The Significance of a CAPA
Program as a ‘Bellwether’ for
Overall Compliance Efforts
Victoria V. Lander
IDEX Corporation
21cfrpart11.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
Records (10%)
CAPA (30%)
PAPC (20%)
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
Source: AMR Research
 Integration into back-end systems
 A modular structure, capable of being incrementally
deployed

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  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

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

Quality System Regulations
EN 46000 ISO 13485 QSR
ISO 13485/8?
ISO 9001

GMP ISO 13485

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

Thank You For Your Attention!
vlander@nugenesis.com