The Significance of a CAPA Program as a ‘Bellwether’ for Overall Compliance Efforts
Victoria V. LanderIDEX Corporation21cfrpart11.com
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
Agenda
The Quality Challenge for the GxP Industry
What is a CAPA?
CAPA Implementation & Issues
ISO 13485 and 21 CFR Part 820
Summary
Background
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
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
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
Top FDA 483 Items
QSIT Inspected Firms
CAPA (30%)PAPC (20%)
Records (10%)
Mgmt (40%)Source: Medical Device & Diagnostic Magazine, January 2002
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
CAPA Basics
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
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.
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
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
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
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?
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
Integration into back-end systems
A modular structure, capable of being incrementally deployed
Source: AMR Research
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
Quality Data Sources
Clinical Adverse Reactions
Internal, External, Supplier and Third Party Audits
Installation Feedback
Spare Part Usage
Acceptance Activity - Records Relating to Components
In Process Failures - Reworks and Discards
Finished Product Failures - Reworks
Complaints - Returns and Repairs
Field Service and/or Warranty Reports
Corrective and Preventive Actions
Lawsuits and Other Legal Actions
Published Literature
Reports from Employees
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)
Quality Regulations
GMP
EN 46000ISO 13485/8? QSR
ISO 13485
ISO 13485
ISO 9001
Quality System Regulations
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)
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”
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”
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
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
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
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
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