CAPA for the

FDA-Regulated
Industry

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The FDA and Worldwide Quality System Requirements Guidebook for
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Amiram Daniel and Ed Kimmelman
Development of FDA-Regulated Medical Products: Prescription Drugs,
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Safe and Sound Software: Creating an Efficient and Effective Quality System
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Thomas H. Faris
Root Cause Analysis: Simplified Tools and Techniques, Second Edition
Bjrn Andersen and Tom Fagerhaug
Mastering and Managing the FDA Maze: Medical Device Overview
Gordon Harnack
Root Cause Analysis: The Core of Problem Solving and Corrective Action
Duke Okes
Get It Right: A Guide to Strategic Quality Systems
Ken Imler
The Internal Auditing Pocket Guide: Preparing, Performing, Reporting and
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J.P. Russell
Measurement Matters: How Effective Assessment Drives Business and
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Brooks Carder and Patrick Ragan
Lean Kaizen: A Simplified Approach to Process Improvements
George Alukal and Anthony Manos
The Certified Manager of Quality/Organizational Excellence Handbook:
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CAPA for the

FDA-Regulated
Industry

Jos Rodrguez-Prez

ASQ Quality Press

Milwaukee, Wisconsin

American Society for Quality, Quality Press, Milwaukee, WI 53203

2011 by ASQ
All rights reserved. Published 2010.
Printed in the United States of America.
16 15 14 13 12 11 10 5 4 3 2 1
Library of Congress Cataloging-in-Publication Data
Rodrguez Prez, Jos, 1961CAPA for the FDA-regulated industry / Jos Rodrguez Prez.
p. cm.
Includes bibliographical references and index.
ISBN 978-0-87389-797-6 (hardcover : alk. paper)
1. Pharmaceutical industry Government policy United States.
2. Food industry and trade Government policy United States.
3. Total quality management United States. I. Title.
HD9666.6.R63 2010
615.10681dc22
2010031139
No part of this book may be reproduced in any form or by any means, electronic,
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Printed on acid-free paper

Dedication
This book is dedicated to my wife Norma and
my son Jos Andrs. Their continuous support
and love made this book possible.

(This page intentionally left blank)

Contents
List of Figures and Tables. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ix

Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
Chapter 1 The Quality System and CAPA . . . . . . . . . . . . . . . . . . .

1.1 The Quality System and CAPA. . . . . . . . . . . . . . . . . . . . . . .

1.2 CAPA Relationship With Other Quality Subsystems . . . .

1.3 Corrective or Preventive?. . . . . . . . . . . . . . . . . . . . . . . . . . . .

1
1
4
6

Chapter 2 CAPA and the Life Sciences Regulated Industry. . . .

2.1 FDA Pharmaceutical CGMP . . . . . . . . . . . . . . . . . . . . . . . . .

2.2 FDA Medical Devices QSR. . . . . . . . . . . . . . . . . . . . . . . . . . .

2.3 FDA Quality System Inspection Technique

(QSIT), 1999 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2.4 FDA Guidance: Investigating Out-of-Specification (OOS)

Test Results for Pharmaceutical Production, 2006 . . . . . . .

2.5 FDA Guidance: Quality Systems Approach to

Pharmaceutical Current Good Manufacturing

Practice Regulations, 2006. . . . . . . . . . . . . . . . . . . . . . . . . . .

2.6 European Pharmaceutical GMP (EudraLex

Volume 4), 2003. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2.7 Harmonization Processes: ICH and GHTF. . . . . . . . . . . . .

2.8 ICH Q10: Pharmaceutical Quality System, 2008. . . . . . . . .

2.9 ISO 13485:2003 and Non-U.S. Medical Devices

Regulations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2.10 GHTF Quality Management SystemMedical

DevicesGuidance on Corrective Action and

Preventive Action and Related QMS Processes, 2009 . . . .

2.11 Current FDA Regulatory Trends for the CAPA System. . .

9
10
11

vii

13
19
21
23
24
25
25
27
28

viii Contents

Chapter 3Effective CAPA Process: From Problem

Detection to Effectiveness Check. . . . . . . . . . . . . . . . . .

3.1 Problem Detection: Discovering Problems . . . . . . . . . . . . .

3.1.1 Source of Data About Product and Quality Issues.

3.1.2 Risk Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.1.3 Initial Impact Assessment. . . . . . . . . . . . . . . . . . . . . .

3.1.4 Process Trending . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.2 Problem Investigation: Discovering Root Causes . . . . . . .

3.2.1 Symptoms, Causal Factors, and Root Causes. . . . .

3.2.2 Problem Description. . . . . . . . . . . . . . . . . . . . . . . . . .

3.2.3 Barrier Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.2.4 Root Cause Identification Processes and Tools. . . .

