FAQs on CTN online submissions and the clinical trials schemes

Yes. The TGA has established a quality standard for medicinal cannabis products which companies that supply medicinal cannabis products in Australia are required to meet. The manufacturer of the medicinal cannabis product is required to declare that their product conforms with the Standard for Medicinal Cannabis (TGO No. 93) by completing the declaration form available on the TGA website.

This declaration form is provided by the manufacturer to the Australian clinical trial sponsor who then completes the section at the end of the form to include the name of the medicinal cannabis product(s) used in the clinical trial as well as the TGA clinical trial application number and protocol number.

The clinical trial sponsor is then required to submit this form as supportive documentation to the TGA with their application or notification, as applicable. In the case of a CTN involving the use of a medicinal cannabis product, the clinical trial sponsor should submit this form via email to clinical.trials@health.gov.au. In the case of a CTX involving the use of a medicinal cannabis product, the clinical trial sponsor should submit this form as part of the CTX application made to the TGA.

To submit CTNs online, you will need access to our secure online TGA Business Services (TBS) site. This applies to organisations that already have a TGA client identification number (Client ID), as well as new organisations.

If your organisation:

• already has online access to TBS - please see your administrator to arrange user access.
• has a Client ID without online access to TBS - please nominate an administrator via the Organisation details form to gain access to TBS.
• does not have a Client ID - go to TGA Business Services: Getting started with the TGA for information and forms to obtain a new Client ID and online access to TBS.

Additional information for using the TBS site can be found at TGA Business Services - How to use the site, and any further questions can be directed to the TBS Helpdesk at ebs@tga.gov.au or 1800 010 624.

The TGA has provided step-by step guidance material on Using the online CTN Form and Completing the online CTN form.

If you experience a system error while using the online form, please advise the clinical trials team via email at clinical.trials@tga.gov.au or contact us.

The current fees for clinical trials can be found on the TGA Schedule of fees and charges.

Applications for clinical trials under the CTX scheme cost more than notifications under the CTN, which reflects the increased work needed to evaluate the data in a CTX application. There is a single fee for CTX that includes both Parts 1 and 2.

It is important to appreciate that the TGA cannot treat subgroups of trialists differently according to their ability to pay.

CTN scheme

A fee is charged for the following:

• a new CTN
• a CTN submitted under a different sponsor entity
• Certain variations to an existing CTN. The following variations to a previously notified trial will incur a fee:
  • addition of new site(s) to a previously notified trial. (The fee for notification of a multi-site trial is the same as that for a single site trial providing the sites involved in the multi-site trial are declared simultaneously.)
  • change to previously notified therapeutic goods that creates separate and distinct goods
  • addition of a new therapeutic good to a previously notified trial

The applicable fee is the same amount as the fee for a new CTN in the current financial year.

The online form will generate an invoice for new CTNs and for variations that involve addition of a new site.

Once you have submitted your CTN, an invoice will be generated within 90 minutes of your submission. This invoice is sent via email to the submitter of the CTN and to the billing contact of your organisation as provided to TGA Business Services. If you have a 'financial role' you will also be able to view and print the invoice in the online portal.

We recommend that you wait for the invoice before making payment as this ensures that there are no delays in matching payment.

Payment may be submitted through a range of options as described in our Payment options webpage.

Payment through the online payment portalis the preferred option. To make a payment of an invoice:

• Select "Biller code '1 - Payment of Invoice'" from the drop down menu
• Enter your Client Identification Number (as shown on your invoice)
• Enter your Invoice Number(as shown on your invoice)
• Enter an email address for Tax receipt
• Enter the amount to be paid (this should correspond to the amount on your invoice)
• Select your payment option and follow the online prompts.

If you have added a new therapeutic good to your CTN or made changes that create a separate and distinct good to the goods previously notified, you will still need to make a payment.

The Therapeutic Goods Administration Business Services (TBS) online portal is unable to generate an invoice for these variations.

You may still make payment for these variations as outlined on our Payment options webpage. Our preferred option is for you to make your payment via the online payment portal. To do this you will need your clinical trial protocol number. Once you have navigated to the online payment portal, please:

• Select one of the following biller codes depending on what you have varied in your CTN
  • 3 - Clinical Trial Notification (CTN) fee - medicine
  • 4 - Clinical Trial Notification (CTN) fee - device
  • 5 - CTN fee - biological human cell tissue
• Enter your Client Identification Number
• Enter your clinical trial protocol number
• Enter the email address for Tax receipt
• Enter the amount to be paid ( this should correspond to the amount on your invoice)
• Select your payment option and follow the online prompts.

You can make variations to a CTN that has been submitted online.

See the Varying trial details section of the Using the online CTN form guidance page for further information.

Any future variations to the details notified via the online CTN form should be updated and submitted to the TGA. Please refer to the Varying trial details section of the document Using the online CTN form for guidance on how to vary your online CTN.

The new online form does not currently generate an invoice for variations to notified clinical trials. The following variations to a previously notified trial will incur a fee:

• addition of new site(s) to a previously notified trial
• change to previously notified therapeutic goods that creates separate and distinct goods
• addition of a new therapeutic good to a previously notified trial

If you are making a variation that incurs a fee, please submit the relevant payment to TGA Accounts Receivable as per the information on the TGA Payment options webpage.

Only the most recent version of the processed CTN can be seen in the 'Clinical Trials Repository'. Older versions are archived in a TGA database.

For more information see the View active and closed clinical trials section of the Using the online CTN form guidance page.

Effective 1 March 2017 the TGA will no longer send acknowledgment letters by email as this information can now be viewed and printed via your online portal.

Instructions on how to obtain these print-outs is available in the section 'Printing, deleting, and copying' of the guidance document Using the online CTN form. The TGA advises clinical trial sponsors to obtain and save a print-out of your notification at each stage of the submission process.

