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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.
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.
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
Kamal Biswas
Proposed 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.
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
ICH
Location 4
Kamal Biswas
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
Figure 3
Productivity improvement function
Early stage detection of problems can improve throughput and make operations
more productive.
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.
Kamal Biswas
Reaction
Steps
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.
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.
Step B
Kamal Biswas
The Vision
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.
Figure 5
Move from Corrective to Preventive Action
Corrective
Action
Preventive
Action
Corrective
Action
Preventive
Action
Kamal Biswas
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%
10
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.
Figure 7
System Features Interact
Analysis
Deviation Flag
CAPA resolution
Knowledge base
Failure analysis
CAPA Monitoring
11
12
Document
Mgmt
Plant
Mgmt
LIMS
MES
Notify
Process
Owner
Create
Deviation
Impact
Analysis
Notify
Regulatory
Manager
Data
Comparison
Deviation Monitoring
Complete
Actions
Approve
Actions
Generate
Investigation
Report
Assign
Actions
Create
Action Plan
Review
Investigation
Report
Complete
Investigation
Notify
Investigators
Define
Investigation
Workflow
Instruct for
Product
Containment
Initiate
Root Cause
Analysis
Initiate
Investigation
Close
CAPA
CAPA Reporting
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
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Kamal Biswas
CFR
GCP
Information Technology
NDA
PAT
QSIT
QSR
R&D
United States
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