Clinical Research Regulation For Australia
Regulatory Authority
Regulatory Authority
Scope of Assessment
Regulatory Fees
Ethics Committee
Ethics Committee
Scope of Review
Ethics Committee Fees
Authorizing Body
Clinical Trial Lifecycle
Submission Process
Submission Content
Timeline of Review
Trial Initiation
Safety Reporting
Progress Reporting
Sponsorship
Definition of Sponsor
Trial Authorization
Insurance
Compensation
Quality, Data & Records Management
Site/Investigator Selection
Informed Consent
Documentation Requirements
Required Elements
Compensation Disclosure
Participant Rights
Special Circumstances/Emergencies
Vulnerable Populations
Children/Minors
Pregnant Women, Fetuses & Neonates
Prisoners
Mentally Impaired
Investigational Products
Definition of Investigational Product
Manufacturing & Import
IMP/IND Quality Requirements
Labeling & Packaging
Product Management
Specimens
Definition of Specimen
Specimen Import & Export
Consent for Specimen
Sources
Requirements
Additional Resources
Forms
QUICK FACTS
Clinical trial application language Unspecified
Regulatory authority & ethics committee review may be conducted at the same time Yes
Clinical trial registration required Yes
In-country sponsor presence/representation required Yes
Age of minors Under 18
Specimens export allowed Yes
Regulatory Authority > Regulatory Authority
Last content review/update: December 17, 2021
Summary

Overview

As per the TGAct, the TGR, and the G-CTHandbook, the Therapeutic Goods Administration (TGA) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections in Australia at the national level. The TGA grants exemptions for the supply of unapproved therapeutic goods to be used in clinical trials for experimental purposes in humans in accordance with the provisions in the TGAct and the TGR. There are two (2) regulatory schemes for supplying unapproved therapeutic goods in clinical investigations, which are more fully examined in the Scope of Assessment section.

As per AUS-28, the TGA is part of the Health Products Regulation Group (HPRG) within the Australian Department of Health. According to the G-TrialsSOP, AUS-32, and AUS-31, the TGA regulates the supply, import, export, manufacturing, and advertising of therapeutic goods—prescription medicines, vaccines, sunscreens, vitamins and minerals, medical devices, blood, and blood products. In addition, per the TGAct, the TGA manages the Australian Register of Therapeutic Goods (ARTG) (AUS-22) for all therapeutic goods for human use, and it grants exemptions from the ARTG for unapproved therapeutic goods to be used in clinical trials.

Contact Information

Therapeutic Goods Administration

Postal Address:
P.O. Box 100
Woden ACT 2606
Australia

Street Address (for deliveries):
136 Narrabundah Lane
Symonston ACT 2609
Australia

For general inquiries:

Phone: 1 800 020 653 (free call within Australia) or +61 2 6289 4124 (international calls)
Fax: 02 6203 1605
E-mail:
info@tga.gov.au

For clinical trial inquiries:

Phone: 1 800 020 653 (free call within Australia), +61 2 6289 4614, or +61 2 6232 8106
Fax: +61 2 6232 8112
E-mail:
clinical.trials@health.gov.au

See AUS-23, AUS-47, and AUS-29 for additional contact details.

Chapter 1 (3), Chapter 2 (9A), and Chapter 3 (Part 3-2 (18, 19, 31A, and 31B))
Part 2C, Part 3 (12AA-12AD), and Schedule 5A
About this handbook and Therapeutic goods legislation
Terms
Contact details
Regulatory Authority > Scope of Assessment
Last content review/update: December 17, 2021
Summary

Overview

In accordance with the TGAct, the TGR, the G-CTHandbook, the G-TrialsSOP, AUS-40, and AUS-47, the Therapeutic Goods Administration (TGA) is responsible for granting an exemption for the supply of unapproved therapeutic goods to be used in clinical trials under two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme and the Clinical Trial Approval (CTA) (formerly known as Clinical Trial Exemption (CTX)) scheme. Under either regulatory scheme, per the TGR and the G-NatlStmt, an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) must approve research protocols, and according to AUS-43, the institution must approve any research in accordance with its research governance framework, including a site-specific assessment for public institutions. Further, per AUS-43, the site-specific assessment and EC ethical and scientific review may occur in parallel. The G-CTHandbook specifies that the scope of the TGA’s assessment includes all trials (Phases I-IV).

The Department of Health’s National Teletrials Compendium (AUS-60), agreed to by all Australian states and territories, consists of two (2) publications that cover principles and standard operating procedures for clinical trials and teletrials (G-TrialsSOP and G-TeletrialPrncpls). As per the G-TrialsSOP and the G-TeletrialPrncpls, a teletrial uses telehealth technology (consultation through video or telephone instead of face to face) to communicate between a primary site and satellite site(s) for some or all aspects of a clinical trial. This technology supports a principal investigator (PI) to supervise associate investigator(s) to conduct a clinical trial at a satellite site, geographically remote from the PI’s primary site. The Teletrials Compendium documents comply with the AU-ICH-GCPs, and the principles are also consistent with the Clinical Oncology Society of Australia’s (COSA) Australasian Tele-trial Model (AUS-2).

Clinical Trial Review Process

Per the G-CTHandbook, the sponsor is responsible for the overall decision as to whether the CTN or CTA scheme should be used. Consulting the EC responsible for protocol approval may assist the sponsor in making the decision. According to AUS-47, some class IV biologicals must be submitted under the CTA scheme. The G-CTHandbook further states that the main difference between the CTN and CTA schemes is the TGA’s level of involvement in reviewing data about the therapeutic goods before the clinical trial commences. See AUS-27 for more information on choosing a clinical trial scheme.

According to the G-CTHandbook, the TGA can request certain information or documents from the sponsor about therapeutic goods exempt under the CTN scheme or approved under the CTA scheme relating to the supply, handling, monitoring, and the results of the supply of the goods.

CTN Scheme

As per the TGAct, the TGR, the G-CTHandbook, the G-TrialsSOP, and AUS-47, under the CTN scheme, the sponsor must notify the TGA of his/her intention to sponsor a clinical trial involving an ‘unapproved’ therapeutic good, which the EC and the institution are to review and approve. The TGA does not assess any data relating to the CTN at the time of submission. As further indicated in AUS-47, sponsors may submit the CTN to the TGA concurrently with the EC’s and institution’s review and approval. However, it is the sponsor’s responsibility to ensure that all relevant approvals are in place before commencement of the trial.

The G-CTHandbook states that the TGA may request additional information if the trial raises any concern, or ask specific questions to address any deficiencies. Further, per the G-CTHandbook and AUS-40, the sponsor cannot supply the unapproved therapeutic goods in the trial until the TGA has been notified using the online CTN form, approvals have been received from the EC and institution, and the appropriate notification fee has been paid.

According to AUS-47, CTN scheme applications are submitted through an online form. The target time for the TGA to process online CTNs is five (5) to seven (7) working days. AUS-49 and AUS-44 provide details on using and submitting the online form. In addition, per AUS-47, the TGA does not send an acknowledgement letter by email since this information is available for viewing and printing via the online portal. The TGA advises clinical trial sponsors to obtain and save a printout of notification at each stage of the submission process.

(For additional requirements, see the Submission Process, Submission Content, Timeline of Review, and Trial Initiation sections.)

CTA Scheme

According to AUS-47, parties that are considering submitting a CTA application are strongly encouraged to contact the TGA at clinical.trials@health.gov.au for advice regarding the application process.

AUS-47 indicates that the CTA scheme consists of a two-part process. Part 1 constitutes the formal CTA application, which the sponsor completes and submits directly to the TGA. Part 2 requires the sponsor to notify the TGA when a trial commences and alert the TGA to new sites in ongoing CTA trials. As per the G-CTHandbook, the TGA reviews relevant, but limited, scientific data, and its primary responsibility is to review the safety of the product.

AUS-47 further specifies that the evaluation of a CTA application includes consideration of the manufacturing and quality and safety data in conjunction with the trial's usage guidelines, to inform a risk-benefit decision by the TGA on whether or not to approve the clinical trial. Any significant changes to the information provided in support of the trial are considered a variation and need to be approved, since they have the potential to affect the initial decision to approve a trial. The TGA advises clinical trial sponsors to contact them via clinical.trials@health.gov.au if they intend to change a previously approved CTA application.

Per AUS-47, the sponsor must complete and submit two (2) forms (AUS-56 and AUS-57) to the TGA via clinical.trials@health.gov.au. AUS-54 indicates that electronic submissions are preferred for CTA applications. For more information, see the Submission Process and Submission Content sections.

Chapter 3 (Part 3-2 (18, 19, 31A, and 31B))
Part 1 (2A), Part 2C, Part 3 (12 and 12AA-12AD), and Schedule 5A
About this handbook, Is the product a therapeutic good?, Determine if the product is ‘unapproved’, Choosing between the CTN and CTA schemes, The CTN scheme, The CTA scheme, and Responsibilities under the CTN and CTA schemes
Introduction and Terms
Purpose, Scope and Limits of this Document, Section 3 (Introduction), and Section 5 (5.1)
CTN Scheme, CTA Scheme, and FAQs
Overarching Legislation and Guidance and Planning a Clinical Trial
Validation and Submission and Manual Submission
Regulatory Authority > Regulatory Fees
Last content review/update: December 17, 2021
Summary

Overview

As per the TGR, the sponsor is responsible for paying a fee to the Therapeutic Goods Administration (TGA) to submit an application under the clinical trial notification (CTN) or clinical trial approval (CTA) (formerly known as clinical trial exemption (CTX)) scheme for evaluation. Per the G-FeesCharges, the fees starting from December 2021 are as follows:

  • $380 Australian dollars for unapproved medicine CTN and for each notification of one (1) or more additional trial sites
  • $1,810 Australian dollars for unapproved medicine CTA for 30-day evaluation
  • $22,500 Australian dollars for unapproved medicine CTA for 50-day evaluation
  • $380 Australian dollars for unapproved biological CTN and for each notification of one (1) or more additional trial sites
  • $27,400 Australian dollars for unapproved biological CTA

According to AUS-47, a higher fee is applicable to clinical trial applications under the CTA scheme due to the more complex nature of the evaluation process. Certain variations to an existing CTN may incur a fee, such as the addition of a new site, change to a previously notified therapeutic good that creates separate and distinct goods, or the addition of a new therapeutic good to a previously notified trial. For additional fee information, refer to Schedules 9 and 9A of the TGR and the G-FeesCharges.

Instructions for Payment of Clinical Trial Application Fees

AUS-66 indicates that regulatory fees and charges may be paid online, by cheque, or by direct deposit. Online payment by credit card is the preferred payment option, and all payments must be in Australian dollars.

As stated in AUS-25, online payment is made via the TGA Online Payment Portal (AUS-16). Once the payment has been finalized, the Portal will confirm that payment has been successful and the user may request an email confirmation.

Schedules 5A, 9 (Part 2), and 9A (Part 2)
Unapproved Medicines and Unapproved Biologicals
FAQs
Ethics Committee > Ethics Committee
Last content review/update: December 17, 2021
Summary

Overview

As indicated in the TGAct, the TGR, the G-CTHandbook, the G-NatlStmt, AUS-47, and AUS-42, Australia has a decentralized process for the ethics review and approval of clinical trial research. According to the TGR and the G-NatlStmt, Australia requires human research protocols to be reviewed by an institutional-level ethics committee (EC). Per the TGAct, ECs are required to be constituted and operate in accordance with the guidelines issued by the National Health and Medical Research Council (NHMRC), and to have notified the NHMRC of their existence. The NHMRC was established by the NHMRCAct. (Note: Institutional ECs are referred to as Human Research Ethics Committees (HRECs) in Australia.)

