Cover
Editors
List of Contributors
Preface
1. The Book Is Outlined as Follows
Foreword
Acknowledgments
1 Microbiological Control Strategy
1. 1.1 Introduction
2. 1.2 Overview of a Microbial Control Strategy Program
3. 1.3 Main Factors to Be Controlled
4. 1.4 Conclusion
5. Bibliography
2 Microbial Contamination Risk Assessment in Non‐sterile Drug Product Manufacturing and Risk Mitigation
1. 2.1 Introduction
2. 2.2 Regulatory, Compendia, and Industry Guidance
3. 2.3 Putting into Perspective the Microbiological Risk Associated with Non‐sterile Products
4. 2.4 Risk Assessment Tools
5. 2.5 Organizational Risk Management Maturity
6. 2.6 Hierarchy of Risks
7. 2.7 Effect of Product Attributes
8. 2.8 Emerging Manufacturing Technologies
9. 2.9 A Case History
10. 2.10 Conclusions
11. Bibliography
3 Qualification of Microbiological Laboratory Personnel and Equipment
1. 3.1 Introduction
2. 3.2 Reasons, Requirements, and Strategies for Qualification
3. 3.3 Critical Aspects of Microbiological Methods
4. 3.4 Practical Examples for Qualification of Laboratory Personnel
5. Acknowledgments
6. Bibliography
4 Introduction to Culture Media in Pharmaceutical Microbiology for Non‐sterile Products
1. 4.1 Introduction
2. 4.2 Culture Media Challenges and Development
3. 4.3 Importance of Culture Media for Patient Safety
4. 4.4 Culture Media Are all Different
5. 4.5 Innovation in Regard to Culture Media
6. 4.6 Quality Controls
7. 4.7 Culture Media Troubleshooting
8. 4.8 Conclusion
9. Bibliography
5 Microbiological Examination of Non‐sterile Final Dosage Forms and Raw Material Including Acceptance Criteria and Testing Frequency
1. 5.1 Microbiological Acceptance Criteria
2. 5.2 Testing Frequency
3. 5.3 Procedure if Microbial Growth Occurs in Routine Testing
4. 5.4 Sampling
5. 5.5 Nutrient Medium Controls
6. 5.6 Test Method Overview
7. 5.7 Verification of the Suitability of the Method
8. 5.8 Microbiological Examination of Non‐sterile Products
9. 5.9 Elements to Consider for Raw Data Sheets
10. Acknowledgments
11. Bibliography
6 Microbial Requirements and Testing of Primary Packaging
1. 6.1 Introduction
2. 6.2 Guidelines and Literature
3. 6.3 Acceptance Criteria and Testing Frequency
4. 6.4 Test Methods
5. 6.5 Suitability Test
6. 6.6 OOS Procedure
7. 6.7 Examples of OOS or OOE Cases
8. 6.8 Conclusion
9. Bibliography
7 Utilities Design and Testing
1. 7.1 Introduction
2. 7.2 Defining, Developing, and Maintaining Utilities
3. 7.3 Review of Critical Utilities
4. 7.4 Conclusion
5. Bibliography
8 Microbiological Environmental Monitoring
1. 8.1 Introduction
2. 8.2 Microbiological Control Strategy
3. 8.3 Cleanliness Zoning Concept for Non‐sterile Products
4. 8.4 Microbiological Environmental Monitoring Strategy
5. 8.5 Microbiological Environmental Monitoring Methods
6. 8.6 Method Validations and Suitability Tests for Microbiological Environmental Monitoring
7. 8.7 Initial Validation of Cleanrooms and Production Equipment
8. 8.8 Definition of a Microbiological Environmental Routine Monitoring Program
9. 8.9 Microbiological Environmental Monitoring: Examples for Users
10. 8.10 Conclusion
11. Bibliography
