Non-Compliance, Serious Breaches & CAPAs
Deviation
A deviation is any breach, divergence or departure from the requirements of GCP or the clinical trial protocol.
Serious Breach
A deviation that is a breach of Good Clinical Practice or the protocol that is likely to affect to a significant degree: a) The safety or rights of a trial participant, or b) The reliability and robustness of the data generated in the clinical trial.
Non-compliance
Non-compliance with the protocol or GCP can lead to:
· Reduced integrity of the trial data, as the reliability and robustness of the clinical trial data is affected
· Compromised participant safety; and
· Nullification of a trial’s insurance/indemnity.
Sponsors and Principal Investigators have responsibilities for reporting and managing non-compliance with GCP, the protocol and trial-related SOPs in accordance with:
· NHMRC: Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for Trials Involving Therapeutic Goods
· TGA: Guideline for Good Clinical Practice [with TGA annotations]
All non-compliance with the protocol and GCP must be reported to the Sponsor. All serious breaches must be reported to both the Sponsor, the reviewing HREC, and the local governance office.
Investigator Reports must be submitted to the sponsor within 72 hours of a suspected serious breach. Your external Sponsor will have processes and systems in place for this, and these will also be documented in your protocol.
Investigator Reports must be submitted to the institution (research governance office) within 72 hours of a confirmed serious breach. At Melbourne Children’s, this reporting is done using ERM.
For more detailed guidance on this topic, including submission pathways and examples of different types of deviations:
If non-compliance with the protocol or GCP results in a serious breach, your external Sponsor should implement a Corrective and Preventive Action Plan, known as a CAPA.
A CAPA is a process for resolving quality issues and preventing reoccurrence. It involves:
· identifying the issue and understanding the underlying cause and extent of the problem
· implementing changes to correct the issue and prevent reoccurrence, and
· documenting that the actions were completed.
Your external Sponsor will work with you to implement a CAPA, if and when one is necessary. The corrective and preventative actions required by this plan should reflect the scale of the breach.
CRDO have developed MCTC061 SOP | Continuous improvement: A Corrective and Preventative Action (CAPA) Plan on how to implement a CAPA, as well as associated MCTC080 Template | CAPA Plan and MCTC081 Template| CAPA Tracking Log.
If you want to learn more about anything covered in this section, these topics are covered in more detail in the A-CTEC Trials Essentials Packages:
A-CTEC Individual Courses | A-CTEC
· Monitoring and auditing clinical trials
· Protocol Compliance & Serious Breaches
They are also covered in some detail in GCP:
· A-CTEC GCP Course (developed by CRDO)