3.2.5 Root Cause Categories . . . . . . . . . . . . . . . . . . . . . . . .

3.2.6 Investigating Human Errors . . . . . . . . . . . . . . . . . . .

3.3 CAPA Plan: Corrective and Preventive Actions to

Fix Root Causes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.3.1 Establish Effective Corrective and

Preventive Actions. . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.3.2 Validation and Verification Prior

to Implementation. . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.3.3 Implementation of Corrective and

Preventive Actions. . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.4 Effectiveness Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.4.1 Verifying That Solutions Worked . . . . . . . . . . . . . . .

3.4.2 Training Effectiveness. . . . . . . . . . . . . . . . . . . . . . . . .

3.5 Management of the CAPA System. . . . . . . . . . . . . . . . . . . .

3.5.1 CAPA System Structure . . . . . . . . . . . . . . . . . . . . . . .

3.5.2 CAPA Process Metrics. . . . . . . . . . . . . . . . . . . . . . . . .

3.5.3 Risk Management and the CAPA System . . . . . . . .

3.5.4 Management of External CAPA. . . . . . . . . . . . . . . . .
Chapter 4 Documenting CAPA. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4.1 Content of the Investigation Report/CAPA Plan Report. . .

4.2 Compliance Writing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

31
33
33
35
42
43
46
47
50
55
56
60
62
76
76
77
78
79
79
80
84
85
85
86
87
89
89
91

Contents ix

Chapter 5The Ten Biggest Opportunities of the

CAPA System and How to Fix Them. . . . . . . . . . . . . . .

5.1 Timeliness (Lack of) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5.2 Everything is an Isolated Event (Lack of

Adequate Trending) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5.3 Root Cause Not Identified. . . . . . . . . . . . . . . . . . . . . . . . . . .

5.4 Correcting the Symptoms Instead of the Cause. . . . . . . . .

5.5 Lack of Interim Corrective Actions. . . . . . . . . . . . . . . . . . . .

5.6 Root Causes Identified but Not Corrected . . . . . . . . . . . . .

5.7 Lack of True Preventive Actions. . . . . . . . . . . . . . . . . . . . . .

5.8 Lack of Effectiveness Verification of the Action Taken . . .

5.9 Multiple CAPA Systems Without Correlation . . . . . . . . . .

5.10 Abuse of Human Error and Retraining. . . . . . . . . . . . . . . .

93
93
96
98
99
100
100
101
102
103
103

Chapter 6 Developing an Internal CAPA Expert Certification. .

6.1 Content of the Certification. . . . . . . . . . . . . . . . . . . . . . . . . .

6.2 Evaluating the Effectiveness of Internal CAPA

Training Efforts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6.3 CAPA Certification Exam Example . . . . . . . . . . . . . . . . . . .

105
105

Chapter 7 CAPA Forms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7.1 Event Description and Investigation. . . . . . . . . . . . . . . . . .

7.2 CAPA Plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7.3 Investigation Report and CAPA Assessment Form. . . . . .

7.4 Human Error Investigation Form. . . . . . . . . . . . . . . . . . . . .

113
114
116
118
122

109
110

Chapter 8 CAPA Final Recommendations . . . . . . . . . . . . . . . . . . . 125

Appendix A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127

Additional Resources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127

Useful Web Sites. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Acronyms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Bibliography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141

(This page intentionally left blank)

List of Figures and Tables

Figure 1.1

The CAPA system and the manufacturing quality system. . . . . . . . . .

Table 1.1

Corrective or preventive?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure 1.2

Figure 2.1

Table 2.1

Figure 2.2

Table 2.2

Feeders of the CAPA system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Top ten FDA observations during drug manufacturer inspections

for fiscal year 2009. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Comparison of top ten observations during drug manufacturer
inspections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Top ten FDA observations during medical devices manufacturer
inspections for fiscal year 2009. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Comparison of top ten observations during medical devices
manufacturer inspections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28
29
29
30

Figure 3.1

The CAPA process flow. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

31

Figure 3.3

The ineffective CAPA circle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

33

Figure 3.2
Table 3.1
Table 3.2
Table 3.3

The CAPA system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Risk assessment criteria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Risk assessment score matrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Type of nonconformance investigations. . . . . . . . . . . . . . . . . . . . . . . . .

41

Figure 3.5

Scrap monthly rates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure 3.7
Table 3.5
Table 3.6

Figure 3.8
Figure 3.9
Table 3.7
Table 3.8

39

40

Risk prioritization of investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure 3.6

36

Example of risk assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Figure 3.4
Table 3.4

32

Root cause elements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CAPA example. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Symptoms, causal factors, and root causes. . . . . . . . . . . . . . . . . . . . . . .

