Biomedical Quality Auditor Handbook (2nd Edition)

292 Pages·2013·4.486 MB·292\292

by  Haggar, Bruce

The Biomedical
Quality Auditor
Handbook
Second Edition

ASQ Biomedical Division
Bruce Haggar, Editor
ASQ Quality Press
Milwaukee, Wisconsin
American Society for Quality, Quality Press, Milwaukee 53203
© 2013 by ASQ
All rights reserved. Published 2012
Printed in the United States of America
18 17 16 15 14 13 12 5 4 3 2 1
Library of Congress Cataloging-in-Publication Data
The biomedical quality auditor handbook / ASQ Biomedical Division, Bruce Haggar,
editor.—Second edition.
pages ; cm
Includes bibliographical references and index.
ISBN 978-0-87389-836-2 (hard cover : alk. paper)
1. Medical instruments and apparatus—Quality control—Handbooks, manuals, etc.
I. Haggar, Bruce, 1952– editor.

R856.6.B55 2012
610.28'4—dc23 2012037401
ISBN: 978-0-87389-836-2
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: William A. Tony
Acquisitions Editor: Matt T. Meinholz
Project 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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Printed on acid-free paper
Preface
The Biomedical Quality Auditor Handbook was written to serve as a source of
information and knowledge to support the application of quality auditor
principles to the biomedical industry. The ASQ Biomedical Division has
long believed that in order for auditors and other biomedical professionals to be
effective in their jobs, the information they need to be aware of is very exten-
sive. Interpretations of that information vary widely from industry to industry,
and specific auditing skills and knowledge may be more important in the medical
industry because of its highly regulated nature. This book provides descriptions
of a wide range of subjects that have specific interpretations unique to the bio-
medical industry. This book, which provides industry-specific interpretation, can
be used in conjunction with The ASQ Auditing Handbook published by the Quality
Audit Division, which provides information on basic auditor skills.
The information in this book is based on a body of knowledge originally
established by the Biomedical Division. However, that body of knowledge is being
changed periodically because it contains references to standards and guidance
documents that are constantly evolving. The Biomedical Division intends to pub-
lish updates to the body of knowledge as required. Those updates will be pub-
lished on the Biomedical Division website and on the ASQ website for reference.
This book does not address ISO 9001 in detail due to the large amount of infor-
mation published on the subject and available through ASQ.
It is important to note that much information that readers may consider impor-
tant knowledge in the biomedical field may not be dealt with in this book. This
book is intended primarily to support the body of knowledge. The body of knowl-
edge was prepared based on surveys and careful evaluation by ASQ and the Bio-
medical Division
The Biomedical Division believes that this publication will be a valuable ref-
erence to biomedical professionals. The Division’s primary mission is education,
both of our members and those associated with the industry. We hope this text
helps to fulfill that mission.
Bruce Haggar
xi
Table of Contents
List of Figures and Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Notes to the Reader . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xii
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
Part I U.S. Base Law and Regulations
Chapter 1 Base U.S. Law .............................................. 2
FDA Regulation of Medical Devices................................... 2
Summary of Medical Device Misbranding Regulations.................. 3
Summary of Adulteration Regulations ................................ 5
FDA Inspection .................................................... 6
Recalls [FDCA § 518(e), 21 USC § 360h(e)].............................. 20
Voluntary Recalls................................................... 22
Recall Strategy ..................................................... 26
Elements of a Recall Strategy......................................... 26
Chapter 2 U.S. Regulation............................................. 33
Quality System Regulation........................................... 33
Preamble .......................................................... 33
Scope ............................................................. 35
Definitions ........................................................ 38
Management Responsibility.......................................... 42
Design Controls .................................................... 48
Documentation and Change Control .................................. 54
Purchasing Controls ................................................ 56
Product Identification and Traceability ................................ 59
Production and Process Controls ..................................... 60
Process Validation .................................................. 64
Acceptance Activities ............................................... 66
Nonconforming Product............................................. 67
Corrective and Preventive Action..................................... 68
Packaging and Labeling Controls..................................... 74
Product Handling, Storage, Distribution, and Installation................ 75
Records ........................................................... 78
Complaint Handling................................................ 82
Servicing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Statistical Techniques ............................................... 86
v
vi Table of Contents
Chapter 3 Labeling................................................... 87
Labeling Regulation 21CFR 801....................................... 87
Subpart A—General Labeling Provisions .............................. 87
Chapter 4 Medical Device Reporting................................... 93
Medical Device Reporting Regulation 21 CFR 803....................... 93
Chapter 5 Recalls .................................................... 129
Voluntary Recalls................................................... 129
Chapter 6 Establishment Registration and Listing ....................... 132
Definitions ........................................................ 132
Regulatory Requirement 21 CFR Part 807 Establishment Registration and
Device Listing for Manufacturers and Initial Importers of Devices...... 133
Summary.......................................................... 136
Chapter 7 Device Tracking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Device Tracking Regulation 21 CFR 821................................ 137
Subpart A—General Provisions ...................................... 138
Subpart D—Records and Inspections.................................. 146
Chapter 8 Electronic Records and Signatures............................ 148
Electronic Records and Electronic Signatures 21 CFR Part 11 ............. 148
Subpart B: Electronic Records ........................................ 148
