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Future State CAPA ManagementA Productivity Improvement Tool

By Kamal Biswas

EXECUTIVE SUMMARY
ABSTRACT
The top spot in the Food and Drug Administration
(FDA) observations (FDA 483) list has almost permanently been taken by Corrective and Preventive
Action (CAPA). Being a major subsystem of FDAs
Quality System Inspection Technique (QSIT), CAPA
is audited in all FDA inspections. Effective CAPA
management is a top priority to ensure compliance. While compliance need is given, it should be
viewed with a broader outlook to use it as a productivity improvement tool. That way it could get all
the stakeholders buy-in, hence better compliance
would result. CAPA should not be regarded as the
headache of the quality functions; it should become
an integral part of operations.

CAPA has been a major stumbling block for many pharmaceutical companies, mainly to manufacturing operations. About 40% FDA 483s seen in the industry relate to
CAPA - the highest single category of FDA non-compliance. Therefore, the FDA does a thorough check during
every inspection it performs in a company. If companies
know that CAPA is a major non-compliance issue, why
are they not taking adequate safeguard measures? It is
the authors opinion that current CAPA measures are
failing because CAPA is often considered a compliance
need rather than as an important mechanism to improve
operational excellence.
Effective CAPA management will not only save pharma
companies in compliance audits, its preventive measures
can help companies improve productivity by radically reducing rework. Effective CAPA management could bring
on time analysis of process execution data to identify deviations and take early action improving quality and productivity. CAPA needs to be viewed with a broader outlook
and made a key focus area for corporate, away from the
traditional view of a point-in-time localized function. Companies can get substantial benefits by taking an enterprising view of CAPA.

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Kamal Biswas

INTRODUCTION

Industry Trend

What is CAPA?
FDA regulations for CAPA for the pharmaceutical company are defined in Code of Federal Regulations (CFR)
21 section 211, as part of the Quality System Regulations (QSR). This process identifies reported and potential causes of product SQUIP- Safety, Quality, Integrity,
Potency or Purity - performs root cause analysis of deviations, and determines appropriate corrective and preventive actions to eliminate repetition of failure. The program ensures that corrective and preventive actions get
implemented through proper management reporting and
review. FDA views this as a linkage to the entire quality
management process. That is why the FDA makes sure
that CAPA audit is done without any deviation at all levels of its inspection in all pharma companies.

CAPA is a very important function, but it does not get


sufficient attention because it does not fall under core
production processes.
FDA reports show that 30%-50% of observations
(FDA 483s) are related to CAPA. In Quality Systems Inspection Techniques (QSIT), management function is
given importance and made responsible for observations, thereby bringing many CAPA management issues
under the management umbrella and reducing CAPA issues, but even the lowest percentages show that CAPA
needs to be addressed with greater priority.

Figure 1
QSIT Inspections - Graphical Analysis

Non-QSIT Inspections
Records: 20
CAPA: 50

QSIT Inspections
Management: 40

Records: 10

PAPC: 20

PAPC: 30

CAPA: 30

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Kamal Biswas

Drivers of the Current Situation

Proposed View

Pharma Companies View

The pharma industrys view is correct, but there is justification for another view. While pharma companies
highlight operational difficulties as the major reason for
CAPA non-compliance, there are many other causes:
CAPA is seen in the narrow light of a compliance need,
and therefore, is considered as extra work by all except
the compliance group.
It is not part of core production processes, and therefore is dis-integrated from core operations.
It is taken as a point-in-time localized problem, not
as part of an enterprise initiative that can bring more
focus.
CAPA plays a big role in corporate risk. It can radically
disrupt businesses, but it does not appear in corporate
risk management programs and remains the responsibility of production managers.

Numerous manual processes required to produce the


final product hamper the CAPA process.
Managing the parent-child relationship in raw materials
across products is challenging. This problem increases
many fold in dispersed operations.
A proliferation of regulations makes compliance cumbersome, expensive and often confusing if not contradictory.

