Validation Standard Operating Procedures
Validation StandardOperating ProceduresA Step-by-Step Guide forAchieving Compliance in thePharmaceutical, Medical Device,and Biotech IndustriesSyed Imtiaz Haider, Ph.D.ST. LUCIE PRES SA CRC Press CompanyBoca Raton London New York Washington, D.C. 2002 by CRC Press LLC
Some content within Val. 600.90, 200.10, 600.70, 600.30, 1100.10, 1100.20 was excerpted or adaptedfrom USP-24 – Chapter 1225 (pp. 2149-2152), Chapter 1227 (pp. 2152-2154), and Chapter 1116 (pp.2099-2104), as well as Water for Injection Specification (p. 1752) and Purified Water Specification (p.1753). United States Pharmacopoeial Convention, Inc., Rockville, MD. Copyright 1999–2000. Withpermission.Some content within Val. 600.30, 600.60 to 600.130 was excerpted or adapted from Carleton, F. J. andAgalloco, J. P., Eds.,Validation of Aseptic Pharmaceutical Process, Marcel Dekker, New York, 1998.With permission.Library of Congress Cataloging-in-Publication DataHaider, Syed Imtiaz.Validation standard operating procedures: a step-by-step guide for achievingcompliance in the pharmaceutical, medical device, and biotech industries/ by Syed Imtiaz Haider.p. cm.ISBN 1-57444-331-31. Pharmaceutical technology—Quality control. 2. Pharmaceuticalindustry—Standards—United States. 3. Biotechnology industries—Standards UnitedStates. 4. Medical instruments and apparatus industry—Standards—United States. I. Title.RS192 .H353 2001681′.761′021873—dc212001048505CIPThis book contains information obtained from authentic and highly regarded sources. Reprinted material isquoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable effortshave been made to publish reliable data and information, but the author and the publisher cannot assumeresponsibility for the validity of all materials or for the consequences of their use.Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronicor mechanical, including photocopying, microfilming, and recording, or by any information storage or retrievalsystem, without prior permission in writing from the publisher.The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, forcreating new works, or for resale. Specific permission must be obtained in writing from CRC Press LLC forsuch copying.Direct all inquiries to CRC Press LLC, 2000 N.W. Corporate Blvd., Boca Raton, Florida 33431.Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are usedonly for identification and explanation, without intent to infringe.Visit the CRC Press Web site at www.crcpress.com 2002 by CRC Press LLCSt. Lucie Press is an imprint of CRC Press LLCNo claim to original U.S. Government worksInternational Standard Book Number 1-57444-331-3Library of Congress Card Number 2001048505Printed in the United States of America 1 2 3 4 5 6 7 8 9 0Printed on acid-free paper 2002 by CRC Press LLC
CONTENTSSection VAL 100.00100.10Introduction to ValidationSection VAL 200.00200.10200.20200.30Fundamentals of Validation SOPsValidation Master Plan and Guideline for DQ, IQ, OQ, and PQDesign Qualification Guideline for Minimizing the Risk ofProduct Cross-Contamination by Air Handling System200.40 Design Qualification Guideline for Minimizing the Risk ofCross-Contamination of Facility, Equipment, and Process200.50 Design Qualification Guideline for HVAC System ofa Pharmaceutical Plant200.60 Design Qualification for the Prevention of Contamination ofNon-Sterile Pharmaceutical Products200.70 Design Qualification Guideline for Cross-Contaminationand Decontamination200.80 Design Specifications for Process Water200.90 Design Specifications for Water for Injection Productionand Distribution200.100 Design Specifications for Purified Water (DIW) Productionand Distribution200.110 Design Specifications for Pure Steam Productionand DistributionSection VAL 300.00300.10300.20300.30300.40300.50Validation GlossaryOrganization for ValidationRevalidationRetrospective ValidationValidation Change Control 2002 by CRC Press LLC
