CAPA in the Pharmaceutical and Biotech Industries

1. Understanding the FDA’s CAPA requirements and regulations

• Part I. 21 CFR part 820.100 for medical devices
• Part II. 21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals
• Part III. The FDA’s current inspectional approaches
• Part IV. QSIT and CAPA: inspectional objectives
• Part V. Quality systems approach to pharmaceutical current good manufacturing practice regulation, September 2006
• Part VI. ISO 13485 and CAPA: inspectional objectives
• Summary to part VI

2. Implementing a CAPA program: Going back to basics

• Corrective and preventive actions
• General requirements
• CAPA process
• Correction/remedial action
• Evaluation of risk
• CAPA process metrics
• Closed-loop corrective action

3. The nine-step CAPA program

• The nine-step process

4. Step 1: identification of the event and writing a proper problem statement

• Write a detailed problem statement
• Use the “Ws” and “Hs”
• Step 1: identification of the problem and effective compliance writing
• Scenario 1
• Scenario 2
• Root cause analysis: methods, whys, and the fishbone diagram
• Understanding the problem statement and the evaluation of the event
• Seeking quality data
• Document the problem
• Explanation of the problem
• Evidence
• Evaluation
• More on report writing
• Summary

5. Step 2: risk assessment and impact assessment

• Why include risk analysis in CAPA programs?
• What it means to integrate risk analysis into CAPA
• Evaluation
• Assessment of risk
• Risk-management process
• The level of investigations, and the extent of corrective and preventive actions
• Some important definitions related to risk
• Maintenance of risk-analysis results/worksheets/forms
• Summary

6. Step 3: evaluate event and initiate remedial actions (correction)

• Part I. Internal corrections
• Part II. Corrections and removals (external corrections)
• Responsibilities
• General requirements
• Recalled/recovered product disposition
• FDA reportable field action
• Nonreportable field actions

7. Step 4: data gathering and analysis

• Potential causes and data collection and analysis
• Data, quality indicators, and triggers
• Levels of reviews
• Data collection should be planned as follows
• Data analysis and the investigation process
• Data collection
• Potential causes and data collection and analysis
• Results and data
• CAPA system data collection and analysis
• The general process for data collection and analysis
• CAPA system review
• Problem analysis
• Improvement
• Investigation process metrics
• Closed loop corrective action

8. Step 5: investigation

• When investigation is needed
• Information may not be completely accurate or reliable
• Responsibilities/resources
• Internal data sources
• External data sources
• Introduction of the investigation process
• Investigation initiation
• Investigation owner and team designation
• Team constitution
• Investigation methodologies definition/selection
• Investigation plan elaboration
• Investigation plan approval
• Execution of the investigation
• Potential causes and data collection and analysis
• Results and data
• Problem analysis
• Investigation results submission
• The risk evaluation update
• Investigation results approval
• The investigation owner is responsible for the following:
• The CAPA coordinator is responsible for the following:
• Ensure accurate documentation
• Step 5: investigation part II: out of specification
• Investigating and assessing OOS results—principles of failure investigation
• Step 5: investigation part III—complaint investigation

9. Step 6: part I—root cause analysis

• Outcome
• How to conduct an RCA and the RCA team
• Definition of the problem
• Gathering relevant data
• Cause/effect analysis
• Open issues/notes
• Action plan
• RCA assessment and maintenance
• Part II: RCA tools
• Philosophy of RCA
• Symptom approach versus root cause
• How do we do RCA?
• RCA major steps
• RCA process charting
• Typical checklist for aspects to be considered when doing the RCA
• Barrier analysis
• Barrier analysis: pros and cons
• Definitions
• Change analysis
• Definitions
• Pros and cons
• Discussion
• What is a suitable basis for comparison?
• The purpose of change analysis
• Brainstorming
• Brainstorming guidelines
• Fishbone diagram
• What does it look like?
• How is it done?
• Guidelines
• People
• Machines
• Measurement
• Material
• Environment
• Methods
• Methods
• 5W techniques or why diagram
• Control charts
• Types of variation
• Types of variation
• Check sheets can be used to gather and group data
• Pareto analysis
• It is critical to determine the whys?
• Mistakes do not just happen
• Preventing human error
• Error proofing: 5S methodology
• Continuous improvement models: 5S
• Human error assessment and reduction technique
• Part III: example of investigation tools for why diagrams and fault tree diagrams
• Containment/correction
• Investigation plan
• Investigation elements
• Summary of root/contributing causes
• Investigation and root cause conclusion

10. Step 7: corrective and preventive action plans

• Completing corrective/preventive action plans

11. Step 8: implement and follow-up on action plans

• Action plans
• Execution of the CAPA plan
• Follow-up action plan
• Follow-up: a fundamental step in the CAPA process
• Upon completion of each corrective action/preventive action
• CAPA and change control
• Classification of the change

12. Step 9: verification of effectiveness

• Verification/effectiveness of the actions
• CAPA verification of effectiveness plan
• Conclusion

13. Examples of procedures

• Procedure example #1. SOP: control of nonconforming product
• Procedure example #2. OOS: SOP
• Procedure example #3. SOP: corrective and preventive
• Procedure example #4. SOP: FMEA SOP
• Procedure example #5. OP: RCA
• Procedure example #6. SOP: quality system data analysis

Conclusion: requirements for an effective CAPA program