As per the TGR, the G-NatlStmt, the G-SftyRpt, the G-TrialsSOP, and AUS-20, institutional ECs ensure that clinical trial research complies with the NHMRC’s ethical standards published in the G-NatlStmt.

As stated in the TGAct, the TGR, the G-SftyRpt, the G-CTHandbook, the G-TrialsSOP, AUS-20, and AUS-40, the NHMRC is responsible for receiving EC registrations. Per AUS-21, NHMRC also maintains a National Certification Scheme for institutional ethics review processes. For more information on the NHMRC registration and certification process, see the Authorizing Body section.

Ethics Committee Composition

As stated in the G-NatlStmt, an EC must be composed of at least eight (8) members representing, to the extent possible, equal numbers of men and women, one third of which are from outside the institution. Specifically, the EC composition should include:

  • A chairperson
  • At least two (2) lay persons, one (1) man and one (1) woman, who have no affiliation with the institution and are not currently involved in medical, science, legal, or academic work
  • At least one (1) person with knowledge of and current experience in the professional care, counseling, and/or treatment of people
  • At least one (1) person who performs a pastoral care role in the community
  • At least one (1) lawyer
  • At least two (2) people with current research experience relevant to the research proposals under consideration by the EC

ECs may also include other members with additional areas of expertise.

Terms of Reference, Review Procedures, and Meeting Schedule

As delineated in the G-NatlStmt, institutional ECs must establish and follow procedures to promote good ethics reviews. The procedures should address:

  • Meeting frequency, attendance, conduct, and structure
  • Minutes and agenda preparation
  • Timely distribution of materials before meetings
  • Presentation and timely consideration of applications for ethics review
  • Management of conflicts of interest
  • Modes of communicating with researchers
  • Institutional reporting
  • Decision-making methods
  • Prompt notification of decisions, including withdrawals of approval
  • Record keeping
  • Monitoring of approved research
  • Reporting and handling of adverse events
  • Receiving and handling of complaints
  • Attendance of observers at meetings
  • Fees, if any
  • Confidentiality of applications and associated reviews

Pursuant to the G-NatlStmt, EC members should be familiar with the G-NatlStmt and other relevant guidelines; prepare for and attend EC meetings or, if unavailable, provide opinions before the meetings; and attend research ethics training at least every three (3) years. ECs must communicate their decisions in writing with reasons substantiated by the G-NatlStmt, and they should maintain a record of all research proposals and decisions in written or electronic form. For more details on the governance and responsibilities of Australian institutional ECs, see the G-NatlStmt.

Part 1 (3), Part 2 (5B, 5C)
Chapter 1 (3) and Chapter 3 (Part 3-2 (18 and 19))
Part 3 (12AA and 12AD)
The CTN and CTA schemes
Terms
Purpose, Scope and Limits of this Document, and Section 5 (5.1 and 5.2)
Part 1: Investigational Medicinal Product (IMP) Trials (C. An Overview of Safety Monitoring and Reporting Responsibilities)
CTN Scheme and CTA Scheme
Planning a Clinical Trial – How to Apply for Ethics Approval and Finding an Ethics Committee
Ethics Committee > Scope of Review
Last content review/update: December 17, 2021
Summary

Overview

According to the G-NatlStmt, the primary scope of information assessed by the institutional ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) relates to protecting the interests of research participants by ensuring adherence to the values of respect, research merit and integrity, justice, and beneficence throughout the conduct of the research project. The EC must pay special attention to reviewing the recruitment and consent processes and to protecting the welfare of certain classes of participants deemed to be vulnerable. (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses, & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations).

Pursuant to the G-NatlStmt, the EC is responsible for conducting a competent review of all ethical aspects of the protocol, evaluating possible risks and expected benefits to participants, confirming the suitability of the researcher(s), facilities, and methods, and verifying the adequacy of confidentiality safeguards.

Role in Clinical Trial Approval Process

According to the G-CTHandbook, the G-TrialsSOP, AUS-47, and AUS-42, ECs are responsible for reviewing and approving protocols involving unapproved therapeutic goods under one (1) of two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme or the Clinical Trial Approval (CTA) (formerly known as Clinical Trial Exemption (CTX)) scheme—prior to the sponsor initiating a trial. Per the G-CTHandbook, the sponsor determines whether to conduct a clinical trial under the CTN or CTA scheme, in consultation with the EC. The two (2) regulatory review schemes are described as follows:

  • CTN scheme – According to the G-CTHandbook, a CTN trial must be notified to the Therapeutic Goods Administration (TGA) before the sponsor can supply the unapproved therapeutic goods in the trial. All materials relating to the proposed trial, including the trial protocol, are submitted directly to the EC, which provides scientific and ethical review. Per AUS-47, EC and institutional review and approval may be conducted in parallel to the CTN form submission to the TGA; however, it is the sponsor’s responsibility to ensure that all relevant approvals are in place before commencement of the trial.
  • CTA scheme – According to G-CTHandbook, the CTA scheme involves the TGA’s review of relevant, but limited, scientific data (which may be preclinical and early clinical data) prior to the start of a trial. Pursuant to the TGAct, the TGR, the G-CTHandbook, and AUS-47, the CTA scheme consists of a two-part process. Part 1 constitutes the formal CTA application, which the sponsor completes and submits directly to the TGA. Under Part 1, the TGA reviews the safety of the product, and the EC performs a scientific and ethical review of the proposed trial protocol. Per AUS-47, Part 2 requires the sponsor to notify the TGA when a trial commences under the CTA scheme and alert the TGA to new sites in ongoing CTA trials. The evaluation of a CTA application includes consideration of the manufacturing and quality and safety data in conjunction with the trial's usage guidelines, to inform a risk-benefit decision by the TGA on whether or not to approve the clinical trial.

According to AUS-47, parties that are considering submitting a CTA application are strongly encouraged to contact the TGA at clinical.trials@health.gov.au for advice regarding the application process.

AUS-46 indicates that the National Health and Medical Research Council (NHMRC) developed the Human Research Ethics Application (HREA) for submitting proposals for research involving humans to ECs (found in AUS-9). The HREA is accepted by institutions in the National Mutual Acceptance (NMA) Scheme, which allows for the acceptance of a single ethics review by multiple public health organizations for most human research. According to the G-CTHandbook, trial sponsors and researchers should use the HREA unless advised otherwise. AUS-19 contains resources for using HREA. More information on the NMA is provided below.

For both the CTN and CTA schemes, the G-CTHandbook and the TGR require that trials comply with the G-NatlStmt, the Guidelines for Good Clinical Practice as adopted by Australia in the AU-ICH-GCPs (which includes annotations by the TGA), and the trial protocol approved by the EC that will monitor the conduct of the trial. According to the AU-ICH-GCPs, if requirements specified in the G-NatlStmt appear to differ from those specified in the AU-ICH-GCPs, the TGA recommends compliance with the G-NatlStmt.

Pursuant to the G-CTHandbook and the TGR, when the EC approves a trial protocol, it takes responsibility for monitoring the progress and conduct of the trial. During its review, the EC also needs to be aware of relevant state and territory laws pertaining to the supply of therapeutic goods or other clinical trial-related matters.

As per AUS-21, under the National Certification Scheme of Institutional Processes Related to the Ethical Review of Multi-centre Research (National Certification Scheme), if a multicenter trial is being conducted and if the project has been reviewed by an EC affiliated with a certified institution, other participating institutions may choose to accept the review of this EC. Certification respects institutional decisions about research governance matters, including whether research should be conducted at a given site. For more information on the NHMRC registration and certification process, see the Authorizing Body section.

As described in AUS-41, AUS-5, and AUS-50, the NMA scheme is a national system for mutual acceptance of scientific and ethical review of multicenter human research projects conducted in publicly funded health services across jurisdictions. AUS-5 indicates that research under the NMA scheme undergoes scientific and ethical review only once by a lead EC, which must be certified under the NMA scheme. Per AUS-50, the Australian Capital Territory, New South Wales, Northern Territory, Queensland, South Australia, Tasmania, Victoria, and Western Australia currently participate in NMA.

According to AUS-46, research proposals to ECs associated with public health institutions in New South Wales, Queensland, South Australia, Australian Capital Territory, and Victoria, as well as Mater Research, should be submitted through the Research GEMS website (AUS-55), the Research Ethics and Governance Information System (REGIS) (AUS-10), or the Ethical Review Manager (ERM) Applications website (AUS-8), as appropriate.

Per AUS-46, ECs located in the Northern Territory, Tasmania, or Western Australia should be contacted for information on their local submission requirements. See AUS-61 for central points of contact for each jurisdiction.

Chapter 1 (3) and Chapter 3 (Part 3-2 (18 and 19))
Part 3 (12 and 12AA-12AD)) and Schedule 5A
Clinical trials involving therapeutic goods, The CTN and CTA schemes, and Role of Human Research Ethics Committees (HRECs)
3
Terms
Preamble, Purpose, Scope and Limits of this Document, and Sections 1, 2, 4, and 5
Research Governance Procedure (4.2)
CTN Scheme, CTA Scheme, and FAQs
Ethics Committee > Ethics Committee Fees
Last content review/update: December 17, 2021
Summary

Overview

As per the G-NatlStmt, institutions that individually or jointly establish ethics committees (ECs) (Human Research Ethics Committees (HRECs) in Australia) should allocate adequate funds to prevent charging fees for ethics reviews in amounts that would discourage research that the institution has an obligation to support. The institutional budget should also enable the EC to achieve the following:

  • Satisfy the requirements for a sound ethics review
  • Communicate with researchers
5
Ethics Committee > Authorizing Body
Last content review/update: December 17, 2021
Summary

Overview

As per the TGAct, the G-NatlStmt, the G-TrialsSOP, and the G-CTHandbook, the National Health and Medical Research Council (NHMRC) is responsible for registering ethics committees (ECs) (Human Research Ethics Committees (HRECs) in Australia). The NHMRC was established by the NHMRCAct. According to the G-CTHandbook, a clinical trial cannot commence until it is approved by an EC. In addition, as per AUS-21, the NHMRC administers a voluntary certification program for ECs to conduct an ethics review of multicenter research.

Registration, Auditing, and Accreditation

As specified in AUS-20, institutions can register their ECs, notify of changes to ECs, or terminate EC registration by submitting the appropriate online forms to the NHMRC. AUS-20 further states that registered ECs should report their activities and compliance with the G-NatlStmt annually to the NHMRC. The NHMRC assesses the annual report and notifies the EC of the outcome of its assessment.

As per AUS-21, the NHMRC is the certifying body for Australia’s national, voluntary certification of ECs for multicenter research. The NHMRC assesses each institution’s interest for certification on a case-by-case basis. Before commencing steps to apply for certification, institutions should contact HREC.admin@nhmrc.gov.au.

Part 1 (3), Part 2 (5B, 5C)
Chapter 1 (3)
Role of Human Research Ethics Committees (HRECs)
Terms
5
Clinical Trial Lifecycle > Submission Process
Last content review/update: December 17, 2021
Summary

Overview

In accordance with the TGAct, the TGR, the G-CTHandbook, the G-TrialsSOP, and AUS-47, Australia requires the sponsor to obtain clinical trial authorization from the Therapeutic Goods Administration (TGA) for the supply of unapproved therapeutic goods for clinical trials for experimental purposes in humans. The sponsor can apply under two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme and the Clinical Trial Approval (CTA) (formerly known as Clinical Trial Exemption (CTX)) scheme. Per the G-CTHandbook and AUS-47, the sponsor is responsible for determining whether the CTN or CTA scheme should be used. According to the G-CTHandbook, consulting the ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) responsible for protocol approval may assist the sponsor in making the decision. Under either regulatory scheme, per the TGR and the G-NatlStmt, an EC must approve research protocols.

