SHAYNE COX GAD, PhD, DABT, ATS, is the Principal of Gad Consulting Services. Dr. Gad has more than thirty years of experience as a toxicologist, statistical consultant, manager, and general consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He is the author of twenty-nine books and numerous papers, presentations, and other publications.

This book is a valuable reference … .The book contains everything you need to ensure full compliance and superior quality control. (Pharmaceutical Technology Magazine, July 2, 2008)

• PREFACE xiiiSECTION 1 GOOD MANUFACTURING PRACTICES (GMP) AND OTHER FDA GUIDELINES 11.1 Good Manufacturing Practices (GMPs) and Related FDA Guidelines 3James R. Harris1.2 Enforcement of Current Good Manufacturing Practices 45Kenneth J. Nolan1.3 Scale-Up and Postapproval Changes (SUPAC) Regulations 67Puneet Sharma, Srinivas Ganta, and Sanjay Garg1.4 GMP-Compliant Propagation of Human Multipotent Mesenchymal Stromal Cells 97Eva Rohde, Katharina Schallmoser, Christina Bartmann, Andreas Reinisch, and Dirk StrunkSECTION 2 INTERNATIONAL REGULATIONS OF GOOD MANUFACTURING PRACTICES 1172.1 National GMP Regulations and Codes and International GMP Guides and Guildelines: Correspondences and Differences 119Marko Närhi and Katrina NordströmSECTION 3 QUALITY 1633.1 Analytical and Computational Methods and Examples for Designing and Controlling Total Quality Management Pharmaceutical Manufacturing Systems 165Paul G. Ranky, Gregory N. Ranky, Richard G. Ranky, and Ashley John3.2 Role of Quality Systems and Audits in Phatmaceutical Manufacturing Environment 201Evan B. Siegel and James M. Barquest3.3 Creating and Managing a Quality Management System 239Edward R. Arling, Michelle E. Dowling, and Paul A. Frankel3.4 Quality Process Improvement 287Jyh-hone WangSECTION 4 PROCESS ANALYTICAL TECHNOLOGY (PAT) 3114.1 Case for Process Analytical Technology: Regulatory and Industrial Perspectives 313Robert P. Cogdill4.2 Process Analytical Technology 353Michel Ulmschneider and Yves Roggo4.3 Chemical Imaging and Chemometrics: Useful Tools for Process Analytical Technology 411Yves Roggo and Michel UlmschneiderSECTION 5 PERSONNEL 4335.1 Personnel Training in Pharmaceutical Manufacturing 435David A. Gallup, Katherine V. Domenick, and Marge GillisSECTION 6 CONTAMINATION AND CONTAMINATION CONTROL 4556.1 Origin of Contamination 457Denise Bohrer6.2 Quantitation of Markers for Gram-Negative and Gram-Positive Endotoxins in Work Environment and as Contaminants in Pharmaceutical Products Using Gas Chromatography–Tandem Mass Spectrometry 533Alvin Fox6.3 Microbiology of Nonsterile Pharmaceutical Manufacturing 543Ranga VelagaletiSECTION 7 DRUG STABILITY 5577.1 Stability and Shelf Life of Pharmaceutical Products 559Ranga Velagaleti7.2 Drug Stability 583Nazario D. Ramirez-Beltran, Harry Rodriguez, and L. Antonio Estévez7.3 Effect of Packaging on Stability of Drugs and Drug Products 641Emmanuel O. Akala7.4 Pharmaceutical Product Stability 687Andrew A. Webster7.5 Alternative Accelerated Methods for Studying Drug Stability: Variable-Parameter Kinetics 701Giuseppe AlibrandiSECTION 8 VALIDATION 7258.1 Analytical Method Validation: Principles and Practices 727Chung Chow Chan8.2 Analytical Method Validation and Quality Assurance 743Isabel Taverniers, Erik Van Bockstaele, and Marc De Loose8.3 Validation of Laboratory Instruments 791Herman Lam8.4 Pharmaceutical Manufacturing Validation Principles 811E. B. Souto T. Vasconcelos D. C. Ferreira, and B. SarmentoINDEX 839

SHAYNE COX GAD, PhD, DABT, ATS, is the Principal of Gad Consulting Services. Dr. Gad has more than thirty years of experience as a toxicologist, statistical consultant, manager, and general consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He is the author of twenty-nine books and numerous papers, presentations, and other publications.

