
286(1)
9.4.5 Proteotypic Systems
287(1)
9.4.5.1 History of MALDI-TOF
287(1)
9.4.5.2 MALDI-TOF Used for Microbial Identification Today
288(1)
9.4.5.3 Performance
289(1)
9.4.5.4 The Use of MALDI-TOF for the Identification of Filamentous Fungi
290(1)
9.4.6 Genotypic Systems
291(1)
9.4.6.1 Sequence-Based Identification Technologies
291(1)
9.4.6.2 Sequence-Based Identification Technologies and Phylogenetic Analyses
292(1)
9.4.6.3 Considerations When Using a Sequence-Based Approach
293(1)
9.4.6.4 Cautions Using Public Databases for Sequence-Based Identifications
294(3)
9.4.7 Next-Generation Sequencing Systems
297(1)
9.4.7.1 Whole Genome Sequencing
298(1)
9.4.7.2 Metagenomics
299(1)
9.4.8 Other Spectroscopy or Spectrometry Methods for Identification and/or Strain Typing
299(1)
9.4.8.1 FT-IR Spectroscopy
299(2)
9.4.8.2 Raman Spectroscopy
301(1)
9.4.8.3 Other Technologies
301(1)
9.4.3 Strain-Level Differentiation
302(1)
9.4.9.1 Fragment-Based Genotypic Technologies for Strain-Level Differentiation
302(3)
9.4.9.2 Sequence-Based Genotypic Technologies for Strain-Level Differentiation
305(1)
9.5 Strengths and Weaknesses with Each Categorical Method
306(3)
9.6 Case Studies from a Contract Testing Lab
309(3)
9.6.1 A Caveat to Identifying QC Strains
309(1)
9.6.2 Odoribacter Are Not Bacillus: The Importance of Accurate Reference Data
310(1)
9.6.3 Synonyms of Fungal Strains: Taxonomic Investigations
311(1)
9.6 A Synonyms of Bacterial Strains: Taxonomic Investigations
312(1)
9.7 Conclusion
313(1)
Bibliography
314(15)
10 Calculating Alert Levels and Trending of Microbiological Data
329(42)
David Roesti
10.1 Introduction
330(2)
10.2 Goal of the
Chapter
332(1)
10.3 Alert Levels Based on Historical Data
332(23)
10.3.1 Introduction
332(3)
10.3.2 Distribution of Microbiological Data
335(3)
10.3.3 Data to Be Included in the Calculations
338(1)
10.3.3.1 Clustering of Data
338(1)
10.3.3.2 Data that Can Be Excluded from the Calculation
338(1)
10.3.3.3 Periodic Reassessment of Alert Levels
339(1)
10.3.4 Calculating Alert Levels Using Control Charts
339(3)
10.3.4.1 Examples of Control Charts
342(4)
10.3.5 Calculating Alert Levels Using Percentile Ranking
346(1)
10.3.5.1 Nonparametric Percentile Ranking Method
347(1)
10.3.5.2 Parametric Percentile Ranking Method
347(1)
10.3.5.3 Comparing Calculation Methods Using Control Charts and Percentile Ranking
348(4)
10.3.6 Conclusion Calculation of Alert Levels
352(3)
10.4 Trending
355(12)
10.4.1 Introduction
355(1)
10.4.2 Defining and Investigating Adverse Trends
355(1)
10.4.2.1 Grouping of Data
355(1)
10.4.2.2 Definitions of Adverse Trend
355(2)
10.4.2.3 Investigating Adverse Trends
357(1)
10.4.3 Examples of Trending Methods
358(1)
10.4.3.1 Graphical Interpretation Using Regression Analysis
358(1)
10.4.3.2 Graphical Interpretation Using Rolling Averages
358(3)
10.4.3.3 Neumann Gradual Trend Test
361(1)
10.4.3.4 Microbiological Contamination Recovery Rate and Number of Exceeding Alert Levels
361(1)
10.4.3.5 Qualitative Value System
362(3)
10.4.3.6 Trending of Identified Isolates
365(2)
10.5 Conclusion
367(1)
Acknowledgments
367(1)
Bibliography
367(4)
11 Exclusion of Objectionable Microorganisms from Non-sterile Pharmaceutical Drug Products
371(30)
Tony Cundell
11.1 Introduction
372(2)
