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ST.

LUCIE PRESS
A CRC Press Company
Boca Raton London New York Washington, D.C.
Validation Standard
Operating Procedures
A Step-by-Step Guide for
Achieving Compliance in the
Pharmaceutical, Medical Device,
and Biotech Industries
Syed Imtiaz Haider, Ph.D.
2002 by CRC Press LLC
Some content within Val. 600.90, 200.10, 600.70, 600.30, 1100.10, 1100.20 was excerpted or adapted
from 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 19992000. With
permission.
Some content within Val. 600.30, 600.60 to 600.130 was excerpted or adapted from Carleton, F. J. and
Agalloco, J. P., Eds.,Validation of Aseptic Pharmaceutical Process, Marcel Dekker, New York, 1998.
With permission.
This book contains information obtained from authentic and highly regarded sources. Reprinted material is
quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts
have been made to publish reliable data and information, but the author and the publisher cannot assume
responsibility 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, electronic
or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval
system, without prior permission in writing from the publisher.
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Visit the CRC Press Web site at www.crcpress.com
2002 by CRC Press LLC
St. Lucie Press is an imprint of CRC Press LLC
No claim to original U.S. Government works
International Standard Book Number 1-57444-331-3
Library of Congress Card Number 2001048505
Printed in the United States of America 1 2 3 4 5 6 7 8 9 0
Printed on acid-free paper
Library of Congress Cataloging-in-Publication Data
Haider, Syed Imtiaz.
Validation standard operating procedures: a step-by-step guide for achieving
compliance in the pharmaceutical, medical device, and biotech industries
/ by Syed Imtiaz Haider.
p. cm.
ISBN 1-57444-331-3
1. Pharmaceutical technologyQuality control. 2. Pharmaceutical
industryStandardsUnited States. 3. Biotechnology industriesStandards United
States. 4. Medical instruments and apparatus industryStandardsUnited States. I. Title.
RS192 .H353 2001
681.761021873dc21 2001048505
CIP
2002 by CRC Press LLC
CONTENTS
Section VAL 100.00
100.10 Introduction to Validation
Section VAL 200.00
200.10 Fundamentals of Validation SOPs
200.20 Validation Master Plan and Guideline for DQ, IQ, OQ, and PQ
200.30 Design Qualification Guideline for Minimizing the Risk of
Product Cross-Contamination by Air Handling System
200.40 Design Qualification Guideline for Minimizing the Risk of
Cross-Contamination of Facility, Equipment, and Process
200.50 Design Qualification Guideline for HVAC System of
a Pharmaceutical Plant
200.60 Design Qualification for the Prevention of Contamination of
Non-Sterile Pharmaceutical Products
200.70 Design Qualification Guideline for Cross-Contamination
and Decontamination
200.80 Design Specifications for Process Water
200.90 Design Specifications for Water for Injection Production
and Distribution
200.100 Design Specifications for Purified Water (DIW) Production
and Distribution
200.110 Design Specifications for Pure Steam Production
and Distribution
Section VAL 300.00
300.10 Validation Glossary
300.20 Organization for Validation
300.30 Revalidation
300.40 Retrospective Validation
300.50 Validation Change Control
2002 by CRC Press LLC
Section VAL 400.00
400.10 Calibration of Instruments
400.20 Periodic Review of the Calibration Program
400.30 Calibration and Validation Equipment
Section VAL 500.00
500.10 Training on the Job
500.20 Good Manufacturing Practices
Section VAL 600.00
600.10 Guidelines for Area Classification and Air Handling
600.20 Guideline for Area Validation: Clean Area
600.30 Aseptic Area Validation Procedures
600.40 Microbiological Monitoring of Areas Used for Production of
Solids, Semi-Solids, and Liquids
600.50 Efficiency Testing for Disinfectants
600.60 Drinking Water
600.70 Purified Water
600.80 Water for Injection
600.90 Validation of a Water System
600.100 Oil-Free Compressed Air System
600.110 Nitrogen Distribution System
600.120 Clean Steam
600.130 Vacuum System
600.140 Validation of an HVAC System
Section VAL 700.00
700.10 Validation of a Steam Sterilizer
700.20 Hot Air Sterilization Tunnel Certification and
Validation Guideline
700.30 Freeze Drier
700.40 Ampule and Vial Washing Machine
700.50 Washing, Sterilizing, and Drying Machine for Stoppers
700.60 Ampule and Vial Filling Machine
700.70 Media Fill Run
700.80 Half-Automatic Inspection Machine
700.90 Ampule Crack Detection Machine
700.100 Laminar Flow Installations
700.110 Sterile Filtration Validation
700.120 Cleaning Efficiency of Production Equipment for Parenterals
2002 by CRC Press LLC
Section VAL 800.00
800.10 Kneading Machine
800.20 Oscillating Granulator
800.30 Milling Machine
800.40 Fluid Bed Drier
800.50 Blender
800.60 Tablet Press
800.70 Metal Check Device for Tablets
800.80 Tablet Coater
Section VAL 900.00