This book is a valuable reference … .The book contains everything you need to ensure full compliance and superior quality control. (Pharmaceutical Technology Magazine, July 2, 2008)

• PREFACE xiiiSECTION 1 GOOD MANUFACTURING PRACTICES (GMP) AND OTHER FDA GUIDELINES 11.1 Good Manufacturing Practices (GMPs) and Related FDA Guidelines 3James R. Harris1.2 Enforcement of Current Good Manufacturing Practices 45Kenneth J. Nolan1.3 Scale-Up and Postapproval Changes (SUPAC) Regulations 67Puneet Sharma, Srinivas Ganta, and Sanjay Garg1.4 GMP-Compliant Propagation of Human Multipotent Mesenchymal Stromal Cells 97Eva Rohde, Katharina Schallmoser, Christina Bartmann, Andreas Reinisch, and Dirk StrunkSECTION 2 INTERNATIONAL REGULATIONS OF GOOD MANUFACTURING PRACTICES 1172.1 National GMP Regulations and Codes and International GMP Guides and Guildelines: Correspondences and Differences 119Marko Närhi and Katrina NordströmSECTION 3 QUALITY 1633.1 Analytical and Computational Methods and Examples for Designing and Controlling Total Quality Management Pharmaceutical Manufacturing Systems 165Paul G. Ranky, Gregory N. Ranky, Richard G. Ranky, and Ashley John3.2 Role of Quality Systems and Audits in Phatmaceutical Manufacturing Environment 201Evan B. Siegel and James M. Barquest3.3 Creating and Managing a Quality Management System 239Edward R. Arling, Michelle E. Dowling, and Paul A. Frankel3.4 Quality Process Improvement 287Jyh-hone WangSECTION 4 PROCESS ANALYTICAL TECHNOLOGY (PAT) 3114.1 Case for Process Analytical Technology: Regulatory and Industrial Perspectives 313Robert P. Cogdill4.2 Process Analytical Technology 353Michel Ulmschneider and Yves Roggo4.3 Chemical Imaging and Chemometrics: Useful Tools for Process Analytical Technology 411Yves Roggo and Michel UlmschneiderSECTION 5 PERSONNEL 4335.1 Personnel Training in Pharmaceutical Manufacturing 435David A. Gallup, Katherine V. Domenick, and Marge GillisSECTION 6 CONTAMINATION AND CONTAMINATION CONTROL 4556.1 Origin of Contamination 457Denise Bohrer6.2 Quantitation of Markers for Gram-Negative and Gram-Positive Endotoxins in Work Environment and as Contaminants in Pharmaceutical Products Using Gas Chromatography–Tandem Mass Spectrometry 533Alvin Fox6.3 Microbiology of Nonsterile Pharmaceutical Manufacturing 543Ranga VelagaletiSECTION 7 DRUG STABILITY 5577.1 Stability and Shelf Life of Pharmaceutical Products 559Ranga Velagaleti7.2 Drug Stability 583Nazario D. Ramirez-Beltran, Harry Rodriguez, and L. Antonio Estévez7.3 Effect of Packaging on Stability of Drugs and Drug Products 641Emmanuel O. Akala7.4 Pharmaceutical Product Stability 687Andrew A. Webster7.5 Alternative Accelerated Methods for Studying Drug Stability: Variable-Parameter Kinetics 701Giuseppe AlibrandiSECTION 8 VALIDATION 7258.1 Analytical Method Validation: Principles and Practices 727Chung Chow Chan8.2 Analytical Method Validation and Quality Assurance 743Isabel Taverniers, Erik Van Bockstaele, and Marc De Loose8.3 Validation of Laboratory Instruments 791Herman Lam8.4 Pharmaceutical Manufacturing Validation Principles 811E. B. Souto T. Vasconcelos D. C. Ferreira, and B. SarmentoINDEX 839

SHAYNE COX GAD, PhD, DABT, ATS, is the Principal of Gad Consulting Services. Dr. Gad has more than thirty years of experience as a toxicologist, statistical consultant, manager, and general consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He is the author of twenty-nine books and numerous papers, presentations, and other publications.

