RISK MANAGEMENT APPLICATIONS IN PHARMACEUTICAL AND BIOPHARMACEUTICAL MANUFACTURING

Transcription

1 RISK MANAGEMENT APPLICATIONS IN PHARMACEUTICAL AND BIOPHARMACEUTICAL MANUFACTURING

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3 RISK MANAGEMENT APPLICATIONS IN PHARMACEUTICAL AND BIOPHARMACEUTICAL MANUFACTURING Edited by A. HAMID MOLLAH MIKE LONG HAROLD S. BASEMAN A JOHN WILEY & SONS, INC., PUBLICATION

4 Copyright 2013 by John Wiley & Sons, Inc. All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) , fax (978) , or on the web at Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) , fax (201) , or online at Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) , outside the United States at (317) or fax (317) Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at Library of Congress Cataloging-in-Publication Data is available. Printed in the United States of America ISBN:

5 CONTENTS Preface Contributors About the Authors vii xi xiii 1 Background and Introduction 1 Harold S. Baseman and A. Hamid Mollah 2 Risk Management Tools 17 Mark Walker and Thomas Busmann 3 Risk Management: Regulatory Expectation, Risk Perception, and Organizational Integration 49 Mike Long 4 Statistical Topics and Analysis in Risk Assessment 75 Mike Long 5 Quality by Design 89 Bruce S. Davis 6 Process Development and Clinical Product Manufacturing 101 Karen S. Ginsbury v

6 vi CONTENTS 7 Points to Consider for Commissioning and Qualification of Manufacturing Facilities and Equipment 129 Harold S. Baseman and Michael Bogan 8 Process Lifecycle Validation 179 A. Hamid Mollah and Scott Bozzone 9 Aseptic Processing: One 227 James P. Agalloco and James E. Akers 10 Aseptic Processing: Two 243 Edward C. Tidswell 11 Pharmaceutical Product Manufacturing 275 Marlene Raschiatore 12 Biopharmaceutical Manufacturing 325 Ruhi Ahmed and Thomas Genova 13 Risk-Based Change Control 367 William Harclerode, Bob Moser, Jorge A. Ferreira, and Christophe Noualhac Index 387

7 PREFACE With the introduction of FDA s 21st century GMP and ICH initiatives (such as Q8 Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System), drug manufacturing entered a new era of risk management. Although regulatory agencies are encouraging the use of risk management in pharmaceutical and biopharmaceutical product manufacturing, regulatory guidance and comprehensive literature on how to use and implement risk management is limited and in need of further development. This book will fill this large void and assist both industry as well as agency to implement a compliant and effective risk management approach. The book has been prepared to provide the readers with some points to consider for managing risks to product quality incurred during the manufacture of biopharmaceutical and pharmaceutical products, including Industry trend towards to use of QRM for manufacturing control Regulatory expectations Use of limited resources and cost control Maintaining and assuring product quality Process and quality improvement Over the years, the authors and editors of this book have presented to and met with numerous people at many companies, plants, and organizations in the pharmaceutical industry, asking about and providing instruction in quality risk management. While audiences have generally become more aware of the topic, including the expectation and perhaps even the benefit of its use, it has not been clear whether the aspects of its implementation have been fully appreciated and vii

8 viii PREFACE taken advantage of. We saw many instances where resources and time were spent to complete hundreds of risk assessments, but never utilized into manufacturing operations. Identification of risk without action has minimal benefit and can be viewed as shifting a company from ignorance to avoidance. This has led the editors of this book to believe that there was a strong need for further explanation and education on approaches for the practical implementation of quality risk management for pharmaceutical and biopharmaceutical processes. Over the past half-decade or more, companies and individuals have explored, developed, implemented, benefited, and refined methods for risk management, assessment, review, and decision making that utilize approaches, models, systems, techniques, schemes and plans some more effective, some less. This book creates this link by exploring risk management of manufacturing processes through a collection of chapters written by some of the leading experts in pharmaceutical and biopharmaceutical product manufacturing. The editors chose topics that represented the most significant challenges in the industry at the time of writing. The ultimate goal of the risk management process is to bring focus and effort to the issues in an organization that imparts the highest risk to product quality and/or patient safety. The degree of formality and rigor applied should be commensurate with the complexity and/or criticality of the element or issue. There are many tools that can be applied, which are new to many in the industry. For risk assessors, there can be confusion with the level and detail of an assessment as well as the potential subjectivity, which can permeate an assessment. These issues are compounded with the uncertainty of the regulatory framework and application of risk. Hence, it is quite important to use proven and compliant risk management approaches to assure acceptable results. This book was written by authors who have used risk management to improve processes, investigate failures, design operations, validate processes, and increase overall quality and productivity of their respective operations. This book is not a collection of history or fundamentals, nor is it a book of theoretical desired states. Although the book does explore and present some background and introduction, it is primarily focused on the practical presentation of points to consider and methods to help the reader make better decisions based on risk and to help manage that risk. This book is written by people who lived through the introduction of this topic to our industry and participated in its implementation. Our authors want to communicate best practices to help the reader better implement and benefit from its use without experiencing the unnecessary burden and redundancies that often accompany activities in this industry. This book provides examples of risk management in areas from the process development to sterile fill operations. Risk management should be a method for making our jobs more doable, adding to our understanding of processes, and helping us make better decisions. It should not be just a checklist item, another corporate directive, of little value. To the contrary, the objective of this book is to help the reader understand, appreciate, use, and benefit from risk management. We hope you will find it useful and enjoyable.