Section VAL 400.00400.10400.20400.30Calibration of InstrumentsPeriodic Review of the Calibration ProgramCalibration and Validation EquipmentSection VAL 500.00500.10500.20Training on the JobGood Manufacturing PracticesSection VAL lines for Area Classification and Air HandlingGuideline for Area Validation: Clean AreaAseptic Area Validation ProceduresMicrobiological Monitoring of Areas Used for Production ofSolids, Semi-Solids, and LiquidsEfficiency Testing for DisinfectantsDrinking WaterPurified WaterWater for InjectionValidation of a Water SystemOil-Free Compressed Air SystemNitrogen Distribution SystemClean SteamVacuum SystemValidation of an HVAC SystemSection VAL 700.00700.10700.20Validation of a Steam SterilizerHot Air Sterilization Tunnel Certification andValidation Guideline700.30 Freeze Drier700.40 Ampule and Vial Washing Machine700.50 Washing, Sterilizing, and Drying Machine for Stoppers700.60 Ampule and Vial Filling Machine700.70 Media Fill Run700.80 Half-Automatic Inspection Machine700.90 Ampule Crack Detection Machine700.100 Laminar Flow Installations700.110 Sterile Filtration Validation700.120 Cleaning Efficiency of Production Equipment for Parenterals 2002 by CRC Press LLC
Section VAL 0.80Kneading MachineOscillating GranulatorMilling MachineFluid Bed DrierBlenderTablet PressMetal Check Device for TabletsTablet CoaterSection VAL 0.80900.90900.100900.110Blistering MachineBlister Filling MachineCode ReaderSachetting MachineCartoning MachineLabeling MachineCheck WeigherShrink Wrapping and Bundling MachineTube Filling and Closing MachineLiquid Filling and Closing MachineTablet Filling and Closing MachineSection VAL 1000.001000.10 Installation Qualification of Computerized Equipment1000.20 Operational Qualification of Computerized Equipment1000.30 Performance Qualification of Computerized EquipmentSection VAL 1100.001100.10 Validation of Microbiological Methods1100.20 Validation of Analytical MethodsSection VAL 1200.001200.10 Vendor CertificationSection VAL 1300.001300.10 Facility QualificationRecommended Reading 2002 by CRC Press LLC
PREFACEAs the validation master plan execution program proceeds and the facility is integratedinto regulatory guidelines of the FDA, current good manufacturing practice (cGMP),good laboratory practice (GLP), and the need for comprehensive and well-definedvalidation supporting standard operating procedures are required. As the validationprogram progresses and the systems are integrated into routine operation, there arefewer deviations and the standard operating procedures become more precise andcomplete.This book and CD-ROM provide an administrative solution for management.The execution of test functions defined in the validation master plan proceduresis provided in the text and the electronic files. The validation standard operatingprocedure can help your company comply with GMP, GLP, and validation requirements imposed by the FDA.The formats and style provided are generic and can be further amended. Thecontents of the standard operating procedures (SOPs) are intended to build qualityinto the regulatory requirements. However, having a set of validation standard operating procedures does not preclude adverse inspection findings, as contents that satisfyone inspector may not satisfy another.The author strongly believes that the facility’s technical management and staffshould read the procedures to ensure that particular needs are addressed with reference to operational control within the organization and individual countries’ regulatory requirements. It is, however, guaranteed to provide management with a tool todevelop a set of validation SOPs in order to support the road map established forthe on-time successful start-up of the facility operation in compliance with the GMPrequirement.Pharmaceutical, medical, and biotech industries are regulated worldwide to bein compliance with cGMP and GLP principles. Each company is required to createvalidation SOPs to qualify its equipment, utilities, buildings, and personnel. Thetemplate validation SOPs available enable end users to understand principles and 2002 by CRC Press LLC
elements of good manufacturing practice and provide documentation languageranging from generic to specific, depending on the detail level of the requirements.Compliance to FDA regulations by the health care industry over the last decade hasbeen a major goal, including those companies intending to export their product to theUS market. As a result, almost 300 companies are inspected around the world by theFDA every year for their GMP and GLP compliance. Only five to six companies areable to seek approval for exportation; one of the reasons behind this is the absence orinadequacy of validation SOPs. Key benefits involve but are not limited �Successful facility operational start-upMinimized