9 Identification of Microorganisms
1. 9.1 Introduction
2. 9.2 History and Challenges of Bacterial Taxonomy and Classification
3. 9.3 History and Challenges of Fungal Taxonomy and Classification
4. 9.4 Current Identification Technologies
5. 9.5 Strengths and Weaknesses with Each Categorical Method
6. 9.6 Case Studies from a Contract Testing Lab
7. 9.7 Conclusion
8. Bibliography
10 Calculating Alert Levels and Trending of Microbiological Data
1. 10.1 Introduction
2. 10.2 Goal of the Chapter
3. 10.3 Alert Levels Based on Historical Data
4. 10.4 Trending
5. 10.5 Conclusion
6. Acknowledgments
7. Bibliography
8. Websites
11 Exclusion of Objectionable Microorganisms from Non‐sterile Pharmaceutical Drug Products
1. 11.1 Introduction
2. 11.2 What Is an Objectionable Microorganism?
3. 11.3 Screening for Objectionable Microorganisms
4. 11.4 Risk‐Based Microbial Testing of Non‐sterile Drug Products
5. 11.5 Sources of Objectionable Microorganisms
6. 11.6 Risk Assessment to Determine if a Microorganism Is Objectionable in a Non‐sterile Drug Product
7. 11.7 Case Histories
8. 11.8 Conclusions
9. Bibliography
12 Data Integrity and Microbiological Excursion Handling
1. 12.1 Data Integrity
2. 12.2 General Concept for Microbiological Excursion
3. 12.3 Considerations for Excursions
4. Bibliography
13 Rapid Microbiological Methods
1. 13.1 Introduction
2. 13.2 The Current State of Microbiology Testing
3. 13.3 Rapid Microbiological Methods
4. 13.4 Applications for Non‐sterile Pharmaceutical Drug Products
5. 13.5 Technology Review
6. 13.6 Validating Rapid Microbiological Methods
7. 13.7 Developing a Business Case for Rapid Methods
8. 13.8 Summary
9. Bibliography
14 Validation of a Rapid Microbiological Method for the Microbiological Examination of Non‐sterile and Nonfilterable Drug Products, APIs, and Excipients
1. 14.1 Introduction
2. 14.2 Method Validation
3. 14.3 Suitability Test (Product‐Specific Method Validation)
4. 14.4 Discussion
5. 14.5 Conclusion
6. Acknowledgments
7. Bibliography
15 An Ex‐Regulator's View of the Microbiology QA/QC Functions in the US Pharmaceutical Industries
1. 15.1 Foods, Drugs, and Quality
2. 15.2 Why Microbes Confound a Census
3. 15.3 Microbiological QA Decisions
4. 15.4 Who Has Responsibility for Quality?
5. 15.5 Product and Process Planning
6. 15.6 Quality and Documentation in Drug Manufacturing
7. 15.7 Summary
8. Bibliography
16 Practical Guide for Microbiological QA/QC of Non‐sterile Pharmaceuticals Manufacturing for EU
1. 16.1 Introduction
2. 16.2 General Requirements
3. 16.3 Audit Assessment Tools of a Microbiological Laboratory
4. 16.4 Regulatory Audits in the Microbiology Department
5. 16.5 Conclusions
6. Bibliography
17 Which Microbiological Tests Can Better Be Performed In‐house and What Can Be Easily Outsourced
1. 17.1 Introduction
2. 17.2 Advantages and Disadvantages of Outsourcing
3. 17.3 Business Case and Hidden Costs
4. 17.4 Hidden Costs
5. 17.5 Quality Agreement Between the Contract Laboratory and the Requesting Company
6. 17.6 Auditing Contract Laboratories
7. 17.7 A Case History
8. 17.8 Conclusions
9. Bibliography
Index
End User License Agreement