9 PREFACE ix We express our gratitude to all the authors for contributing to this book. Thanks to Anurag Rathore for his encouragement and persuasion to complete this book. We also thank Lynn Torbeck at Torbeck and Association, Kevin O Donnel at the IMB (Irish Medicines Board), Emma Ramnarine and David Reifsnyder at Genentech, Penny Butterell and Simon Smith at Pfizer, and Brian Turley and Walter Henkels at Valsource for providing feedback. Thank you, The Editors

10 CONTRIBUTORS James P. Agalloco, Agalloco & Associates, Belle Mead, NJ Ruhi Ahmed, Regulatory Affairs, Ultragenyx, Novato, CA James E. Akers, Akers Kennedy & Associates, Kansas City, MO Harold S. Baseman, ValSource LLC, Jupiter, FL Michael Bogan, Integrated Commissioning & Qualification, LLC, Hope Valley, RI Scott Bozzone, Pfizer Inc., Peapack, NJ Thomas Busmann, Focus Compliance & Validation Services, Knoxville, TN Bruce S. Davis, Bruce Davis (Global Consulting), Haslemere, Surrey, UK Jorge A. Ferreira, Jacobs Engineering Group, Conshohocken, PA Thomas Genova, Johnson & Johnson, Raritan, NJ Karen S. Ginsbury, PCI Pharmaceutical Consulting Israel, Petach Tikvah, Israel A. Hamid Mollah, Quality Engineering and Validation, XOMA Corporation, Berkeley, CA William Harclerode, Forest Labs, Harborside Financial Center, Jersey City, NJ Mike Long, ConcordiaValSource, Wayland, MA Bob Moser, Jacobs Engineering, Conshohocken, PA xi

11 xii CONTRIBUTORS Christophe Noualhac, Product Development, Halo Pharmaceutical, Whippany, NJ Marlene Raschiatore, Johnson & Johnson, Glen Mills, PA Edward C. Tidswell, Baxter Healthcare Corp, Sterility Assurance Department, Round Lake, IL Mark Walker, Focus Compliance & Validation Services, Knoxville, TN

12 ABOUT THE AUTHORS James Agalloco, President, Agalloco & Associates, is a pharmaceutical manufacturing expert with more than 40 years of experience. He worked in organic synthesis, pharmaceutical formulation, pharmaceutical production, project/process engineering, and validation during his career at Merck, Pfizer, and Bristol-Myers Squibb. Since the formation of A&A in 1991, Jim has assisted more than 100 firms with validation, sterilization, aseptic processing, and compliance. He has edited/coedited four texts, authored/coauthored more than 40 chapters, published more than 100 papers, and lectured extensively on numerous subjects. He is a past president of the Parenteral Drug Association (PDA), a current member of USP s Microbiology Expert Committee, the Editorial Advisory Board for Pharmaceutical Technology and Pharmaceutical Manufacturing. Ruhi Ahmed is currently the Senior Director in the Regulatory Affairs department at Ultragenyx Pharmaceutical, Inc. She has previously worked in the Regulatory Affairs at Watson Pharmaceuticals and BioMarin Pharmaceutical Inc. Dr. Ahmed graduated in 2003 from the University of Southern California (USC) with a PhD in Molecular Pharmacology and Toxicology. She also has an MS degree in Regulatory Science from the USC and an MA degree in Biochemistry from the University of Texas at Austin. Dr. Ahmed has earned her RAC certification for both the European Union and the United States. As a member of PDA s Task Force on Quality Risk Management, Dr. Ahmed has participated in coauthoring PDA Technical Report #44 on Quality Risk Management for Aseptic Processes. She is currently leading a PDA Task Force on assessing general applications of Quality Risk Management for Biopharmaceutical APIs. James E. Akers, PhD, is the President of Akers Kennedy & Associates, Inc., located in Kansas City, Missouri. Dr. Akers has over 25 years experience in the xiii

