Milton A.

Anderson

GLP QUALITY
AUDIT MANUAL
THIRD EDITION

© 2000 by CRC Press LLC

 GLP QUALITY AUDIT MANUAL
Third Edition

Milton A. Anderson

Library of Congress Cataloging-in-Publication Data

Anderson, Milton A.
GLP quality audit manual/Milton A. Anderson.-3rd ed.
p. cm.
Includes bibliographical references.
ISBN 1-57491-106-6
1. Medical laboratories-quality control. I. Title.
R860.A53 2000
616.07’56’0685—dc21 00-056738

10 9 8 7 6 5 4 3 2 1

ISBN: 1-57491-106-6
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© 2000 by CRC Press LLC

 GLP QUALITY
AUDIT MANUAL
Third Edition

Milton A. Anderson

Interpharm /CRC

Boca Raton London New York Washington, D.C.

© 2000 by CRC Press LLC

 Library of Congress Cataloging-in-Publication Data

Anderson, Milton A.
GLP quality audit manual/Milton A. Anderson.-3rd ed.
p. cm.
Includes bibliographical references and index.
ISBN 1-57491-106-6
1. Medical laboratories-quality control. I. Title.
R860.A53 2000
616.07'56'0685—dc21 00-056738

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© 2000 by CRC Press LLC

 CONTENTS

Introduction
Acknowledgments
How to Use This Manual

Section I—Good Laboratory Practices

1. Development of Regulations and Guidelines
A. International Development
B. United States Development
2. The Quality Assurance Unit
A. Personnel
B. Responsibilities
C. Standard Operating Procedures
D. Training
E. GLP Audit Checklists
3. Quality Inspections and Audits
A. Assuring Integrity
B. Initiation Phase
C. In-Process Phase
D. Completion Phase
E. Reporting Phase
F. Statistical Auditing
G. Computer Applications
4. Contract Laboratory Audits
A. Preplacement Evaluation
B. Evaluation of the QAU
C. Study Audit
5. System Audits
A. Effectiveness
B. Scheduling Convenience
C. Preparing
D. Conducting
E. Reporting
6. Internet Resources
A. Organizations
B. Internet Terms
7. Contributions to GLP Understanding
A. FDA Management Briefing and Inquiry Publications
B. Preambles to the GLP
C. Freedom of Information
D. Compliance Program Guidance Manual—Good Laboratory Practice

© 2000 by CRC Press LLC

 Glossary
References

Section II—Quality Audit Checklists

1. GLP Audit Checklist—Complete
2. Abbreviated GLP Audit Checklists
A. Preplacement and Maintenance
B. Initiation Phase
C. In-Process Phase
D. Completion Phase
E. Reporting Phase
Section III—Document/Report Examples
1. Quality Assurance Documents
Master Schedule
Study Inspection Record—Version 1
Study Inspection Record—Version 2
Inspection Report
Quality Assurance Unit Statement
2. Inspection Report Examples
Inspection Report—Initiation Phase
Inspection Report—In-Process Phase
Inspection Report—Completion Phase
Inspection Report—Reporting Phase
Audit Report
Audit Report (Contract Laboratory)
Section IV—References/Regulatory Texts
1. Federal Register, Friday, December 22, 1978: U.S. Food and Drug Administration, Nonclinical
Laboratory Studies, Good Laboratory Practice Regulations, Code of Federal Regulations,
Title 21, Part 58, Effective June 20, 1979
2. Federal Register, Friday, September 4, 1987: U.S. Food and Drug Administration, Nonclinical
Laboratory Studies, Good Laboratory Practice Regulations, Code of Federal Regulations,
Title 21, Part 58, Effective October 5, 1987
3. The OECD Principles of Good Laboratory Practice and Compliance Monitoring,
Number 1, Revised 1997
4. Guidance for Industry, Good Laboratory Practice Regulations Management Briefings,
Post Conference Report, August 1979, Revised November 1998
5. Good Laboratory Practice Regulations, Question and Answers,
Bioresearch Monitoring Staff, FDA, 1981
6. Compliance Program Guidance Manual, FDA, Program 7348.808, Revised 1998
7. Code of Federal Regulations, FDA. Part 58—Good Laboratory Practice for
Nonclinical Laboratory Studies, Revised as of April 1, 2000

© 2000 by CRC Press LLC

 INTRODUCTION

As we enter the 21st century and the new millennium, our experience in the Good Laboratory Practice
regulations and principles has extended over more than twenty years. Initially implemented reluctantly
by many, these rules are now overwhelmingly accepted by the worldwide community. They have
through the years given excellent direction to developing a consistent and efficient pathway for assur-
ing the quality and integrity of research data. This mandate has provided the multinational approving
authorities a high degree of confidence in the decisions they must provide regarding the scientific re-
search data that sponsors have submitted.