List of Tables

Chapter 1
1. Table 1.1 Examples of preservatives used in non‐sterile drug product formulation...
Chapter 2
1. Table 2.1 Patient populations with higher risk of microbial infection.
2. Table 2.2 A simple impact matrix for consequences and likelihood of risk.
3. Table 2.3 Risk analysis for excipient based on manufacturing process.
4. Table 2.4 Procurement of pharmaceutical ingredients.
5. Table 2.5 Wet granulation and milling.
6. Table 2.6 Film coating.
7. Table 2.7 Organizational risk management maturity level.
8. Table 2.8 Common excipients used in compressed tablets.
9. Table 2.9 Classification of excipients by starting material and manufacturing pr...
10. Table 2.10 USP/NF microbial limit requirements of commonly used excipients.
11. Table 2.11 Summary of unit processing steps in descending order of risk for diff...
12. Table 2.12 Microbial contamination risk based on dosage form and unit manufactur...
13. Table 2.13 Hostility levels as related to selected product physicochemical and m...
14. Table 2.14 Examples of physiological requirements of some common bacterial patho...
Chapter 4
1. Table 4.1 Harmonized microbial enumeration tests of non‐sterile products.
2. Table 4.2 Differences between old and harmonized enrichment approaches.
3. Table 4.3 Requirements for the Growth Promotion Test according to Ph. Eur. chapt...
4. Table 4.4 Growth promoting, inhibitory and indicative properties of media from P...
Chapter 5
1. Table 5.1 Acceptance criteria of final dosage forms based on harmonized Ph. E...
2. Table 5.2 Examples of critical and noncritical factors for microbial contamin...
3. Table 5.3 Suggested testing frequencies based on product route of administrat...
4. Table 5.4 Example of raw material testing frequency decision table.
5. Table 5.5 Standard sample volume for microbiological examination of non‐steri...
6. Table 5.6 Growth promotion test of agar and liquid media for TAMC and TYMC.
7. Table 5.7 Growth promotion test of agar and liquid media for the detection of...
8. Table 5.8 Overview of test methods based on the nature of the product.
9. Table 5.9 Test microorganisms and incubation conditions for determining the s...
10. Table 5.10 Most‐probable‐number values of microorganisms.
11. Table 5.11 Example of MPN calculation product A.
12. Table 5.12 Example of MPN calculation product B.
13. Table 5.13 Example of MPN calculation product C.
14. Table 5.14 Indicative reactions of specified microorganisms in the method sui...
15. Table 5.15 Common neutralizing agents and neutralizing method for interfering...
Chapter 6
1. Table 6.1 Summary of the data from Negretti (1981).
2. Table 6.2 Summary of the number of accepted and rejected batches tested per year...
3. Table 6.3 Summary of the number of CFU found for each group of primary packaging...
4. Table 6.4 Summary of some antimicrobial active substances.
5. Table 6.5 Overview of regulatory and guiding documents for primary packaging ...
6. Table 6.6 The harmonized acceptance criteria for non‐sterile pharmaceutical p...
7. Table 6.7 Summary of the acceptance criteria for primary packaging according to ...
8. Table 6.8 User example of acceptance criteria for primary packaging.
9. Table 6.9 User example of acceptance criteria for primary packaging.
10. Table 6.10 Some examples of acceptance criteria for primary packaging used in fo...
11. Table 6.11 Tabular summary of further investigation with CAPAs.
Chapter 7
1. Table 7.1 Maximum number of permitted particulates used in the pharmaceutical in...
2. Table 7.2 Comparison of microbiological requirements in different standards/heal...
3. Table 7.3 Example of minimum microbiological requirements for gas monitoring.
4. Table 7.4 Example of microbiological/biological requirements of water used in ph...
Chapter 8
1. Table 8.1 Incubation schemes defined in different guidelines/regulations.
2. Table 8.2 Examples for microbiological control levels for active air monitoring^a
3. Table 8.3 Examples for microbiological control levels for surface monitoring on ...
4. Table 8.4 Examples for microbiological control levels for surface monitoring on ...
5. Table 8.5 Examples for microbiological environmental monitoring frequencies.
6. Table 8.6 Summary of the sampling locations and methods based on the risk ration...
Chapter 9
1. Table 9.1 Example of the diversity of type and non‐type strains forMicrococcu...
2. Table 9.2 Different identification systems have different strengths and weakn...
3. Table 9.3 Different identification systems have different strengths and weakn...
4. Table 9.4 Different identification systems have different strengths and weakn...
5. Table 9.5 Different identification systems have different strengths and weakn...
6. Table 9.6 Categories to consider prior to adopting an identification or strai...
Chapter 10
1. Table 10.1 Common transformations whereY′ is the transform of the data Y usin...
2. Table 10.2 Probability of a normal distribution calculated with the Shapiro–W...
3. Table 10.3 Percentage of observations falling either within mean ± k sigma ra...
4. Table 10.4 Comparison of the calculated alert levels using control charts and...
5. Table 10.5 Comparison of percentiles, number of analysis, and theoretical amo...
6. Table 10.6 Example of evaluation of qualitative values for environmental moni...
7. Table 10.7 Results of week 22 environmental monitoring testing product manufa...
Chapter 11
1. Table 11.1 Top five pathogens causing domestically acquired foodborne illness...
2. Table 11.2 Descriptions ofSalmonella spp., Staphylococcus aureus, and Bacillu...
3. Table 11.3 WHO priority pathogens for the development of new antibiotics.
4. Table 11.4 Key biochemical and physiological characteristics ofBurkholderia cepa...
Chapter 12
1. Table 12.1 Risk matrix example for microbiological tests.
2. Table 12.2 Examples on risk analysis of a selection of tests performed ...
3. Table 12.3 Example of microbiology laboratory checklist.
4. Table 12.4 Example of an “Is/Is Not” tool.
5. Table 12.5 Example of comparing possible causes with the facts.
6. Table 12.6 Example of a checklist for the root cause investigation by the produc...
Chapter 13
1. Table 13.1 Validation criteria for qualitative methods.
2. Table 13.2 Validation criteria for quantitative methods.
3. Table 13.3 Validation criteria for microbial identification methods.
Chapter 14
1. Table 14.1 Variables affecting test power.
2. Table 14.2 Examples of our modified test power calculation based on hypothetical...
3. Table 14.3 Strain selection used for validation of specificity.
4. Table 14.4 Strain‐specific specificity results.
5. Table 14.5 Specificity results pooled data from all strains.
6. Table 14.6 Example statistical significant tests comparing the rate of false‐pos...
7. Table 14.7 Equivalence in routine operation.
Chapter 16
1. Table 16.1 Product‐related activities for non‐sterile products.

