The Certified Pharmaceutical GMP Professional Handbook

Description

The purpose of this handbook is to assist individuals for the Certified Pharmaceutical Good Manufacturing Practices Professional (CPGP) examination and provide a reference for the practitioner. The second edition reflects the Body of Knowledge which was updated in 2015. This edition has also incorporated additional information including updated references. The updates reflect the current trends and expectations of the evolving pharmaceutical industry driven by consumer expectations and regulatory oversight.
This handbook covers compliance with good manufacturing practices (GMPs), as regulated and guided by national and international agencies for the pharmaceutical industry. It covers finished human and veterinary drugs and biologics, and combination devices, as well as their component raw materials (including active pharmaceutical ingredients (APIs) and excipients), and packaging and labeling operations.

Sujets

• Techniques
• Automatisation et Contrôle
• Contrôle des processus
• Automatisation
• Automate
• ASQ
• Engineering
• Technology
• Sciences et techniques
• Quality Control

Informations

• Publié par: ASQ Quality Press
• Date de parution: 23 mai 2016
• Nombre de lectures: 0
• EAN13: 9781951058890
• Langue: English
• Poids de l'ouvrage: 5 Mo

Extrait

The Certified Pharmaceutical GMP Professional Handbook

Also available from ASQ Quality Press:

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Statistical Process Control for the FDARegulated Industry Manuel E. Peña-Rodríguez

The FDA and Worldwide Current Good Manufacturing Practices and Quality System Requirements Guidebook for Finished Pharmaceuticals José Rodríguez-Pérez

Quality Risk Management in the FDARegulated Industry José Rodríguez-Pérez

Mastering and Managing the FDA Maze, Second Edition: Medical Device Overview Gordon Harnack

How to Establish a Document Control System for Compliance with ISO 9001:2015, ISO 13485:2016, and FDA Requirements Stephanie L. Skipper

The FDA and Worldwide Quality System Requirements Guidebook for Medical Devices, Second Edition Amiram Daniel and Ed Kimmelman

Development of FDARegulated Medical Products, Second Edition Elaine Whitmore

Medical Device Design and Regulation Carl T. DeMarco

The Quality Toolbox, Second Edition Nancy R. Tague

Root Cause Analysis: Simplified Tools and Techniques, Second Edition Bjørn Andersen and Tom Fagerhaug

The Certified Manager of Quality/Organizational Excellence Handbook, Fourth Edition Russell T. Westcott, editor

The ASQ Auditing Handbook, Fourth Edition J.P. Russell, editor

To request a complimentary catalog of ASQ Quality Press publications, call 800-248-1946, or visit our website at http://www.asq.org/quality-press.

The Certified Pharmaceutical GMP Professional Handbook

Second Edition

Mark Allen Durivage, Editor

ASQ Quality Press Milwaukee, Wisconsin

American Society for Quality, Quality Press, Milwaukee 53203 © 2016 by ASQ All rights reserved. Published 2016 Printed in the United States of America 22 21 20 19 18 17 16 5 4 3 2 1

Library of Congress CataloginginPublication Data

Names: Durivage, Mark Allen, editor. Title: The certified pharmaceutical GMP professional handbook / Mark Allen  Durivage, editor. Description: Second edition. | Milwaukee, Wisconsin : ASQ Quality Press,  2016. | Includes bibliographical references and index. Identifiers: LCCN 2016011717 | ISBN 9780873899338 (hard cover : alk. paper) Subjects: LCSH: Pharmaceutical industry—Quality control. | Drug development.  | Drugs—Standards. Classification: LCC RM301.25 C456 2016 | DDC 615.1/9—dc23 LC record available at http://lccn.loc.gov/2016011717

ISBN: 978-0-87389-933-8

No part of this book may be reproduced in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher.

Publisher: Seiche Sanders Acquisitions Editor: Matt T. Meinholz Managing Editor: Paul Daniel O’Mara Production Administrator: Randall Benson

ASQ Mission: The American Society for Quality advances individual, organizational, and community excellence worldwide through learning, quality improvement, and knowledge exchange.

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To place orders or to request ASQ membership information, call 800-248-1946. Visit our website at http://www.asq.org/quality-press.

