Corrective and Preventive Action

Both the TGA: ICH Guideline for Good Clinical Practice and the NHMRC: Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for Trials Involving Therapeutic Goods require the Sponsor-Investigator to perform a root cause analysis and implement an appropriate Corrective and Preventive Action plan (CAPA) if a serious breach occurs. 

A CAPA is a quality system plan and incorporates: 

  1. Identifying the issue, including scope and impact
  2. Identifying the root cause of the issue – how/why it occurred
  3. Identifying actions to prevent recurrence of the issue (corrective action) or, identify actions to prevent an issue from occurring (preventive action)
  4. Documenting that the corrective actions/preventive actions were completed
  5. Documenting that the corrective/preventive action has resolved the problem

Process for implementing CAPAs

The Sponsor-Investigator (or sponsoring institution) is responsible for developing a process for the management of CAPAs, including a CAPA template. This may be provided to sites to use for implementing CAPAs in response to a local serious breach when there is not a local CAPA process.  

See the MCRI: SOP Continuous improvement: a corrective and preventive action (CAPA) plan for an example SOP with CAPA template.  

Responsibilities for managing CAPAs

Both the Sponsor-Investigator (or sponsoring institution) or Site Principal Investigator (PI) may be responsible for implementing a CAPA, depending on whether the issue being addressed is Sponsor or site-level specific, respectively.  

HRECs may also assess whether any corrective and/or preventative actions implemented or planned by the Sponsor-Investigator are appropriate and have adequately addressed the underlying issue.  

For site issues, the Site PI should work with the institution or sponsor, as appropriate, to implement any corrective and preventative actions that may be required at their site. 

Document management

All documentation that permits evaluation of the CAPA process undertaken for any problem/issue, must be maintained in the Trial Master File and Investigator Site File, including CAPA plans/forms and associated correspondence between the Sponsor-Investigator, Site PI, reviewing HREC and local research governance office.  

In addition, some Sponsoring institutions may require the Sponsor-Investigator to maintain a CAPA tracking log that documents all CAPAs for the study and their open/closed status and CAPA owner. See the MCRI: SOP Continuous improvement: a corrective and preventive action (CAPA) plan for an example SOP with CAPA Tracking Log.  

Guidelines

TGA: ICH Guideline for Good Clinical Practice

NHMRC: Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for Trials Involving Therapeutic Goods


NHMRC: Safety monitoring and reporting in clinical trials involving therapeutic goods