List of Illustrations

Chapter 1
1. Figure 1.1 Balance between excessive and insufficient microbial controls.
2. Figure 1.2 Examples of factors, controls, and monitoring implicated in a compr...
3. Figure 1.3 Fictive example of hurdle technology applied to a semisolid product...
Chapter 2
1. Figure 2.1 2014 U.S. National Vital Statistics Report, the top causes of death...
2. Figure 2.2 Hierarchy of risk by excipients.
3. Figure 2.3 Hierarchy of risk by dosage form.
4. Figure 2.4 Hierarchy of risk by utilities.
Chapter 3
1. Figure 3.1 Steps of a successful analyst qualification.
2. Figure 3.2 Validation cascade.
3. Figure 3.3 Impact assessment according to ISPE Baseline Vol. 5, decision tree.
4. Figure 3.4 Categorization defines “working packages.”
5. Figure 3.5 Scheme of antibiotic susceptibility testing (AST) prior and after i...
6. Figure 3.6 Agar plate with antibiotic disk after incubation and microbial grow...
7. Figure 3.7 Example of evaluating the “reaction zone” (measuring the diameter m...
8. Figure 3.8 Enlargement of Figure 4.6. Comparison of different challengeable an...
9. Figure 3.9 Different evaluations lead to results that may comply or may not co...
10. Figure 3.10 Example scheme of swab sampling.
Chapter 4
1. Figure 4.1 Example of product requirements for a culture media and their compa...
2. Figure 4.2 Example of adjustment of the trypticase concentration to adapt the ...
3. Figure 4.3 Main manufacturing steps for a culture medium: Step 1: The raw mate...
4. Figure 4.4 Example of a product development process.
5. Figure 4.5 Example of a stability study of different culture media batches inc...
6. Figure 4.6 Example of a frozen agar.
7. Figure 4.7 Example of water condensation.
8. Figure 4.8 Example of Ishikawa methodology for a growth promotion failure inve...
9. Figure 4.9 Crystal on XLD agar.
Chapter 5
1. Figure 5.1 Example of procedure if microbial growth occurs. OOS, out of specif...
2. Figure 5.2 Example of laminar flow hoods within a microbiological laboratory....
3. Figure 5.3 Weighing of a cream in a sample container placed on a precision bal...
4. Figure 5.4 Pour plating medium into Petri dishes.
5. Figure 5.5 Solidified pour‐plated agar plates in the incubator.
6. Figure 5.6 Schematic overview of the MPN serial dilutions.
Chapter 6
1. Figure 6.1 Summary of the different functionalities of primary packaging mater...
2. Figure 6.2 Simplified procedure for handling a deviation or an out of specific...
Chapter 7
1. Figure 7.1 Primary process flows for non‐sterile manufacturing.
Chapter 8
1. Figure 8.1 Production area with personnel and material entry room.
2. Figure 8.2 Production area from Figure 8.1 with the sampling locations accordi...
Chapter 9
1. Figure 9.1 The rRNA region for bacteria.
2. Figure 9.2 Example dendrogram or tree showing phylogenetic relationships. Neig...
3. Figure 9.3 Fungi can be unicellular like (a) the yeast Candida albicans, form ...
4. Figure 9.4 The rRNA region for fungi.
5. Figure 9.5 Summary of the three different systems to differentiate microorgani...
6. Figure 9.6 The identification rate of previously unidentified isolates using 1...
7. Figure 9.7 Resolving the Burkholderia cepacia complex (Bcc).
8. Figure 9.8 Example portion of a spectrum of Cronobacter sakazakii using IR spe...