Figure 2
Complex Compliance Issues
Too complex a situation for efficient compliance - multiple regulations, multiple
products, multiple locations
Location 2

Location 3

FDA

LOCATION-1

OSHA

Location 5

Operations

Purchase

Quality

R&D

Sales

Continuous
Improvement

Customer Care

EHS

Field Services

Finance

Engineering
Support

HR

ITY

Legal

Marketing

EPA

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ICH

Location 4

Kamal Biswas

DESIGN CAPA WITH A


BROADER PERSPECTIVE

Make CAPA Part of Core Operations


To make CAPA part of core operations, it must, as a
system, provide added value to operations.

While CAPA covers remedial corrections of an identified problem, root cause analysis with corrective action
to help understand the cause of the deviation and
potentially prevent recurrence of a similar problem, and
preventive action to avert recurrence of a similar potential problem as part of Quality Systems, it needs to be
expanded with a broader outlook and go beyond quality
systems into core operational excellence. The following
four major steps can make this happen:
Make CAPA part of core operations
Integrate CAPA review as part of Corporate Risk Management
Make it mandatory for all business divisions to participate in and collaborate with the CAPA program
Make the CAPA program part of the financial turnaround

Use it as a productivity improvement tool


U tilize the program to increase operational
success predictability

CAPA Review as Part of Corporate Risk


Management
Design the CAPA program as part of the corporate
mandate. The CAPA program must be seen as a core
operation that can put the organization at risk if not
properly acted upon. Corporate risk management needs
to mandate all CAPA incidents to be reported at the corporate level and must include CAPA incidents as part of
performance metrics. They should be as critical as other
business performance metrics such as top-line and bottom-line growth. Ineffective CAPA management can truly
impact the top- and bottom-lines of companies.

Figure 3
Productivity improvement function
Early stage detection of problems can improve throughput and make operations
more productive.

Example: How CAPA can help improve productivity and throughput


Reaction
Steps

Step A
80% yield

Step B
80% yield

Step C
90% yield

Hypothesis

If product D fails in final quality check, it needs to be reprocessed that sheds ~20%
of Product D. This reduces the overall yield to 46%.

Throughput
Productivity

CAPA can detect the problem early enough in the reaction lifecycle that will help
avoiding the reprocessing-hence the overall yield improved to 58%. Elimination of
reprocessing improves the production productivity.

Special Edition: Corrective and Preventive Action Vol. II

Example: How CAPA can help improve product quality

Kamal Biswas

Reaction
Steps

Example: How CAPA can help improve productivity and throughput

Step A
80% yield

Step B
80% yield

Step C
90% yield

If product D fails in final quality check, it needs to be reprocessed that sheds ~20%
Figure
4
Hypothesis
of Product D. This reduces the overall yield to 46%.
Predictability of Occurrence and Impact on SQUIP- Safety,
Quality, Identity,CAPA
andcan
Purity
orthe
Potency
detect
problem early enough in the reaction lifecycle that will help
Throughput
avoiding
the
reprocessing-hence
the overall yield of
improved
to 58%.
Elimination
of of
Use
enterprise
CAPA
system
to
improve
predictability
success,
both
in terms
Productivity
reprocessing
improves
the
production
productivity.
quality and cost of the final product.

Example: How CAPA can help improve product quality


Reaction
Steps
Hypothesis
Quality

Step A
80% yield

80% yield

Step C
90% yield

Due to deviation in process, some of the reaction steps may remain incomplete
leading to more impurities in product D.
Routine QC checks are designed to test pre-defined tests that may not be enough
to detect impurities due to process deviation. A robust CAPA system can find the
deviation early to enable appropriate remediation steps.

Some of the sample metrics that can be tracked


include:
Product reprocessing loss
CAPA incidents with potential impact on product quality
Impact on regulatory commitments
Impact on validation status
Other product or lots potentially impacted
Need for an NDA Field Alert report or recall
Pre-defined periodic monitoring of metrics at the Corporate Risk Management Council would surface CAPA trend
and loss of productivity. The visibility at top management
on the productivity loss could bring more seriousness into
the CAPA initiative to make it more successful.