11.2 What Is an Objectionable Microorganism?
374(9)
11.3 Screening for Objectionable Microorganisms
383(5)
11.3.1 Microbial Characterization, Identification, and Strain Typing
383(1)
11.3.2 Screening of Objectionable Microorganisms
384(1)
11.3.3 How Should We Screen Non-sterile Drug Products for Objectionable Microorganisms?
385(1)
11.3.4 Selectivity of the USP Absence of Specified Microorganism Tests with Regards to B. cepacia Complex
385(3)
11.3.5 Method Suitability
388(1)
11.4 Risk-Based Microbial Testing of Non-sterile Drug Products
388(1)
11.4.1 Low-Risk Products
388(1)
11.4.2 Moderate Risk Products
389(1)
11.4.3 High-Risk Products
389(1)
11.5 Sources of Objectionable Microorganisms
389(3)
11.5.1 Pharmaceutical Ingredients
389(2)
11.5.2 Ingredient Water
391(1)
11.5.3 Manufacturing Personnel
391(1)
11.5.4 Process Equipment
391(1)
11.5.5 Manufacturing Environment
391(1)
11.6 Risk Assessment to Determine if a Microorganism Is Objectionable in a Non-sterile Drug Product
392(3)
11.6.1 Microorganism of Concern
393(1)
11.6.2 Potential Microbial Proliferation in the Drug Product
393(1)
11.6.3 Risk Level in Targeted Patient Populations
394(1)
11.7 Case Histories
395(3)
11.7.1 Allopurinol Tablets for Cancer Patients
395(1)
11.7.2 Laxative Recommended for Infants
396(1)
11.7.3 Alcohol-Free Mouthwash in Hospital Settings
396(1)
11.7.4 Non-sterile Alcohol Wipes in an Intensive Care Unit
396(1)
11.7.5 Metformin Hydrochloride Oral Solution
397(1)
11.7.6 Comforts for Baby Water with Fluoride
397(1)
11.8 Conclusions
398(1)
Bibliography
399(2)
12 Data Integrity and Microbiological Excursion Handling
401(28)
David Roesti
Marcel Goverde
12.1 Data Integrity
401(9)
12.2 General Concept for Microbiological Excursion
410(10)
12.2.1 Level 1 Investigation
411(2)
12.2.2 Level 2 Investigation
413(7)
12.3 Considerations for Excursions
420(7)
12.3.1 Excursion with Environmental Monitoring
420(2)
12.3.2 Excursion with Water Testing
422(2)
12.3.3 Excursion in the Growth Promotion Test
424(2)
12.3.4 Excursion with Microbiological Examination of Non-sterile Products
426(1)
Bibliography
427(2)
13 Rapid Microbiological Methods
429(30)
Michael J. Miller
13.1 Introduction
429(2)
13.2 The Current State of Microbiology Testing
431(1)
13.3 Rapid Microbiological Methods
432(1)
13.4 Applications for Non-sterile Pharmaceutical Drug Products
433(2)
13.5 Technology Review
435(12)
13.5.1 Growth-Based RMMs
436(2)
13.5.2 Cellular Component-Based Technologies
438(2)
13.5.3 Viability-Based Technologies
440(1)
13.5.4 Spectroscopy-Based Technologies
441(3)
13.5.5 Nucleic Acid Amplification-Based Technologies
444(3)
13.6 Validating Rapid Microbiological Methods
447(7)
13.7 Developing a Business Case for Rapid Methods
454(1)
13.8 Summary
455(1)
Bibliography
456(3)
14 Validation of a Rapid Microbiological Method for the Microbiological Examination of Non-sterile and Nonfilterable Drug Products, APIs, and Excipients
459(30)
Oliver Gordon
David Roesti
14.1 Introduction
460(2)
14.1.1 Workflow Rapid MET
461(1)
14.1.2 Evaluation of Test Results
462(1)
14.2 Method Validation
462(17)
14.2.1 General Validation Strategy
462(1)
14.2.2 Statistical Data Evaluation
463(1)
14.2.2.1 Fisher's Exact Test and Chi-Square Test
463(1)
14.2.2.2 Sample Size and Test Power
464(4)
14.2.2.3 Equivalence Tests
468(1)
14.2.3 Experimental Conditions for Validation Experiments
468(1)
14.2.3.1 Rapid MET
468(1)
14.2.3.2 Compendial Method
468(1)
14.2.4 Method Validation Results
469(1)
14.2.4.1 Robustness
469(1)
14.2.4.2 Ruggedness
470(1)
14.2.4.3 Repeatability
471(1)
14.2.4.4 Specificity
471(1)
14.2.4.5 Limit of Detection
472(5)
14.2.4.6 Accuracy and Precision (According to Ph. Eur. 5.1.6)
477(1)
14.2.4.7 Equivalence in Routine Operation
478(1)
14.3 Suitability Test (Product-Specific Method Validation)
479(4)
14.3.1 Sample Effects Study
479(2)
14.3.2 Suitability of the Test Method
481(2)
14.4 Discussion
483(3)
14.5 Conclusion
486(1)
Acknowledgments
486(1)
Bibliography
487(2)
15 An Ex-Regulator's View of the Microbiology QA/QC Functions in the US Pharmaceutical Industries
489(6)
David Hussong
15.1 Foods, Drugs, and Quality
489(3)
15.2 Why Microbes Confound a Census
492(2)
15.3 Microbiological QA Decisions
494(1)
