PHARMACEUTICAL MANUFACTURING HANDBOOK

1 PHARMACEUTICAL MANUFACTURING HANDBOOKR egulations and QualitySHAYNE COX GAD, , Consulting ServicesCary, North CarolinaA JOHN WILEY & SONS, INC., PUBLICATIONPHARMACEUTICAL MANUFACTURING HANDBOOKR egulations and QualityPHARMACEUTICAL MANUFACTURING HANDBOOKR egulations and QualitySHAYNE COX GAD, , Consulting ServicesCary, North CarolinaA JOHN WILEY & SONS, INC., PUBLICATIONC opyright 2008 by John Wiley & Sons, Inc. All rights reservedPublished by John Wiley & Sons, Inc., Hoboken, New JerseyPublished simultaneously in CanadaNo 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.

2 , 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, 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) 748-6011, fax (201) 748-6008, or online at 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 contents of this book and specifi cally disclaim any implied warranties of merchantability or fi tness 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.

3 You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profi t or any other commercial damages, including but not limited to special, incidental, consequential, or other general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 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 of Congress Cataloging-in-Publication Data is : 978-0-470-25959-7 Printed in the United States of America10 9 8 7 6 5 4 3 2 1 CONTRIBUTORS vEmmanuel O.

4 Akala, Department of PHARMACEUTICAL Sciences, School of Pharmacy, Howard University, Washington, DC, Effect of Packaging on Stability of Drugs and Drug ProductsGiuseppe Alibrandi, Universit di Messina, Messina, Italy, Alternative Accelerated Methods for Studying Drug Stability: Variable - Parameter KineticsEdward R. Arling, Amgen, Inc., Thousand Oaks, California, Creating and Managing a quality Management SystemChristina Bartmann, Medical University of Graz, Graz, Austria, GMP - Compliant Propagation of Human Multipotent Mesenchymal Stromal CellsJames M. Barquest, Ground Zero Pharmaceuticals, Inc., Irvine, California, Role of quality Systems and Audits in PHARMACEUTICAL MANUFACTURING EnvironmentDenise Bohrer, Chemistry Department, Universidade Federal de Santa Maria, Santa Maria, Brazil, Origin of ContaminationChung Chow Chan, Azopharma Contract PHARMACEUTICAL Services, Miramar, Florida, Analytical Method Validation: Principles and PracticesRobert P.

5 Cogdill, Duquense University Center for PHARMACEUTICAL Technology, Pittsburgh, Pennsylvania, Case for Process Analytical Technology: Regulatory and Industrial PerspectivesMarc De Loose, Institute for Agricultural and Fisheries Research (ILVO), Scientifi c Institute for the Flemish Community, Merelbeke, Belgium, Analytical Method Validation and quality AssuranceKatherine V. Domenick, Training and Communications Group, Inc., Berwyn, Pennsylvania, Personnel Training in PHARMACEUTICAL ManufacturingviCONTRIBUTORSM ichelle E. Dowling, Amgen, Inc., Thousand Oaks, California, Creating and Man-aging a quality Management SystemL. Antonio Est vez, University of Puerto Rico, Mayag ez, Puerto Rico, Ferreira, Faculty of Pharmacy, University of Porto, Porto, Portugal, Pharma-ceutical MANUFACTURING Validation PrinciplesAlvin Fox, University of South Carolina, Columbia, South Carolina, Quantita-tion of Markers for Gram - Negative and Gram - Positive Endotoxins in Work Environment and as Contaminants in PHARMACEUTICAL Products Using Gas Chromatography Tandem Mass SpectrometryPaul A.

6 Frankel, Amgen, Inc., Thousand Oaks, California, Creating and Managing a quality Management SystemDavid A. Gallup, Training and Communications Group, Inc., Berwyn, Pennsylvania, Personnel Training in PHARMACEUTICAL ManufacturingSrinivas Ganta, University of Auckland, Auckland, New Zealand, Scale - Up and Postapproval Changes (SUPAC) RegulationsSanjay Garg, University of Auckland, Auckland, New Zealand, Scale - Up and Post-approval Changes (SUPAC) RegulationsMarge Gillis, Training and Communications Group, Inc., Berwyn, Pennsylvania, Personnel Training in PHARMACEUTICAL ManufacturingJames R. Harris, James Harris Associates, Inc., Durham, North Carolina, GoodManufacturing Practices (GMP) and Related FDA GuidelinesAshley John, New Jersey Institute of Technology, Newark, New Jersey, Analyticaland Computational Methods and Examples for Designing and Controlling Total quality Management PHARMACEUTICAL MANUFACTURING SystemsHerman Lam, Wild Crane Horizon, Inc.

