Clinical trials

9 January 2018

Clinical trials conducted in Australia are subject to various regulatory controls to ensure the safety of participants. We regulate the use of therapeutic goods supplied in clinical trials in Australia under the therapeutic goods legislation.

Clinical trial sponsors must be aware of the requirements to import, export, manufacture and supply therapeutic goods in Australia.

The following avenues provide for the importation into and/or supply in Australia of 'unapproved' therapeutic goods for use in a clinical trial:

  • Clinical Trial Notification (CTN) scheme; and
  • Clinical Trial Exemption (CTX) scheme.

Clinical trials that do not involve 'unapproved' therapeutic goods are not subject to requirements of the CTN or CTX schemes. It is the responsibility of the Australian clinical trial sponsor to determine whether a product is considered an 'unapproved' therapeutic good.

Information about clinical trials for consumers, health care providers, researchers, industry and sponsors is available on the National Health and Medical Research Council's Australian clinical trials website.

CTN Scheme

The CTN Scheme is a notification process involving the following:

  • The Australian clinical trial sponsor must notify us of the intent to sponsor a clinical trial involving an 'unapproved' therapeutic good. This must take place before starting to use the goods. The notification form must be submitted online and accompanied by the relevant fee.
  • We may give the sponsor of the trial written notice to provide specified information relating to goods notified in the CTN form.
  • We do not evaluate any data relating to the clinical trial at the time of submission. The Human Research Ethics Committee (HREC) reviews the scientific validity of the trial design, the balance of risk versus harm of the therapeutic good, the ethical acceptability of the trial process, and approves the trial protocol. The HREC is also responsible for monitoring the conduct of the trial.
  • The institution or organisation at which the trial will be conducted, referred to as the 'Approving Authority', gives the final approval for the conduct of the trial at the site, having due regard to advice from the HREC.
  • It is the responsibility of the sponsor to ensure that all relevant approvals are in place before supplying the 'unapproved' therapeutic goods in the clinical trial.

Under the Australian regulatory framework for biologicals certain Class 4 biologicals are not able to be supplied under the CTN Scheme and must be submitted under the CTX scheme.

CTN form

The online CTN form can be accessed via the TGA business services website.

For step-by-step instructions on how to obtain access to this form and submit a CTN, see the CTN form - user guide.

The CTN Scheme transitioned from paper-based applications to an online submission process on 1 July 2015. If a CTN has not been migrated to the new online portal, please contact the clinical trials team at clinical.trials@health.gov.au.

CTX Scheme

The CTX Scheme is an approval process involving the following:

  • A sponsor submits an application to us seeking approval to supply 'unapproved' therapeutic goods in a clinical trial. The application must be accompanied by the relevant fee.
  • We evaluate summary information about the product including relevant, but limited, scientific data (which may be preclinical and early clinical data) prior to the start of a trial.
  • The HREC is responsible for considering the scientific and ethical issues of the proposed trial protocol.
  • The sponsor must notify us of each trial conducted using the unapproved therapeutic good(s) approved in the CTX application.

The CTX scheme application procedure is currently undergoing review by us. If you are considering submitting a CTX application, you are strongly encouraged to contact us for advice regarding the application process.

CTX forms

CTX applications are submitted using paper-based forms. There are two forms that must be completed by the sponsor and submitted to us via post.

Part 1: The application

Part 1 is the formal CTX application. It must be completed by the sponsor of the trial and submitted to us with data for evaluation. The appropriate fee must be paid.

The CTX application form can be emailed to us. However, the signed original form must also be sent to us via post.

How to access a pdf or Word document

Supporting data for the CTX application should be provided in electronic format. It is preferable for data to be sent on USB or CD-ROM via post.

Part 2: Notification of the conduct of a trial under the CTX scheme

Part 2 is used to notify us of the commencement of each new trial conducted as per the usage guidelines approved in the CTX application. There is no fee for notification of trials under the CTX scheme.

CTX clinical trial completion advice form

The CTX clinical trial completion form is to notify us of the completion of trials conducted under the CTX scheme.

On completion the form can be emailed to us followed by the signed original via post.

Clinical trials guidance

We have published the following policy documents for use by clinical trial sponsors, investigators and Human Research Ethics Committees (HRECs):

The following guidelines are also relevant to clinical trials conducted under the CTN and CTX schemes:

The Clinical Trial Notification (CTN) form: user guide has been created to provide information on how to access and use the online clinical trial notification (CTN) form. It provides step-by-step guidance on how to access TGA Business Services, create a new CTN, submit the CTN and make payment. You will also learn how to edit, save, validate, print and check the status of your submission.

We have also published several videos explaining the online CTN form.