noncomplianceReduced reworksReduced rejected lotsAvoidance of recalled lotsHelp in new drug approvalSatisfactory inspectionsCorporate imageFinancial gainSecure third-party contractsCorporate legal protectionUtility cost reductionMinimized capital expendituresFewer complaintsReduced testingImproved employee awarenessThe validation standard operating procedures on the CD-ROM are valuable toolsfor companies in the process of developing or revising VSOPs to achieve FDA,GMP, and GLP compliance. The documentation package is especially relevant toquality assurance personnel, engineers, utilities engineers, computer engineers, validation designers, internal and external auditors, or to anyone interested in developing a qualification documentation matrix.The author believes that by following the broadly based example of these VSOPs,both new and experienced companies can benefit by enhancing their existing documentation to meet FDA and other regulatory requirements. Currently, no GMP document specifically describes the format of these validation standard operatingprocedures.Syed Imtiaz Haider, Ph.D.July 2001 2002 by CRC Press LLC
DEDICATIONThis book is dedicated to my loving father Syed Mohsin Raza for his continuousmotivation. I am also indebted to my wife Shazia for her patience while I compiledthis book. 2002 by CRC Press LLC
ACKNOWLEDGMENTThe author would like to thank his friends and colleagues, especially Mr. JavedZamir and Mr. Zahid Haleem for their help and encouragement and for creatinga professional environment. Special thanks to the staff of CRC Press, particularlyDrew Gierman and Judith Simon Kamin for their patience and diligence in theproduction of this book. 2002 by CRC Press LLC
ABOUT THE AUTHORSyed Imtiaz Haider earned his Ph.D. in chemistryand is a quality assurance specialist with over ten yearsexperience in aseptic and nonaseptic pharmaceuticalprocesses, equipment validation, and in-process controland auditing. Dr. Haider is the author and co-author ofmore than 20 research publications in international refereed journals dealing with products of pharmaceuticalinterest, their isolation, and structure development. Aprofessional technical writer, Haider has authored morethan 500 standard operating procedures based on FDAregulations, ISO 9001, and ISO 14001 standards. He isa certified auditor of IRCA and a registered associate environmental auditor of EARA.He has written more than ten quality system manuals for multidisciplinary industries.Dr. Haider has also written ISO 9001:2000: Document Development Compliance Manual: AComplete Guide and CD-ROM, published by CRC Press and holds the copyright certificateof registration on an electronic documentation package on ISO 14001 from the Canadianintellectual property office. 2002 by CRC Press LLC
ABOUT THE BOOKThis book and CD-ROM take into account all major international regulations, suchas FDA, cGMP, GLP, PDA technical monographs, PDA technical reports, PMA’sconcepts, Journal of PDA, GCP, and industry standard ISO 9000, to be in compliance with documentation guidelines. No other book in print deals exclusivelywith the key elements of validation procedure for pharmaceutical plants and provides hands-on templates to be tailored to achieve FDA compliance.Validation standard operating procedures are written to provide explicitinstruction on how to achieve the standards for those responsible for writingand executing master validation plans for drug, drug-device combination, diagnostic, pharmaceutical biotechnology, and bulk pharmaceutical chemicals products.Included is the ready-to-use template so that one can immediately save time andexpense without missing any critical elements.The book provides instant answers to validation engineers, validation specialists,quality professionals, quality assurance auditors, and protocol writers about whatto include in validation standard operating procedures and how to enhance ��䡲SOP FormatSOP NumberSOP TitleDateAuthorChecked byApproved byRevisionSubjectResponsibility 2002 by CRC Press LLC
䡲 Purpose䡲 Procedure䡲 Reasons For RevisionThe book and CD-ROM are designed for individuals specifically involved inwriting and execution of master validation plans, development of protocols, andapplicable procedures. This book provides a complete, single-source referencedetailing conceptual design elements and more than 70 explicit procedures forvalidation. 2002 by CRC Press LLC
