Professional Documents
Culture Documents
CAPA For The FDA Regulated Industry
CAPA For The FDA Regulated Industry
FDA-Regulated
Industry
Jos Rodrguez-Prez
Dedication
This book is dedicated to my wife Norma and
my son Jos Andrs. Their continuous support
and love made this book possible.
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
9
10
11
vii
13
19
21
23
24
25
25
27
28
viii Contents
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
93
93
96
98
99
100
100
101
102
103
103
105
105
113
114
116
118
122
109
110
Table 1.1
Corrective or preventive?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1.2
Figure 2.1
Table 2.1
Figure 2.2
Table 2.2
28
29
29
30
Figure 3.1
31
Figure 3.3
33
Figure 3.2
Table 3.1
Table 3.2
Table 3.3
41
Figure 3.5
Figure 3.7
Table 3.5
Table 3.6
Figure 3.8
Figure 3.9
Table 3.7
Table 3.8
39
40
Figure 3.6
36
Figure 3.4
Table 3.4
32
41
46
47
49
50
51
53
53
55
55
Figure 3.10
58
Table 3.9
65
Figure 3.11
Table 3.10
Table 3.11
64
75
82
Table 4.1
92
Table 6.1
106
Table 7.1
123
Table 6.2
110
Preface
xiv Preface
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).
4 Chapter One
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]
External
[supplier]
6 Chapter One
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
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
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
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
failure investigation
procedures, 17, 20
requirements for, 11
timelines of, 38
fallibility, 75, 104
fault tree analysis, 56, 5758, 58, 99
144 Index
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
146 Index
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
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
W-X-Y-Z
Vision
By making quality a global priority,
an organizational imperative, and
a personal ethic, ASQ becomes the
community of choice for everyone who
seeks quality technology, concepts,
or tools to improve themselves and
their world.
ASQ is
More than 90,000 individuals
and 700 companies in more than
100 countries
The worlds largest organization
dedicated to promoting quality
A community of professionals
striving to bring quality to their
work and their lives
The administrator of the Malcolm
Baldrige National Quality Award
A supporter of quality in all
sectors including manufacturing,
service, healthcare, government,
and education
YOU
ASQ Membership
Research shows that people who join
associations experience increased
job satisfaction, earn more, and are
generally happier.* ASQ membership
can help you achieve this while
providing the tools you need to
be successful in your industry and
to distinguish yourself from your
competition. So why wouldnt
you want to be a part of ASQ?
Solutions
Find answers to all your quality
problems, big and small, with
ASQs Knowledge Center, mentoring
program, various e-newsletters,
Quality Progress magazine, and
industry-specific products.
Networking
Access to Information
Professional Development
Advocacy Programs
ASQ Certification
ASQ certification is formal recognition
by ASQ that an individual has
demonstrated a proficiency within,
and comprehension of, a specified
body of knowledge at a point in
time. Nearly 150,000 certifications
have been issued. ASQ has members
in more than 100 countries, in all
industries, and in all cultures. ASQ
certification is internationally accepted
and recognized.
Certifications Include
Calibration Technician CCT
HACCP Auditor CHA
Pharmaceutical GMP Professional
CPGP
Quality Inspector CQI
Quality Auditor CQA
Quality Engineer CQE
Quality Improvement Associate
CQIA
Quality Technician CQT
Quality Process Analyst CQPA
Reliability Engineer CRE
Six Sigma Black Belt CSSBB
Six Sigma Green Belt CSSGB
Software Quality Engineer CSQE
Manager of Quality/Organizational
Excellence CMQ/OE
Self-paced Online
Programs
These online programs allow you to
work at your own pace while obtaining
the quality knowledge you need.
Access them whenever it is convenient
for you, accommodating your schedule.
ASQ Training
Classroom-based Training
Basic Quality
Auditing
Engineering
Education
Healthcare
Government
Food Safety
ISO
Leadership
Lean
Quality Management
Reliability
Six Sigma
Web-based Training
Social Responsibility
Virtual Courses
ASQs virtual courses provide the same
expert instructors, course materials,
interaction with other students, and
ability to earn CEUs and RUs as our
classroom-based training, without the
hassle and expenses of travel. Learn
in the comfort of your own home or
workplace. All you need is a computer
with Internet access and a telephone.