FAQs

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General

An 'unapproved' therapeutic good for the purposes of the CTN and CTX schemes includes:

  • any medicine not included in the Australian Register of Therapeutic Goods (ARTG), such as 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 (including an in vitro diagnostic device (IVD)) not included in the ARTG, such as any new sponsor, manufacturer, device nomenclature system code, classification or unique product identifier (for certain classes of medical devices only) of a medical device already in the ARTG
    • any in-house IVD medical device, used for the purpose of a clinical trial, where the laboratory providing the in-house IVD is unable to comply with the regulatory requirements for in-house IVDs
  • any biological not included in the ARTG such as:
    • any new applicable standards, intended clinical use or principal manufacturer of a Class 1 or 2 biological already in the ARTG
    • 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
  • therapeutic goods already included in the ARTG to be used in a manner not covered by the existing entry in the ARTG.

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

The CTX route is generally designed for high-risk or novel treatments where there is no or limited knowledge of safety. For medical device trials, the CTX scheme may be more appropriate where the experimental device introduces new technology, new material or a new treatment concept which has not been evaluated previously in clinical trials in any country. The CTX scheme should also be considered for medical devices that pose a risk of serious patient harm.

The determining factor for an HREC is whether the committee has access to appropriate scientific and technical expertise in order to assess the safety of the product.

However, under the Australian regulatory framework for biologicals certain Class 4 biologicals are not able to be supplied under the CTN Scheme and must be submitted under the CTX scheme.

Sponsors should notify us of trial completion once the clinical trial-related activity afforded by a CTN exemption or CTX approval is no longer required. It is, however, the responsibility of the sponsor to determine when the exemption or approval 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.

The online CTN should be used to submit a completion advice to us. Please refer to the Clinical trial notification (CTN) form: User guide for further information.

The sponsor of a trial can be an individual, company, institution, or organisation which takes responsibility for the initiation, management, and/or financing of a clinical trial.

The type of sponsor will vary from trial to trial, depending on who takes overall responsibility for the conduct of the trial. If the investigator initiates and organises the trial, he or she is defined as the sponsor of the trial and will be responsible for the sponsor's functions.

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

The Australian clinical trial sponsor is responsible for submitting the CTN or CTX.

The clinical trial sponsor's responsibilities in relation to Good Clinical Practice (GCP) are set out in section 5 of the ICH Guideline for Good Clinical Practice with TGA annotations. The clinical trial sponsor must also comply with the requirements of the therapeutic goods legislation as well as any other Commonwealth or state/territory legislation in relation to clinical trials and the supply of therapeutic goods.

The Australian sponsor of a clinical trial is also responsible for safety reporting. The guidance document Safety monitoring and reporting in clinical trials involving therapeutic goods addresses safety monitoring and reporting requirements for investigational products in Australia.

A sponsor may transfer any or all of the sponsor's trial-related duties and functions, including adverse drug reaction reporting, to a Contract Research Organisation (CRO). However, please note that the ultimate responsibility resides with the trial sponsor.

Online CTN form

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 a TGA client ID and online access to TBS - please see your organisation's TBS administrator who can add you as a user.
  • has a TGA Client ID without online access to TBS - please nominate an administrator via the Organisation details form to gain online access to TBS.
  • does not have a TGA 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. Any further questions can be directed to the TBS Helpdesk at ebs@tga.gov.au or 1800 010 624.

Yes. We have provided a step-by step Clinical Trial Notification (CTN) form: User guide.

If you experience any difficulties using the online CTN form, please contact the clinical trials team at clinical.trials@health.gov.au or call 02 6232 8106.

If you have prematurely submitted a CTN and need to correct administrative errors, you may request that we 'push-back' the notification. Such requests should be sent via email to the clinical trials team at clinical.trials@health.gov.au.

If any details of your trial have changed after the CTN has been processed, you need to submit a variation using the online portal. See the Varying trial details section of the Clinical Trial Notification (CTN) form: User guide for further information.

Please note that certain variations to a previously notified CTN may incur a fee.

Any changes to details notified in the online CTN form should be updated and submitted to us. See the Varying trial details section of the Clinical Trial Notification (CTN) form: User guide for guidance on how to vary your online CTN.

The target time to process online CTNs is 5-7 working days; however we endeavour to process the notification as soon as possible. Please note that this timeframe does not include the time taken for TGA finance to match the payment (if required) to your submission.

You can track the status of your CTN by logging onto the TBS online portal. Refer to the section How to check the status of your CTN in the Clinical Trial Notification (CTN) form: User guide.

We will accept CTN form submissions 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 commencement of the trial.

We encourage all parties to be in agreement as to when the CTN form should be submitted.

The therapeutic goods legislation requires that the trial be run with appropriate governance in place and in accordance with the ICH Guideline for Good Clinical Practice (GCP) with TGA annotations. 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 clinical trial sponsor must acknowledge that the goods only remain exempt so long as:

As soon as the requirements set out under Item 3 of Schedule 5A of the Therapeutic Goods Regulations 1990 (the Regulations) and Item 2.3 of Schedule 4 of the Therapeutic Goods (Medical Devices) Regulations 2002 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), 32CA(2) and 41HA of the Therapeutic Goods Act 1989 (the Act) comes into effect, and the sponsor can supply the goods.