9. Figure 9.9 Example of the restriction patterns for seven isolates of Bacillus ...
Chapter 10
1. Figure 10.1 Plotting of microbiological monitoring data representing single an...
2. Figure 10.2 Plotting of microbiological monitoring data. Arrow represents pote...
3. Figure 10.3 Normal distributed data plot with mean = 2 and standard deviation ...
4. Figure 10.4 Poisson distributed data plot with average = variance = 2. Plot wa...
5. Figure 10.5 Negative binomial distributed data plot with number of events 1 an...
6. Figure 10.6 Plotting of two different data sets of microbiological data agains...
7. Figure 10.7 I‐charts of data sets 1 and 2. Top row charts were computed with u...
8. Figure 10.8 Example of alert level calculation using the percentile ranking me...
9. Figure 10.9 Example of alert level calculation using the percentile ranking me...
10. Figure 10.10 Plotting of data sets 1 and 2 as well as calculated alert levels ...
11. Figure 10.11 Alert levels of different microbiological data sets. The alert le...
12. Figure 10.12 Survey trending tool used in pharmaceutical companies (107 respon...
13. Figure 10.13 Examples of plotting microbiological data to evaluate the adverse...
14. Figure 10.14 Regression analysis of data sets 3 and 4. The regression analysis...
15. Figure 10.15 Rolling average calculation using data set 4 with a subgroup size...
16. Figure 10.16 Calculation of data set 3 using the Neumann gradual trend method....
17. Figure 10.17 Examples of trending using alert levels and unexpected high count...
18. Figure 10.18 Example of plotting weekly sums of qualitative values per trend a...
19. Figure 10.19 Example of comparison of proportions of different types of microo...
Chapter 11
1. Figure 11.1 Percentage of recalls by product category and the percentage of im...
2. Figure 11.2 Most frequent species implicated in nosocomial outbreaks (expresse...
3. Figure 11.3 Objectionable microorganism risk decision tree.
Chapter 12
1. Figure 12.1 Graphical representation of the number of FDA warning letters addr...
2. Figure 12.2 Data integrity principles based on the ALCOA+ concept.
3. Figure 12.3 Typical process flow for OOS, OOT, or OOE investigations in the mi...
4. Figure 12.4 Example of an Ishikawa chart.
Chapter 14
1. Figure 14.1 Robustness toward different incubation and glass bead treatment ti...
2. Figure 14.2 Repeatability on different days and daytimes. Results for repeatab...
3. Figure 14.3 Limit of detection. Results of limit of detection compendial metho...
4. Figure 14.4 Comparison of the obtained MPN/g values. Plotting of the MPN/g res...
5. Figure 14.5 Definition of the product‐specific positive/negative discriminatio...
6. Figure 14.6 Schematic overview of result evaluation with the Rapid MET if grow...
Chapter 15
1. Figure 15.1 Illustration of the United States Pharmacopoeia I from 1820 (left)...
Chapter 16
1. Figure 16.1 Overview of critical success factors for the inspection of microbi...
2. Figure 16.2 Overview of observations in specific areas within the microbiologi...
Chapter 17
1. Figure 17.1 Overview of outsourcing workflow. The organization of an outsourci...
2. Figure 17.2 Overview of outsourcing responsibilities.

