Originally published July 2005
- The Therapeutic Goods Administration ("TGA") and the National Health and Medical Research Council ("NH&MRC") handed down their report on the Review of Access to Unapproved Therapeutic Goods in Australia in late February this year. The Report evaluates existing regulatory controls for clinical trials and access to unapproved therapeutic goods in Australia and New Zealand. It makes 49 recommendations, many of which concern the role of the future trans-Tasman agency.
The report says the trans-Tasman agency should actively monitor clinical trial activity, and in particular:
- advise the Human Research Ethics Committees ("HREC") and the NH&MRC of regulatory requirements for clinical trials;
- assist HRECs in determining how specific trials should be evaluated if requested;
- review adverse drug reactions that are both serious and unexpected; and
- conduct a trial inspection program.
The report also suggests that the clinical trial system be harmonised by having either the regulator or an ethics committee with substantial membership and scope for review assess certain types of trials. Finally, it also recommends the establishment of a mandatory, comprehensive register including all clinical trials conducted with medicinal products in Australia and New Zealand.
We will summarise these recommendations and focus on those that present the biggest changes to the pharmaceutical industry.
Legislative overview of access to unapproved therapeutic products
Under the Therapeutic Goods Act 1989 (Cth) ("The Act") and its associated Regulations, therapeutic goods for human use, which are imported into Australia, manufactured in Australia, supplied by a corporation, supplied interstate or to the Commonwealth, or exported from Australia must be included in the Australian Register of Therapeutic Goods ("ARTG") unless specifically exempted from that requirement.
The legislation permits the supply of products not included in the ARTG (so called "unapproved therapeutic goods"), in the following limited situations:
- clinical trials;
- provision under the Special Access Scheme ("SAS");
- provision by Authorised Prescribers; and
- importation for personal use.
In regulating the supply of unapproved therapeutic goods, the TGA is obliged to balance two competing considerations. On the one hand there is a broad community interest that therapeutic products available in Australia have acceptable quality, safety and efficacy standards. Unapproved therapeutic goods would have undergone no evaluation by the TGA. Use of any such goods, therefore, carries with it some risks that have not been defined in the Australian context. On the other hand, the need for timely access to potentially lifesaving and enhancing treatments is an important consideration. It is arguable that patients who have serious illness with reduced life expectancy should be granted access to certain unapproved therapeutic goods.
Current regulatory framework
Clinical Trials in Australia are currently regulated by the TGA under two schemes - the Clinical Trial Notification ("CTN") Scheme and the Clinical Trial Exemption ("CTX") Scheme.
The major difference between the schemes is the TGA's level of involvement in reviewing data about the therapeutic good involved in the trial before the trial begins.
Under the CTN Scheme, the TGA does not review any of the data before the trial begins. All material relating to the trial is submitted directly to the HREC of the institution where the trial will be conducted. Approval for the conduct of the trial is given by this institution on the advice of its HREC after review of the scientific and ethical validity of the trial. The trial can commence once the TGA has been notified of these approvals by the sponsor of the trial. The HREC is responsible for monitoring the conduct of the trial at its institution. Of note, almost all trials in Australia are currently being conducted under the CTN Scheme.
Under the CTX Scheme, applications to conduct clinical trials must be submitted to the TGA for evaluation and comment. The TGA then reviews summary scientific data about the safety of the product and decides whether or not to object to its proposed usage. Clinical trials cannot proceed until any TGA objections have been overcome. If no objection is raised by the TGA, the sponsor may conduct any number of clinical trials of the product under that particular CTX approval without further assessment by the TGA, provided such use falls within usage guidelines approved by the TGA. However, approval to conduct individual trials under the CTX Scheme must also be given by the HREC of the organisation carrying out the trial, which is responsible for review and approval of the trial protocol and the ethical approval for the study.
The Review essentially endorsed the current system of access to clinical trials for unapproved therapeutic goods, approved the CTN trial process and made the following recommendations:
- giving HREC guidance in determining how best to undertake scientific reviews;
- establishing a limited number of Nationally Accredited Human Research Ethics Committees. Their purpose would be to provide ethical review for large-scale, multi-site clinical trials;
- that there be an increase in the auditing of clinical trials by the TGA. After comparing the audit rate of Australian trials with global figures, Australia was noted to be "significantly behind the rest of the world"; and
- that a proposed trans-Tasman agency should develop an inspection program based on compliance with internationally accepted Good Clinical Practice requirements and should aim to audit between one percent and three percent of trial sites or HRECs within three years.
Clinical trials register
The Review discussed the advantages and disadvantages of having a register of all clinical trials conducted with medicinal products in Australia and New Zealand. It noted that the overarching concern of the pharmaceutical industry appeared to be that commercial-in-confidence information should not be disclosed about their research.
Nevertheless, the Review recommended establishing a mandatory, comprehensive register disclosing all clinical trials being carried out in Australia. This register is to be maintained and kept up to date by the TGA/ trans-Tasman agency with the cost of establishing and maintaining the register being met by Government. Its purpose would be to foster greater knowledge of trials that are ongoing, as well as completed. The register should be in the public domain, and at a minimum should contain information on the disease being treated, contact details to enable the public to enquire about the trial, and the start and completion dates of the trial.
Special Access Scheme
The SAS allows access to unapproved products by individual patients on a case by case basis. The arrangements rely on different sections of the Act depending on the classification of the patient.
Category A patients are those defined by the Regulations as "persons who are seriously ill with a condition from which death is reasonably likely to occur within a matter of months, or from which premature death is reasonably likely to occur in the absence of early treatment". For Category A patients, use of an unregistered medicine or medical device is obtained via a process of authorisation by their medical practitioner, and notification to the TGA. The treating medical practitioner is required to complete an "Authority to Supply" form and send it to the sponsor of the product. This provides the sponsor with the legal authority to supply the product. A copy of this form must then be sent to the TPA. The TGA has no discretion at law to refuse a Category A notification from a registered medical practitioner.
For all other patients ("Category B" patients), access is obtained by approval from a TGA delegate, or an external delegate.
The Review Committee recommended that there be no substantial change to the SAS scheme.
Authorised Prescriber Scheme
Under the Act, the TGA is able to grant medical practitioners the authority to prescribe specified unregistered therapeutic goods or classes of unregistered medical products to specified recipients or classes of recipients. Requirements for authorisation are contained in Regulation 12B. Upon authorisation, the practitioner (or "Authorised Prescriber") may continue to prescribe such goods to their patients without the need for further authorisation. This authorisation may be revoked by the TGA.
The Review Committee recommended that there be no substantial change to the Authorised Prescriber Scheme.
The legislation allows for a person to import a limited quantity of most medical products for themselves or their immediate family. The limitation on this is that goods containing a substance which is a prohibited import and injections containing material of human or animal origin are prohibited from being imported. The Review Committee made no recommendation about personal importation.
Overall, the Review endorses the current regulatory framework of clinical trials in Australia. It is supportive of the low level of involvement by the TGA in many aspects of the clinical trials process. Where changes have been recommended, it is important to bear in mind that they must be negotiated with representatives from both Australia and New Zealand due to the proposed establishment of the trans-Tasman agency.
Public comment on the report has now closed. We will monitor future developments in Insights.
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