According to AUS-43 and the G-TrialsSOP, the institution must approve any research in accordance with its research governance framework, including a site-specific assessment (SSA) for public institutions. The SSA and EC ethical and scientific review may occur in parallel. However, the G-TrialsSOP further specifies that EC approval must be obtained and submitted to the research governance officer (RGO) before the final RGO authorization is granted. Additionally, in the case of a teletrial, an SSA is required for each satellite site. Per the G-CodeConduct, Australian institutions must establish and maintain good governance and management practices for responsible research conduct. In addition, according to the G-CodeConduct, researchers have a responsibility to ensure that appropriate approvals have been obtained before commencing research, and to comply with the relevant laws, regulations, disciplinary standards, ethics guidelines, and institutional policies related to responsible research conduct.

AUS-46 indicates that the National Health and Medical Research Council (NHMRC) developed the Human Research Ethics Application (HREA) for submitting proposals for research involving humans to ECs. The HREA is accepted by institutions in the National Mutual Acceptance (NMA) Scheme, which allows for the acceptance of a single ethics review by multiple public health organizations for most human research. (See AUS-9 to login and create an HREA). According to the G-CTHandbook, trial sponsors and researchers should use the HREA unless advised otherwise.

Per AUS-46, research proposals should be submitted via the Research GEMS system (AUS-55), the Ethical Review Manager (ERM) site (AUS-8), and the Research Ethics and Governance Information System (REGIS) (AUS-10) to ECs associated with public health institutions in New South Wales, Queensland, South Australia, Australian Capital Territory, and Victoria, as well as Mater Research. For research in the Northern Territory, Tasmania, or Western Australia, the EC should be contacted for their local submission requirements. AUS-19 contains resources for using the HREA, and AUS-61 contains contact information for each jurisdiction. For more information on NMA, see the Scope of Review section.

Delivery Information for Clinical Trial Application

CTN Scheme

As per the G-CTHandbook, all materials relating to the proposed trial, including the trial protocol, are submitted directly to the EC, which provides scientific and ethical review. AUS-47 indicates that the review and approval by an EC and institution may be conducted in parallel to the CTN form submission to the TGA, but it is the sponsor’s responsibility to ensure that all relevant approvals are in place before commencement of the trial.

According to AUS-47 and AUS-30, to submit a CTN application, a sponsor must have a TGA Client Identification Number, which is obtained through TGA Business Services. See AUS-30 for additional details.

As indicated in AUS-47, CTN scheme applications are submitted through an online form. AUS-30 indicates that the applicant must use his/her Client Identification Number in order to access the online CTN form through the TGA Business Services webpage (AUS-36). AUS-49 provides details on using and submitting the online form.

CTA Scheme

According to AUS-47, the sponsor must complete and submit two (2) forms (AUS-56 and AUS-57) to the TGA via email at clinical.trials@health.gov.au. Supporting data for the CTA application should be provided in electronic format, preferably on USB or CD-ROM via post. The trial commencement notification form (AUS-57) must be sent to the TGA within 28 days of commencing supply of the unapproved therapeutic goods.

AUS-54 indicates that electronic submissions are preferred for CTA applications. However, AUS-47 further states that those with queries regarding the CTA scheme are encouraged to contact the TGA directly at clinical.trials@health.gov.au.

Assembly and Number of Copies

CTN Scheme

As per AUS-49, to submit the online CTN form successfully through AUS-36, the sponsor must accept a declaration to assume responsibility for the trial. According to AUS-47, the TGA does not send an acknowledgement letter by email since this information is available for viewing and printing via the online portal. The TGA advises clinical trial sponsors to obtain and save a printout of notification at each stage of the submission process.

CTA Scheme

Per AUS-47, those with queries regarding the CTA scheme are encouraged to contact the TGA directly at clinical.trials@health.gov.au.

Clinical Trial Application Language Requirements

While there is no language requirement stated in the requirements, the official language of Australia is English.

Chapter 3 (Part 3-2 (18, 19, 31A, and 31B))
Part 3 (12 and 12AA-12AD) and Schedule 5A
About this Handbook, Determine if the product is ‘unapproved’, The CTN and CTA schemes, and Role of Human Research Ethics Committees (HRECs)
Responsibilities of institutions
Terms and SOP 05
Purpose, Scope and Limits of this Document and Section 3 (Introduction)
CTN Scheme, CTA Scheme, Clinical Trials Guidance, and FAQs
Manual Submission
Clinical Trial Lifecycle > Submission Content
Last content review/update: March 10, 2022
Summary

Overview

In accordance with the TGAct, the TGR, the G-CTHandbook, the G-TrialsSOP, AUS-47, and AUS-42, the Therapeutic Goods Administration (TGA) requires the sponsor to either notify or apply for clinical trial authorization for the supply of unapproved therapeutic goods for use for experimental purposes in humans. Per the TGR and the G-NatlStmt, under either the Clinical Trial Notification (CTN) scheme or the Clinical Trial Approval (CTA) (formerly known as Clinical Trial Exemption (CTX)) scheme, an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) must approve research protocols.

According to AUS-43 and the G-TrialsSOP, the institution must approve any research in accordance with its research governance framework, including a site-specific assessment (SSA) for public institutions. The SSA and EC ethical and scientific review may occur in parallel. However, the G-TrialsSOP further specifies that EC approval must be obtained and submitted to the research governance officer (RGO) before the final RGO authorization is granted. Additionally, in the case of a teletrial, an SSA is required for each satellite site. In addition, according to AUS-47, the TGA accepts CTN form submissions while the sponsor is obtaining the necessary endorsements, such as from the EC. See the Scope of Assessment section for detailed review and approval process information.

Regulatory Authority Requirements

CTN Scheme

As delineated in AUS-49, the following documentation must be submitted to the TGA in the CTN online notification form:

  • Sponsor name and address
  • Sponsor declaration
  • Notification fee (See Regulatory Fees section)
  • Organization-nominated contact’s name, phone number, and email
  • An optional alternative contact, which may be chosen from the contacts for the agent or sponsor organization submitting the CTN
  • Protocol number
  • Expected trial start and completion dates
  • Potential use of restricted goods
  • Study title
  • Trial type and description
  • Total number of trial participants
  • Therapeutic area
  • Investigational product (IP) details
  • Whether it is a multi-center trial
  • Whether the trial is being conducted in other countries
  • Preceding trial details
  • Trial site details
  • EC name and contact information

CTA Scheme

AUS-47 specifies that the evaluation of a CTA application includes consideration of the manufacturing and quality and safety data in conjunction with the trial's usage guidelines, to inform a risk-benefit decision by the TGA on whether or not to approve the clinical trial.

AUS-47 states that the sponsor must complete and submit two (2) forms (AUS-56 and AUS-57) to the TGA via clinical.trials@health.gov.au. Parties that are considering submitting a CTA application are strongly encouraged to contact the TGA at clinical.trials@health.gov.au for advice regarding the application process.

Ethics Committee Requirements

Per the G-CTHandbook, the TGA has adopted a risk-based approach to the governance of clinical trials in Australia, a concept that is supported by the Organisation for Economic Cooperation and Development (OECD) in their Recommendation on the Governance of Clinical Trials (AUS-1). The G-CTHandbook further indicates that institutional ECs have a high level of independence and are responsible for establishing their own processes for receiving and reviewing research proposals.

According to the G-CTHandbook, unless advised otherwise, trial sponsors and researchers should use the Human Research Ethics Application (HREA) for submitting proposals for research involving humans to ECs. The HREA is accepted by institutions in the National Mutual Acceptance (NMA) Scheme, which allows for the acceptance of a single ethics review by multiple public health organizations for most human research. See AUS-9 to create an account and complete an HREA. AUS-19 also contains resources for using HREA. For more information on NMA, see the Scope of Review section.

Research Governance

As described in the G-GovHndbk and AUS-43, research governance encompasses the institution’s processes to ensure that they are accountable for the research conducted under their auspices. To be properly governed, research must be conducted according to established ethical principles, guidelines for responsible research conduct, relevant legislation and regulations, and institutional policy. Research governance also includes credentialing and training of researchers and managing institutional risk.

Public health organizations are required to conduct a SSA to evaluate whether the site has the capacity to conduct the research (e.g., physical resources, staff, and insurance). The investigator submits the SSA to the institution’s research governance officer (RGO). Research projects cannot commence until the investigator has received authorization from the institution’s RGO. The SSA and EC reviews may occur in parallel, though some aspects of the SSA must occur after EC review. AUS-43 further indicates that all SSA applications must be submitted using the SSA form for that state or territory to the RGO within each public health organization. Clinical trials in public health organizations in South Australia must use the online SSA form found in the Research GEMS system (AUS-55), while the Ethical Review Manager (ERM) Applications website (AUS-8) is used for SSA form submission in Mater Health, Queensland, and Victoria. New South Wales and Australian Capital Territory use the Research Ethics and Governance Information System (REGIS) (AUS-10) for site governance applications.

The Clinical Trial Research Agreement (CTRA)—a component of research governance—must be completed by parties involved in the research. The agreement is reviewed by the institution during the SSA process. States and territories with clinical trials occurring solely in their jurisdictions may have specific, required CTRA forms. For examples, see AUS-34, AUS-18, and AUS-5. Multicenter clinical trials should use the CTRA templates in AUS-38, which were developed by jurisdictions participating in the NMA scheme and are maintained by Medicines Australia. The G-TrialsSOP further indicates that in the case of a teletrial, a clinical trial sub-contract is required for each satellite site as part of the SSA application.

The National Health and Medical Research Council (NHMRC) developed the GPP-SiteAssess to help institutions streamline the research governance process and shorten clinical trial start-up times. See the GPP-SiteAssess for more information.

Per AUS-63, the Australian Commission on Safety and Quality in Health Care also developed the National Clinical Trials Governance Framework as a first step towards a nationally consistent approach to the accreditation of health services for the conduct of clinical trials. The framework embeds clinical trials into routine health service provision and strengthens the clinical and corporate governance arrangements for parties that deliver clinical trials. In February 2022, all jurisdictions agreed to implement the framework in health service organizations. The anticipated implementation of the framework is the second half of 2022. For more information, see AUS-63.

Clinical Protocol

Per the G-CTHandbook, the TGA has adopted a risk-based approach to the governance of clinical trials in Australia. ECs, which are responsible for approval of the trial protocol under both the CTN and CTA schemes, have a high level of independence and are responsible for establishing their own processes for receiving and reviewing research proposals. In addition, the EC and the institution must determine what information should be provided in support of an application and how the application will be reviewed by the committee. The EC should request any additional information that it believes is necessary to review the proposed research.

However, the G-TrialsSOP further indicates that where the investigator is responsible for the protocol development, he/she must ensure the protocol follows the outline in the AU-ICH-GCPs. Specific content of a protocol will vary depending on the subject of the research, the level of risk to participants, the phase of the research and study design, and whether a medicinal product or a device or a therapeutic intervention is being researched. If satellite sites for a teletrial are involved in the study, no specific additional wording is required in the protocol, as relevant considerations will be addressed in other study-specific documents which may be annexed to the protocol.