Examples of causal factors and root causes . . . . . . . . . . . . . . . . . . . . . .
Timeline of event. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Change analysis graph. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Barrier controls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Barrier control analysis example. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
xi

41
46
47
49
50
51
53
53
55
55

xii List of Figures and Tables

Figure 3.10

Fault tree analysis example. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

58

Table 3.9

Slips and lapses of memory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

65

Figure 3.11
Table 3.10
Table 3.11

Types of human errors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Human error investigation and prevention Dos and Donts . . . . . . .
The four levels of the Kirkpatrick model. . . . . . . . . . . . . . . . . . . . . . . . .

64
75
82

Table 4.1

Compliance writing Dos and Donts. . . . . . . . . . . . . . . . . . . . . . . . . . . .

92

Table 6.1

Content of the CAPA expert certification . . . . . . . . . . . . . . . . . . . . . . . .

106

Table 7.1

Human error investigation form. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

123

Table 6.2

CAPA expert certification evaluation levels. . . . . . . . . . . . . . . . . . . . . .

110

Preface

edical devices, biopharmaceutical, and traditional drug manu

facturing companies devote an important part of their resources
to dealing with incidents, investigations, and corrective and
preventive actions. The corrective and preventive action system is known
as the CAPA system. The CAPA system is second to none in terms of
frequency and criticality of its deviations, and most of the regulatory
actions taken by the FDA and foreign regulators are linked to inadequate
CAPA systems. This guidance book provides useful and up-to-date
information about this critical topic to thousands of engineers, scientists,
and manufacturing and quality personnel across the life sciences
industries.
Understanding the CAPA system is a fundamental prerequisite to
improving it. Investigating and discovering the root cause of any event is
just the starting point of the CAPA journey. After that, we must develop
and implement adequate and effective corrective and/or preventive
actions. A formal process must be established to evaluate how well
implemented actions prevent the recurrence of those causes. Although
preventive actions are half of the CAPA system, many companies do not
have any true preventive actions. Understanding and improving the
corrective and preventive actions system as a whole is the focal point of
this book, the first of its kind dealing exclusively with this critical system
within this highly regulated industry.
These pages evolved from hundreds of training sessions I have
conducted as a consultant to dozens of regulated companies. By reviewing
CAPA systems of nearly one hundred manufacturing plants (pharma
ceuticals, medical devices, biological products, and food manufacturing),
I developed firsthand awareness of the real issues of the CAPA system.
These are addressed in this book in the form of a decalogue, a set of ten
basic rules. Thus, the objective of this book is to help these industries
improve their CAPA systems and succeed in their mission of producing
safe and effective products.
xiii

xiv Preface

Chapter 1 establishes the relationship between the CAPA system

(identification, investigation, and fixing of problems) and the quality
system environment. It also includes the most important definitions and
concept of the CAPA world. I strongly recommend you begin by reading
and understanding those critical concepts. Many people involved in
developing and implementing corrective and preventive actions have
trouble providing correct definitions of those concepts.
Chapter 2 describes the current requirements and regulations by type
of products and by country (U.S., European Community) and by
international harmonized documents. It also includes a review of
ISO 13485:2003 requirements as they apply to medical device manu
facturers as well as a review of the recent international guidance on
CAPA for medical devices published September 2009. This chapter
finishes with an overview of the current FDA regulatory trends related to
the CAPA system.
Chapter 3 describes sequentially the entire CAPA process. It starts
with problem detection, continues with root cause investigation, genera
tion, and implementation of corrective and preventive actions, and ends
with the evaluation of their effectiveness and the management of the
CAPA system. Topics such as trending, evaluation of training effective
ness, and risk management concepts and their relation to CAPA are
discussed in this chapter. Special emphasis is dedicated to the inves
tigation of so-called human error.
Chapter 4 contains useful hints to properly document the elements of
the CAPA process.
Chapter 5 describes a decalogue containing the ten most common
opportunities found in the CAPA system and how to fix them. Real
examples are analyzed and best practices are discussed for each.
Chapter 6 presents the basic elements to be included as part of an
internal CAPA expert certification, which is one of the recommended
ways to reinforce your CAPA system.
Chapter 7 includes several forms that can be used as templates during
failure investigations, development of corrective and preventive actions,
and evaluations of effectiveness. These forms include dozens of questions
that provide guidance and are a great help during the process of
investigation and generation of effective actions to avoid the recurrence
of unwanted situations. Also included is a form to be used when
investigating human errors.
Finally, Chapter 8 presents a list of key recommendations to improve
your CAPA system.