7 , Scarborough, Ontario, Canada, Validation of Laboratory InstrumentsMarko N rhi, Helsinki University of Technology, Helsinki, Finland, National GMP Regulations and Codes and International GMP Guides and Guidelines: Corre-spondences and DifferencesKenneth J. Nolan, Nolan & Auerbach, Fort Lauderdale, Florida, Enforcement of Good MANUFACTURING PracticesKatrina Nordstr m, Helsinki University of Technology, Helsinki, Finland, NationalGMP Regulations and Codes and International GMP Guides and Guidelines: Correspondences and DifferencesNazario D. Ramirez - Beltran, University of Puerto Rico, Mayag ez, Puerto Rico, Drug StabilityGregory N. Ranky, Public Research University of New Jersey, Newark, New Jersey, Analytical and Computational Methods and Examples for Designing and Control-ling Total quality Management PHARMACEUTICAL MANUFACTURING SystemsCONTRIBUTORSviiPaul G.

8 Ranky, New Jersey Institute of Technology, Newark, New Jersey, Analyticaland Computational Methods and Examples for Designing and Controlling Total quality Management PHARMACEUTICAL MANUFACTURING SystemsRichard G. Ranky, New Jersey Institute of Technology, Newark, New Jersey, Ana-lytical and Computational Methods and Examples for Designing and Controlling Total quality Management PHARMACEUTICAL MANUFACTURING SystemsAndreas Reinisch, Medical University of Graz, Graz, Austria, GMP - Compliant Propagation of Human Multipotent Mesenchymal Stromal CellsHarry Rodriguez, Cordis LLC, a Johnson & Johnson Company, San Juan, Puerto Rico, Drug StabilityYves Roggo, F. Hoffmann - La Roche, Ltd., Basel, Switzerland, Process Analytical Technology; Chemical Imaging and Chemometrics: Useful Tools for Process Ana-lytical TechnologyEva Rohde, Medical University of Graz, Graz, Austria, GMP - Compliant Propaga-tion of Human Multipotent Mesenchymal Stromal CellsB.

9 Saramento, Faculty of Pharmacy, University of Porto, Porto, Portugal, Pharma-ceutical MANUFACTURING Validation PrinciplesKatharina Schallmoser, Medical University of Graz, Graz, Austria, GMP - Compliant Propagation of Human Multipotent Mesenchymal Stromal CellsPuneet Sharma, University of Auckland, Auckland, New Zealand, Scale - Up and Postapproval Changes (SUPAC) RegulationsEvan B. Siegel, Ground Zero Pharmaceuticals, Inc., Irvine, California, Role of quality Systems and Audits in PHARMACEUTICAL MANUFACTURING Souto, Free University of Berlin, Berlin, Germany; Faculty of Pharmacy, University of Porto, Porto, Portugal, PHARMACEUTICAL MANUFACTURING Validation PrinciplesDirk Strunk, Medical University of Graz, Graz, Austria, GMP - Compliant Propaga-tion of Human Multipotent Mesenchymal Stromal CellsMichel Ulmschneider, F.

10 Hoffman - La Roche, Ltd., Basel, Switzerland, Process Ana-lytical Technology; Chemical Imaging and Chemometrics: Useful Tools for Process Analytical TechnologyIsabel Taverniers, Institute for Agricultural and Fisheries Research (ILVO), Scien-tifi c Institute for the Flemish Community, Merelbeke, Belgium, Analytical Method Validation and quality AssuranceErik Van Bockstaele, Institute for Agricultural and Fisheries Research (ILVO), Scientifi c Institute for the Flemish Community, Merelbeke, Belgium, AnalyticalMethod Validation and quality AssuranceT. Vasconcelos, Laboratory of PHARMACEUTICAL Development, BIAL, Mamede do Coronado, Portugal; Faculty of Pharmacy, University of Porto, Porto, Portugal, PHARMACEUTICAL MANUFACTURING Validation PrinciplesviiiCONTRIBUTORSR anga Velagaleti, BASF Corporation, Florham Park, New Jersey, Microbiology of Nonsterile PHARMACEUTICAL MANUFACTURING ; Stability and Shelf Life of Pharmaceu-tical ProductsAndrew A.