Effective 1 March 2017 the TGA no longer sends 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 'Printing' section of the Clinical Trial Notification (CTN) form: User guide. We advise clinical trial sponsors to obtain and save a print-out of the CTN form at each stage of the submission process.

Note:

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

Print-outs obtained from the Clinical Trials Repository serve as evidence that the clinical trial has been notified to the TGA.

Submitting and printing a CTN

See the Submitting section of the Clinical Trial Notification (CTN) form: User guide, for further assistance.

See the Printing section of the Clinical Trial Notification (CTN) form: User guide, for further assistance.

You will need to allow pop-ups and clear your browser cache.

  • First try clearing your browser cache and allowing pop ups from the TBS online portal.
  • Instructions can be obtained from the internet.
  • If you need assistance, please email clinical.trials@health.gov.au and provide the name of the browser you are using (i.e Internet Explorer, Google Chrome, Firefox, etc.).

If you get the following error or any other error message

Clinical Trial Error Loading Data

please email clinical.trials@health.gov.au and provide:

  • A screen shot of the error message
  • Your CTN application ID
  • A short description of any steps you have taken to try and resolve the problem.

Fees, invoices and payments

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

A fee is charged for a CTN submitted by a different sponsor as a result of transfer of sponsor responsibility.

A higher fee is applicable to applications for clinical trials under the CTX scheme due to the more complex nature of the evaluation process.

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.

Certain variations to existing CTNs may incur a fee. The applicable fee is that of a new CTN as published in the schedule of fees and charges.

The following variations to a previously notified trial will incur a fee:

  • addition of a 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.

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 web page. Credit card or account details should not be sent to the clinical trials team. Once payment has been made, please forward proof of payment to clinical.trials@health.gov.au.

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 web page.

Payment through the online payment portal is 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 an existing CTN or have 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 website. Our preferred option is for you to make your payment via the online payment portal. To do this you will need your CTN Application ID. 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 (select one option only):
    • 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 (As shown in any of your post-January 2017 CTN invoice e.g. TGA00XXXXX)
  • Enter your CTN Application ID and version number
  • Enter the email address for Tax receipt
  • Enter the amount to be paid

Select your payment option and follow the online prompts. If you make a variation that incurs a fee, and payment is not received within 48 hours, the TGA clinical trials team will send you a request for payment via email.

We are unable to process your variation if the required payment has not been received.

Once payment has been received, accounts receivable will issue a tax invoice (payment receipt).

Import, export and labelling

Therapeutic goods may be imported and held under the direct control of the sponsor until the goods are included in a notification made to us through the CTN scheme. The goods must be kept in a warehouse or other properly secured area. The term 'sponsor' in these circumstances refers to the sponsor of therapeutic goods (the importer) as opposed to the sponsor of the clinical trial.

In other words, the importer does not require approval from the TGA prior to importation of the clinical trial goods; however the trial must be notified to the TGA through the CTN scheme prior to supply of the goods to the trial sites.

Sponsors are advised to contact other relevant agencies as there may be further restrictions on importation imposed through other legislation such as the Customs (Prohibited Imports) Regulation 1956, the Biosecurity Act 2015 and the Environment Protection and Biodiversity Conservation Act 1999.

You will need to apply for TGA approval to export therapeutic goods overseas for use in clinical trials. Application forms and guidance are available on the Import/export of unapproved therapeutic goods for experimental purposes page of our website.

Approvals are usually issued for a 12-month duration allowing for multiple consignments and distribution to the countries specified in the approval. If further countries are added to the trial, a subsequent application would need to be submitted including the additional countries.

A report detailing the quantity of goods that have been exported to each clinical trial site must be submitted to the TGA every six months and should also include a list of trial sites, recipients and site addresses.

We aim to process applications within three weeks and there is no applicable fee.

Additional restrictions may be imposed on the exportation of unapproved therapeutic goods through the Biosecurity Act 2015 and Customs (Prohibited Exports) Regulations 1958.

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

Clinical trials involving medical cannabis products

Yes. The TGA has established a quality standard for medicinal cannabis products which companies supplying 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 and supporting documentation (including the representative Certification of Analysis (CoA) and specifications for the raw material and finished product) 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 and supporting documentation as part of the CTX application made to the TGA.


Other requirements

The therapeutic goods legislation requires that the use of therapeutic goods in a clinical trial conducted under the CTN/CTX schemes must be in accordance with:

Contact details

If your enquiry is not specifically about clinical trials, see: Contact the TGA

Email: clinical.trials@health.gov.au

Phone: 1800 020 653 (freecall within Australia) or +61 2 6232 8106

Users who are deaf or have a hearing or speech impairment can call through the National Relay Service:

  • TTY or computer with modem users: phone 1800 555 677 then ask for 1800 020 653
  • Speak and listen (speech to speech relay) users: phone 1800 555 727 then ask for 1800 020 653

Fax: +61 2 6232 8112