CAPA (Corrective and Preventive Action) is a quality system plan which aims to resolve compliance issues and to prevent any further recurrences. A CAPA plan is crucial to a clinical trial as it helps keep trial participants safe and protects their rights. It also prevents the study data from being compromised.
CAPA processes include:
- Identifying a potential issue
- Identifying the root cause of the issue
- Identifying actions to prevent the recurrence of the issue (Corrective Action) and identifying actions to prevent a problem from occurring (Preventive Action)
- Documenting that the Corrective and Preventive Actions were carried out
- Documenting that the Corrective and Preventive Actions has resolved the issue(s)
The Therapeutic Goods Association’s (TGA) ICH Guideline for Good Clinical Practice (GCP) and the National Health and Medical Research Council (NHMRC): Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for Trials Involving Therapeutic Goods require the clinical trial Sponsor-Investigator to perform a thorough analysis and implement a Corrective and Preventive Action (CAPA) plan if a serious breach takes place.
Corrective Action is reactive, while Preventive Action is proactive and although they both use similar procedures, they are not always used together.
The 5 Whys
The 5 Whys is a simple but powerful tool to help determine the root cause of a problem by repeatedly asking why something occurred in various ways until the cause is identified.
Corrective Action is the immediate action taken in response to a problem that has already occurred or which has been identified.
It includes the identification, documentation and elimination of a root cause of a nonconformity or problem to prevent the problem from happening again.
Corrective Action procedures include:
- Identify and document the issue: Use the ‘5 Whys’ questioning tool to determine if this is an isolated event or if it has the potential to recur. Ensure that it is a real problem and not a perceived problem.
- Identify how big the problem is: What is the scope of the problem? Understand how serious it is before beginning to address it.
- Implement a correction/containment or temporary repair: How can the problem be avoided while fixing the root cause?
- Find the Cause of the Issue: Use 5 Whys to determine the root cause of the problem.
- Find a solution: What do you need to change to eliminate the root cause? Find a solution (changes to processes, safety procedures, etc) to prevent a problem from recurring.
- Implement Corrective Action: Implement the Corrective Action and ensure that all the important information is documented.
- Verify that the resolution is effective: Wait a suitable amount of time to ensure that the problem doesn’t recur and document the evidence of continued success.
Preventive Action refers to the actions which are taken to eliminate the root cause of a potential problem(s).
Preventive Actions exist to prevent potential problems from happening before they occur and also to identify any improvements that can be made.
Preventive Action Processes include:
- Detailed Preventive Action plan: Creating a detailed preventive action plan to reduce the risk of potential problems.
- Implement controls: Implement controls to ensure that any preventive measures which are introduced continue to be effective. These controls are important to prevent and check for any possible breaches.
Responsibilities for Managing CAPAs
- The clinical trial Sponsor-Investigator is responsible for implementing a CAPA plan template and developing procedures for the management of CAPAs.
- The Human Research Ethics Committee (HRECs) assesses whether the Corrective and Preventive Actions implemented by the Sponsor-Investigator are appropriate and have thoroughly addressed the root cause.
- For any issues that arise on the clinical trial site, the Principal Investigator needs to work with the institution or Sponsor to implement CAPAs.
- All documentation relating to the CAPA processes need to be added to the Trial Master File (TMF) and the Investigator Site File. This includes any correspondence between the Sponsor-Investigator, Principal Investigator and the reviewing Human Research Ethics Committee (HREC).
CAPA Action Plan
A CAPA plan identifies issues that arise during a clinical trial, the root cause of those issues and the Corrective and Preventive Actions taken to prevent a recurrence of the problem. It should be detailed and thorough and should include the following:
- A detailed account of what occurred
- A summary of the investigation and root cause analysis
- A description of the root cause
- A list of Corrective and Preventive Actions and the plan for implementing them
- Signatures of the Principal Investigator, Research Coordinator, Quality Assurance Manager and other key people involved.
Each individual issue needs its own CAPA plan which should be reviewed, signed and dated by the individual who creates the plan and the Principal Investigator. It needs to then be submitted to the appropriate regulatory body.
A summary of the CAPAs need to be kept in a CAPA tracking log and stored with other important clinical trial documents in the Trial Master File (TMF).
After a CAPA plan has been created, the plan needs to be shared with other appropriate personnel, and a timeline needs to be created for the Corrective and Preventive Actions. When all the actions have been implemented, the CAPA process can then be considered completed.
CAPA Action Plan Outline
Date: The date that the CAPA is written.
To: Who the CAPA plan is addressed to (the Sponsor, or HREC, etc).
From (the person responsible for the CAPA): Details including: their name, title, the site/institutional affiliation of the author and their signature.
Protocol Title/Research Study
Human Research Ethics Committee (HREC) Number
Issue/Deficiency Identified: Outline the issues/problems being addressed (can be in a paragraph or a list).
Root Cause: State the reason why the issue arose in the first place.
Corrective Action Plan: Description of the Corrective Actions taken/planned. Indicate if the site was asked to perform the Corrective Actions and by who (Sponsor, etc) and on what date.
Implementation: A description of the processes used to document the resolution of the problem, and the people responsible for the procedures, etc.
Effective Date of Resolution: The date the effective Corrective Action took place.
Preventive Action: Description of the Preventive Actions taken/planned by the site. Indicate if the site was asked to perform the Preventive Actions and by who (Sponsor, etc) and on what date.
Evaluation/Follow-Up: Any plan/processes to evaluate the implementation and completion, the people responsible for the evaluations and the timeframe, etc.
Comments: Any additional comments or observations not mentioned above.
Principal Investigator Signature/Date