900.10 Blistering Machine
900.20 Blister Filling Machine
900.30 Code Reader
900.40 Sachetting Machine
900.50 Cartoning Machine
900.60 Labeling Machine
900.70 Check Weigher
900.80 Shrink Wrapping and Bundling Machine
900.90 Tube Filling and Closing Machine
900.100 Liquid Filling and Closing Machine
900.110 Tablet Filling and Closing Machine
Section VAL 1000.00
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
1100.10 Validation of Microbiological Methods
1100.20 Validation of Analytical Methods
Section VAL 1200.00
1200.10 Vendor Certification
Section VAL 1300.00
1300.10 Facility Qualification
Recommended Reading
2002 by CRC Press LLC
PREFACE
As the validation master plan execution program proceeds and the facility is integrated
into regulatory guidelines of the FDA, current good manufacturing practice (cGMP),
good laboratory practice (GLP), and the need for comprehensive and well-defined
validation supporting standard operating procedures are required. As the validation
program progresses and the systems are integrated into routine operation, there are
fewer deviations and the standard operating procedures become more precise and
complete.
This book and CD-ROM provide an administrative solution for management.
The execution of test functions defined in the validation master plan procedures
is provided in the text and the electronic files. The validation standard operating
procedure can help your company comply with GMP, GLP, and validation require-
ments imposed by the FDA.
The formats and style provided are generic and can be further amended. The
contents of the standard operating procedures (SOPs) are intended to build quality
into the regulatory requirements. However, having a set of validation standard oper-
ating procedures does not preclude adverse inspection findings, as contents that satisfy
one inspector may not satisfy another.
The author strongly believes that the facilitys technical management and staff
should read the procedures to ensure that particular needs are addressed with refer-
ence to operational control within the organization and individual countries regula-
tory requirements. It is, however, guaranteed to provide management with a tool to
develop a set of validation SOPs in order to support the road map established for
the on-time successful start-up of the facility operation in compliance with the GMP
requirement.
Pharmaceutical, medical, and biotech industries are regulated worldwide to be
in compliance with cGMP and GLP principles. Each company is required to create
validation SOPs to qualify its equipment, utilities, buildings, and personnel. The
template validation SOPs available enable end users to understand principles and
2002 by CRC Press LLC
elements of good manufacturing practice and provide documentation language
ranging 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 has
been a major goal, including those companies intending to export their product to the
US market. As a result, almost 300 companies are inspected around the world by the
FDA every year for their GMP and GLP compliance. Only five to six companies are
able to seek approval for exportation; one of the reasons behind this is the absence or
inadequacy of validation SOPs. Key benefits involve but are not limited to:
Successful facility operational start-up
Minimized noncompliance
Reduced reworks
Reduced rejected lots
Avoidance of recalled lots
Help in new drug approval
Satisfactory inspections
Corporate image
Financial gain
Secure third-party contracts
Corporate legal protection
Utility cost reduction
Minimized capital expenditures
Fewer complaints
Reduced testing
Improved employee awareness
The validation standard operating procedures on the CD-ROM are valuable tools
for companies in the process of developing or revising VSOPs to achieve FDA,
GMP, and GLP compliance. The documentation package is especially relevant to
quality assurance personnel, engineers, utilities engineers, computer engineers, val-
idation designers, internal and external auditors, or to anyone interested in devel-
oping 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 docu-
mentation to meet FDA and other regulatory requirements. Currently, no GMP doc-
ument specifically describes the format of these validation standard operating
procedures.
Syed Imtiaz Haider, Ph.D.
July 2001
2002 by CRC Press LLC
DEDICATION
This book is dedicated to my loving father Syed Mohsin Raza for his continuous
motivation. I am also indebted to my wife Shazia for her patience while I compiled
this book.
2002 by CRC Press LLC
ACKNOWLEDGMENT
The author would like to thank his friends and colleagues, especially Mr. Javed
Zamir and Mr. Zahid Haleem for their help and encouragement and for creating
a professional environment. Special thanks to the staff of CRC Press, particularly
Drew Gierman and Judith Simon Kamin for their patience and diligence in the
production of this book.