1
The Quality System
and CAPA
1.1 THE QUALITY SYSTEM AND CAPA
A quality system is a set of formalized business practices that define
management responsibilities for organizational structure, processes,
procedures, and resources needed to fulfill product or service require
ments, customer satisfaction, and continuous improvement. A quality
management system (QMS) is a set of interrelated elements (processes)
used to direct and control an organization with regard to quality. In other
words, a quality system dictates how quality policies are implemented
and quality objectives are achieved.
Continuous improvement is the result of ongoing activities to
evaluate and enhance products, processes, and the entire quality system
to increase effectiveness. The organization must continuously improve
the effectiveness and efficacy of its QMS through the use of its quality
policy, quality objectives, audit results, analysis of data, corrective and
preventive actions, and the management review processes.
Analyzing data is an essential activity for any possible improvement
at any level (system, process, and product/service). The organization
must collect and analyze appropriate data to demonstrate the suitability
and effectiveness of the QMS. This must include data generated as a
result of monitoring and measurement and from other relevant sources.
The analysis of data will provide information on customer satisfaction,
conformity to product or service requirements, trends of processes and
products including opportunities for preventive action, and suppliers.
Corrective action is one of the most important improvement activities.
It identifies actions needed to correct the causes of identified problems.
It seeks to eliminate permanently the causes of problems that have a
negative impact on systems, processes, and products. Corrective action
involves finding the causes of some specific problem and then putting in
place the necessary actions to avoid a reoccurrence. Preventive actions are
aimed at preventing the occurrence of potential problems. Correction of
the problem is the third basic element of the corrective and preventive
1

2 Chapter One

action system. These efforts attack symptoms rather than causes and
sometimes are mentioned as immediate, remedial or containment actions.
The concept of CAPA is not restricted to any particular industry or
sector. It is a widely accepted concept, basic to any quality management
system. Since quality systems strive to continuously improve systems,
processes, and products/services, there must be mechanisms in place to
recognize existing or potential quality issues, take the appropriate steps
necessary to investigate and resolve those issues, and, finally, make sure
the same issues do not recur. Processes of the life sciences regulated
industries (the manufacturing of medical devices, biopharmaceuticals,
and traditional drugs) are plagued with deviations and nonconformities.
Worldwide regulatory agencies perform thousands of inspections every
year; often CAPA system violations are at the top of the list.
Within the United States, lack of adequate investigations, no true
root cause analysis, lack of effective corrective actions, and lack of true
preventive actions are common findings pointed out by Food and Drug
Administration (FDA) inspectors. As evidenced by the significant number
of problems related to this issue, companies are facing many challenges
in making the CAPA system work as intended. Life sciences regulated
companies must ensure that their CAPA system looks beyond product
issues and considers other quality issues including problems associated
with processes and systems. Unfortunately, a significant number of
regulated companies are approaching the CAPA system very lightly,
implementing corrections but no true corrective and preventive actions.
CAPA systems are inherently data driven. Without adequate,
relevant data, it can be difficult to draw definitive conclusions about
systems, processes, or product quality issues. One of the challenges
many companies face is the proliferation of uncorrelated data repository
systems within the organization. A typical example for U.S. companies
is the existence of two separate systems (domestic and foreign) for
investigating customer claims. Another example is the lack of relationship
between supplier and internal CAPA systems. By having a correlated
CAPA system, a company will be better able to diagnose the health of its
quality system and will have a better chance of recognizing and resolving
important quality issues.
As the quality system within an organization matures, there should
be a natural shift in emphasis from corrective action to preventive
action. Issues that must be corrected usually become obvious. However,
issues that have the potential for becoming a problem are less readily
recognized. How can a firm pore over its internal data to find those few
situations that might be the precursors of problems down the road? The
answer is part of the regulations. Companies must establish methods
to evaluate both the nonconformance data (which will feed the corrective
action portion of the system) and the in-conformance data (which will be
the basis of preventive actions).

The Quality System and CAPA 3

An effective CAPA system must be a closed loop system. This term

refers to at least two elements of the CAPA system. First, it means there
are sufficient controls in place to ensure that the CAPA process runs
through all the required steps to completion, and that management and
those responsible for quality have visibility and input to the process.
In addition, top management must review the outputs of the CAPA
system. Very often companies focus on completing the individual tasks
of a particular corrective action, yet lose track of the original purpose of
the CAPA system. For example, a particular product problem may be
resolved, but no evaluation is ever performed to ensure that the solution
was effective. In this example, the loop was never closed.
Second, a good CAPA system closes the loop on many of the docu
mented issues by directly providing input into basic elements of the QMS
such as design control. For example, nonconforming product procedures
are directed at assuring that the nonconforming product is identified
and corrected prior to distribution or prevented from being distributed.
Frequently, a correction or temporary change will be implemented to
assure that the affected material is fixed. An effective CAPA system will
require that the problem be investigated and its root causes effectively
attacked with the appropriate corrective actions.
A documented procedure for CAPA must define requirements for the
following elements:
1. Collect and analyze quality data to identify existing and potential
causes of nonconforming products or other quality problems.
2. Investigate the causes of existing and potential nonconformities.
3. Identify corrective and preventive actions.