The AU-ICH-GCPs provides the following outline of the protocol:

  • General information (protocol title, identifying number, and date; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study)
  • Background information
  • Objectives and purpose
  • Trial design
  • Selection, withdrawal, and treatment of participants
  • Assessment of efficacy
  • Assessment of safety
  • A description of the statistical methods to be used in the trial
  • Direct access to source data and documents
  • Quality control and quality assurance
  • Ethical considerations
  • Data handling and recordkeeping
  • Financing and insurance
  • Publication policy
Chapter 3 (Part 3-2 (18, 19, 31A, and 31B))
Part 3 (12 and 12AA-12AD)
About this Handbook, Determine if the product is ‘unapproved’, The CTN and CTA schemes, and Role of Human Research Ethics Committees (HRECs)
Report of the pilot of the Good Practice Process – Executive summary
Terms and SOPs 04 and 05
Purpose, Scope and Limits of this Document and Section 3 (Introduction)
Research Governance Procedures
Clinical Trial Research Agreements
CTN Scheme, CTA Scheme, and FAQs
Creating a New CTN Form
Research Agreements
Clinical Trial Lifecycle > Timeline of Review
Last content review/update: March 10, 2022
Summary

Overview

In accordance with the TGAct, the TGR, the G-CTHandbook, the G-TrialsSOP, and AUS-47, the Therapeutic Goods Administration (TGA) is responsible for providing access to the supply of unapproved therapeutic goods for clinical trials under two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme and the Clinical Trial Approval (CTA) (formerly known as Clinical Trial Exemption (CTX)) scheme. According to the TGR and the G-NatlStmt, under either regulatory scheme, an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) must approve research protocols. Per AUS-43 and the G-TrialsSOP, the institution must approve any research in accordance with its research governance framework, including a site-specific assessment (SSA) for public institutions. The SSA and EC ethical and scientific review may occur in parallel. However, the G-TrialsSOP further specifies that EC approval must be obtained and submitted to the research governance officer (RGO) before the final RGO authorization is granted. Additionally, in the case of a teletrial, an SSA is required for each satellite site.

Regulatory Authority Approval

CTN Scheme

As per the TGAct, the TGR, the G-CTHandbook, the G-TrialsSOP, and AUS-47, under the CTN scheme, the TGA is notified of a clinical trial. AUS-47 indicates that the sponsor may submit the CTN form simultaneously while obtaining the necessary endorsements. 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. AUS-47 further states the TGA’s target time to process online CTNs is five (5) to seven (7) working days. According to the G-CTHandbook, the TGA may request additional information if the trial raises any concern. CTN trials can commence once the trial has been reported to the TGA and the appropriate notification fee paid. Per AUS-47, the TGA no longer sends acknowledgment letters by email as this information can now be viewed and printed via the online portal. The TGA advises clinical trial sponsors to obtain and save a printout of the notification received at each stage of the submission process.

CTA Scheme

As per the G-CTHandbook, the CTA scheme involves the TGA’s review of relevant, but limited, scientific data (which may be preclinical and early clinical data) prior to the start of a trial. The TGA’s primary responsibility is to review the safety of the product, and the EC is responsible for considering the scientific and ethical issues of the proposed trial protocol.

AUS-47 specifies that the evaluation of a CTA application includes consideration of the manufacturing and quality and safety data in conjunction with the trial's usage guidelines, to inform a risk-benefit decision by the TGA on whether or not to approve the clinical trial. Parties that are considering submitting a CTA application are strongly encouraged to contact the TGA at clinical.trials@health.gov.au for advice regarding the application process.

Ethics Committee Approval

The EC review and approval process timeline varies by institution. However, according to the G-NatlStmt, the institutional EC should review a proposed clinical trial and make its decision in a timely manner.

Research Governance

Per the G-GovHndbk, research must be governed by the institution at all stages of a project. While some parts of the research governance review must occur after the EC review, the G-GovHndbk recommends that as part of the National Approach to Single Ethical Review, institutions establish processes to facilitate parallel review. Project documentation processes related to site assessment may be considered as falling into these categories:

  • that which can be assessed independent of ethical review, such as evidence of research qualifications, supporting department approval forms, contracts, budgets, and insurance and indemnity documents
  • that which is subject to ethical review, but can be submitted prior to or in parallel with ethical review to enable independent assessment of other documentation, such as initial project application documents
  • that which can only be assessed subsequent to ethical approval, such as approved project application documents, fully signed regulatory documents, and a certificate of ethical approval

Finally, per the G-GovHndbk and AUS-43, because evidence of EC approval is a component of the research governance process, institutional authorization of a research project cannot be given until EC approval has been provided.

The National Health and Medical Research Council (NHMRC) developed the GPP-SiteAssess to help institutions streamline the research governance process and shorten clinical trial start-up times. See the GPP-SiteAssess for more information.

Per AUS-63, the Australian Commission on Safety and Quality in Health Care also developed the National Clinical Trials Governance Framework as a first step towards a nationally consistent approach to the accreditation of health services for the conduct of clinical trials. The framework embeds clinical trials into routine health service provision and strengthens the clinical and corporate governance arrangements for parties that deliver clinical trials. In February 2022, all jurisdictions agreed to implement the framework in health service organizations. The anticipated implementation of the framework is the second half of 2022. For more information, see AUS-63.

Chapter 3 (Part 3-2 (18, 19, 31A, and 31B)) and Chapter 7 (60)
Part 3 (12 and 12AA-12AD) and Schedule 5A
The CTN and CTA schemes
Report of the pilot of the Good Practice Process – Executive summary
Terms and SOP 05
Purpose, Scope and Limits of this Document, Section 3 (Introduction), and Section 5 (5.1)
CTN Scheme, CTA Scheme, and FAQs
Clinical Trial Lifecycle > Trial Initiation
Last content review/update: December 17, 2021
Summary

Overview

In accordance with the TGAct, the TGR, the G-TrialsSOP, and the G-CTHandbook, and AUS-47, clinical trials involving unapproved therapeutic goods can only commence under the Clinical Trial Notification (CTN) scheme or the Clinical Trial Approval (CTA) (formerly known as Clinical Trial Exemption (CTX)) scheme. According to the G-GovHndbk, the G-TrialsSOP, and AUS-43, under either scheme, both ethics approval and research governance authorization are required before a research project can commence at a site.

The National Health and Medical Research Council (NHMRC) developed the GPP-SiteAssess to help institutions streamline the research governance process and shorten clinical trial start-up times. See the GPP-SiteAssess for more information.

According to the G-TrialsSOP, the principal investigator (PI) must ensure that a study master file (SMF) is created, if not provided by the sponsor, prior to study commencement, and ensure that it contains the relevant study-related essential documents (see Appendix 8 of the G-TrialsSOP).

The G-TrialsSOP states that prior to the initiation of a study, the investigator must mutually agree with the sponsor on a scheduled date, time, and location for a study initiation visit at the participating site to ensure the site is prepared to commence the study. In the case of a teletrial, this may be at the primary site only, or could include (remotely) the satellite site(s) as determined by the study complexity by the sponsor/PI. See the G-TrialsSOP for more information on site initiation requirements, and AUS-64 for more researcher resources.

CTN Scheme

As delineated in the G-CTHandbook and AUS-47, the sponsor must notify the Therapeutic Goods Administration (TGA) about the trial through submittal of the online CTN form and pay the appropriate notification fee.

CTA Scheme

The G-CTHandbook and AUS-47 indicate that for trials conducted under a CTA, the sponsor must submit an application (AUS-56) and relevant fee to the TGA, which reviews relevant scientific data prior to the start of a trial. An ethics committee (EC) (Human Research Ethics Committees (HRECs) in Australia) must also approve the conduct of the trial.

AUS-47 further indicates that the TGA is currently reviewing the CTA scheme application procedure. Individuals who are considering submitting a CTA application are strongly encouraged to contact the TGA at clinical.trials@health.gov.au for advice regarding the application process.

According to AUS-14, prior to approving a clinical trial, the EC must be satisfied that the trial protocol complies with the following requirements:

Clinical Trial Agreement

Prior to initiating the trial, as delineated in the AU-ICH-GCPs, the sponsor must sign an agreement between all involved parties, including ECs, Qualified Investigators (QIs), contract research organizations, and others, to ensure full compliance with the regulatory requirements.

As part of the research governance process (including site-specific assessment (SSA) for public entities), a Clinical Trial Research Agreement (CTRA) must be completed by parties involved in the research. States and territories with clinical trials occurring solely in their jurisdictions may have specific required CTRA forms. The G-TrialsSOP further indicates that in the case of a teletrial, an SSA application, including a clinical trial sub-contract, is required for each satellite site.

Ethics Committee Confirmation of Review and Approval

As per AUS-21, under the National Certification Scheme of Institutional Processes Related to the Ethical Review of Multi-centre Research (National Certification Scheme), if a multicenter trial is being conducted and if the project has been reviewed by an EC affiliated with a certified institution, other participating institutions may choose to accept the review of this EC. Certification respects institutional decisions about research governance matters, including whether research should be conducted at a given site. (See Scope of Review section for detailed information on the institutional EC review and approval process).

Clinical Trial Registration

The G-NatlStmt requires that a clinical trial be registered on a publicly accessible register complying with international standards before recruitment of the first participant. For information on these standards, see the World Health Organization (WHO)'s International Clinical Trials Registry Platform (ICTRP). Per AUS-15, the Australian New Zealand Clinical Trials Registry (ANZCTR) (AUS-12) is one (1) of the primary registries in the WHO Registry Network (AUS-33).

Data Safety Monitoring Board

G-DSMB indicates that the sponsor may establish a Data Safety Monitoring Board (DSMB) to review accumulating trial data in order to monitor the progress of a trial. The role of a DSMB is to provide advice on safety and/or trial conduct issues by making recommendations to the sponsor or trial steering committee on whether to continue, modify, or stop a trial. The members of a DSMB are generally appointed by the sponsor or trial steering committee, and the size of a DSMB varies depending on the trial type and expertise required.

The AU-ICH-GCPs also recommends establishing a DSMB to assess the progress of a clinical trial.

According to the G-TrialsSOP, the sponsor may utilize a DSMB or independent individuals (e.g., a medical monitor) to:

  • Review accruing trial safety data in either an unblinded or blinded manner to assess treatment exposure
  • Access, assess, and review emerging efficacy data for the trial
  • Assess the balance of risks and benefits within the trial
  • Document the outcome of these reviews
Chapter 3 (Part 3-2 (18, 19, 31A, and 31B))
Part 3 (12 and 12AA-12AD)
The CTN and CTA schemes
What is a DSMB and what is its role? and How is a DSMB established?
Report of the pilot of the Good Practice Process – Executive summary
1
Terms; SOPs 05, 06, 07, and 12; and Appendix 8
Section 3 (3.1.7) and Section 5 (5.1)
CTN Scheme, CTA Scheme, and FAQs
Clinical Trial Lifecycle > Safety Reporting
Last content review/update: December 17, 2021
Summary

Overview

According to the G-SftyRpt, the following definitions provide a basis for a common understanding of Australia’s safety reporting requirements:

  • Adverse Event (AE) – Any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product and that does not necessarily have to have a causal relationship with this treatment
  • Adverse Reaction (AR) – Any untoward and unintended response to an investigational medicinal product related to any dose administered
  • Unexpected Adverse Reaction (UAR) – An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., investigator's brochure (IB) for an unapproved investigational medicinal product)
  • Serious Adverse Event (SAE) or Serious Adverse Reaction (SAR) – Any adverse event/adverse reaction that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect
  • Suspected Unexpected Serious Adverse Reaction (SUSAR) – An adverse reaction that is both serious and unexpected

Reporting Requirements for AEs/ARs

Investigator Responsibilities

As specified in the G-SftyRpt, the investigator is responsible for recording and assessing all AEs that occur at the site. The investigator is also required to inform the sponsor of all SAEs and all urgent safety measures instigated by the site within 24 hours of becoming aware of the event. All safety critical events must be reported to the sponsor, and for reported deaths, the investigator should supply the sponsor with any additional requested information. Further, the investigator must report to the institution all significant safety issues, and SUSARs arising from the local site, within 72 hours of becoming aware of the event.