SubPart C: Electronic Signatures...................................... 150
Part 11: Compliance Policy Guide..................................... 152
Summary.......................................................... 152
Chapter 9 In Vitro Diagnostic Product Guidance ........................ 153
FDA Standards..................................................... 153
In Vitro Diagnostic Products ......................................... 154
Chapter 10 Design Review Guidance................................... 155
Regulatory Requirement............................................. 155
Discussion......................................................... 156
Chapter 11 Risk Management Guidance................................ 158
Risk Management Process ........................................... 158
Analysis of Risks ................................................... 158
Risk Estimation .................................................... 159
Risk Control ....................................................... 160
Precedence of Actions for Risk Reduction.............................. 161
Risk Management Report............................................ 161
Risk Management Maintenance ...................................... 162
Summary.......................................................... 162
Chapter 12 Quality System Inspection Technique ....................... 163
Applicability....................................................... 163
Subsystems ........................................................ 164
Sampling Tables.................................................... 165
Chapter 13 U.S. Compliance Programs for Medical Devices .............. 166
Discussion......................................................... 166
Table of Contents vii
Part II Technical Knowledge
Chapter 14 Sterilization............................................... 170
Definitions ........................................................ 174
Methods........................................................... 177
Packaging of Sterile Products ........................................ 180
Chapter 15 Biocompatibility........................................... 184
Chapter 16 Controlled Environments and Utility Systems................ 186
Regulatory Requirement............................................. 186
Utilities ........................................................... 187
Facility Qualification................................................ 187
Chapter 17 Software.................................................. 188
Software Development Process....................................... 189
Requirements Definition ............................................ 189
Design Architecture ................................................ 190
Implementation .................................................... 190
Validation Test ..................................................... 190
Design Transfer .................................................... 191
Design Release . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Engineering Changes ............................................... 192
How to Validate Process Software .................................... 192
Guidelines for a Successful Software Development Program ............. 193
Chapter 18 Laboratory Testing......................................... 195
Definitions ........................................................ 196
Applicable Standards for Laboratory Testing ........................... 196
Management Systems ............................................... 197
Operating and Testing Procedures.................................... 197
Biological Testing................................................... 198
Analytical Testing .................................................. 198
Chapter 19 Process Improvement Techniques ........................... 203
Process Capability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Six Sigma.......................................................... 203
Lean Tools......................................................... 204
Measurement Systems Analysis ...................................... 204
Cost of Quality..................................................... 205
Qualitative versus Quantitative Analysis .............................. 205
Attributes and Variable Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
Quality Tool References ............................................. 206
Six Sigma References................................................ 207
Lean References.................................................... 207
Measurement Systems Analsyis References ............................ 207
Cost of Quality References........................................... 207
Chapter 20 Reprocessing.............................................. 208
Guidance Introduction .............................................. 208
Guidance Background............................................... 208
Guidance Scope .................................................... 209
viii Table of Contents
Part III International Standards and Guidance
Chapter 21 International Quality System Guidance...................... 212
Overview of European Harmonized Standards......................... 212
Discussion......................................................... 213
Harmonized Standards.............................................. 213
International Standards ............................................. 213
National Standards ................................................. 213
Chapter 22 The EU Medical Device Directives .......................... 214
Definitions ........................................................ 215
Purpose of the Medical Device Directives.............................. 217
Requirements for Compliance........................................ 217
Determining Whether the Product Has to
Comply with the Medical Device Directives ......................... 218
Discussion......................................................... 218
Classification of Medical Devices ..................................... 219
Discussion......................................................... 219
Conformity Assessment Route ....................................... 220
Compliance with Essential Requirements.............................. 220
Risk Analysis ...................................................... 221
Technical File/Design Dossier........................................ 223
Authorized Representative........................................... 224
Post-Market Surveillance—Including Device Incident Reporting
(Vigilance) ...................................................... 224
CE Marking........................................................ 225
Declaration of Conformity........................................... 226
Chapter 23 International Auditing Guidelines .......................... 227
GHTF Auditing Guidelines .......................................... 227
General Auditing Principles.......................................... 229
Audit Process ...................................................... 233
