Australian clinical trial handbook

1 Australian clinical trial handbook Guidance on conducting clinical trials in Australia using unapproved therapeutic goods Version , August 2021 Therapeutic Goods Administration Australian clinical trial handbook August 2021 Page 2 of 62 Copyright Commonwealth of Australia 2021 This work is copyright. You may reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given specific written permission from the Commonwealth to do so.

2 Requests and inquiries concerning reproduction and rights are to be sent to the TGA Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to Therapeutic Goods Administration Australian clinical trial handbook August 2021 Page 3 of 62 Contents About this handbook _____ 6 clinical trials involving therapeutic goods _____ 7 Is the product a therapeutic good? _____ 8 Determine the type of therapeutic good _____ 8 Types of therapeutic goods ---------------------------------------- --------------------- 10 Determine if the product is unapproved _____ 11 Other pathways for accessing unapproved therapeutic goods -------------- 12 Certain unapproved therapeutic goods used in clinical trials _____ 12 Placebos ---------------------------------------- ---------------------------------------- ------ 12 Comparators ---------------------------------------- ---------------------------------------- 12 Medical software and mobile medical apps --------------------------------------- 13 Laboratory kits and procedure packs ---------------------------------------- -------- 13 Non-investigational products used in clinical trials ------------------------------ 13 Genetically Modified Organisms (GMO)

3 ---------------------------------------- ----- 13 The Australian regulatory environment _____ 14 Therapeutic goods legislation _____ 14 Legislative and regulatory provisions for the CTN and CTA schemes ------- 14 Declaration of Helsinki _____ 16 The National Statement on Ethical Conduct in Human Research _____ 16 Good clinical Practice (GCP) _____ 16 Guideline for Good clinical Practice ---------------------------------------- ---------- 16 ISO 14155 ---------------------------------------- ---------------------------------------- ---- 17 State and territory requirements _____ 17 The CTN and CTA schemes _____ 18 Choosing between the CTN and CTA schemes _____ 18 Medicines and biologicals ---------------------------------------- ----------------------- 18 Medical devices ---------------------------------------- ------------------------------------- 19 The CTN scheme _____ 19 Variations to a CTN ---------------------------------------- -------------------------------- 20 Notification of completion of a clinical trial under a CTN ----------------------- 20 The CTA scheme _____ 20 CTA forms ---------------------------------------- ---------------------------------------- --- 21 Variation to a CTA

4 ---------------------------------------- -------------------------------- 21 Therapeutic Goods Administration Australian clinical trial handbook August 2021 Page 4 of 62 Notification of a trial completion under a CTA ---- Error! Bookmark not defined. Extensions of clinical trials _____ 21 Post- trial provisions _____ 21 Responsibilities under the CTN and CTA schemes __ 23 Role of trial sponsors _____ 23 Sponsor definition ---------------------------------------- --------------------------------- 23 trial sponsors and the therapeutic goods legislation --------------------------- 23 Investigator-initiated trials ---------------------------------------- --------------------- 24 trial sponsor oversight of delegated functions ----------------------------------- 24 Reporting a change or transfer of trial sponsor ----------------------------------- 24 trial sponsor responsibility of trial management and monitoring ---------- 25 Conducting ongoing safety evaluation and safety reporting ------------------- 25 Record keeping obligations ---------------------------------------- --------------------- 25 Registration

5 Of trial ---------------------------------------- ------------------------------- 26 Notifying trial sites ---------------------------------------- -------------------------------- 26 Role of Human Research Ethics Committees (HRECs) _____ 26 HRECs and the therapeutic goods legislation -------------------------------------- 27 The HRECs role in monitoring a clinical trial -------------------------------------- 27 Withdrawal of approval by a HREC ---------------------------------------- ----------- 28 Role of approving authorities _____ 29 Approving authorities and the therapeutic goods legislation ----------------- 29 Site authorisation ---------------------------------------- ---------------------------------- 29 Monitoring by the approving authority ---------------------------------------- ------ 29 Role of principal investigators _____ 30 Role of TGA _____ 30 Requests for information ---------------------------------------- ------------------------ 30 When further action is required ---------------------------------------- --------------- 31 Release of information