However, the G-TrialsSOP states that the investigator must also report any SUSARs to the sponsor within 24 hours of becoming aware of the event, and urgent safety measures instigated by the investigator or site must be reported to the sponsor within 72 hours. Furthermore, the investigator must report all other significant issues to the sponsor within 15 days of instigating or becoming aware of the event. The investigator must notify the sponsor promptly regarding any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants. The investigator must also be available to meet with the sponsor to discuss study progress, issues, and safety.

The G-TrialsSOP requires that within 72 hours of instigating or becoming aware of the event, the investigator must notify the institution of:

  • Urgent safety measures
  • SUSARs arising from the local site
  • Any information received from the sponsor that may be new and have an impact on the continued ethical acceptability of the trial or may indicate the need for amendments to the trial protocol, including monitoring of safety

The G-TrialsSOP indicates that for satellite site(s) in teletrials, staff must report safety issues directly to the sponsor as per the timelines specified in the clinical trial protocol and the safety monitoring plan or similar document, in the same way as the primary site. Certified copies of the relevant safety reports/documentation generated at the satellite site must be sent to the primary site for filing in a study master file.

According to the G-TrialsSOP, the PI must ensure that study staff, including those at teletrial satellite sites, are trained in the protocol, IB, study procedures, and AE/SAE reporting. The PI must also ensure that a system for safety reporting duties is in place for all study staff. For more information on investigator responsibilities related to standard operating procedures (SOPs), see the G-TrialsSOP.

Sponsor Responsibilities

As delineated in the G-SafetyDataMgt, the G-SftyRpt, and the G-CTHandbook, the sponsor is required to expedite reporting of SUSARs to the Therapeutic Goods Administration (TGA).

The G-SafetyDataMgt indicates that other situations requiring expedited reporting may include information that might materially influence the benefit-risk assessment of an investigational product, or that would be sufficient to consider changes in the administration or conduct of a clinical trial.

According to the G-SftyRpt and the G-TrialsSOP, expedited reporting requires the sponsor to file reports to the TGA in the following specified timelines:

  • For an Australian SUSAR that is fatal or life-threatening, immediately, but no later than seven (7) calendar days, with any follow-up information within eight (8) calendar days
  • For all other Australian SUSARs, no later than 15 calendar days after becoming aware of the case

The TGA, the ethics committee (EC), and investigators must also be notified of all significant safety issues that adversely affect the safety of participants, or materially impact the continued ethical acceptability or conduct of the trial. Significant safety issues that meet the definition of an urgent safety measure should be reported within 72 hours, and all other significant safety issues should be reported within 15 calendar days of the sponsor being made aware of the issue. It is strongly recommended that the sponsor contact the TGA within 24 hours of an urgent safety measure being taken, and if initial contact is by telephone, it should be followed up with a written notification provided by facsimile or e-mail within 72 hours.

Per the G-SftyRpt, submitting individual reports of AEs, SAEs, and SUSARs to ECs, institutions, and investigators are no longer required. However, according to the G-TrialsSOP, the sponsor must provide the EC with an updated IB at least annually that supports trial oversight, depicts a clear picture of the evolving trial safety profile, and provides evidence that the sponsor is conducting its safety monitoring appropriately.

The G-CTHandbook and the G-SftyRpt further require the sponsor to maintain records of all other single case AEs and submit them to the TGA upon request. The G-CTHandbook indicates that the TGA does not require sponsors to submit individual SUSARs from outside Australia. Sponsors should continually monitor the safety of their clinical program and advise the TGA of any significant safety issues that arise from their analysis of overseas reports, or of any action that has been taken by another country's regulatory agency. Investigators and ECs should also be informed of this information, and sponsors must be able to provide the TGA with the clinical details of any individual overseas AE reports if requested.

According to the G-TrialsSOP, the sponsor’s plans for safety data monitoring should be documented in a safety monitoring plan or similar document and be given to the principal investigator (PI) prior to commencement of the clinical trial. The plan must be continually reviewed and updated during the trial, as real-time assessments of safety data are performed, and outcomes are made available.

Form Completion & Delivery Requirements

As per the G-CTHandbook, all SUSARs from Australian sites must be reported to the TGA using one (1) of three (3) formats:

  • The new Electronic Data Interchange (EDI) functionality, which allows sponsors to submit AE reports directly from their system to the TGA (more information can be found at AUS-26)
  • The new online reporting form, which can be accessed from AUS-51
  • The CIOMS Form I (AUS-4) or the TGA’s Blue Card Adverse Reaction Reporting Form (AUS-3), emailed to adr.reports@health.gov.au

More information about reporting to the TGA may be found at AUS-7.

Data Safety Monitoring Board

The G-DSMB indicates that the sponsor may establish a Data Safety Monitoring Board (DSMB) to review accumulating trial data in order to monitor the progress of a trial. The role of a DSMB is to provide advice on safety and/or trial conduct issues by making recommendations to the sponsor or trial steering committee on whether to continue, modify, or stop a trial. The members of a DSMB are generally appointed by the sponsor or trial steering committee, and the size of a DSMB varies depending on the trial type and expertise required.

The AU-ICH-GCPs also recommends establishing a DSMB to assess the progress of a clinical trial.

According to the G-TrialsSOP, the sponsor may utilize a DSMB or independent individuals (e.g., a medical monitor) to:

  • Review accruing trial safety data in either an unblinded or blinded manner to assess treatment exposure
  • Access, assess, and review emerging efficacy data for the trial
  • Assess the balance of risks and benefits within the trial
  • Document the outcome of these reviews
Safety reporting to TGA for CTN and CTA trials
What is a DSMB and what is its role? and How is a DSMB established?
5
SOPs 02, 05, and 12
Introduction, Definitions and Terminology Associated with Clinical Safety Experience, Standards for Expedited Reporting, and Attachment 1
Summary of Main Changes to Reporting Requirements and Part 1: Investigational Medicinal Product (IMP) Trials (C. An Overview of Safety Monitoring and Reporting Responsibilities)
Clinical Trial Lifecycle > Progress Reporting
Last content review/update: December 17, 2021
Summary

Overview

As per the AU-ICH-GCPs, the G-NatlStmt, and the G-TrialsSOP, the investigator(s) is responsible for submitting progress reports to the ethics committee (EC) (known as Human Research Ethics Committee in Australia) annually, or more frequently if requested. If there are significant changes in trial conduct or safety, the investigator should submit a written report to the sponsor, the EC, and where applicable, the institution. The AU-ICH-GCPs and the G-TrialsSOP further indicate that the investigator should provide the EC with a final clinical study report. As per the G-TrialsSOP, the investigator must also notify the research governance officer that the trial has terminated/closed.

Interim and Annual Progress Reports

The G-SftyRpt delineates that the sponsor must provide the EC with an annual safety report including a clear summary of the evolving trial safety profile. The annual safety report should generally include:

  • A brief description and analysis of new and relevant findings
  • For investigational products (IPs) not on the Australian Register of Therapeutic Goods, a brief analysis of the safety profile of the IP and its implications for participants
  • A brief discussion of the implications of the safety data to the trial’s risk-benefit ratio
  • A description of any measures taken or proposed to minimize risks

A Development Safety Update Report (DSUR) or other similar document may also serve as the annual safety report. See the G-SftyRpt for more information.

Final Report

According to AUS-54, the sponsor should make the final report available to the Therapeutic Goods Administration (TGA) upon request. If requested, the report should be provided electronically, via email, USB, or CD in any format the sponsor chooses.

AUS-47 indicates that for trials conducted under the Clinical Trial Approval (CTA) scheme, the CTA clinical trial completion form (AUS-58) is used to notify the TGA of the trial completion. Upon completion, the form may be emailed to the TGA at clinical.trials@health.gov.au.

4
SOP 05
Section 5 (5.5)
Part 1: Investigational Medicinal Product (IMP) Trials (C. An Overview of Safety Monitoring and Reporting Responsibilities)
CTA Scheme
Sponsorship > Definition of Sponsor
Last content review/update: December 17, 2021
Summary

Overview

As per the AU-ICH-GCPs and the G-TrialsSOP, a sponsor is defined as an individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.

In accordance with the AU-ICH-GCPs, Australia permits a sponsor to transfer any or all of its trial-related duties and functions to a contract research organization (CRO). Any trial-related duties and functions transferred to a CRO should be specified in a written agreement, and the sponsor should ensure oversight of such transferred responsibilities. Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor. The AU-ICH-GCPs further indicates that the sponsor retains overall responsibility for the trial data’s quality and integrity, as well as the conduct of the trial. As stated in the G-TrialsSOP, the sponsor is also responsible for ensuring that appropriate approvals are obtained prior to the commencement of the clinical trial, that conditions of any approvals are adhered to during the course of the clinical trial, and that the ethics principles of research merit and integrity, justice, beneficence, and respect are applied to the conduct of clinical trials.

According to the G-CTHandbook, if the investigator initiates and organizes the trial, he or she assumes the role of trial sponsor. If another party (such as a pharmaceutical company) provides the investigational product or other support for an investigator-led trial, that party is not required to assume the sponsor role.

As per the G-CTHandbook, the G-TrialsSOP, AUS-47, and AUS-13, a sponsor must be an Australian entity.

Determine if the product is ‘unapproved’ and Role of trial sponsors
1.53 and 5.2
Terms
FAQs
Sponsorship > Trial Authorization
Last content review/update: December 17, 2021
Summary

Overview

In accordance with the TGAct, the TGR, the G-CTHandbook, the G-TrialsSOP, AUS-47, and AUS-42, the sponsor either notifies or applies to the Therapeutic Goods Administration (TGA) for authorization to supply unapproved therapeutic goods for clinical trials for experimental purposes in humans. These two (2) regulatory schemes are known as the Clinical Trial Notification (CTN) scheme and the Clinical Trial Approval (CTA) (formerly known as Clinical Trial Exemption (CTX)) scheme, respectively. Per the G-CTHandbook and AUS-47, the sponsor, followed by the ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia), is responsible for determining whether the CTN or CTA scheme should be used. Under either regulatory scheme, an EC must approve the protocol. According to AUS-47, the TGA accepts CTN form submissions while the sponsor is obtaining the necessary endorsements, such as from the EC.

CTN Scheme

Under the CTN scheme, AUS-49 indicates that the investigational products (IPs) for the trial must be approved by the sponsor (or by the entity conducting the trial for the sponsor), having regard for the advice of the EC, which approved the protocol and is responsible for monitoring trial conduct. Furthermore, the terms of approval of the sponsor must be no less restrictive than terms advised by the EC.

As delineated in AUS-49, the sponsor must submit the following documentation to the TGA in the CTN online notification form, which is available by logging into the TGA Business Services website (AUS-36):

  • Sponsor name and address
  • Sponsor declaration
  • Notification fee (See Regulatory Fees section)
  • Organization-nominated contact’s name, phone number, and email
  • An optional alternative contact, which may be chosen from the contacts for the agent or sponsor organization submitting the CTN
  • Protocol number
  • Expected trial start and completion dates
  • Potential use of restricted goods
  • Study title
  • Trial type and description
  • Total number of trial participants
  • Therapeutic area
  • IP details
  • Whether it is a multi-center trial
  • Whether the trial is being conducted in other countries
  • Preceding trial details
  • Trial site details
  • EC name and contact information

As indicated in AUS-47 and AUS-30, to submit a CTN application, a sponsor must have a TGA Client Identification Number, which is obtained through TGA Business Services. See AUS-30 for additional details.