Step B

Make it Mandatory for all Business


Divisions
to Participate and Collaborate
CAPA programs must be implemented across business
functions such as manufacturing, engineering, maintenance, automation, safety, and even research and
development. Many functions, such as early stage R&D,
do not follow CAPA because they are viewed as compliance functions. But, if CAPA is treated as a mechanism
to identify the root causes of failures, it can help R&D
functions become more productive; for example: CAPA
applies to protocol deviation as well as GCP Note to
File investigations and remediation. A robust electronic
quality management system would accommodate all
GXP, not only cGMP.

Special Edition: Corrective and Preventive Action Vol. II

Kamal Biswas

Make it Part of Financial Turnaround

The Vision

Accountants must report the loss of revenue due to CAPA


incidents. This should include direct productivity loss as
well as loss of time. FDA regulations do not allow release
of a product until all CAPA issues for that batch are
closed. This, at times, increases inventory at the manufacturing plant and creates shortage of product supply in the
market, thereby reducing cash flow the throughput impact
due to rework increases manufacturing cost significantly.
These important metrics fortracking the performance of
the whole organization can be improved by placing more
importance on CAPA.

Make CAPA a part of core activities and provide a system to execute the program efficiently.
The strategy to develop an efficient CAPA program is
accomplished by changing the 90%+ corrective action
scenario to 90%+ preventive action mode. Information
Technology (IT) systems can help achieve this.

HOW INFORMATION
TECHNOLOGY CAN HELP
Information Technology (IT) can help pharma companies
reduce CAPA incidents and improve quality, while improving productivity by detecting issues very early in production.

The System Requirements


Well defined requirements specifying the internal and
external needs must be covered. They must include the
proper handling of quality deviations, process deviations, audit findings, Non Conformance Reports, operational disruptions, change management, quality assurance checks, and customer complaints.
It is very important to include all business functions and
their processes to monitor and track CAPA incidents. CAPA
architecture must be robust to scale enterprise needs. It
must also be flexible to accommodate process customization for multiple sites, regions, countries, or regulations.

Figure 5
Move from Corrective to Preventive Action

Corrective
Action

Preventive
Action

Corrective
Action

Preventive
Action

Special Edition: Corrective and Preventive Action Vol. II

Kamal Biswas

Data analysis to help resolve CAPA incidents has to be


built into the system to make the system critical enough
for operational teams.
Create the system keeping in mind a future state of
compliance - make it 21 CFR Part 11 compliant. This will
help the company in taking a step forward to electronic
submissions and Process Analytical Technology (PAT).

The Solution
A well defined requirement can help in building a system that meets all business needs.
Define user requirement specifications and a strong
business case to support development of the system. Executive sponsorship is a must for a successful program
and early user buy-in makes the program useful. A strong
business case and a change management initiative are
always useful.

Figure 6
Sample Business Case Parameters
Process Variables

Benefit Calculation

Description

Current

1. Number of CAPA incidents
5
2. Average time spent in looking for documents,
templates
25%

3. Average time spent in document handling
10%

4. Average time spent in status trackingmeetings, phone calls
20%

5.
...
Description
Current

Reduction in CAPA management time
2.80%

Future

4

5%

0%

5%

...
Future

0.85%

Annual Cash Flow Benefit

10

Special Edition: Corrective and Preventive Action Vol. II

Delta

20%

20%

10%

15%

...
Delta

1.95

$146,250

Kamal Biswas

SUCCESS STORY

System Features
The IT system should be able to continuously monitor data against the standard and create deviation
alerts.
The system must be able to provide features that dive
deep into earlier data and help solve CAPA issues.
It must show CAPA status on a real-time basis.
CAPA players should be able to manage all actions
using the workflow.
All required data must be accessible from the systems.
Manual collection of data and its upload into the system will reduce its popularity.
The system should be self-sufficient to manage CAPA
end-to-end.