 Printed on acid-free paper

Table of Contents

List of Figures and Tables. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix Acronyms and Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxiii Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxxiii Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxxv

Part I Regulatory Agency Governance . . . . . . . . . . . . . . . . . . . . . . . Chapter 1 Global Regulatory Framework . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . United States Federal Statutes Relevant to Pharmaceuticals . . . . . . . . . . . . . . The Administrative Procedure Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . United States Federal Food, Drug, and Cosmetic Act . . . . . . . . . . . . . . . . United States Public Health Service Act . . . . . . . . . . . . . . . . . . . . . . . . . . . The Virus-Serum-Toxin Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . European Union’s Legal System Relevant to Pharmaceuticals . . . . . . . . . . . . . Japan’s Legal System Relevant to Pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . China’s Legal System Relevant to Pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . India’s Legal System Relevant to Pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . Chapter 2 Regulations and Guidances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) . . . . . . . . . . . . . . . . . . . . . . . . . . . . Health Canada . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . World Health Organization (WHO) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . International Conference on Harmonization . . . . . . . . . . . . . . . . . . . . . . . . . . . European Medicines Agency (EMA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The United States Food and Drug Administration . . . . . . . . . . . . . . . . . . . . . . Therapeutic Goods Administration (TGA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . United States Department of Agriculture (USDA) 9 CFR—Animals and Animal Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . USDA Veterinary Service Memorandum No. 800.65 . . . . . . . . . . . . . . . . . . . . . International Pharmaceutical Excipients Council . . . . . . . . . . . . . . . . . . . . . . . Japanese Ministry of Health, Labour, and Welfare (MHLW) . . . . . . . . . . . . . Chapter 3 Mutual Recognition Agreements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mutual Recognition Agreements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MRAs Established by the European Union and Partner Countries . . . . Key Elements of Mutual Recognition Agreements. . . . . . . . . . . . . . . . . . . Pharmaceutical Inspection Co-operation Scheme . . . . . . . . . . . . . . . . . . .

v

1 3 3 3 3 4 4 4 7 8 8 11

11 12 13 13 15 16 17

18 19 19 20 21 21 21 22 22

vi

Table of Contents

Chapter 4 Regulatory Inspections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Inspection Authority . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Types of Inspections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sharing of Inspection Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Inspections of Foreign Drug Manufacturers . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reviewing Documents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Validation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cultural Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Documentation of Violations of cGMPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . Inspection Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Inspection Process of a U.S. Firm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chapter 5 Enforcement Actions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Types of Enforcement Actions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Notice of Observations/Violations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . FDA Untitled Letters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Warning Letters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Product Seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Injunctions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Loss of Marketing License . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Loss of Establishment License . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Debarment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Voluntary Actions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chapter 6 Regulatory Agency Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Planned Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Evaluating Post-Marketing Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Technical Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analytical Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Equivalence Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Adverse Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reporting Strategy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Regulatory Reporting Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Planned Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Unplanned Events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chapter 7 Site Master File (SMF), Validation Master Plan (VMP), Drug Master File (DMF), and Site Reference File (SRF) . . . . . . . . . . . . . . . . . Site Master File . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Content of Site Master Files . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Validation Master Plan (VMP) and Master Validation Plan (MVP) . . . . . . . . . Drug Master File . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Types of Drug Master Files . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Changes to Drug Master Files . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preparing a Site Master File (SMF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Content of Site Master File . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Appendixes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

25 25 26 26 27 28 29 30 30 30 31

33 34 34 35 35 36 36 37 38 38 38

41 41 42 42 43 43 43 43 44 44 46

49 49 50 56 56 57 58 59 59 60

Table of Contents

Part II Quality Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 8 Quality Management System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Establishing a Quality Management System. . . . . . . . . . . . . . . . . . . . . . . . . . . . Quality Management System Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quality Management System Practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Audits, Reviews, and Assessments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ICH Q10:Pharmaceutical Quality System. . . . . . . . . . . . . . . . . . . . . . . . . . .. ICH Q10 Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Enablers: Knowledge Management and Quality Risk Management . . . Design and Content Considerations, Quality Manual . . . . . . . . . . . . . . . Management Responsibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Management Commitment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quality Policy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quality Planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Resource Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Internal Communication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Management Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Management of Outsourced Activities and Purchased Materials . . . . . Management of Change in Product Ownership . . . . . . . . . . . . . . . . . . . . Continual Improvement of Process Performance and Product Quality . . . . . Life Cycle Stage Goals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical Quality Management System Elements . . . . . . . . . . . . . Continual Improvement of the Pharmaceutical Quality System . . . . . . . . . . . Management Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Monitoring of Internal and External Factors . . . . . . . . . . . . . . . . . . . . . . . Outcomes of Management Review and Monitoring . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 9 Quality Unit (Site) Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Qualified Person . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Responsibilities of the Qualified Person . . . . . . . . . . . . . . . . . . . . . . . . . . . Specific Requirements for the Qualified Person . . . . . . . . . . . . . . . . . . . . . Certification of Batch Release. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Maintenance of a Quality Management System . . . . . . . . . . . . . . . . . . . . . . . . . The Qualified Person and the Product Quality Review . . . . . . . . . . . . . . The Qualified Person and Reference and Retention Samples. . . . . . . . . . External Qualified Persons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Delegation of Tasks/Absence of a Qualified Person . . . . . . . . . . . . . . . . . Organizational Duties to Be Established by the Company of the Qualified Person . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Annex 16 to the EU Guide to GMP Certification and Batch Release . . . . . . . . Principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Batch Testing and Release of Products Manufactured in the EC/EEA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