CTA Scheme

As per the G-CTHandbook, the TGA reviews the safety of the product. The EC is responsible for reviewing the scientific and ethical issues of the trial protocol.

According to AUS-47, the sponsor must complete and submit two (2) forms (AUS-56 and AUS-57) to the TGA via clinical.trials@health.gov.au. Supporting data for the CTA application should be provided in electronic format, preferably on USB or CD-ROM via post. The trial commencement notification form (AUS-57) must be sent to the TGA within 28 days of commencing supply of the unapproved therapeutic goods.

AUS-54 indicates that electronic submissions are preferred for CTA applications. However, AUS-47 further states that parties that are considering submitting a CTA application are strongly encouraged to contact the TGA at clinical.trials@health.gov.au for advice regarding the application process.

Chapter 3 (Part 3-2 (18, 19, 31A, and 31B)) and Schedule 5
Part 3 (12 and 12AA-12AD) and Schedule 5A
The CTN and CTA schemes, Role of trial sponsors, and Role of Human Research Ethics Committees (HRECs)
Terms
CTN Scheme, CTA Scheme, and FAQs
Creating a New CTN Form and Full Text of Sponsor Declaration
Sponsorship > Insurance
Last content review/update: December 17, 2021
Summary

Overview

The TGR directs the sponsor to comply with the requirements in the AU-ICH-GCPs and the G-NatlStmt, which, in turn, state that the sponsor should provide insurance in accordance with applicable regulatory requirements. In addition, according to the G-NatlStmt, institutions must ensure that sponsors have insurance arrangements in accordance with applicable regulatory requirements. The federal documents cited here do not explicitly require insurance.

Per the G-GovHndbk, the institution and investigator are responsible for managing risks of any proposed research, including providing appropriate insurance coverage. The G-TrialsSOP further states that if the investigator is notified or becomes aware that a trial participant intends to make a claim against the institution or sponsor for injuries arising as a result of participating in a clinical trial undertaken at the institution (or any of the satellite sites under supervision by the institution in a teletrial), the investigator must promptly notify the following parties in writing that such an action is intended:

  • The institution’s authority
  • The coordinating principal investigator (PI)/PI/associate investigator, as relevant
  • The sponsor

The G-CTInsurance indicates that in the private sector, sites that conduct clinical trials will usually purchase clinical trials insurance from a commercial insurer. Unimutual (AUS-6) covers trials conducted by university researchers. In the public sector, each state or territory provides indemnity or insurance coverage in relation to its clinical trial activities. The G-CTInsurance provides more details for each state and territory scheme.

Part 3 (12AD) and Schedule 5A
5 and 8
Executive Summary
SOP 05
Section 5 (5.1)
IV
Sponsorship > Compensation
Last content review/update: December 17, 2021
Summary

Overview

The TGR directs the sponsor to comply with the requirements in the AU-ICH-GCPs and the G-NatlStmt, which, in turn, state that the sponsor should provide compensation for trial participants in accordance with applicable regulatory requirements. According to the G-NatlStmt, institutions must ensure that sponsors have indemnity and compensation arrangements as mandated by such requirements, and must be able to compensate trial participants for harm resulting from negligence. The AU-ICH-GCPs further indicates that the sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries. The federal documents cited here do not explicitly require indemnity or compensation.

According to the G-ResearchPayment, any proposal for payment of participants should be considered by the ethics committee (EC) reviewing the research. The EC should be provided with a payment plan that includes:

  • A rationale for the proposed payments
  • The method and timing of any disbursements, including how they have been calculated, and
  • Information about how prospective participants will be advised of the provision of payment

Payment of participants is ethically appropriate if it is equitable and proportionate to the burden of the research, and does not:

  • Undermine a participant’s capacity to provide voluntary and informed consent
  • Unduly influence a participant to accept a risk or burden that is greater than they would otherwise accept in everyday living or to compromise their fundamental values
  • Unduly influence a participant to make false representations about or conceal information that is relevant to their eligibility for the research, their contribution to the research, or the risks related to participation

To minimize the likelihood of a payment acting as an undue influence, the G-ResearchPayment further indicates that payment of participants should generally be limited to reimbursement of documented expenses and remuneration for time and inconvenience. Payment may be offered as an incentive to participate in cases where the research offers little or no benefit to individuals or where the research requires the participation of target populations that are difficult to recruit. In these cases, adequate processes must be in place to promote valid consent. For more information and examples of payment models, see the G-ResearchPayment.

Per the G-NatlStmt, any compensation or payment to participants must not be disproportionate to the time involved. Further, compensation decisions should consider customs and practices of the community in which the trial will be conducted.

The G-TrialsSOP further states that the investigator must immediately notify the sponsor of any notification received from a trial participant that he/she intends to initiate a claim for compensation against either the sponsor and/or the institution. In addition, if the institution is notified or becomes aware that a trial participant intends to make a claim for compensation against the institution or sponsor for injuries arising as a result of participating in a clinical trial undertaken at the institution (or any of the satellite sites under supervision by the institution in a teletrial), the institution must promptly notify the institution’s insurer in writing that such an action is intended.

According to the AU-ICH-GCPs, the written informed consent form (ICF) should contain information regarding any payment to participants, including a description of the anticipated prorated payment. (See Compensation Disclosure section for more information on participant compensation rights).

Part 3 (12AD) and Schedule 5A Item 3 (g)
3, 4.8, 5.8, and 8
SOP 05
Sections 2 and 5 (5.1)
Guidance Statements
Sponsorship > Quality, Data & Records Management
Last content review/update: December 17, 2021
Summary

Overview

As per the TGR and the AU-ICH-GCPs, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results.

According to the AU-ICH-GCPs, the quality management system should use a risk-based approach that includes:

  • Identifying processes and data that are critical to ensure participant protection and the reliability of trial results during protocol development
  • Identifying risks to critical trial processes and data
  • Evaluating the identified risks, against existing risk controls
  • Deciding which risks to reduce and/or which risks to accept
  • Documenting quality management activities and communicate to those involved in or affected by these activities
  • Periodically reviewing risk control measures to ascertain whether the implemented quality management activities are effective and relevant
  • Describing the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report

The G-RBMgmtMntring provides further guidance on the application of risk-based trial processes, particularly as a reference to sponsors of non-commercial trials.

The AU-ICH-GCPs further indicates that the sponsor is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data generated, recorded, and reported in compliance with the protocol, the AU-ICH-GCPs, and the applicable regulatory requirements. The sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial-related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. The sponsor should implement a system to manage quality throughout all stages of the trial process, and QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed. Any agreements between the sponsor and investigator, or with any other parties involved in the clinical trial, should be written, either within the protocol or in a separate agreement.

Responsible Research Conduct

The G-CodeConduct outlines principles, responsibilities, and expectations for institutions and researchers to facilitate responsible research practices. Compliance with the code is a requirement to receiving funding from the National Health and Medical Research Council (NHMRC) or the Australian Research Council (ARC). The G-CodeBreaches describes the preferred model for institutions to use to investigate and manage potential code breaches, to determine any corrective actions, and when a finding of research misconduct may be made. The Australian Research Integrity Committee uses the G-CodeBreaches as a guide for reviewing how NHMRC- and ARC-funded institutions manage potential code breaches.

The G-RptBreachGCP requires the sponsor to notify the reviewing ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) within seven (7) days of confirming a serious breach of good clinical practice (GCP). A serious breach is defined as one that is likely to affect to a significant degree: the safety or rights of a trial participant or the reliability and robustness of the data generated in the trial. Sponsors should also develop documented processes for managing serious breaches.

The supplementary guidance G-RptBreachGCP should be read alongside the G-CodeConduct and the G-CodeBreaches.

As described in the G-GovHndbk and AUS-43, research governance encompasses the institution’s processes to ensure that they are accountable for the research conducted under their auspices. To be properly governed, research must be conducted according to established ethical principles, guidelines for responsible research conduct, relevant legislation and regulations, and institutional policy. The Clinical Trial Research Agreement (CTRA)—a component of research governance—must be completed by parties to the clinical trial. The institution reviews the agreement during the site-specific assessment (SSA) process. Research governance also includes credentialing and training of researchers and managing institutional risk. The G-TrialsSOP further indicates that in the case of a teletrial, an SSA application, including a clinical trial sub-contract, is required for each satellite site.

Electronic Data Processing System

When using electronic trial data handling systems, the sponsor must ensure and document that the electronic data processing system conforms to his/her established requirements for completeness, accuracy, reliability, and consistent intended performance, and that he/she maintains SOPs for using these systems. Refer to the AU-ICH-GCPs for additional information.

Records Management

According to the G-CodeConduct and the G-DataInfoMgt, institutions must provide access to facilities for the safe and secure storage and management of research data, records, and primary materials.

The G-DataInfoMgt requires that institutional policy include guidance for managing research data and primary materials that addresses the following:

  • Ownership, stewardship, and control
  • Storage, retention, and disposal
  • Safety, security, and confidentiality
  • Access by interested parties

Furthermore, institutional policies on ownership of, and access to, databases and archives must require that:

  • Researchers are informed of relevant confidentiality agreements and restrictions on the use of research data
  • Computing systems are secure
  • Information technology personnel understand their responsibilities for network security and access control
  • Those holding primary material, including electronic material, understand their responsibilities for security and access

The G-CodeConduct and the G-DataInfoMgt further state that researchers must retain clear, accurate, secure, and complete records of all research including research data and primary materials.

The G-NatlStmt indicates that when multiple researchers are collaborating on the collection, storage, and/or analysis of data or information, they should agree to the arrangements for custodianship, storage, retention, and destruction of those materials, as well as the rights of access, rights to analyze/use and re-use the data or information, and the right to produce research outputs based upon them.

According to the G-NatlStmt and the G-DataInfoMgt, researchers should create a data management plan, which should be developed as early as possible in the research process and should include details regarding:

  • Physical, network, system security, and any other technological security measures
  • Policies and procedures
  • Contractual and licensing arrangements and confidentiality agreements
  • Training for members of the project team and others, as appropriate
  • The form in which the data or information will be stored
  • The purposes for which the data or information will be used and/or disclosed
  • The conditions under which access to the data or information may be granted to others
  • What information from the data management plan, if any, needs to be communicated to potential participants

The G-NatlStmt states that researchers should clarify whether they will seek extended or unspecified consent for future research, or permission from a review body to waive the requirement for consent. In addition, the security arrangements specified in the data management plan should be proportional to the risks of the research project and the sensitivity of the information.

In accordance with the G-NatlStmt, researchers must comply with all relevant legal and regulatory requirements that pertain to the data or information collected, used, or disclosed as well as the conditions of the consent provided by participants. Data, information, and biospecimens used in research should be disposed of in a manner that is safe and secure, consistent with the consent obtained and any legal requirements, and appropriate to the research design.

The G-NatlStmt indicates that in the absence of justifiable ethical reasons and to promote access to the benefits of research, researchers should collect and store data, or information generated by research projects, in such a way that they can be used in future research projects. A justification must be provided when a researcher believes there are valid reasons for not making data or information accessible. More details are provided in the G-NatlStmt.

In addition, for details related to secondary use and sharing of data or information, see the G-NatlStmt.

According to the G-TrialsSOP, the investigator must maintain adequate source documents and trial records, including all key observations on each of the trial participants. The investigator must also store all trial related documents in a study master file (SMF) and take measures to prevent accidental or premature destruction of these documents. In the case of a teletrial, the SMF is stored at the primary site, and the principal investigator (PI) must have control of all essential documents and records generated by the investigator(s), institution, and satellite site(s) before, during, and after the trial. The PI must also establish the maintenance rules of the SMF and relationship between the primary site’s SMF and any satellite site study files. For more information on the SMF, see the G-TrialsSOP.