Chapter 24 Common Medical Device Directives and Standards........... 238
Chapter 25 International Regulations .................................. 240
Canada............................................................ 240
Japan ............................................................. 242
Australia .......................................................... 243
Brazil ............................................................. 244
Appendix A: Body of Knowledge........................................ 245
Appendix B: Glossary.................................................. 255
Endnotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
Part I
U.S. Base Law and Regulations
Chapter 1 Base U.S. Law
Chapter 2 U.S. Regulation
Chapter 3 Labeling
Chapter 4 Medical Device Reporting
Chapter 5 Recalls, Corrections, and Removals
Chapter 6 Establishment Registration and Listing
Chapter 7 Device Tracking
Chapter 8 Electronic Records and Signatures
Chapter 9 In-Vitro Diagnostic Product Guidance
Chapter 10 Design Review Guidance
Chapter 11 Risk Management Guidance
Chapter 12 Quality System Inspection Technique
Chapter 13 U .S. Compliance Programs for Medical
Devices
1
chapter 1
Base U.S. Law
FDA RegulAtIon oF MeDIcAl DevIces
The Federal Food, Drug, and Cosmetic Act (FDCA) allows for extensive regu-
lation of medical devices. The FDCA currently governs the entire life-span of a
device, from premarket certification, through the manufacturing process, subse-
quent release to the market, and use by the consumer. However, Congress’s origi-
nal Food and Drug Act did not govern medical devices.
The Federal Pure Food and Drug Act, promulgated in 1906, regulated only
drugs and not medical devices. After repealing the act in 1938, Congress recast it as
the FDCA, adding specific provisions for enforcement actions concerning devices.
However, the actions were limited to policing post-market activity through prohi-
bition of adulteration and misbranding. The 1938 act did not provide for premar-
ket review or post-market surveillance of devices. When Congress amended the
act in 1962, it still did not include provisions for those regulatory activities.
With the passage of the Medical Device Amendments of 1976 (MDA), Con-
gress expanded the Food and Drug Administration’s (FDA) authority to regulate
devices. One significant change was a broadened definition of “device.” The term
included “implements, machines, implants, in vitro reagents, and other similar or
related articles.”1 Additionally, the MDA increased the conditions that qualified
a device for regulation under the FDCA. Inclusion in the National Formulary or
the U.S. Pharmacopeia (USP), or any supplement documents, became qualifying
criteria. The definition of “device” was also fine-tuned by adding limitations. To
be regulated by the MDA, a device must neither (1) “achieve any of its principal
intended purposes through chemical action within or on the body of humans or
animals,” nor (2) be “dependent upon being metabolized for the achievement
of any of its principal intended purposes.”2
The MDA gave FDA the authority to inspect devices. This authority included
new requirements that device manufacturers or importers maintain records and
provide reports to assure that devices are safe and effective. Additionally, FDA
representatives could physically inspect the materials, facilities, equipment, and
vehicles used for manufacturing or transporting devices.3
The MDA also granted FDA the power to control the commercial release of
medical devices. The amendments created a three-tiered scheme for premarket
regulation and post-market review. For this purpose, devices were divided into
three classes based on their perceived safety risk. Class I devices, those deemed
2
Chapter 1: Base U.S. Law 3
to pose the least risk of harm, were to be the least regulated, while Class III would
be the most heavily regulated.
The MDA provided two procedures by which devices could receive approval
for release. They were 510(k) premarket notifications and premarket approval applica-
tions (PMAs). FDA was also granted the authority to impose performance stan-
dards and to ban devices entirely.
More than 10 years later, Congress passed the Safe Medical Devices Act of
1990 (SMDA) to enhance FDA’s regulation of devices. This new legislation fol-
lowed in the wake of criticism by congressional investigators and others of the
limits of the earlier act. The SMDA imposed more-stringent premarket and post-
market requirements, as well as new mechanisms for enforcement. Now FDA
must issue an order of approval before a manufacturer can market a device pur-
suant to a 510(k) notification. The SMDA also added the authority for FDA to set
performance standards. Further, it included a provision allowing post-market sur-
veillance of Class II or III devices that may pose serious health risks, are life sup-
porting or sustaining, or are meant to be implanted in humans for more than one
year. Additionally, the FDCA added civil penalties to FDA’s enforcement options.
The device statutes of the FDCA had two further revisions in the 1990s. The
Medical Device Amendments of 1992 did not include major changes to existing
device law. However, the FDA Modernization Act of 1997 is notable for the pro-
gressiveness of two of its statutes. Both provide greater access to state-of-the-art
device technology. The first provision permits device manufacturers and distribu-
tors to disseminate information to medical practitioners and insurers concerning
new uses for devices already in commercial distribution. Permissible informa-
tion is limited to peer-reviewed articles or reference publications based on clinical
investigation.4 The companion statute allows shipment of investigational devices
in emergency situations or to combat serious conditions.5 The law further enables
patients being treated by licensed physicians to request and receive these devices
directly from the manufacturer or distributor. Both of these provisions reflect
a major shift for the FDCA. Since its inception, the amendments to the FDCA
imposed tighter restrictions on distribution of devices in the interest of safety.
Here, the countervailing interest of allowing greater access to medical advances is
balanced against the FDCA’s primary safety concerns.
suMMARy oF MeDIcAl DevIce MIsbRAnDIng
RegulAtIons
Prohibitions against misbranding and adulteration are two long-standing con-
sumer safeguards provided by the FDCA. Both were included in the original Pure
Food and Drug Act of 1906.6 Misbranding regulations protect against the sale of
unregistered and exceptionally risky devices, as well as against false or insuffi-
cient statements appearing in product packaging or advertisements. Adulteration
laws are intended to ensure that a device conforms to its original certification, and
continues to meet that standard throughout its life.
For purposes of this section, it is important to note that Section 520 of the
FDCA creates a category for devices that are restricted. These are devices that