4. Verify or validate corrective and preventive action prior to

implementation.
5. Implement corrective and preventive actions.

6. Evaluate the effectiveness of corrective and preventive actions.

7. Ensure that the information related to quality problems or
nonconforming products is disseminated to those directly
responsible for assuring the quality of such product or the
prevention of such problems.

8. Submit relevant information on identified quality problems, as

well as corrective and preventive actions, for management review.
Finally, all CAPA system activities, and all quality system activities in
general, must follow a risk-based approach. Because all existing and
potential problems do not have the same importance and criticality, the
prioritization of actions must correlate with the risk and the magnitude
of each situation.

4 Chapter One

The four key CAPA definitions are:

CAPA (corrective and preventive action): A systematic

approach that includes actions needed to correct (correction),
avoid recurrence (corrective action), and eliminate the cause of
potential nonconforming product and other quality problems
(preventive action).
Correction: Action to eliminate a detected nonconformity.
Corrections typically are one-time fixes. A correction is an
immediate solution such as repair or rework. Corrections are
also known as remedial or containment action.

Corrective action: Action to eliminate the causes of a detected

nonconformity or other undesirable situation. The corrective
action should eliminate the recurrence of the issue.

Preventive action: Action to eliminate the cause of a potential

nonconformity or other undesirable potential situation. Preventive
action should prevent the occurrence of the potential issue.

1.2 CAPA relationship

with other quality subsystems
The CAPA system is a critical component of an effective QMS and it must
maintain a close relationship with other quality subsystems (as depicted
in Figure 1.1). The ultimate goal of any regulated company must be
to have a CAPA system that is compliant, effective, and efficient. All
relevant subsystems that may produce nonconformances must be part of
the process.
There are multiple feeders to the CAPA system, both internal and
external to the company (as represented in Figure 1.2). Internal processes
encompass both nonconformance and in-conformance results, internal audits
and assessments, management reviews, and so on. External sources of
CAPA process inputs are supplier audits and assessments, customer
feedback, and results from external audits and assessment such as
regulatory agencies, ISO, and so on. A detailed discussion of those feeders
can be found in Chapter 3.1.1

The Quality System and CAPA 5

Management
controls
Records, document,
and change
controls

Material
controls
Corrective and
preventive actions
Production,
laboratory, and
process controls

Design
controls
Equipment and
facility controls

Figure 1.1 The CAPA system and the manufacturing quality system.

Internal
processes

External
[customer
feedback]

CAPA

External
[3rd-party
audit and
inspection]

Figure 1.2 Feeders of the CAPA system.

External
[supplier]

6 Chapter One

1.3 Corrective or Preventive?

One of the most sterile debates one can witness is the discussion between
two CAPA professionals about whether a specific action they are work
ing on should be considered corrective or preventive. The debate is
pointless because what really matters is whether the action would attack
a root cause.
To add even more confusion, one need only read the formal definition
of corrective action. ANSI/ISO/ASQ Q9001-2008 section 8.5.2 defines
corrective action as action to eliminate the causes of nonconformities in
order to prevent recurrence. ANSI/AAMI/ISO 13485-2003 contains the
same definition, and the FDA regulation for medical devices (Title 21 CFR
820.100) establishes that each manufacturer shall identify the action(s)
needed to correct and prevent recurrence of nonconforming product and
other quality problems. They use the word prevent as part of the corrective
action definition.
To avoid any confusion, the word prevent is replaced by the word
eliminate throughout this book; the definition of corrective action will
read action to eliminate the causes of a detected nonconformity or
other undesirable situation. The corrective action should eliminate the
recurrence of the issue.
A second common source of confusion and misunderstanding is
deeper and more philosophical. Lets say that company A has a situation
where root cause Z is creating a potentially dangerous upward trend, but
the result is still within specification. Someone can argue that because the
result is still within conformance, the action to be taken can be categorized
as preventive. Others may perfectly well argue that it is a corrective action
because the cause was already acting, even though the final result is still
in conformance. My opinion is that it is a preventive action, but whatever
you choose is fine; the important issue is to implement the action as soon
as possible.
For the sake of clarification, Table 1.1 contains the rules followed in
this book.
A typical situation that occurs during nonconformance investigations
is the discovery of both existing and potential root causes simultaneously.
In those cases, actions taken to eliminate the causes of nonconformance
will be corrective actions, while actions taken against identified potential
causes will be considered preventive actions. It is perfectly possible to have
both categories of actions within the same CAPA plan.

The Quality System and CAPA 7

Table 1.1 Corrective or preventive?