INTRODUCTIONThis book was designed and written for validation professionals responsible forwriting and maintaining quality management systems for the successful operationof their companies. It provides a set of standard operating procedures (SOPs) thatcan be used to manage and document critical validation and revalidation tasks in apharmaceutical manufacturing facility.The numbering of the sections and related SOPs begins with 200 and goesthrough 1300. In addition the reader may add SOPs that are unique to his facility.The term responsible person is used extensively throughout the SOPs. The term refersto the person who has been delegated authority by management and deemedresponsible for performing duties associated with validation tasks within the facility.SOP FormatAll SOPs have been uniformally designed and formatted. Information common toall SOPs is described below.First PageCompany Name — At the top of each SOP, a box is provided to enteryour company name.SOP Number — Each SOP is assigned a unique number that appearsat the upper-left corner of each page.Title — The title of each SOP appears at the top of the first two pagesbelow the SOP number. The title describes the subject of the SOP.Date — Each SOP is assigned an effective date at the top of the page,to the right of the SOP number. The date describes the month, day,and year of implementation. 2002 by CRC Press LLC
Author — Each SOP is assigned a space to provide the author name,title, and the department, along with signatures and dates.Checked by — Each SOP is assigned a space to provide the name,title, and the department of the person responsible for checking thecontents of the SOP requiring the signature and date.Approved By — Each page of the SOP provides a space for the signatureof the quality assurance or manager approving the SOP to preventunauthorized changes.Revisions — At the end of each page is the revisions box. This boxdocuments the revision number, section, pages, initials, and date.Other PagesSubject — Each SOP begins with the subject to provide key descriptionof the SOP.Purpose — Each SOP is supported with reasons, describing thepurpose.Responsibility — The space for responsibility clearly identifies whohas to follow the procedures and who is responsible for the overallcompliance with the SOP.Procedure — Following the purpose statement are the individualsteps of the SOP, arranged in logical order to make the SOP easy toperform.Reason for Revision — At the end of each SOP, a space is providedto list the reasons why the SOP is changed, along with the date.CD-ROM — An electronic copy of the generic validation standardoperating procedures is provided.DISCLAIMEREvery effort has been made to ensure that the contents of the generic validationstandard operating procedures are accurate and that recommendations are appropriate and made in good faith. The author accepts no responsibility for inaccuraciesor actions taken by companies subsequent to these recommendations.The similarity in the contents of the procedure with a particular reference tothe test functions, acceptance criteria, qualification protocols, and checks may beincidental because of the similarity in principle and operations of pharmaceuticalequipment. 2002 by CRC Press LLC
SECTIONVAL 100.00 2002 by CRC Press LLC
YOUR COMPANYVALIDATION STANDARD OPERATING PROCEDURESOP No. Val. 100.10Effective date: mm/dd/yyyyApproved by:TITLE:Introduction to teCHECKED BY:Name/Title/DepartmentSignature/DateAPPROVED . 2002 by CRC Press LLCSectionPagesInitials/Date
SOP No. Val. 100.10Effective date: mm/dd/yyyyApproved by:SUBJECT: Introduction to ValidationPURPOSETo describe the definition, types, and benefits of validationRESPONSIBILITYIt is the responsibility of validation team members to follow the procedures. Thequality assurance (QA) manager is responsible for SOP compliance.PROCEDURE1. Definition of ValidationValidation is a systematic approach to gathering and analyzing sufficient data whichwill give reasonable assurance (documented evidence), based upon scientific judgment,that a process, when operating within specified parameters, will consistently produceresults within predetermined specifications.2. Type of Validation䡲䡲䡲䡲Retrospective ValidationProspective ValidationConcurrent ValidationRevalidation2.1 Retrospective ValidationValidation of a process for a product already in distribution, based on accumulatedproduction, testing, and control dates. Summary of existing historical data.2.2 Prospective ValidationValidation conducted prior to distribution either of a new product, or a productmade under a revised manufacturing process. Validation is completed and the resultsare approved prior to any product release. 2002 by CRC Press LLC