6 ---------------------------------------- --------------------------- 32 Concerns or complaints about a clinical trial -------------------------------------- 32 Safety reporting to TGA for CTN and CTA trials ____ 33 Safety reporting timeframes for CTN and CTA trials _____ 34 1. Single case events from Australian sites: SUSARS and USADEs ------------ 34 2. Significant safety issues* and overseas regulatory action ------------------- 36 3. Other report types ---------------------------------------- ------------------------------ 37 Single case events from Australian sites: SUSARs and USADEs _____ 37 Managing blinded trials ---------------------------------------- -------------------------- 37 Therapeutic Goods Administration Australian clinical trial handbook August 2021 Page 5 of 62 Reporting of overdoses and interactions between therapeutic goods ------ 38 Significant safety issues including urgent safety measures _____ 40 Other report types _____ 42 Non- Australian SUSARs and USADEs ---------------------------------------- --------- 42 Reports from post-market studies ---------------------------------------- ------------ 42 clinical trial phases and stages _____ 43 Summary of clinical trial phases for medicines and biologicals _____ 43 Summary of clinical trial stages for medical devices _____ 45 Early phase trials _____ 45 Medical device stages _____ 48 Advertising unapproved therapeutic goods _____ 49

7 Manufacturing _____ 50 Manufacturing medicines and biologicals for use in a clinical trial __ 50 Manufacture in Australia ---------------------------------------- ------------------------ 50 Manufacture overseas ---------------------------------------- ---------------------------- 51 Labelling medicines ---------------------------------------- ------------------------------- 52 Manufacturing medical devices for use in a clinical trial _____ 53 Manufacturing records and evidence of compliance ----------------------------- 54 Technical documentation ---------------------------------------- ----------------------- 54 Labelling medical devices ---------------------------------------- ----------------------- 55 Manufacturing exemptions _____ 55 Manufacturing exemptions for medicines and biologicals --------------------- 55 Manufacturing exemptions for medical devices--------------------------------- -- 56 Importing _____ 57 Import restrictions for therapeutic goods _____ 57 Importing therapeutic goods for use in clinical trials in Australia ___ 57 Six monthly reports_____ 58 Retrieval, destruction and export of unused clinical trial material __ 59 Therapeutic Goods Administration Australian clinical trial handbook August 2021 Page 6 of 62 About this handbook This handbook provides guidance on the legislative, regulatory and good clinical practice (GCP) requirements when conducting clinical trials in Australia using unapproved therapeutic goods.

8 It assists trial sponsors, Human Research Ethics Committees (HRECs), investigators and approving authorities (institutions) to understand their roles and responsibilities under the therapeutic goods legislation. Information about clinical trials for consumers can be found on the Australian clinical Trials website. This handbook does not describe all of the requirements for conducting clinical trials in Australia. It refers to other relevant publications throughout that should be read in conjunction with this guidance. This handbook describes the two schemes under which clinical trials involving unapproved therapeutic goods may be conducted in Australia: clinical trial Notification (CTN) scheme clinical trial Approval (CTA) scheme clinical trials that do not involve the use of unapproved therapeutic goods are not subject to the requirements of the CTN and CTA schemes.

9 This guidance has been developed by the Therapeutic Goods Administration (TGA) and therefore the use of we and us throughout refers to TGA. See TGA glossary for definitions relevant to the regulation of therapeutic goods in Australia. Therapeutic Goods Administration Australian clinical trial handbook August 2021 Page 7 of 62 clinical trials involving therapeutic goods clinical trials involving therapeutic goods are generally undertaken to assess the effects, efficacy, performance and/or safety of the product. It is therefore necessary that clinical trials are conducted using appropriate experimental designs to obtain valid data without exposing participants to unnecessary risks. Before starting a clinical trial , all parties should be satisfied that the rights, safety and well-being of trial participants will be protected and that clinical trial data generated will be reliable and robust.

10 To achieve such objectives, clinical trials involving unapproved therapeutic goods must be conducted in accordance with: the requirements of the therapeutic goods legislation the principles that have their origin in the World Medical Association Declaration of Helsinki the National Statement on Ethical Conduct in Human Research (the National Statement) as in force from time to time the relevant Good clinical Practice (GCP) guideline other relevant requirements of Commonwealth and/or state and territory legislation site specific requirements See the clinical Trials Toolkit on the Australian clinical Trials website for further information and useful resources. Before conducting a clinical trial in Australia, the trial sponsor will need to consult a HREC to determine whether an exemption under the CTN scheme or approval under the CTA scheme is required for the trial .