As set forth in the annotated AU-ICH-GCPs, the Therapeutic Goods Administration (TGA) requires that the sponsor retain records for 15 years following the completion of a clinical trial. However, product liability is the overriding consideration and the sponsor should be able to produce records at any time, including possibly beyond the life of a product, in the event of an adverse event claim. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

Audit Requirements

As part of its QA system, the AU-ICH-GCPs notes that the sponsor should ensure the trial is monitored and audited. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, the AU-ICH-GCPs, and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. The sponsor should ensure that the auditors are qualified by training and experience, and the auditor’s qualifications should be documented. The sponsor must also ensure that the audit is conducted in accordance with his/her own SOPs and that the auditor’s observations are documented.

Premature Study Termination/Suspension

The AU-ICH-GCPs states that if a trial is prematurely terminated or suspended, the sponsor should promptly inform the investigator(s), institution(s), the EC, and the TGA. The sponsor should provide the reason(s) for the termination or suspension.

According to the G-TrialsSOP, if a trial is prematurely terminated or suspended for any reason, the investigator must:

  • Promptly inform the sponsor, EC, research governance officer, associate investigator, any satellite site (in the case of a teletrial), and the TGA by providing a detailed written explanation of the premature termination or suspension
  • Promptly inform the trial participant and his/her primary care physician where the trial participant has consented, of the termination or suspension and, if applicable, of the investigational product (IP) and dose that was administered
  • Assure appropriate therapy and follow up for the participant’s continued care

Multicenter Studies

As delineated in the AU-ICH-GCPs, in the event of a multicenter trial, the sponsor must ensure that:

  • All investigators conduct the trial in strict compliance with the protocol that was agreed to by the sponsor and the TGA (if required), and that was approved by the EC
  • The case report forms (CRFs) capture the required data at all multicenter trial sites
  • The responsibilities of coordinating investigator(s) and the other participating investigators are documented prior to the start of the trial
  • All investigators are given instructions on following the protocol, on complying with a uniform set of standards to assess clinical and laboratory findings, and on completing the CRFs
  • Communication among investigators is facilitated
Part 3 (12AB)
Preamble, Responsibilities of Institutions, and Responsibilities of Researchers
Introduction
5
Responsibilities of Institutions and Responsibilities of Researchers
SOPs 05, 07, 08, and 13
Section 3 (3.1)
Research Governance Framework
Background and Scope
Sponsorship > Site/Investigator Selection
Last content review/update: December 17, 2021
Summary

Overview

As set forth in the AU-ICH-GCPs, the sponsor should select the investigator(s) and the institution(s) for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. According to AU-ICH-GCPs, the sponsor must also ensure that the investigator(s) are qualified by training and experience. Prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure. Furthermore, per the AU-ICH-GCPs, the G-GovHndbk, and AUS-43, the sponsor must sign a Clinical Trial Research Agreement with the participating investigator(s) and institution(s), and submit it to the institution for its research governance assessment review. (See the Submission Content section for additional information on clinical trial application requirements). According to the G-TrialsSOP, the principal investigator (PI) must ensure that all required staff who assist with the clinical trial are informed about and trained on the protocol, any investigational product, and their research-related duties and functions. This can be in the form of an initiation meeting held by any communication means, including face-to-face, videoconference, telehealth, etc.

The G-TrialsSOP further indicates that when a teletrial is being conducted, the PI, who is always at the primary site and never at the satellite site, remains responsible for the trial across the cluster. The PI must demonstrate the potential for recruiting the required number of suitable participants, either from the primary site only, or from the primary site and associated satellite sites, within the specified recruitment period. For more information on PI site staff training and qualification requirements, see the G-TrialsSOP.

For a list of Australian clinical trial sites, including their capacity and capability, see AUS-62.

Foreign Sponsor Responsibilities

As per the G-CTHandbook, the G-TrialsSOP, AUS-47, and AUS-13, a sponsor must be an Australian entity.

Data Safety Monitoring Boards (DSMBs)

G-DSMB indicates that the sponsor may establish a Data Safety Monitoring Board (DSMB) to review accumulating trial data in order to monitor the progress of a trial. The role of a DSMB is to provide advice on safety and/or trial conduct issues by making recommendations to the sponsor or trial steering committee on whether to continue, modify, or stop a trial. Per the AU-ICH-GCPs, the DSMB should have written standard operating procedures (SOPs) and maintain written records of all its meetings.

According to the G-TrialsSOP, the sponsor may utilize a DSMB or independent individuals (e.g., a medical monitor) to:

  • Review accruing trial safety data in either an unblinded or blinded manner to assess treatment exposure
  • Access, assess, and review emerging efficacy data for the trial
  • Assess the balance of risks and benefits within the trial
  • Document the outcome of these reviews
Role of trial sponsors
What is a DSMB and what is its role?
5
Terms, SOP 03, and SOP 12
Informed Consent > Documentation Requirements
Last content review/update: December 17, 2021
Summary

Overview

In all Australian clinical trials, a freely given informed consent is required from each participant in accordance with the requirements set forth in the AU-ICH-GCPs and the G-NatlStmt. According to the AU-ICH-GCPs, if requirements specified in the G-NatlStmt appear to differ from those specified in the AU-ICH-GCPs, the Therapeutic Goods Administration (TGA) recommends compliance with the G-NatlStmt.

As per the AU-ICH-GCPs, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an institutional ethics committee (EC) (known as a Human Research Ethics Committee in Australia) and kept on file before the trial commences. (See the Required Elements section for details on what should be included in the form.)

According to the G-TrialsSOP, the principal investigator (PI) for any research project retains overall responsibility for ensuring a participant’s consent has been obtained in the correct manner prior to the participant’s entry into the project. This includes where consent is obtained from participants at satellite sites in a teletrial. The PI can delegate the duty for obtaining consent to a suitably qualified associate investigator at his/her discretion, but the PI remains responsible for any delegated activity. Furthermore, the investigator must ensure he/she has obtained the relevant research governance approval, inclusive of approval by an appropriate EC, for all written information and any other media used to provide information to potential participants prior to their usage to obtain consent from any participant.

The AU-ICH-GCPs states that the investigator must provide detailed research study information to the participant and/or his/her legal representative(s) or guardian(s). The ICF content should be as non-technical as practical and understandable to the participants and/or his/her legal representative(s) or guardian(s). The G-TrialsSOP further indicates that the ICF and relevant EC-approved participant information documents can be provided in person, by telehealth, or by telephone and email or weblink. If informed consent is obtained by telephone, this must be recorded on the ICF and in the participant’s health and medical record, and/or source document, stating (as an example): “The protocol was discussed with [participant’s name] via telephone on [DD/MM/YYYY].”

According to the G-TrialsSOP, e-consent may be the preferable option for teletrials, as consent signatures can be obtained contemporaneously at both primary and satellite sites. For more information on obtaining consent using telehealth, see the G-TrialsSOP.

As per the AU-ICH-GCPs and the G-NatlStmt, the ICF content should be clearly presented orally, or in a written language, that is easy to understand, and commensurate with the age and comprehension level of the research participant. The participant and his/her legal representative(s) or guardian(s) should also be given adequate time to consider whether to participate. According to G-NatlStmt, information presented to potential participants should help them make good choices. To this end, the investigator should take into account cultural and language barriers, the need for accurate and reliable translation, and whether there is a visual, hearing, or communication impairment. See AUS-65 for researcher guidance on how to talk to potential participants.

Furthermore, as delineated in the G-TrialsSOP, the PI or delegate must assess the potential participant’s understanding of what they are agreeing to, that they are aware of the purpose of the study, what will be involved, and any risks that may exist. The participants must demonstrate that they fully understand the implications of decisions that may be made within the course of the research.

Per the G-NatlStmt, special rules apply for individuals unable to consent, either due to a legal disability (such as age) or because they otherwise lack decision-making capacity. Enrollment of individuals who lack decision-making capacity in clinical trials is not always possible and may be dependent on any relevant state and territory guardianship laws. See the Special Circumstances/Emergencies, Children/Minors, Prisoners, and Mentally Impaired sections for additional information about these populations.

Per the G-NatlStmt, when a researcher and potential participant have a pre-existing relationship, it should be considered whether an independent person should seek the consent of the participant. Researchers should make clear to the participant if there are any intended therapeutic benefits from the trial, and if the treatment will be available only through participation in the trial. In addition, researchers should make it clear to the participant whether they will have access to the treatment or information they received after completion of the trial.

Re-Consent

According to the AU-ICH-GCPs, the G-TrialsSOP, and the G-NatlStmt, any change in the ICF that is relevant to the participant’s consent should be approved by the EC prior to implementing any changes. The participant and/or his/her legal representative(s) or guardian(s) should also be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented. The G-TrialsSOP further specifies that unless there is a significant safety concern, ECs will not usually require that participants be recontacted immediately since there are potential implications related to blinding. If approved by the EC, continued consent may be obtained verbally and recorded in the participant’s medical records and relevant documents. Re-consent may also be obtained by telephone if approved by an EC.

Language Requirements

Pursuant to the G-NatlStmt, methods for presenting research information to participants should take into account the need for accurate and reliable translation into the participant’s first language or dialect, as well as culture and its effects on how language is understood. According to the G-TrialsSOP, in cases where translation is required, a professional interpreter should facilitate the process.

Documentation Copies

The AU-ICH-GCPs and the G-TrialsSOP state that the participant and/or the participant’s legal representative(s) or guardian(s), and the investigator(s) must sign and date the ICF. Where the participant is unable to read, and/or his/her legal representative(s) or guardian(s) is unable to read, an impartial witness should be present during the entire informed consent discussion. After the following steps have occurred, the witness should sign and date the ICF attesting that the information in the ICF was accurately explained to, and apparently understood by the participant and/or his/her legal representative(s) or guardian(s):

  • The written ICF and any other written information to be provided to the participant is read and explained to the participant and/or his/her legal representative(s) and/or guardian(s)
  • The participant and/or his/her legal representative(s) and/or guardian(s) has orally consented to the participant’s involvement in the trial, and has signed and dated the ICF, if capable of doing so

Before participating in the study, the participant or his/her legal representative(s) and/or guardian(s) should receive a copy of the signed and dated ICF. The G-TrialsSOP further indicates that where consent is obtained by telehealth or telephone, once the ICF is signed and dated by both the participant and the investigator (and any other person present, for example an interpreter), the participant must select the statement identifying that consent was obtained by telehealth or telephone with the name of the investigator. Similarly, the investigator must select the statement identifying that consent was obtained by telehealth or telephone with the name of the participant. For more information on informed consent documentation, see the G-TrialsSOP.

1, 3, 4, and 8
SOP 09
Purpose, Scope and Limits of this Document, Section 2 (2.2), Section 3 (3.1), Section 4 (4.3), and Section 5 (5.2)
Informed Consent > Required Elements
Last content review/update: December 17, 2021
Summary

Overview

As delineated in the AU-ICH-GCPs, the G-TrialsSOP, and the G-NatlStmt, prior to beginning a clinical trial, the investigator is required to obtain ethics committee (EC) (known as Human Research Ethics Committee in Australia) approval for the written informed consent form (ICF) and any other information being provided to the research participant and/or his/her legal representative(s) or guardian(s). For details on the requirements for obtaining consent, see the Documentation Requirements section.

No Coercion

As per the AU-ICH-GCPs, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant and/or his/her legal representative(s) and/or guardian(s) to waive or to appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representative(s) from liability for negligence. Per the G-NatlStmt, no person should be subject to coercion or pressure in deciding whether to participate in a trial.

