Proactive monitoring of highest-risk medical device clinical trials

We are reviewing the safety information supporting notifications of the highest-risk implantable and cardiac invasive medical devices used in first-in-human clinical trials. 

This was part of our commitment in the 2019 Action Plan for Medical Devices, and the changes have been made in response to feedback from the consultation on proposed regulatory changes for clinical trials of medical devices.

Find out about the changes we have implemented and how they impact you as a sponsor. 

Clinical Trials Notification (CTN) form enhancements 

The CTN form now includes new mandatory fields to:

1. Better characterise the medical device in the clinical trial, for example:
   • risk classification
   • intended purpose
   • whether it’s an invasive or implantable medical device.
2. Identify first-in-human trials and trials halted overseas for safety reasons. 

There is also a new attachment upload feature, which sponsors are encouraged to use to upload the Investigator’s Brochure (or another equivalent document) to minimise requests for further information. 

These changes came into effect on 5 April 2024. 

Legislative changes 

Legislative changes have been made to:

1. Enable us to require information about the safety of medical devices used in clinical trials. For example, information regarding materials, engineering and sterility.
2. Enable inspection of medical device trials conducted under a CTN, and the documentation supporting them, to make sure they’re compliant with Good Clinical Practice.

The Therapeutic Goods Legislation Amendment (2023 Measures No. 2) Regulations 2023, which included these changes, came into effect on 28 November 2023.

Impact on trials

From 5 April 2024, the updated CTN form will help us identify first-in-human trials for the following devices at high risk of immediate, catastrophic consequences if they fail to perform:

• cardiac assist devices (artificial hearts, ventricular assist devices, intra-aortic balloon pumps, cardiomyoplasty devices)
• heart valves and valve repair devices (surgical/percutaneous/mechanical valves, annuloplasty rings, valve repair clips)
• pacemakers and leads
• implantable cardiac defibrillators 
• transcatheter cardiac occluder devices 
• cardiac mapping and ablation catheter devices
• implanted intracerebral/subcortical stimulator devices
• aortic stent and aortic graft devices.

We consider ‘first-in-human’ to mean trials in which the investigational device has not been used in humans previously. 

For trials involving these devices, we may review the Investigator’s Brochure (or another equivalent document) to assess potential risks to trial participants and make sure appropriate mitigation strategies are in place. Reviews will be performed by TGA clinical assessors and other assessors in relevant disciplines (e.g. engineering, biomaterials, microbiology).

Once you have submitted your notification and payment has been received, you can start the trial. Sometimes our Clinical Trials team will ask you for further information to process the form, separate to this review process. Reviews will not affect trial startup timelines as this is part of the CTN scheme and you will not need to receive an ‘approval’ prior to commencement.  

There will be no additional fee for review.

We may contact you if:

• it's not clear what the trial device is
• we would like to review the Investigator’s Brochure but you have not submitted one
• we have uncertainties or concerns about the information in the Investigator’s Brochure.

We won't routinely contact you unless we have concerns or questions.

We may take further action if significant safety concerns are found. They will be proportionate to risk, after discussing with you.

This may include:

• requesting a pause in the trial while we investigate
• discussing our concerns with the approving authorities or overseeing HREC
• GCP inspection
• proposing to stop the trial.

You can contact us at clinical.trials@health.gov.au if you have questions about these changes.