Australian regulatory

CTN

CTN is a notification scheme and over 95% of all trials are approved via this route. Via this route the onus is on the HREC to bear the responsibility for approving:

• the safety and efficacy of the medicine or device,
• the ethical acceptability of the trial process,
• approval of the trial protocol, and
• evaluating the scientific merit of the trial.

The TGA does not review any data relating to the clinical trial but acknowledges the trial in writing within 10 days of receipt of the signed CTN form and appropriate payment. It is increasingly common for the TGA to request copies of the protocol and Investigator Brochure at some stage after issuing a Letter of Acknowledgement and on occasion may request some additional information. The TGA is empowered to place an ongoing study on “Clinical Hold” should their concerns be significant. This is extremely rare and likely to only affect phase I studies being conducted under a CTN.

A separate CTN form must be completed for each potential trial site. It is standard for all fees to be reimbursed to the CRO by the sponsor as part of the trial budget. CTN trials cannot commence until the trial has been notified to the TGA and the appropriate notification fee paid.

CTX

The CTX approach is rarely used in Australia but is a modified approval process by which a sponsor submits an application to conduct a clinical trial to the TGA for evaluation and comment. A TGA delegate then decides whether or not to object to the proposed usage guidelines for the product. If an objection is raised, trials may not proceed until the objection has been addressed to the delegate’s satisfaction.

If no objection is raised, the sponsor may conduct any number of clinical trials under the CTX application without further assessment by the TGA, provided that use of the product in the trials falls within the original approved usage guidelines. Each trial conducted must be notified to the TGA.

A sponsor cannot commence a CTX trial until written advice has been received from the TGA regarding the application and approval for the conduct of the trial has been obtained from a HREC at each institution where the trial will be conducted. Two forms, each reflecting these separate processes, must be submitted to the TGA by the sponsor:

• Part 1 constitutes the formal CTX application. It must be completed by the sponsor of the trial and submitted to TGA with data for evaluation.
• Part 2 is used to notify the commencement of each new trial conducted under the CTX as well as new sites in ongoing CTX trials. This Part 2 form must be submitted within 28 days of the commencement of supply of goods under the CTX.

There is no fee for notification of trials under the CTX scheme.

Clinical trials in which registered or listed medicines or medical devices are used within the conditions of their marketing approval are not subject to CTN or CTX requirements but still need to be approved by a HREC before the trial may commence.