A CAPA (corrective and preventative action) program is an important indicator of a company's overall compliance efforts. It is considered a "bellwether" by the FDA. An effective CAPA program follows a closed-loop process to identify, correct, and eliminate quality issues and potential problems. It analyzes multiple sources of quality data. Failing to properly establish and maintain CAPA procedures is a common violation cited by the FDA. Ensuring a strong CAPA program that satisfies regulations like ISO 13485 and 21 CFR Part 820 can help reduce compliance risks during FDA inspections.
QMS Effectiveness: Tracking and Trending Quality Data - OMTEC 2017
Capa ‘Bellwether’
1. The Significance of a CAPA
Program as a ‘Bellwether’ for
Overall Compliance Efforts
Victoria V. Lander
IDEX Corporation
21cfrpart11.com
2. What is the Cost of Quality?
"Cost of quality is the amount of money a business
loses because its product was not done right in the
first place. From fixing a warped piece on the assembly
line to having to deal with a lawsuit because of a
malfunctioning machine or a badly performed service,
businesses lose money every day due to poor quality.
For most businesses, this can run from 15 to 30
percent of their total costs."
- American Society for Quality
3. Agenda
The Quality Challenge for the GxP
Industry
What is a CAPA?
CAPA Implementation & Issues
ISO 13485 and 21 CFR Part 820
Summary
5. Quality Challenges
Increasing Role for Pharmaceuticals in Health Care
Increased Number of Products
Greater number, and wider range, of drugs being manufactured
Globalization of the Pharmaceutical Industry
Increase in foreign manufacturing sites
Advances in Pharmaceutical Science, Like Application of
Biotechnology to Drug Discovery and Manufacturing
More Complex and Diverse Manufacturing
Increasing Number of Manufacturing Supplements Submitted
for Agency Review
6. Benefits of a CAPA System
To Strive to Improve Quality
To Recognize Existing or Potential Quality Issues
To Initiate Appropriate Steps Necessary to Investigate and
Resolve these Issues
To Make Sure that the Same Issues Do Not Reoccur
Reduce Risk to Patients
Increase Quality Suppliers and Components
Products Designed and Tested to Meet Customer
Requirements
Waste Elimination
7. Satisfying Compliance With CAPA
A Proactive, Automated Approach to a Quality System
Capturing All Corrective Action Issues and Tracking CA
Processes to Completion
About 30% to 50% of All FDA 483s are Related to Problems
with CAPA Processes
Corrective Action is Core of Quality Management Disciplines
Such As...
Six Sigma DMAIC (Define, Measure, Analyze, Improve and
Control)
TOPS-8D (Team-Oriented Problem Solving, 8 Disciplines)
ISO 9000
8. Top FDA 483 Items
QSIT Inspected Firms
Records (10%)
CAPA (30%)
PAPC (20%)
Mgmt (40%)
Source: Medical Device & Diagnostic Magazine, January 2002
9. Common CAPA Violations
No Established Procedures for Implementing CAPA
No True Root-cause Analysis, Failure Investigations Inadequate
Complaint Handling Too Specific, Do Not Look at Overall System
Failure to Document CAPA Action
No Validation
Failure to Designate & Document Executive Responsibilities
Infrequent Quality Audits
Inadequate Procedures for Quality Audits
Inadequate Procedures for Design Changes
Inadequate Procedures for Documenting CAPA
Lori S. Lawless, FDA, RAPS, October 2003 in Baltimore
11. Definition
•Corrective Action – The Action to
Eliminate the Causes of a Detected
Nonconformity or Other Undesirable
Situation
•The CA Should Eliminate the
vRecurrence of an Issue
12. Definition
• Preventive Action - Action to Eliminate
the Cause of a Potential Nonconformity or
Other Undesirable Potential Situation
• PA Should Prevent Occurrence
• Examples:
• Design Reviews, Trend Activities, Audits, Process
vMonitoring, Risk Management Processes, etc.
13. CAPA is a Systematic Approach
Define the Problem
Determine Root Cause
Implement Corrective Action
Implement Preventive Action
Verify Effectiveness of Implemented CAPA
Document and Disseminate “Close-out”
A CAPA Follows an Assigned Workflow
Process…Assures All Variables Related
to Quality are Addressed
14. Key Elements of a CAPA System
Corrective Action to Eliminate the Cause of the Issues
Preventive Action to Prevent Potential Issues from
Occurring
Data Collection, Analysis and Monitoring
Prioritization of Issues Based on Risks
Active Management Participation
Comprehensive, Complete CAPA Records / Documentation
“Close the Loop” - Was the Resolution Effective?
Initiate for Deviations, Nonconformance, Out-of-Specifications,
Complaints (Reactive)
BUT… Approach Should Also be Proactive
A CAPA Solution Must be an Integrated Part of a Quality and
Compliance Solution
15. Enterprise-Wide Approach
An Internal Agreement for CAPA Definition
Must be reflected throughout entire firm
All Departments Will be Involved in CAPA
Not just Quality Assurance or Compliance
CAPA as an Integrated Part of a Sound Quality
System
It can’t function in a vacuum
Also Used to Evaluate Entire Quality System and
Other Sources of Quality Data
Effective CAPA Programs Should Fully Interact with
Change Control System
16. Define Your CAPA Process:
Key Questions
Who Will Initiate CAPAs?
How Will they be Initiated?
Will other systems drive the CAPA initiation?
How Will CAPAs be Assessed and Investigated?
How Will All CAPAs be Evaluated for their Applicability?
What Completion Requirements Set for Certain CAPA
Activities?