Situation
Name it corrective action only if you
already have a product nonconformance
or process noncompliance

Examples
Product failing specifications
Confirmed customer complaint
Use of obsolete documents
Audit finding of product
nonconformance or process
noncompliance

Name it preventive action whenever the

product, process, or system is still in
conformance but you discover root
causes with the potential to create
nonconformities

Developing adverse trends from a

monitoring system (run chart or
control chart)
Shifts
Trends
High variability, and so on

Name it preventive action if it is purely a

recommendation to enhance or improve
any product, process, or system

Changing to new material or new

design
Implement new (enhanced) processes

A third controversy occurs when the same action can be considered

both corrective and preventive when applied to different situations.
Some CAPA professionals believe that once you have a corrective action
(because you already had a nonconformance) to whatever product,
process, or system you extend it, it will always be a corrective action.
Other professionals, including myself, believe that if the same action can
be extended to other products/processes/systems not yet affected by this
root cause, then it should be considered a preventive action.

(This page intentionally left blank)

Index
Page numbers in italics refer to tables
or illustrations.
documenting, 3, 8991
external process inputs, 4
final recommendations, 125126
procedures, 34
process metrics, 85
quality subsystems, 45
quality systems, 14
regulatory importance of, 106
and retraining, 74
and risk management, 3541
system structure, 85
three separate concepts of, 2223
widely accepted concept, 2
CAPA circle, 33
CAPA expert certification
content, 105108
effectiveness evaluation, 109
exam example, 110
CAPA forms
CAPA Plan, 116
Event Description and Investigation,
114
Human Error Investigation, 122
Investigation Report and CAPA
Assessment, 118
CAPA opportunities
effectiveness evaluation, 95
effectiveness verification, 102
human error and retraining, 103
interim corrective actions, 100
isolated events, 9698
root cause identification, 98

actions not as planned, 65

actions taken, 89
active failures, 66
Active Implantable Medical Devices
Directive 90/385 EEC (AIMD), 9
adequate trending, 9698
administrative barriers, 55, 5556
adverse trends, 86
Analyze Data for Trends, 43
ANOVA, 54

barrier control analysis, 55, 5556

batch records, 6263, 72, 75
behavior (transfer of training), 83
benchmarking, 74
best practices, 9495, 96, 97, 9899, 100,
101
blaming, 75
Boolean logic, 5758

calibration and maintenance records, 34

Canadian national standards, 26
CAPA
data sources, 34
debate 6, 7
deficiencies and warning letters, 30
definitions, 4
141

142 Index

symptoms v. causes, 99
timelines, 9395
trending, 9697
true preventive actions, 101
uncorrelated systems, 103
CAPA Plan (form), 116
CAPA plans
best practices, 95
compliance writing, 89
correction/containment action, 90
effective corrective and preventive
actions, 7677
effectiveness evaluation, 7984
executive summary/abstract, 91
final disposition, 91
implementation of, 7879
preventive action, 91
reports, 89
sequential elements, 76
team effort, 77
time requirement, 76
training effectiveness, 8084
validation and verification prior to
implementation, 7778
CAPA processes
effectiveness evaluation, 7980
fixing root causes, 7678
problem detection, 3345
problem investigation, 4675
process flow, 31
system management, 8488
CAPA systems, 32
closed loop, 3
data driven, 2
defined, 1
external CAPA, 87
fault tree analysis, 5859
FDA regulatory trends, 28
feeders to, 4, 5
management of, 8487
management review, 3
and manufacturing quality system, 5
opportunities, 93103
process metrics, 8586
processes and systems, 2
product issues, 2
QSIT description of, 14
risk-based approach, 3

risk management and, 86

structure, 85
causal factors, 4748, 49, 50, 51
cause-and-effect diagrams, 5657, 99
Center for Drug Evaluation and
Research (CDER), 20
certification, internal CAPA expert,
105109, 106, 110
change analysis, 51, 52
change analysis graph, 53
chronology, 51, 52, 56, 99
clinical adverse events, 34
closed loop systems, 3
Commission Directive 91/356/EEC, 9
commission errors, 65, 66
comparison matrix, 51, 54, 56, 99
complaints, 13, 22, 34
compliance writing, 91, 92, 108
comprehensive quality systems (QS)
model, 21
conclusions, about root causes, 90
containment action, 4, 90
continuous improvement defined, 1
control barrier analysis, 5556
corrective action, 1, 4, 6, 2223, 49
corrective and preventive action.
See CAPA
corrective v. preventive action
debate, 67, 7
current good manufacturing
practice (CGMP)
Analyze Data for Trends, 43
CAPA regulations and, 9
defined, 132
FDA guidance, 2123, 43
Medical Devices: CGMP Final Rule, 11
current thinking (in FDA guidance), n.9
customer feedback, 4, 34

Daniel, A., 84
data analysis, 1, 2, 15, 4346, 54
data segregation, 54
defects (nonconformance), 63
defects v. error, 63
deficiencies and warning letters, 30