This inherent system of providing “perpetual” data certification has also reduced the need for replicat-
ing studies, resulting in extensive research cost reductions and the saving of animal lives. Additionally,
and perhaps most importantly, this confirmation of data quality and integrity has expedited the acces-
sibility by consumers of deserving products, potentially benefiting and saving lives of the ultimate
users—all of us.

Beginning in the last years of the 20th century, we also have been assisted by the ability to rapidly ac-
cess information from around the world via the Internet. No longer is it necessary to wait weeks for
a mailed response from a colleague overseas or days for a voluminous regulatory document to be
shipped. Now these can be immediately accessed, reviewed, and downloaded, and printed instanta-
neously over the Internet. This convenience is a major change that will enhance the timeline of re-
search, and, within the quality assurance functions, will provide immeasurable improvements in
inspections, auditing, archiving, and administration. The future looks bright.

Milton Anderson
June 2000

© 2000 by CRC Press LLC

 ACKNOWLEDGMENTS

I would like to thank my many friends and colleagues at Abbott Laboratories, the Society of Quality
Assurance, the American Society for Quality, and other professional organizations for their mutual in-
terest in furthering the progress and understanding of the Good Laboratory Practices. For those who
have been engaged in the development of the quality assurance role in GLP, I want to thank you. You
have contributed to my overall GLP experience, knowledge, and encouragement to write this manual
on Good Laboratory Practices.

I would also like to express my thanks to those individuals who recently urged me to proceed with a
third edition of the GLP Quality Audit Manual. This manual should continue as a benefit to those of
you engaged in the Good Laboratory Practices or the OECD Principles of Good Laboratory Practice.
This version includes a new chapter on Internet Resources, which should be enlightening to many of
you who have access to the Internet. The information from this global resource is endless, and its
timeliness should result in improved quality assurance operations worldwide.

My enduring appreciation to my late wife, Dorothy, for her inspiration in my writing the initial publi-
cation, and the continued support and encouragement from my family and friends—Edward, Vickie,
John, Brendan, Erin, Alexandria, Amanda, Peter, Marge, and Karen—to complete this third edition.

© 2000 by CRC Press LLC

 HOW TO USE THIS MANUAL

This manual is written as four separate sections:

Section I—Good Laboratory Practices

The reader is advised to read this section as background to understanding the development and the
need for Good Laboratory Practice auditing in the healthcare and chemical industries. These chapters
also provide a foundation of information in designing and initiating a Good Laboratory Practice qual-
ity assurance program.

Section II—Quality Audit Checklists

There are available in this section two types of checklists. First is the complete questionnaire checklist,
which addresses all the relevant regulatory requirements. Secondly, are the abbreviated, condensed
form, addressing preplacement audit and specific phases in auditing.

[The publisher grants permission to the original purchaser of this book to photocopy the Audit
Checklists in reasonable quantities for use specifically by the purchaser in performing his/her job func-
tion at his/her job location. Permission is not granted for companies to copy the Audit Checklists for
use by other personnel at other geographic locations or other distinct corporate units at the same
location.]

Section III—Appendixes

The Quality Assurance Unit (QAU) described throughout the manual has some basic document re-
quirements; those illustrated in this section may be helpful in achieving a better understanding of the
QAU function.

Section IV—Regulatory Texts

For reader convenience, several helpful texts are provided in this section, including the full texts of
both the U.S. Food and Drug Administration’s (FDA) Good Laboratory Practice Regulations and the

© 2000 by CRC Press LLC

 Organization for Economic Co-operation and Development’s (OECD) Principles of Good Laboratory
Practice. To provide convenient references to the FDA’s rationale for including or excluding certain
regulations, the Federal Register comments sections for the June 20, 1979, and September 4, 1987, is-
sues are furnished in this manual.

© 2000 by CRC Press LLC