2. Using Australian Clinical Sites – Challenges for International Sponsors Prof A J (Tony) Webber Clinical Network Services Pty Ltd Brisbane, Australia

3. General Considerations Australian Health Care System public and private sector providers supported by a federal Medicare system both sectors considered to provide quality health care major hospitals in both sectors exhibit a strong commitment to medical research many are experienced clinical trial sites access to trained study/site coordinators

4. Australian Regulatory System Two major Australian Government Bodies Therapeutics Goods Administration (TGA) The National Health and Medical Research Council (NH&MRC)

5. Therapeutic Goods Administration TGA – acts as Australia’s regulatory authority in relation to the registration and/or listing of pharmaceuticals, neutraceuticals, and medical devices Has adopted ICH GCP in principal – minor amendments concerning membership of Institutional Review Boards and comments concerning informed consent, retention of records and adverse drug reporting

6. National Health & Medical Research Council Allocates funds for health and medical research Provides health advice Considers ethical issues Regulates sensitive medical research activities

7. Other Organizations Office of the Gene Technology Regulator (ORTG) An additional level of approval for genetically modified products Gene and Related Therapies Research Advisory Panel (GTRAP) GTRAP is a subcommittee of the Research Committee, a principal committee of the NHMRC. Provides advice to Council on scientific, medical and technical issues related to gene and related therapies, xenotransplantation and human stem cell research; Medicines Australia Represents Australian pharmaceutical manufactures Gives guidance on issues such as the form of indemnity governing clinical trials and patient compensation

8. Approval for the Conduct of a Clinical Trial – The Sponsor The Sponsor of a clinical trial to be undertaken in Australia MUST be an Australian legal entity Contract Research Organizations holding a TGA “Enterprise Number” can perform the role of Australian Sponsor when an overseas company does not have Australian office or agent

9. Regulatory Approval to Conduct a Clinical Trial – Two Routes Clinical Trial Notification (CTN) 95% of all trials approved by the CTN route Onus on Human Research Ethics Committees (HREC) for ethical considerations scientific merit/safety of the study. TGA will provide written acknowledgement within 10 days of receiving notification via a CTN form and appropriate payment. A separate CTN form for each site

10. Regulatory Approval to Conduct a Clinical Trial – Two Routes Clinical Trial Exemption (CTX) Sponsor submits an application to the TGA for its evaluation and comment. Review of clinical and pre clinical data is required to be completed within 50 days. This clock may be stopped for questions Once approved, the study can then be considered by HRECs and conducted at any number of sites If a HREC is concerned with scientific/ safety issues of a study submitted to it for CTN approval it can require that the study go through the CTX process

11. Clinical Trials in Australia - CTN Applications

12. Clinical Trials in Australia - CTX Applications

13. Summary of Australian Regulatory Process Process CTN (Clinical Trial Notification) CTX (Clinical Trial Exemption) TGA ReviewNot required  HREC Approval  Agency Timelines 7-14 days30 days or 50 days Fees$A240 ($US188) $A15,300 ($US11,964) % per year991 CTX similar to IND

14. Ethics Approval Irrespective of route, CTN or CTX, all clinical trials must be submitted to an Australian Independent Ethics Committee, termed HRECs in Australia HRECs must comply with the requirements laid down by the NH&MRC who has a responsibility to oversee their operation

15. Approval Times Most HRECs and their Research Committees meet monthly Some will not meet December/January Submission dates range from 2-6 weeks before scheduled meetings Approval between 5 weeks to 8 weeks from submission to approval Typically, overall process takes 8 13 weeks

16. Informed Consent Forms (ICF) Must conform with the particular HREC’s requirements (template) and ICH GCP Likely to require major changes from the sample ICF often provided by overseas sponsors Australian details on data protection, patient compensation and reimbursement must be included

17. Patient Recruitment Issues Payments reimbursement all out of pocket expenses associated with attending clinical trial visits – Must be approved by the HREC and detailed in the patient information sheets Advertising Advertising and accelerated recruitment strategies require HREC approval

18. Indemnity and Insurance The majority of HRECs have standardised on, and require sponsors to use, the “Form of Indemnity for Clinical Trials” published by Medicines Australia www.medicinesaustralia.com.au www.medicinesaustralia.com.au While clinical trial insurance may be held by the overseas sponsor, some Australian states require clinical trial insurance to be held by an Australian legal entity

19. Labelling Requirements Major points Name of the Sponsor – must be the sponsor listed on the CTN form Pharmaceutical dosage form, administration route etc Batch and/or code number Trial subject identification – where appropriate Directions for use “for clinical trial use only” www.tga.gov.au/docs/pdf/unapproved/un app.pdf

20. Study Close-out and Archiving Australian regulations stipulate records be retained for 15 years following completion of a clinical trial, or As per ICH GCP requirements, whichever is longer Investigational sites often request additional financial support from the sponsor for off site archiving by a third party or that the sponsor supports this process directly.

21. Thank you!