Index 143

deviations
in life sciences regulated industries, 2
and nonconformities, 38
written procedures and, 10
device master and history files, 63, 75
Do It By DesignAn Introduction to
Human Factors in Medical Devices, 63
document writers, 72
double digit rule, 80, 97, 102
drug and biotech products
observations, 28, 29

effectiveness evaluation, 7980, 96,

109111
effectiveness verification, 102
elements of certification, 110
eliminate (part of corrective action
definition), 6
environment, 62
equipment, 60
error v. defects, 63
errors. See human error
errors of commission, 65, 66
errors of omission, 65, 66
EudraLex, Volume 4, 9, 23
European pharmaceutical GMP, 9, 23
Event Description and Investigation
(form), 114
event information, 89
execution errors, 65
executive summary/abstract, 91
external audits and assessments,
4, 22, 34
external CAPA, management of, 8788
external processes inputs, 4

failure investigation
procedures, 17, 20
requirements for, 11
timelines of, 38
fallibility, 75, 104
fault tree analysis, 56, 5758, 58, 99

FDA (Food and Drug Administration)

beyond compliance approach, 11
common findings in the

United States, 2
comprehensiveness of regulations, 9
consideration of human factors, 63
current thinking, n.9
drug and biotech products
observations, 28, 29
guidance, n.9
medical devices observations, 29, 30
medical devices QSR, 1112
out-of-specification (OOS) guidance,
1920
pharmaceutical CGMP, 1011
quality system inspection technique
(QSIT), 1319
quality systems approach to
pharmaceutical CGMP guidance,
2122
regulatory trends, 28
Sterile Product Guidance, 43
ten inspectional objectives, 1416
time requirements, 93
training effectiveness, 8084
warning letters, 30
field service reports, 34
final disposition, 91
final recommendations, 125126
finished drugs, CGMP for, 9
fishbone diagrams, 5657
5 Ms and 1E (investigative technique),
57
5 Whys (investigative technique), 48,
57, 59
fixable root causes, 48
flowcharts, 51, 52
Food and Drug Administration. See FDA
frequency of event, 37

GHTF quality management system, 27

Global Harmonization Task Force
(GHTF), 25
Guttman, H. E., 66

144 Index

HACCP (hazard analysis and critical

control point) methodology, 35
harmonization processes, GHTF and
ICH, 24
hazard analysis, 35
historical records, 34
human condition, 75, 104
Human Drug CGMP Notes, 93
human error, 6275
abuse of, 103104
better documents, 7475
defined, 64
and human factors, 6364
investigation and prevention,
6869, 75
psychology and classification of,
6468
in regulated companies, 7172
and retraining, 103
simplistic approach, 62
supervision, 75
task analysis and, 52
training, 75
training module, 107
types of, 64
Human Error Investigation (form), 122
human factors, 6364
human factors training module, 107
human reliability engineering, 63
human reliability factors, 61

I-J

ICH Q9, 35
ICH Q10, 25
immediate actions taken, 89
impact assessment, 4243, 89
in-conformance data, 2, 4346
In Vitro Diagnostic Directive 79/98 EC
(IVDD), 9
ineffective CAPA circle, 33
initial impact assessment, 4243, 89
inspection findings, examples, 103
inspectional objectives, 1416
instructions, 61
interim corrective actions, 100
internal audits, 22
internal complaints, 34

internal processes, 4
interview process, 6871
interview techniques, 6869
investigation details, 90
Investigation Report and CAPA
Assessment (form), 118
investigation reports, 89
investigation stage, 94
investigations, risk management and,
3536
IsIs Not matrix, 54
ISO 13485:2003, 2527
isolated events, 9698
issue descriptions, 89

K-T diagram, 54
Kepner, Charles T., 54
Kimmelman, E., 84
Kirkpatrick, Donald L., 81, 83, 84
Kirkpatrick Model for Training
Effectiveness Evaluation, 81, 82, 109
knowledge-based mistakes, 64, 64, 65

lack of attention, 62
lapses of memory, 64, 65, 65
latent failures, 66, 67
lawsuits, 34
learning (from training), 82
legal actions, 34
life sciences regulated industries
deviations and nonconformities, 2
European pharmaceutical GMP, 19, 21
FDA guidance, 19, 21
FDA medical devices QSR, 11
FDA pharmaceutical CGMP, 10
FDA quality system inspection
technique (QSIT), 13
FDA regulatory trends for CAPA, 28
GHTF quality management system, 27
harmonization processes, 24
ICH Q10, 25
ISO 13485:2003, 25
plagued with deviations and
nonconformities, 2
process stability, 45
long-term trending, 4445