SOP No. Val. 100.10Effective date: mm/dd/yyyyApproved by:2.3 Concurrent ValidationA combination of retrospective and prospective validation. Performed against anapproved protocol but product is released on a lot-by-lot basis. Usually used onan existing product not previously validated or insufficiently validated.2.4 RevalidationTo validate change in equipment, packaging, formulation operating procedure, orprocess that could impact product safety, efficacy, or potency. It is important toestablish a revalidation program for critical equipment to maintain validity.3. Importance of ed throughputReduction in rejections and reworkingReduction in utility costsAvoidance of capital expendituresFewer complaints about process-related failuresReduced testing in-process and in finished goodsMore rapid and reliable start-up of new equipmentEasier scale-up from development workEasier maintenance of equipmentImproved employee awareness of processesMore rapid automationREASONS FOR REVISIONEffective date: mm/dd/yyyy䡲 First time issued for your company, affiliates and contract manufacturers 2002 by CRC Press LLC
SECTIONVAL 200.00 2002 by CRC Press LLC
YOUR COMPANYVALIDATION STANDARD OPERATING PROCEDURESOP No. Val. 200.10Effective date: mm/dd/yyyyApproved by:TITLE:Fundamentals of Validation KED BY:Name/Title/DepartmentSignature/DateAPPROVED . 2002 b
1000.10 Installation Qualification of Computerized Equipment 1000.20 Operational Qualification of Computerized Equipment 1000.30 Performance Qualification of Computerized Equipment Section VAL 1100.00 . template validation SOPs available enable end users to understand principles and
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Cleaning validation Process validation Analytical method validation Computer system validation Similarly, the activity of qualifying systems and . Keywords: Process validation, validation protocol, pharmaceutical process control. Nitish Maini*, Saroj Jain, Satish ABSTRACTABSTRACT Sardana Hindu College of Pharmacy, J. Adv. Pharm. Edu. & Res.
Validation guidelines 1. ICH Q2A Text on validation of analytical procedures: Definitions and terminology (March 1995) 2. ICH Q2B Validation of analytical procedures: Methodology (June 1997) 3. FDA (Draft) Guidance for Industry: Analytical procedures and methods validation 4. Pharmacopoeias USP and European Pharmacopoeia Guidelines
2. Standard Operation Procedure for Receiving of Pharmaceutical products 3. Standard Operating Procedure for Dispatch and Transport 4. Standard Operating Procedure for Inventory 5. Standard Operating Procedure for Cleaning 6. Standard Operating Procedure for Self-inspection 7. Standard operating
Dipl.-Ing. Becker EN ISO 13849-1 validation EN ISO 13849-2: Validation START Design consideration validation-plan validation-principles documents criteria for fault exclusions faults-lists testing is the testing complete? Validation record end 05/28/13 Seite 4 Analysis category 2,3,4 all
Validation of standardized methods (ISO 17468) described the rules for validation or re-validation of standardized (ISO or CEN) methods. Based on principles described in ISO 16140-2. -Single lab validation . describes the validation against a reference method or without a reference method using a classical approach or a factorial design approach.
Pharmaceutical Engineers (ISPE) GAMP 5. Our validation service is executed in accordance with GxP standards producing a validation library that features the following documents: Validation and Compliance Plan The Validation and Compliance Plan (VCP) defines the methodology, deliverables, and responsibilities for the validation of Qualer.
heard. These goals relate closely to the Validation principles. Validation Principles and Group Work The following eleven axioms are the Validation Principles as revised in 2007. I have tried to find various ways of incorporating the principles into teaching Group Validation and by doing so, anchoring group work to theory. 1.