vii

61 63 63 64 66 66 67 67 68 69 69 70 70 70 71 71 71 71 72 72 72 73 77 77 77 77 78 79 79 80 81 82 82 82 83 83 83

83 84 84 84 85

86

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Batch Testing and Release of Products Imported from a Third Country . . . . General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Location of Sampling for Testing in EC/EEA . . . . . . . . . . . . . . . . . . . . . . . Batch Testing and Release of Products Imported from a Third Country with EC MRA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Routine Duties of a Qualified Person . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 10 Risk Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General Quality Risk Management Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risk Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risk Communication and Risk Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risk Management Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Integration into Industry and Regulatory Operations. . . . . . . . . . . . . . . . . . . . Methods and Tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Basic Risk Management Facilitation Methods. . . . . . . . . . . . . . . . . . . . . . . Failure Mode and Effects Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Failure Mode, Effects, and Criticality Analysis . . . . . . . . . . . . . . . . . . . . . Fault Tree Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hazard Analysis and Critical Control Points . . . . . . . . . . . . . . . . . . . . . . . Hazard Operability Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preliminary Hazard Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risk Ranking and Filtering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Supporting Quality and Statistical Tools . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 11 Training and Personnel Qualifications. . . . . . . . . . . . . . . . . . . . . . . Job-Specific Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Good Manufacturing Practices Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Training Effectiveness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Employee Qualifications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Documentation of Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Employee Proficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 12 Change Control and Management . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 13 Investigations and Corrective and Preventive Action (CAPA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CAPA Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General Considerations for CAPA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CFR 211.192 Production Record Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . FDA 21 CFR 820.100 Corrective and Preventive Action . . . . . . . . . . . . . . . FDA Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . FDA Guide to Inspections of Quality Systems . . . . . . . . . . . . . . . . . . . . . . Chapter 14 Audits and SelfInspections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Audit Types. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . First-Party Audits. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Audit Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Written Procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

88 88 88

89 89 91 91 92 92 93 93 93 94 94 94 95 95 97 98 98 99 99

103 103 103 104 105 105 105 107

109 111 113 113 113

114 114 117 117 117 118 119

Table of Contents

Audit Schedule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Qualified, Independent Auditors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analyze Audit Results to Assess Conformance to Requirements . . . . . . Documentation of Findings and Corrective Actions . . . . . . . . . . . . . . . . . Management Responsibility for Implementation of Corrective Actions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Verification of Corrective Actions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 15 Documents and Records Management . . . . . . . . . . . . . . . . . . . . . . . Documentation Hierarchy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Documents and Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Good Documentation Practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Master Documents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Executed Documents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GMP Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Training Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Facility Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Material Receipts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Batch Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Log Books . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Complaint Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Records Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Record Retention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Litigation Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 16 Product Quality Complaints and Adverse Event Reports. . . . . . . Importance of Post-Market Surveillance and Reporting . . . . . . . . . . . . . . . . . . Building an Effective Complaint Management System . . . . . . . . . . . . . . . . . . . Adverse Event Reporting—FAERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Differences between Complaints and Adverse Events . . . . . . . . . . . . . . . . . . . Keys to Compliance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 17 Product Trend Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Regulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Annual Product Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General Requirements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Data Elements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Product Quality Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General Requirements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Data Elements Mandated by EU Regulations . . . . . . . . . . . . . . . . . . . . . . . Additional Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 18 Supplier and Contractor Quality Management . . . . . . . . . . . . . . . . Requirements for Materials and Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . On-Site Audit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quality System Survey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Change Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Trending . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Supplier Certification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Supply Chain Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ix

119 120 120 121

122 122 125 125 127 127 127 127 128 128 129 129 130 130 131 131 131 131 133 133 134 135 135 135

137 137 138 138 138 139 139 140 140

141 142 145 145 146 146 147 147