Effective CAPA design can have a major impact in


product release cycle time. This has been observed
for a major U.S. pharma company. The author was
involved in helping them to design, develop, and roll
out a product release and CAPA system for their
manufacturing unit. The system helps the product
release team create a single view of manufacturing
artifacts with all CAPA incidents and their status. Key
metrics collected to support the companys decision
to invest in the CAPA initiative included:
60% reduction in product release time
Extensive reduction in CAPA incidents
Increased confidence in product release with all re-

Figure 7
System Features Interact

CAPA Action and Closure

Historical data analysis

Compare with Standards

Analysis

Deviation Flag

CAPA resolution
Knowledge base
Failure analysis

CAPA Monitoring

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12

Document
Mgmt

Plant
Mgmt

LIMS

MES

Notify
Process
Owner

Create
Deviation

Impact
Analysis

Notify
Regulatory
Manager

Data
Comparison

Deviation Monitoring

Special Edition: Corrective and Preventive Action Vol. II

Complete
Actions

Approve
Actions

Generate
Investigation
Report

Assign
Actions

Create
Action Plan

Review
Investigation
Report

Complete
Investigation

Notify
Investigators

Define
Investigation
Workflow

21 CFR Part 11 Compliance Audit Trail

Change Control Management

Instruct for
Product
Containment

Initiate
Root Cause
Analysis

Initiate
Investigation

Close
CAPA

CAPA Reporting

CAPA Status Monitoring

Historical Data
Analysis

Figure 8
CAPA Management
Control Chart

Materials
Mgmt

Input System

CAPA Tracking

Kamal Biswas

Analytics

Kamal Biswas

quired documents compiled and stored online to enable easy retrievability for audits
Production database created to analyze historical data
and for use as a knowledge base
A step toward FDA e-submission
The problem was viewed as an end-to-end manufacturing problem and provided a solution not only to reduce compliance issues but also improve operational efficiency.
The system has separate CAPA components for R&D
and manufacturing to keep the two processes separate.
The system is designed to get data from existing applications with a provision for manual entry as well. It has a
deviation monitoring component to send alerts to concerned stakeholders and for workflow-driven end-to-end
CAPA tracking.

CONCLUSION

REFERENCES
1. QSIT workshop material on Corrective And Preventive Actions:
http://www.fda.gov/cdrh/comp/qsitpage.html
2. Internal Research- Infosys Technologies Ltd: http://www.infosys.com
3. Food and Drug Administration : http://www.fda.gov

ABOUT THE AUTHOR


Kamal Biswas is with Life Sciences Consulting in Infosys
Technologies Limited. Kamal is an expert in Pharma IT
strategy and regulatory compliance in FDA regulated
industry. He has over a decade experience in pharmaceutical manufacturing operations and IT. He is a
thought leader in pharma IT strategy, IT enabled productivity in pharmaceutical manufacturing operations, and
regulatory compliance transformation. Kamal is based in
New York City /New Jersey, USA, and can be reached
at kamal_biswas@infosys.com.

Historically, pharma companies have not provided


enough attention to CAPA programs and CAPA management. The compliance focus needs to be strengthened
by adding CAPA as a part of the core activity. Production
team should use this as a productivity improvement function and not just as a compliance need. Making it a key
performance indicator for corporate risk management will
help in monitoring it more closely. Company finance teams
must be more vigilant to this function and must report loss
of revenue due to it.
Good CAPA management improves compliance and
productivity, and also builds the image of a good quality
system practices company. This helps in building a brand
that drives customer excellence and satisfies regulatory
authorities. An enterprise-level CAPA strategy, backed by
strong IT system support, can help achieve this.

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Kamal Biswas

Article Acronym Listing


CAPA

Corrective Action Preventive Action

CFR

Code of Federal Regulations

cGMP Current Good Manufacturing Practice


FDA

Food and Drug Administration

GCP

Good Clinical Practice

CGXP Current Good Clinical, Laboratory, Manufacturing Practice


IT

Information Technology

NDA

New Drug Application

PAT

Process Analytical Technology

QSIT

Quality System Inspection Technique

QSR

Quality System Regulation

R&D

Research and Development

SQUIP Safety, Quality, Identity, Purity/Potency


U.S.

United States

Originally published in the October 2007 issue of The Journal of GXP

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Special Edition: Corrective and Preventive Action Vol. II