13 xiv ABOUT THE AUTHORS pharmaceutical industry and has worked at various director-level positions within the industry and for the past decade as a consultant. Dr. Akers areas of expertise include aseptic processing, contamination control, sterilization, biological products, and advanced aseptic technologies. Dr. Akers served as President of the PDA from 1991 to 1993 and as a member of the PDA Board of Directors from 1986 to Currently, he is the Chairman of the USP Committee of Experts Microbiology and has served on a number of PDA Task Forces. Hal Baseman has over 30 years of experience in pharmaceutical operations, validation, and regulatory compliance. Hal has held positions in executive management and technical operations at several manufacturing and consulting firms. He is a long-time member and a frequent presenter for PDA and ISPE (International Society for Pharmaceutical Engineering). Hal has held positions as a member of the PDA Board of Directors, the Cochair of the PDA Science Advisory Board, the Coleader of the PDA Validation Interest Group, the Cochair of the PDA Aseptic Process Simulation Task Force, and the Cochair of the PDA Quality Risk Management Task Force. Hal Baseman holds an MBA from the LaSalle University and a BS degree from the Ursinus College. Michael Bogan is the President of Integrated Commissioning & Qualification Consultants Corp. During his 20-year career in the life sciences industry, Michael also held various leadership roles in project management, process development, and manufacturing. Michael has also held a position with Amgen as the Senior Manager of Validation, who is responsible for validation activities at various plants. He has presented on the subject of commissioning and qualification strategies to industry trade associations, including the ISPE. He holds his degree from the Franklin Pierce College, with additional study in Biology at the Northeastern University. Scott Bozzone is the Senior Manager in the Quality Systems and Technical Services, Validation for Pfizer, Inc. based in Peapack, New Jersey. He has been at Pfizer for 26 years and prior to that worked several years at Revlon Health Care Group (Armour/USV). In his current position, he is responsible for validation site support and leads Pfizer s global Validation Community of Practice. He also serves on Pfizer s Quality Risk Management training team. He has a doctoral degree in Industrial Pharmacy from the St. John s University in New York. Thomas Busmann is a Vice President of Focus Compliance & Validation Services. He is a registered professional chemical engineer with over 30 years of experience serving numerous clients in the pharmaceutical, biopharma, medical device, and chemical industries to assist them in achieving regulatory compliance with their processes and projects. Areas of expertise include risk management,

14 ABOUT THE AUTHORS xv verification of process control systems, computer system validation, process validation, utility equipment validation, training, and hazard and safety analysis. Bruce Davis runs his own Consultancy in Quality by Design (QbD) and engineering. He carries out in-house and external training in this area and also helps run a UK university QbD course. He is a professional engineer with a wide international knowledge of the pharmaceutical industry, having previously worked at AstraZeneca, where his responsibilities included managing international engineering, facilitating QbD, and leading a global change process for enhanced qualification. He is a past chair of the ISPE Board of Directors and, for them, leads a crosscompany case study for practical implementation of QbD. He is the Secretary to ASTM E55.03 on General Pharmaceutical Standards. Jorge A. Ferreira is the Technology Manager with Jacobs Engineering Group. Before this, he held project management, engineering, and operations positions with Bristol-Myers Squibb. Mr. Ferreira has been involved in the pharmaceutical industry for more than 25 years with expertise in engineering design, construction, and plant operations, including supervision and management responsibilities for aseptic manufacturing operations. His background includes clean utilities, formulation, component preparation, sterilization and depyrogenation, aseptic filling, lyophilization, inspection, packaging, and warehousing logistics. He holds a BS in Mechanical Engineering from the New Jersey Institute of Technology, New Jersey. Thomas Genova, PhD, is a Johnson & Johnson Quality Fellow supporting the development of combination products and risk management activities. He began his career qualifying ethylene oxide and gamma irradiation processes. His career evolved to include steam and dry heat processes, filtration operations, and aseptic filling processes. At the Temple University, he taught graduate classes in Sterilization Processes and High Purity Water Systems. He was a member of the PhARMA Water Quality Committee, the Technical Advisory Group of ISO/TC 209 Cleanrooms and Associated Environments, and the PDA Risk Management Task Force. Tom is an ASQ Certified Quality Engineer (CQE) and a Six Sigma Master Black Belt. He holds a PhD in Immunotoxicology from the Rutgers University. Karen S. Ginsbury, BPharm, MSc, MRPS, is a London-trained pharmacist who has worked for the past 25 years in the field of pharmaceutical quality assurance and compliance. Karen also has a Master of Science degree in Microbiology from the Birkbeck College, University of London. Currently, Ms. Ginsbury is the President and the CEO of PCI Pharmaceutical Consulting Israel Ltd., a consultancy company working with multinational as well as small start-up companies, and has acquired considerable expertise in the field of Investigational Products. Also, she is currently chairing the PDA s Task Force in preparing a Technical Report