Length of Investigation Before Creating Correction SOP?
Interoperability of CAPA with Other Quality Processes?
e.g., PAT, QSIT, Risk Management
Did You Include Your Change Control System in Your
Planning?
How Will You Monitor CAPA System for Effectiveness?
17. Software and CAPA
Software Helps in Managing & Tracking CAPA
Process
Functionalities in a CAPA IM System Should
Include …
Web-based change management, audit trails and tracking
Visualization, reporting, and quality performance analytics
Configurable workflows
Standard template-based best practice workflows
Roles-based information view
Event management
Source: AMR Research
Integration into back-end systems
A modular structure, capable of being incrementally
deployed
18. CAPA Data Considerations
Product and Quality Data Sources
How will the Data be Captured
How will the Data be Analyzed
Including methods of analysis
When will the Data be Analyzed
What Steps are Taken After Analysis
“Review of the CAPA system document noted that all quality data
sources have not been identified, such as:
• All in-process production test data sources and the routine
analysis performed on these data sources;
• Various data sources for complaints, failure analysis and
repair data from in-house to distributors”
JUNE 11,2003
Roche Diagnostics Corporation
Indianapolis, Indiana, USA
19. Quality Data Sources
Clinical Adverse Reactions Field Service and/or
Internal, External, Supplier Warranty Reports
and Third Party Audits Corrective and Preventive
Installation Feedback Actions
Spare Part Usage Lawsuits and Other Legal
Acceptance Activity - Actions
Records Relating to Published Literature
Components Reports from Employees
In Process Failures -
Reworks and Discards
Finished Product Failures -
Reworks
Complaints - Returns and
Repairs
20. Elements of an Effective System
Use a “Closed-loop Process”
Include Written Procedures and SOPs Used to
Define the Closed-loop Process
Define Responsibility for Managing the CAPA and
Distributed it to the Organization
Establish Sequential Activities that Identify, Correct
or Eliminate Existing or Potential Problems
The tool for managing the closed-loop system
Implement an Information System for Managing the
Information Associated with CAPA
Use Effectiveness Checks to Confirm that Action
Prevented the Recurrence (or Occurrence)
23. About ISO 13485 & ISO 13488
Harmonized EU Medical Device Quality System Similar to
EN 46000 plus Additional Requirements
ISO 13485:1996: Medical Devices - Used with ISO 9001
For manufacturers performing own design activities
ISO 13488:1996: Medical Devices - Used with ISO 9002
For manufacturers without design activities
Certification of a Quality Management System to
ISO 9001/ISO 13485 (EN 46001)
Essential for Global Exportation
Third-party Verification that System Meets Requirements
US 21 CFR 820 Based on this (and ISO 9000)
24. ISO 13485 Corrective Actions
Requirements
ID Nonconformities & Determine their Cause
Including customer complaints
Evaluate Need for Action to Prevent Recurrence of
Nonconformities
Determine and Implement Action Needed, Including
Updating Documentation
Record Results of Any Investigation & Action Taken
Review Corrective Action Taken and Effectiveness
“Shall be Appropriate to the Effects of
the Nonconformities Encountered”
25. ISO 13485 Preventative Actions
Requirements
ID Potential Nonconformities and their Causes
Evaluate Need for Action to Prevent Occurrence of
Nonconformities
Determine and Implement Any Action Needed
Record Results of Any Investigation and Actions
Taken
Review Preventative Actions Taken and
Effectiveness
“Eliminate Causes of Potential Nonconformities
to Prevent their Occurrence”
26. 21 CFR Part 820: Sub-part J
ID Action Needed to Correct and/or Prevent Nonconformance
and Other Quality Problems
Employ Appropriate Statistical Methodology to Detect
Recurring Quality Problems
Investigate Causes of Nonconformities for Product, Processes
and Quality System
Ensure that Information for Quality Problems is Disseminated
to those Responsible for Assuring Product Quality
Submit Information on Quality Problems and CAPA for
Management Review
Document All Activities and Results Required Under this
Section
Verify or Validate the CAPA
27. 21 CFR Part 820: Sub-part J
Analyze the Following to ID Causes of
Nonconformance or Other Quality Problems …
Processes
Work operations
Concessions
Quality audit reports
Quality records
Service records
Complaints
Returned products
Other sources of quality data
28. FDA Warning Letter
“Failure to adequately establish and maintain
procedures for implementing corrective and
preventive action, which include requirements
for analyzing processes, work operations,
concessions, quality audit reports, quality
records, service records, complaints,
returned product, and other sources of
quality data to identify existing and potential
causes of nonconforming product or other quality
problems, as required by 21 CFR 820.100(a)
(1).” June 11, 2003
Roche Diagnostics Corporation
Indianapolis, Indiana, USA
29. The FDA and CAPA
Strength of CAPA Program is Important Indicator that
Impacts FDA Inspectors’ View of Other Compliance
Efforts
e.g. 21 CFR Part 11, Predicate Rules
When FDA Finds Strong CAPA Program at Outset of
Inspection, it’s a “Bellwether” for Your Overall Quality
Compliance Programs
Despite the FDA’s Recent Moves to Narrow Enforcement
of Part 11, Regulated Firms Should Bank on Agency
Scrutinizing CAPA More During Inspections
http://www.fda.gov/cder/gmp/index.htm
30. Summary
Address Your Culture
Conduct Independent Reviews
Simplify Documentation
Use a “Closed-Loop” System
Monitor Your Process
Change With Your Business
Participate in Industry Meetings
Talk to People/Peers
Never Stop