15 A Who Has Responsibility for Quality?
495(10)
15.5 Product and Process Planning
496(3)
15.6 Quality and Documentation in Drug Manufacturing
499(1)
15.7 Summary
500(1)
Bibliography
501(4)
16 Practical Guide for Microbiological QA/QC of Non-sterile Pharmaceuticals Manufacturing for EU
505(14)
Ina Bach
16.1 Introduction
505(1)
16.2 General Requirements
506(2)
16.3 Audit Assessment Tools of a Microbiological Laboratory
508(6)
16.3.1 General Overview
508(1)
16.3.2 Organization and Personnel
509(1)
16.3.3 Documentation 5i0
16.3.4 Culture Media
510(1)
16.3.5 Trends
511(1)
16.3.6 Microbiological Methods
512(1)
16.3.7 Facilities
512(1)
16.3.8 Equipment
513(1)
16.3.9 Reference Cultures
514(1)
16.4 Regulatory Audits in the Microbiology Department
514(2)
16.5 Conclusions
516(1)
Bibliography
517(2)
17 Which Microbiological Tests Can Better Be Performed In-house and What Can Be Easily Outsourced
519(20)
Thomas Meindl
Ingo Grimm
17.1 Introduction
519(3)
17.2 Advantages and Disadvantages of Outsourcing
522(2)
17.2.1 Specialization and Know-How in Analytical Testing
522(1)
17.2.2 Challenges for Outsourcing
523(1)
17.3 Business Case and Hidden Costs
524(4)
17.3.1 The New Challenges in Pharmaceutical Environment
524(1)
17.3.2 Outsourcing to Strengthen the Core Business
525(1)
17.3.3 Which Testing May Be Outsourced
526(1)
17.3.4 Sample Hold Time and Transport
527(1)
17.4 Hidden Costs
528(1)
17.5 Quality Agreement Between the Contract Laboratory and the Requesting Company
529(3)
17.5.1 Regulatory Environment
529(1)
17.5.2 Regulatory Aspects and Contents of a Modern Quality Agreement
529(3)
17.6 Auditing Contract Laboratories
532(1)
17.7 A Case History
532(3)
17.7.1 Example 1: Implementation of a New Technology - Qualification and Validation
532(1)
17.7.2 Example 2: System Suitability Test, Setup of Test for Microbiological Quality
533(1)
17.7.3 Example 3: Setup Environmental Monitoring for Microbial Contamination
534(1)
17.8 Conclusions
535(1)
Bibliography
536(3)
Index 539
David Roesti, PhD, works at Novartis Pharma AG in Stein, Switzerland, and is responsible for defining the microbial control strategy at the site and is a global subject matter expert in microbiology for the Novartis group. He is also is an elected member of the General Chapters Microbiology Expert Committee of the Unites States Pharmacopoeia 2015–2020 revision cycle.

Marcel Goverde, PhD, runs MGP Consulting GmbH for consulting, training and project management in GMP-relevant areas with a focus on microbiology, hygiene and deviation management. He is the Swiss expert in the EDQM group for Modern Microbiological Methods since 2003, which was then integrated into Group 1 (Microbiological Methods and Statistical Analysis) in 2015.