15 xvi ABOUT THE AUTHORS on GMP Points to Consider for Investigational Products, and she has particular knowledge in the application of risk management to the field of product and process development throughout the product lifecycle. William Harclerode has been with Forest Labs since 2006 in the Corporate Quality Risk Management Department. He is currently responsible for providing leadership and support for implementation of quality risk management activities across the product supply chain. Before that, he worked as Validation Manager and Production Manager at Abbott Labs and Knoll Pharmaceutical Company. He holds an MBA from the Fairleigh Dickinson University, a BS in Chemical Engineering from the Drexel University, and a BS in Biology from the St. Lawrence University. Dr. Mike Long has two decades of experience leading product, process development and validation efforts on a wide range of pharmaceutical, medical device, and combination products. He is a frequent speaker/writer on topics such as Risk Management, Quality Systems, QbD, Process Validation, and Process Robustness. He is an active member on industry committees including the PDA s Science Advisory Board. Mike has instructed graduate courses in Data Analysis and in Risk Management and Quality Systems. Mike is a Master Black Belt with a BS from the Worcester Polytechnic Institute, an MS from the Tufts University, and a doctorate from the Northeastern University. A. Hamid Mollah is currently the head of Quality Engineering and Validation at XOMA. He held positions at Genentech Inc. and Baxter BioScience and has 14 years of pharmaceutical and biopharmaceutical industry experience in the areas of process development, manufacturing, validation, and regulatory affairs. Before joining the pharmaceutical industry, he worked on fermentation process development, design, scale-up, optimization, and project management for 7 years. He received his PhD in Biochemical Engineering from the Imperial College of Science, Technology, and Medicine in London, England. Hamid has given talks at various conferences (PDA, IBC, IQPC) and is published in a number of peerreviewed journals, including articles on risk assessment and risk-based validation. He is an RAPS-certified regulatory affair professional (RAC) and ASQ CQE. Bob Moser has been working at Jacobs Engineering for the past 11 years, most recently, as a Senior Engineer and Supervisor. Mr. Moser is a chemical engineer with 25 years experience in quality, environmental, safety, and risk management within the chemical, pharmaceutical, and general manufacturing industries. He has broad domestic and international (Europe and Asia) experience. His background includes leadership of FMEA (Failure Modes and Effects Analysis) processes for both quality and reliability. He holds a BS in Chemical Engineering from the Pennsylvania State University. His designations include

16 ABOUT THE AUTHORS xvii Professional Engineer (PE), Certified Safety Professional (CSP), and Associate Risk Manager (ARM). Christophe Noualhac is currently the Project Manager at Halo Pharmaceutical. He is responsible for directing and coordinating activities associated with pharmaceutical development projects. Before joining Halo Pharmaceutical in 2009, he worked as Validation Manager at PAR Pharmaceuticals and Technical Support at Abbott Laboratories. He holds a Master Degree in Pharmaceutical Chemistry from the University of Toulouse (France) and a Master Degree in Applied Physics and Chemistry from the University of Montpellier (France). Marlene Raschiatore is the Director of Global Regulatory Compliance for Johnson and Johnson, Consumer Sector. During her career, she has held quality, compliance, and regulatory affairs positions with pharmaceutical product manufacturing companies, including Elkins-Sinn Inc. and Wyeth Pharmaceutical. She was an author and contributor on the PDA s Technical Report No. 44, Risk Management for Aseptic Processing. Ms. Raschiatore holds a Juris Doctor from the Beasley School of Law and a Bachelor of Science in Medical Technology from the Temple University in Philadelphia, Pennsylvania. Edward C. Tidswell, BSc, PhD, is the Senior Director of Sterility Assurance for Baxter Healthcare located north of Chicago, Illinois. His organization provides support for more than 40 facilities globally, encompassing the entire breadth of microbiological control, sterilization, and sterility assurance across a diversified healthcare company. Dr. Tidswell is a leading authority on risk, aseptic, and sterile manufacture. In 2004, he received the Parenteral Society s George Sykes Memorial Award for his contribution to pharmaceutical risk assessment. In June 2010, Dr. Tidswell joined the USP expert committee on Microbiology & Sterility Assurance. Mark Walker is a Vice President of Focus Compliance & Validation Services (Focus CVS) located in Knoxville, Tennessee. Focus CVS is dedicated to providing regulatory compliance, risk assessment, validation, training, and process engineering services to pharmaceutical, biotechnology, and medical device industries. Mr. Walker has more than 25 years experience in providing consulting, project management, and business development services. His expertise includes risk assessment, regulatory compliance, computer systems validation, GMP and validation training, process validation, document management, local area network system design, database system design and implementation, and business development services to the pharmaceutical, medical device, and biotech industries. Mr. Walker currently serves on the Association for the Advancement of Medical Instrumentation s (AAMI) medical device software work group.