Please note:

Within the online portal, there are three different stages during the CTN submission process at which you can preview and print the submission: Drafts, Lodged Submissions and Clinical Trials Repository.

Only those print-outs obtained from the Clinical Trials Repository serve as evidence that the clinical trial has been notified to the TGA. These print-outs will display the application ID, the submission date and the phrase 'Acknowledged by TGA' in the top of the document. See an example of this below:

The TGA is happy to work with any sponsors who experience any difficulties with the print preview function in the new online form. Contact the TGA clinical trials team at clinical.trials@tga.gov.au for assistance.

No.

Original signatures are no longer required for a CTN, and have been replaced by an online sponsor declaration.

Under the previous paper-based system, sponsors were required to obtain and submit to the TGA original signatures from the Principal Investigator, Approving Authority and Human Research Ethics Committee. Under the online submission process the TGA does not require the original signatures. However, we require a sponsor declaration acknowledging that the requirements of the Therapeutic Goods legislation are complied with. The sponsor must still ensure the relevant approvals are in place before commencement of the trial and use of the therapeutic goods.

The legislation underpinning the CTN application process has not changed and requires that the trial be run with appropriate governance in place and in accordance with the Guidelines for Clinical Practice (GCP). Section 8.2 of these guidelines outlines the documents and signed agreements that should be on file before the clinical phase of the trial commences. The TGA advises that all parties are in agreement as to when the CTN form should be submitted.

As defined in the Regulations, the clinical trial sponsor must acknowledge that the goods only remain exempt so long as:

• appropriate advice has been received from a Human Research Ethics Committee
• the trial is conducted in accordance with the:
  • Guidelines for Clinical Practice
  • National Statement on the Ethical Conduct in Research involving Humans (published by the National Health and Medical Research Council).

The TGA has no issues with the submission of the CTN form while the sponsor is obtaining the necessary endorsements. However, it is the responsibility of the sponsor to ensure that all relevant approvals are in place before supplying the therapeutic goods in the clinical trial.

No. The TGA will continue to process CTX applications under the clinical trials scheme using the paper-based process. CTX forms are available on the TGA website. The new online system is currently only available for the CTN scheme.

You do not have to wait for an acknowledgment letter from us before supplying the unapproved goods. As soon as the requirements set out under Item 3 of Schedule 5A of the Therapeutic Goods Regulations 1990 (the Regulations) have been met (i.e. submission of the online CTN form with payment of the relevant fee to the TGA), the clinical trial is deemed to have been notified.

Once this occurs, the exemption under Section 18(1) of the Therapeutic Goods Act 1989 (the Act) comes into effect, and the sponsor can supply the goods.

The notification to the TGA of trial completion can be done once the clinical trial-related activity afforded by a CTN exemption is no longer required. It is however up to the sponsor to determine when the exemption is no longer required. Notification of completion of a clinical trial should be made only after the trial has been completed at all sites. It is not necessary to notify completion dates for individual trial sites.

Please note that notification of trial completion must now be done via the new online form. Please refer to the Using the online CTN form guidance document for further information.

The sponsor must be an Australian entity (see Does the sponsor of a clinical trial in Australia have to be an Australian entity?).

Clinical trials can be sponsored by:

• individuals (for example, medical practitioners)
• bodies and organisations (for example, hospitals, Area Health Services, non-government organisations)
• companies (for example, pharmaceutical companies).

The type of sponsor will vary from trial to trial, depending on who takes overall responsibility for the conduct of the trial.

The sponsor usually initiates, organises and supports a clinical study, and carries the medico-legal responsibility associated with the conduct of the trial.

If the investigator initiates and organises the trial, he or she is to be defined as the sponsor of the trial and will be responsible for the sponsor's functions. This includes, for example, where another party (usually a pharmaceutical company) provides the medicinal product used in the clinical trial, but has no other involvement in the conduct of the trial.

Yes.

An overseas company or person or entity, for the purpose of the Australian legislation, is not the 'sponsor' of the trial in Australia.

The general responsibilities of sponsors of clinical trials are set out in section 5 of the CPMP/ICH Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95). The sponsor must also fulfil all regulatory requirements of the TGA and comply with State and Territory legislation in relation to the supply of therapeutic goods.

The sponsor is also responsible for establishing legal and financial agreements between the sponsor, investigators and participating institutions/organisations. These should address issues such as indemnity of the parties involved in the trial and compensation and treatment of trial participants in the case of injury or death.

The TGA has adopted the PIC/S Guide for Good Manufacturing Practice for Medicinal Products 2009, with Annex 13 of this guide referring to the manufacture of investigational medicinal products. Labelling requirements are outlined under items 26-33.

The Clinical Trials Notification (CTN) and Clinical Trials Exemption (CTX) schemes provide two avenues through which 'unapproved therapeutic goods' may be lawfully supplied for use solely for experimental purposes in humans. An 'unapproved therapeutic good' includes:

• any medicine not entered on the ARTG, including any new formulation, strength or size, dosage form, name, indications, directions for use or type of container of a medicine already in the ARTG.
• any medical device not entered in the ARTG, including any new design specification, model, technology, material or treatment modality of a medical device already in the ARTG.
• any biological not entered in the ARTG:
  • including any new applicable standards, intended clinical use or principal manufacturer of a Class 1 or 2 biological already in the ARTG.
  • including any new product name, dosage form, formulation or composition, therapeutic indication, type of container or principal manufacturer of a Class 3 or 4 biological already in the ARTG.
• a therapeutic good already in the ARTG that is used beyond the conditions of its marketing approval including labelling.

The choice of which route to use (CTN or CTX) lies firstly with the sponsor and then with the Human Research Ethics Committee (HREC) that reviews the protocol.