This book is a valuable reference … .The book contains everything you need to ensure full compliance and superior quality control. (Pharmaceutical Technology Magazine, July 2, 2008)

• PREFACE xiiiSECTION 1 GOOD MANUFACTURING PRACTICES (GMP) AND OTHER FDA GUIDELINES 11.1 Good Manufacturing Practices (GMPs) and Related FDA Guidelines 3James R. Harris1.2 Enforcement of Current Good Manufacturing Practices 45Kenneth J. Nolan1.3 Scale-Up and Postapproval Changes (SUPAC) Regulations 67Puneet Sharma, Srinivas Ganta, and Sanjay Garg1.4 GMP-Compliant Propagation of Human Multipotent Mesenchymal Stromal Cells 97Eva Rohde, Katharina Schallmoser, Christina Bartmann, Andreas Reinisch, and Dirk StrunkSECTION 2 INTERNATIONAL REGULATIONS OF GOOD MANUFACTURING PRACTICES 1172.1 National GMP Regulations and Codes and International GMP Guides and Guildelines: Correspondences and Differences 119Marko Närhi and Katrina NordströmSECTION 3 QUALITY 1633.1 Analytical and Computational Methods and Examples for Designing and Controlling Total Quality Management Pharmaceutical Manufacturing Systems 165Paul G. Ranky, Gregory N. Ranky, Richard G. Ranky, and Ashley John3.2 Role of Quality Systems and Audits in Phatmaceutical Manufacturing Environment 201Evan B. Siegel and James M. Barquest3.3 Creating and Managing a Quality Management System 239Edward R. Arling, Michelle E. Dowling, and Paul A. Frankel3.4 Quality Process Improvement 287Jyh-hone WangSECTION 4 PROCESS ANALYTICAL TECHNOLOGY (PAT) 3114.1 Case for Process Analytical Technology: Regulatory and Industrial Perspectives 313Robert P. Cogdill4.2 Process Analytical Technology 353Michel Ulmschneider and Yves Roggo4.3 Chemical Imaging and Chemometrics: Useful Tools for Process Analytical Technology 411Yves Roggo and Michel UlmschneiderSECTION 5 PERSONNEL 4335.1 Personnel Training in Pharmaceutical Manufacturing 435David A. Gallup, Katherine V. Domenick, and Marge GillisSECTION 6 CONTAMINATION AND CONTAMINATION CONTROL 4556.1 Origin of Contamination 457Denise Bohrer6.2 Quantitation of Markers for Gram-Negative and Gram-Positive Endotoxins in Work Environment and as Contaminants in Pharmaceutical Products Using Gas Chromatography–Tandem Mass Spectrometry 533Alvin Fox6.3 Microbiology of Nonsterile Pharmaceutical Manufacturing 543Ranga VelagaletiSECTION 7 DRUG STABILITY 5577.1 Stability and Shelf Life of Pharmaceutical Products 559Ranga Velagaleti7.2 Drug Stability 583Nazario D. Ramirez-Beltran, Harry Rodriguez, and L. Antonio Estévez7.3 Effect of Packaging on Stability of Drugs and Drug Products 641Emmanuel O. Akala7.4 Pharmaceutical Product Stability 687Andrew A. Webster7.5 Alternative Accelerated Methods for Studying Drug Stability: Variable-Parameter Kinetics 701Giuseppe AlibrandiSECTION 8 VALIDATION 7258.1 Analytical Method Validation: Principles and Practices 727Chung Chow Chan8.2 Analytical Method Validation and Quality Assurance 743Isabel Taverniers, Erik Van Bockstaele, and Marc De Loose8.3 Validation of Laboratory Instruments 791Herman Lam8.4 Pharmaceutical Manufacturing Validation Principles 811E. B. Souto T. Vasconcelos D. C. Ferreira, and B. SarmentoINDEX 839