List of Contributors

Ina Bach, PhD
Global Compliance Assistance, St. Gallen, Switzerland
ina.bach@dr‐bach.ch

Dr. Ina Bach is an independent consultant specializing in the areas of quality assurance, compliance, and auditing, with particular application to the pharmaceutical and biotech industry. Ina Bach has worked over 15 years as a senior compliance auditor in a Global Auditing and Compliance group of one of the top 10 international pharmaceutical companies and as an inspector for the Swiss regulator authority. When she was working for the authorities, she also worked closely with international health organization as a nominated inspector in several of prequalification projects. Additionally, she can look back on many years of experience in the pharmaceutical industry in which she was in responsible positions involved in the development, manufacture of various dosage forms, in project management, as well as in quality assurance and quality control.

Tony Cundell, PhD
Microbiological Consulting, LLC, Scarsdale, NY, USA
tonycundell@gmail.com

Dr. Tony Cundell consults with a number of pharmaceutical, consumer health, and dietary supplement companies; microbiology instrument manufacturers; contract testing laboratories; and sterile compounding pharmacies in the areas of microbial risk assessment, regulatory affairs, and microbiological testing. Prior to November 2013, he worked for Merck Research Laboratories in Summit, New Jersey, as the Senior Principal Scientist in early phase drug development. Earlier in his career, Tony Cundell worked at a director level in Quality Control and Product Development organizations at the New York Blood Center, Lederle Laboratories, Wyeth Pharmaceuticals, and Schering‐Plough. He is a member of the 2015–2020 USP Microbiology Committee of Experts where he takes a leadership role in the area of modern microbiology methods, cochairing the USP Expert Panel that published a stimuli article in the September–October 2017 Pharmacopeial Forum entitled The Development of Compendial Rapid Sterility Tests. Tony Cundell chaired the PDA task force responsible for the ground‐breaking 2000 Technical Report No. 33 The Development, Validation, and Implementation of New (Rapid) Microbiological Methods. In June 2009, he coedited with Anthony Fontana a book entitled Water Activity Applications in the Pharmaceutical Industry and contributed two chapters to the book. He was cochair of the PDA task force responsible for 2014 Technical Report No. 67 Exclusion of Objectionable Microorganisms from Non‐Sterile Drug Products. He received the 2016 PDA Martin Van Trieste Pharmaceutical Science Award for outstanding contributions to the advancement of pharmaceutical science. He has a PhD in microbiology from Lincoln University, Canterbury, New Zealand.

Christine E. Farrance, PhD
Senior Director of R&D and Scientific Affairs, Charles River Laboratories, Inc., Newark, DE, USA
Christine.Farrance@crl.com

Dr. Christine E. Farrance received a Ph.D. in Cellular and Molecular Biology from the University of Pennsylvania, a B.S. in Biochemistry from Cornell University, and has more than 20 years of experience conducting both applied and basic research using molecular, microbial, genetic, and biochemical techniques. Currently, Senior Director of R&D and Scientific Affairs at Charles River Laboratories, Inc., she manages the scientific development projects and priorities across a cross‐functional team. She is also involved in coordinating research studies, and developing technical content for publications, presentations, and training. In addition, she provides her expertise to other business units within Charles River for technical trouble shooting and evaluation of new technologies. Before joining Accugenix/Charles River, she was a scientist at a nonprofit institute developing a plant‐based production system for recombinant vaccines and protein therapeutics. Her work has also included research in the food safety industry, and in plant‐based production systems for monoclonal antibodies as a Research Assistant Professor. Christine Farrance brings unique scientific and technical experiences to Charles River.

Oliver Gordon, PhD
The Francis Crick Institute, London, United Kingdom
Oliver.Gordon@crick.ac.uk

Dr. Oliver Gordon studied Molecular Biology (main focus in Microbiology and Infection Biology) at the Biocenter and the University Hospital in Basel, Switzerland. From 2010 to 2014, he was working at Novartis Pharma AG in Switzerland in the QA/QC‐Microbiology department in the Launch Center for Rapid Microbiological Methods. As Rapid Microbiology Specialist, he played a leading role in evaluation and validation of Rapid Microbiological Methods and the subsequent replacement of Traditional Microbiological Methods, including method transfers to interested Novartis sites worldwide. In 2014, he started a PhD in the lab of Caetano Reis e Sousa at the Francis Crick Institute in London, where his research focuses on understanding how molecules released from dead cells modulate immune and tissue repair responses.