2002 by CRC Press LLC
ABOUT THE AUTHOR
Syed Imtiaz Haider earned his Ph.D. in chemistry
and is a quality assurance specialist with over ten years
experience in aseptic and nonaseptic pharmaceutical
processes, equipment validation, and in-process control
and auditing. Dr. Haider is the author and co-author of
more than 20 research publications in international ref-
ereed journals dealing with products of pharmaceutical
interest, their isolation, and structure development. A
professional technical writer, Haider has authored more
than 500 standard operating procedures based on FDA
regulations, ISO 9001, and ISO 14001 standards. He is
a 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: A
Complete Guide and CD-ROM, published by CRC Press and holds the copyright certificate
of registration on an electronic documentation package on ISO 14001 from the Canadian
intellectual property office.
2002 by CRC Press LLC
ABOUT THE BOOK
This book and CD-ROM take into account all major international regulations, such
as FDA, cGMP, GLP, PDA technical monographs, PDA technical reports, PMAs
concepts, Journal of PDA, GCP, and industry standard ISO 9000, to be in com-
pliance with documentation guidelines. No other book in print deals exclusively
with the key elements of validation procedure for pharmaceutical plants and pro-
vides hands-on templates to be tailored to achieve FDA compliance.
Validation standard operating procedures are written to provide explicit
instruction on how to achieve the standards for those responsible for writing
and executing master validation plans for drug, drug-device combination, diag-
nostic, pharmaceutical biotechnology, and bulk pharmaceutical chemicals products.
Included is the ready-to-use template so that one can immediately save time and
expense without missing any critical elements.
The book provides instant answers to validation engineers, validation specialists,
quality professionals, quality assurance auditors, and protocol writers about what
to include in validation standard operating procedures and how to enhance pro-
ductivity.
Introduction
SOP Format
SOP Number
SOP Title
Date
Author
Checked by
Approved by
Revision
Subject
Responsibility
2002 by CRC Press LLC
Purpose
Procedure
Reasons For Revision
The book and CD-ROM are designed for individuals specifically involved in
writing and execution of master validation plans, development of protocols, and
applicable procedures. This book provides a complete, single-source reference
detailing conceptual design elements and more than 70 explicit procedures for
validation.
2002 by CRC Press LLC
INTRODUCTION
This book was designed and written for validation professionals responsible for
writing and maintaining quality management systems for the successful operation
of their companies. It provides a set of standard operating procedures (SOPs) that
can be used to manage and document critical validation and revalidation tasks in a
pharmaceutical manufacturing facility.
The numbering of the sections and related SOPs begins with 200 and goes
through 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 refers
to the person who has been delegated authority by management and deemed
responsible for performing duties associated with validation tasks within the facility.
SOP Format
All SOPs have been uniformally designed and formatted. Information common to
all SOPs is described below.
First Page
Company Name At the top of each SOP, a box is provided to enter
your company name.
SOP Number Each SOP is assigned a unique number that appears
at the upper-left corner of each page.
Title The title of each SOP appears at the top of the first two pages
below 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 the
contents of the SOP requiring the signature and date.
Approved By Each page of the SOP provides a space for the signature
of the quality assurance or manager approving the SOP to prevent
unauthorized changes.
Revisions At the end of each page is the revisions box. This box
documents the revision number, section, pages, initials, and date.
Other Pages
Subject Each SOP begins with the subject to provide key description
of the SOP.
Purpose Each SOP is supported with reasons, describing the
purpose.
Responsibility The space for responsibility clearly identifies who
has to follow the procedures and who is responsible for the overall
compliance with the SOP.
Procedure Following the purpose statement are the individual
steps of the SOP, arranged in logical order to make the SOP easy to
perform.
Reason for Revision At the end of each SOP, a space is provided
to list the reasons why the SOP is changed, along with the date.
CD-ROM An electronic copy of the generic validation standard
operating procedures is provided.
DISCLAIMER
Every effort has been made to ensure that the contents of the generic validation
standard operating procedures are accurate and that recommendations are appro-
priate and made in good faith. The author accepts no responsibility for inaccuracies
or actions taken by companies subsequent to these recommendations.
The similarity in the contents of the procedure with a particular reference to
the test functions, acceptance criteria, qualification protocols, and checks may be
incidental because of the similarity in principle and operations of pharmaceutical
equipment.
2002 by CRC Press LLC