Index 145

management factors, 62
management review, 3, 19, 22
manufacturing quality systems,
CAPA and, 5
materials, 61
Medical Device Directive 93/42 EEC
(MDD), 9
medical devices
CGMP for, 9
control of nonconforming product,
1213
FDA observations, 29, 30
regulations, non-U.S., 25
Medical Devices: Current Good
Manufacturing Practice Final Rule:
Quality System Regulations, 11
medicinal products, GMP for, 23
metrics, process, 86
mistakes (error), 63, 64
monitoring activities, 16

non-U.S. medical devices regulations,

25
nonconformance data, 2, 38
nonconformance investigations, 45
risk prioritization of, 41
root causes and, 6
types of, 41
nonconforming product
control of, 12
procedures, 3
nonverbal communication, 70

omission errors, 65, 66

out-of-specification (OOS) guidance,
1921

performance shaping factors (PSF), 63

personal performance, 60
pharmaceutical CGMP, 10
ICH Q10, 25
quality systems approach to, 2122

physical barriers, 55, 5556

poka-yoke (mistake-proofing), 73
potential root causes, 51, 57
prevent (part of corrective action
definition), 6
preventive action, 4, 22
previous corrections, 34
problem description, 5054
problem investigation, 4648
problem-solving tools, 5660
procedures and instructions, 61
process metrics, 8586
process metrics training module, 109
process monitoring data, 34
process trending, 4346, 109
product and quality issues, source
data, 3334
product quality review, 24
production record review, 11

QMS (quality management systems)

CAPA systems and, 45
importance of data analysis, 1
QSIT (quality system inspection
technique), 1319
quality control, 24
quality control unit, responsibilities
of, 10
quality data, sources of, 34
quality management system (QMS)
defined, 1
quality system inspection technique
(QSIT), 1319
quality systems
approach to pharmaceutical CGMP,
2122
defined, 1
maturation of, 2
The Quality Toolbox (Tague), 51
query elements, 98
questions (to determine root causes),
4748

146 Index

reaction (to training, 81

Reason, James, 64, 66, 67, 75
reasonable time lines, 93
record keeping, 13
remedial action, 4
results (impact of training), 84
retraining, abuse of, 74, 103104
returned product, 22, 34
risk assessment, 3541
criteria for, 3637
score matrix, 39, 40
risk-based approach to CAPA, 3
risk management
CAPA and, 3541, 86
training module, 108
root cause analysis, 106
root cause elements, 47
root causes, 49, 50, 51
CAPA to fix, 7678
categories, 6062
conclusions about, 90
existing and potential, 6
and human performance, 71
identification processes, 5660
inability to determine, 59
initial impact assessment, 4243
nonconformance investigations
and, 6
not identified, 9899
other category, 5960
questions to determine, 4748
symptoms, 9899
tools, 5660
rule-based mistakes, 64, 64, 65

sabotage, 62
sampling tables, 17, 18
scrap, rework, and other concessions,
34, 46
sequence errors, 66
severity of event, 37
shaming, 75
short-term trending, 44
should (in FDA guidance), n.9
significant corrective action, 18
silence as communication motivator, 70

situational factors, 6263, 65

skill-based slips and lapses, 64, 64
slips, lapses, and mistakes, 62, 65
slips of action, 64, 65
source data, product and quality issue,
3334
spare parts usage, 34
stability issues, 34
standard operating procedures, 97
statistical process control (SPC), 16
statistical tools, 44
Sterile Product Guidance, 43
stratification analysis, 54
Study Group 3, 27
Subpart J 820.100, 12, 20
supervision, 73, 75
supervision and management, 62
supplier audits and assessments, 4
suppliers, nonconformance and, 87
Swain, A.D., 66
Swiss cheese model of system
failure, 67
symptoms, 49, 50

Tague, Nancy R.
The Quality Toolbox, 51
task analysis chart, 52
time requirements, 79, 80, 85, 86, 93
timelines, event, 51, 52, 53
timing errors, 66
Title 21 Code of Federal Regulations,
210 and 211, 9, 10
Title 21 Code of Federal Regulations,
820, 9, 1314
tools
problem-description, 51
problem-solving, 5660, 99
top-down subsystem approach, 14
training, 34, 60, 7273, 75
as a corrective action, 81
effectiveness of, 8084
training modules
certification, 106, 106109
human error, 107
process metrics, 109
process trending, 109
risk management, 108
root cause analysis, 106

Index 147

Tregoe, Benjamin, 54
trending
adequate, 9698
process, 4346
of root cause categories, 59
unfavorable, 1516
true preventive actions, 100

unattended root causes, 100

uncorrelated data repository systems, 2
uncorrelated systems, 103
unfavorable trends, 1516
United States v Barr Laboratories, Inc.
(1993), 11, 19, 4243

validation protocols, 18, 7678

verification protocols, 18, 7678
violations, 64, 65, 66

W-X-Y-Z

warning letters, FDA, 30

working instructions, 72, 104
written procedures, deviations and, 10

(This page intentionally left blank)

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