Ingo Grimm
Director Sales & Services, Labor LS, Bad Bocklet, Germany
ingo.grimm@labor‐ls.de

Ingo Grimm is an experienced specialist in sales and business development activities in the field of microbiological and analytical testing of pharmaceutical products (small molecules and biotech) and medical devices. Within the last 15 years he became an expert in the needs of these industries, especially in the DACH‐region. Currently, Ingo Grimm works as Head of Sales & Services at Labor LS SE & Co. KG which is one of the leading cGMP‐laboratories in Europe. He graduated at the University of Applied Sciences Würzburg‐Schweinfurt and holds a Master of Business Administration.

David Hussong, PhD
Chief Technical Officer, Eagle Analytical Services, Houston, TX, USA
David.Hussong@outlook.com

Dr. David Hussong is currently the Chief Technical Officer at Eagle Analytical Services (Houston, TX). He has previously served as a regulatory microbiology consultant (2015–2017). In 2014, David Hussong retired from the Commissioned Corps of the US Public Health Service after 30 years with the Food and Drug Administration (FDA), where he had served in many positions, culminating as the Associate Director for New Drug Microbiology in the Office of Pharmaceutical Science. In addition, he is currently the chair of the USP Microbiology Expert Committee for the 2015–2020 cycle. David Hussong earned his PhD in microbiology from the University of Maryland at College Park (UMCP), and he previously served as a research microbiologist at UMCP, the US Department of Agriculture, and the US Naval Medical Research Institute.

Laurent Leblanc
R&D Manager Health and Personal Care Business, bioMérieux
Laurent.LEBLANC@biomerieux.com

Laurent Leblanc is the R&D Manager of bioMérieux' Health and Personal Care business. He holds a Master's degree in Biotechnology from the University of Limoges, France. For the last 15 years, he worked in several biotechnology companies and before joining bioMérieux in 2008, he worked in microbiological control in the pharmaceutical industry. He is now involved in designing and bringing to the market the new innovative and efficient solutions dedicated to the pharmaceutical and cosmetic industries.

Marion Louis
Global Solution Manager for Pharmaceutical Culture Media of the Healthcare Business, bioMérieux
marion.louis@biomerieux.com

Marion Louis is a Global Solution Manager for Pharmaceutical Culture Media in the HealthCare Business of bioMérieux. Graduated with an Engineering degree in Biotechnologies from Polytech, graduate schools of engineering in France, Marion Louis holds as well a Master degree in Management from University of Clermont‐Ferrand. With 10 years' experience in microbiology as a Senior Application Engineer in pharmaceutical industries, she is now responsible to provide performant solutions to pharmaceutical industries.

Thomas Meindl, PhD
Senior Consultant, Labor LS, Bad Bocklet, Germany
thomas.meindl@labor‐ls.de

Dr. Thomas Meindl studied biology in Mainz and Tübingen, Germany, and received a PhD from the University of Basel. He started his career at Novartis, Basel, working on receptor–ligand interaction studies. Then, he moved to Sympore GmbH, a start‐up company in Tübingen, where he helped to develop new drugs in the field of immune suppression and inflammation. From there he moved to SKM oncology, Fürth, Germany, a company active in clinical trials. Finally, he moved to Labor LS SE, formally known as Labor L + S AG, in Bad Bocklet, Germany. There he worked as head of department and division manager for several departments (assays, endotoxin testing, molecular biology, disinfectant testing, research and development, validation of computerized systems, and implementation of LIMS); until today he works as a senior consultant for release testing of pharmaceuticals.

Michael J. Miller, PhD
President, Microbiology Consultants, LLC, Lutz, USA
mjm@microbiologyconsultants.com

Dr. Michael J. Miller is an internationally recognized microbiologist and subject matter expert in pharmaceutical microbiology, contamination control, aseptic processing, sterilization, laboratory design, and the validation and implementation of rapid microbiological methods (RMMs). He is currently the President of Microbiology Consultants, LLC (microbiologyconsultants.com) and owner of rapidmicromethods.com, a website dedicated to the advancement of rapid methods within healthcare‐related industries. For 30 years, he has held numerous R&D, manufacturing, quality, business development, and executive leadership roles at multinational firms such as Johnson & Johnson, Eli Lilly and Company, and Bausch & Lomb. In his current role, Michael Miller consults with multinational companies in providing technical, quality, regulatory, and training solutions in support of RMMs; sterile and non‐sterile pharmaceutical manufacturing; contamination control; isolator technology; environmental monitoring; sterilization; and antimicrobial effectiveness. Michael Miller has authored more than 100 technical publications and presentations and is the editor of PDA's Encyclopedia of Rapid Microbiological Methods. He currently serves on the editorial and scientific review boards for American Pharmaceutical Review, European Pharmaceutical Review, and the PDA Journal of Science and Technology. Michael Miller also was the chairperson during the revision of PDA Technical Report #33: Evaluation, Validation and Implementation of New Microbiological Testing Methods. He currently serves as an advisor to the USP Microbiology Expert Committee in the area of rapid sterility testing. Michael Miller holds a PhD in Microbiology and Biochemistry from Georgia State University (GSU), a BA in Anthropology, and Sociology from Hobart College.

Félix A. Montero Julian, PhD
Scientific Director of the Healthcare Business, bioMérieux
felix.monterojulian@biomerieux.com

Dr. Félix Montero is a Scientific Director of the Healthcare Business of bioMérieux. He has over 25 years of experience in industrial and clinical diagnostics and previously served as the Chemunex R&D Director in bioMérieux. Félix Montero graduated from the Autonomous Metropolitan University in Mexico as Industrial Biochemistry Engineer and obtained a PhD in Immunology from the Aix Marseille II University in France. He is a member of different scientific organizations (PDA, ISAC) and served as an expert in a panel for the Development of Compendial Rapid Sterility Tests for the USP. Félix Montero has been and continues to be extensively involved in the implementation and acceptance of rapid and alternative microbiological methods. He is a prominent speaker at congresses and conferences and a regular contributor to bioMérieux whitepapers.

Tim Sandle, PhD
Head of Microbiology, Bio Products Laboratory, Hertfordshire, United Kingdom
Tim.Sandle@bpl.co.uk

Dr. Tim Sandle is a pharmaceutical microbiologist, with experience in microbiological testing, research and development, risk assessment, and investigation. Tim Sandle is Head of Microbiology at Bio Products Laboratory, United Kingdom and a visiting tutor at University College London and the School of Pharmacy and Pharmaceutical Sciences, University of Manchester. In addition, he serves on several national and international committees, including the microbiology society Pharmig. Tim Sandle has written over 600 book chapters, peer‐reviewed papers, and technical articles, largely relating to microbiology and pharmaceutical sciences.

Robert Schwarz
University Lecturer, University of Applied Sciences, Wien, Austria
robert.schwarz@edu.fh‐campuswien.ac.at

Robert Schwarz worked after his education as a medical‐technical analyst and as a biomedical analyst at a medical laboratory in Vienna with his core responsibilities in clinical chemistry, hematology, and hemostaseology. From 2001 to 2005, he led the environmental monitoring team at Baxter Bioscience in Vienna with the core tasks microbiological and physical clean room monitoring and qualification. Meanwhile, he completed his studies at the University of Applied Sciences FH Campus Wien in parallel with his professional career and successfully graduated hereby with the double degree “Bioprocess Engineering” and “Biotechnological Quality Management.” From 2005 to 2018, he was a validation specialist and was besides equipment qualification responsible for sterilization, decontamination, and cleaning validation as well. Since 2010, he has also been working as a university lecturer at FH Campus Wien in the field of biotechnology with a focus on validation/qualification, aseptic process methods, and clean room technology. He is now starting his business as a freelancing consultant and trainer for pharmaceutical industry.

Alexandra Stärk
MS&T Technical Steward Sterility Assurance, Novartis Pharma Stein AG, Stein, Switzerland
alexandra.staerk@novartis.com

After studying Hygiene Technology at the Technical University of Albstadt‐Sigmaringen, Alexandra Stärk worked since 1995 at Novartis Pharma Stein AG in the microbiological QA/QC department, first as team leader and then 8 years as head of this department. Since 2016, she moved into a new role within Novartis Pharma Stein AG and is now responsible for a team of microbiological experts in the department of Manufacturing, Science & Technology which defined the microbiological control strategies for sterile, non‐sterile, and cell‐gene‐therapy production on a global and local level.

Pharmaceutical Microbiological Quality Assurance and Control

Practical Guide for Non‐Sterile Manufacturing

Editors

List of Contributors