Informed Consent Form Required Elements

Based on the AU-ICH-GCPs and the G-NatlStmt, the ICF should include the following statements or descriptions, as applicable (Note: The regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

  • The study involves research and an explanation of its purpose and duration
  • The trial treatment(s) and the probability for random assignment to each treatment
  • The procedures to be followed, including all invasive procedures
  • The participant’s responsibilities
  • Those aspects of the trial that are experimental
  • Any reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant
  • Any reasonably expected benefits; if no benefit is expected, the participant should be made aware of this
  • The disclosure of specific alternative procedure(s) or therapies available to the participant, and their important potential benefits and risks
  • Compensation and/or treatment available to the participant in the event of a trial-related injury
  • The anticipated prorated payment, if any, to the participant for participating in the trial
  • Any expenses the participant needs to pay to participate in the trial
  • That participation is voluntary, and that the participant can refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the participant is otherwise entitled
  • Confidentiality of records identifying the participant will be maintained, and permission given to monitors, the auditors, the ethics committee, and the Therapeutic Goods Administration (TGA) to access the participant’s medical records to verify the procedures and/or data, without violating the confidentiality of the participant, insofar as the applicable laws and regulations permit, and that, by signing a written ICF, the participant or the participant’s legal representative(s) or guardian(s) is authorizing such access
  • That records identifying the participant will not be made publicly available, insofar as the applicable laws and/or regulations permit; if the results of the trial are published, the participant’s identity will remain confidential
  • The participant and/or his/her legal representative(s) or guardian(s) will be notified in a timely manner if information becomes available that may affect the participant’s willingness to continue
  • The investigator’s contact information for further information regarding the trial and the rights of participants, and whom to contact in the event of a trial-related injury or complaint
  • Foreseeable circumstances and/or reasons under which the participant’s involvement in the trial may be terminated
  • The approximate number of participants in the trial
  • How the trial will be monitored
  • The amount and sources of funding for the research
  • Financial or other declarations of interests of researchers, sponsors, or institutions
  • Other relevant information, including research-specific information required under the G-NatlStmt

See the Compensation Disclosure, Vulnerable Populations, and Consent for Specimen sections for further information.

4
SOP 09
Section 2 (2.2) and Section 5 (5.1 and 5.2)
Informed Consent > Compensation Disclosure
Last content review/update: December 17, 2021
Summary

Overview

In accordance with the AU-ICH-GCPs and the G-NatlStmt, the informed consent form (ICF) should contain information regarding the compensation or medical treatment a participant can receive for participating in a clinical trial.

Compensation for Participation in Research

As per the AU-ICH-GCPs, payments to a participant should be prorated and not wholly contingent on completion of the trial by the participant. The ICF should contain a description of the anticipated prorated payment to the participant(s) for participating in the trial. Per the G-NatlStmt, any compensation or payment to participants must be approved by the ethics committee (EC) (known as Human Research Ethics Committee in Australia), as part of the ICF approval, and may not be disproportionate to the time involved, or include other incentives that encourage them to take risks. Further, compensation decisions should consider customs and practices of the community in which the trial will be conducted.

Compensation for Injury

As per the AU-ICH-GCPs, the ICF should include a statement advising the participant about whether compensation and medical treatment is available in the event of any trial-related injury. (See the Required Elements section for additional details on what should be included in the ICF.)

See AUS-39 for indemnity and compensation guidelines for commercially-sponsored trials.

3 and 4
Section 2 (2.2) and Section 5 (5.2)
Informed Consent > Participant Rights
Last content review/update: December 17, 2021
Summary

Overview

In accordance with the AU-ICH-GCPs and the G-NatlStmt, Australia’s ethical standards protect participants’ rights and promote respect for human beings, research merit and integrity, justice, and beneficence. The G-NatlStmt further recognizes that state or territory authorities may have additional statutes regarding the use of human tissues, guardianship, and illegal and unprofessional conduct. Furthermore, a participant’s rights must be clearly addressed in the informed consent form (ICF).

The Right to Participate, Abstain, or Withdraw

As stated in the AU-ICH-GCPs and the G-NatlStmt, the participant and/or his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled. The G-TrialsSOP further specifies that participants may withdraw their consent at any time without giving a reason.

Per the G-NatlStmt, the participant should be informed of any implications of withdrawal and whether it is possible to withdraw data.

The Right to Information

As per the AU-ICH-GCPs and the G-NatlStmt, a potential research participant and/or his legal representative(s) or guardian(s) has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

According to the AU-ICH-GCPs and the G-NatlStmt, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. Privacy is also subject to national, state, and territory laws, including the PrivacyAct. As per the G-TrialsSOP, if telehealth is used, all measures must be taken to ensure privacy and confidentiality of the participant’s identity.

The Right of Inquiry/Appeal

The AU-ICH-GCPs and the G-NatlStmt state that the research participant and/or his/her legal representative(s) or guardian(s) should be provided with contact information for the individual responsible for addressing trial-related inquiries and/or his/her rights. AUS-45 guides the participant and/or his/her legal representative(s) or guardian(s) with information on who to contact regarding a concern with the clinical trial—option 1 is the investigator, option 2 is the ethics committee (EC) (known as Human Research Ethics Committee in Australia), option 3 is the institution, and option 4 is the healthcare complaints entity in the state or territory.

The Right to Safety and Welfare

The AU-ICH-GCPs (which upholds the Declaration of Helsinki (AUS-52)) and the G-NatlStmt clearly state that a research participant’s right to safety and the protection of his/her health and welfare must take precedence over the interests of science and society.

See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.

Part II
Introduction, 2, and 4
SOP 09
Purpose, Scope, and Limits of this Document, Section 1, and Section 2 (2.2 and 2.3)
Informed Consent > Special Circumstances/Emergencies
Last content review/update: December 17, 2021
Summary

Overview

The AU-ICH-GCPs and the G-NatlStmt make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by special circumstances. Special circumstances can be medical emergencies or when a participant is mentally incapacitated, e.g., unconscious. In addition, per the G-NatlStmt, when a researcher and potential participant have a pre-existing relationship, it should be considered whether an independent person should seek the consent of the participant.

Medical Emergencies

As per the AU-ICH-GCPs, if the signed informed consent form (ICF) has not been obtained from the research participant and/or his/her legal representative(s) or guardian(s), or, if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted, subject to any overriding state or territory laws as per the G-NatlStmt. However, the method used on the participant must be explained clearly in the trial protocol, and the ethics committee (EC) (known as the Human Research Ethics Committee in Australia) must approve the protocol in advance. The participant and/or his/her legal representative(s) or guardian(s) should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

Research Involving Unconscious Persons

The G-NatlStmt states when prior consent is not possible for research involving unconscious persons, consent should be provided by the participant’s legal representative(s) or guardian(s). However, relevant jurisdictional laws must be taken into account. Because of their extreme vulnerability, unconscious persons should be excluded from all but minimally invasive research, or in research designed both to be therapeutic for them and to improve treatment for the condition from which they suffer.

The G-TrialsSOP notes that as per the Declaration of Helsinki (AUS-52), for research involving participants who are physically or mentally incapable of giving consent (e.g., unconscious patients/participants), the study must be relevant to the physical or mental condition of the participant(s) that prevents them from being able to consent to participate in the study.

See section 4.4 of the G-NatlStmt for more information regarding research involving unconscious persons and other people highly dependent on medical care.

Alteration or Waiver of Consent

The G-NatlStmt specifies that although voluntary informed consent is a requirement for every trial, the EC may approve an alteration to the consent requirements. Limited disclosure to participants of the aims and/or methods of research may be justifiable. However, only an EC can review and approve research that involves active concealment or planned deception, or aims to expose illegal activity.

It may be appropriate to use an opt-out approach for participant recruitment when obtaining explicit consent is neither practical nor feasible. An EC may approve the use of an opt-out approach for research if the study satisfies all of the following conditions:

  • It involves only low risk to participants
  • The public interest in the proposed activity substantially outweighs the public interest in the protection of privacy
  • The research activity is likely to be compromised if the participation rate is not near complete, and the requirement for explicit consent would compromise the necessary level of participation
  • Reasonable attempts are made to provide participants with appropriate plain language information explaining the nature of the information to be collected, the purpose of collecting it, and procedure to decline participation or withdraw from the research
  • A reasonable time period is allowed between the provision of information to prospective participants and the use of their data so that an opportunity for them to decline to participate is provided before the research begins
  • A mechanism is provided for prospective participants to obtain further information and decline to participate
  • The data collected will be managed and maintained in accordance with relevant security standards
  • There is a governance process in place that delineates specific responsibility for the project and for the appropriate management of the data
  • The opt-out approach is not prohibited by state, federal, or international law

According to the G-NatlStmt, only an EC may grant a waiver of consent for research using personal information in medical research, or personal health information. However, other review bodies may grant a waiver of consent for other research. In order to help maintain public confidence in the research process, each institution must make publicly accessible summary descriptions of all its research projects for which consent has been waived.

An EC may waive the requirement for consent (other than in the case of research aiming to expose illegal activity), if the study satisfies all of the following conditions:

  • Involvement in the research carries no more than low risk to participants
  • The benefits from the research justify any risks of harm associated with not seeking consent
  • It is impracticable to obtain consent (for example, due to the quantity, age, or accessibility of records)
  • There is no known or likely reason for thinking that participants would not have consented if they had been asked
  • There is sufficient protection of their privacy
  • There is an adequate plan to protect the confidentiality of data
  • There is, where practicable, a plan for making information arising from the research available to participants in cases where the results have significance for their welfare
  • The possibility of commercial exploitation of derivatives of the data or tissue will not deprive the participants of any financial benefits to which they would be entitled
  • The waiver is not prohibited by state, federal, or international law
4
SOP 09
Section 2 (2.3) and Section 4 (4.3 and 4.4)
Informed Consent > Vulnerable Populations
Last content review/update: December 17, 2021
Summary

Overview

All Australian clinical trials that involve research participants selected from vulnerable populations must follow special processes for consent, as delineated in the G-NatlStmt.

The G-NatlStmt cautions that dependent or unequal relationships that might compromise the voluntary character of a participant’s decision should be considered. Examples of such relationships include caregivers and people with chronic conditions/disabilities; health care professionals and their patients; teachers and their students; prison authorities and prisoners; governmental authorities and refugees; employers/supervisors and their employees (including members of police and Defense Forces); and service-providers and especially vulnerable communities to whom the services are provided. Where potential participants are especially vulnerable or powerless, consideration should be given to the appointment of a participant advocate.

The AU-ICH-GCPs characterizes vulnerable populations as those who may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation in a clinical trial, or of a retaliatory response for not participating. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, residents of nursing homes, unemployed or impoverished persons, patients in emergency situations, homeless persons, nomads, refugees, minors, and those incapable of giving consent. Per the G-NatlStmt, people who may be involved in illegal activities, Aboriginal and Torres Strait Islander peoples, ethnic minority groups, and people in other countries are other groups for which specific ethical considerations are required.

Participants Highly Dependent on Medical Care

The G-NatlStmt indicates that when a researcher is also the treating health professional, it should be considered whether an independent person should seek the consent of potential participants who are highly dependent on medical care. In addition, the participant and/or the participant’s relatives and an authorized representative should be informed of the participant’s inclusion in the research and of the option to withdraw from it without any reduction in quality of care.

The G-NatlStmt further provides specific requirements related to conducting research on participants in terminal care, which is characterized by the short remaining life expectancy of the participants and their vulnerability to unrealistic expectations of benefits. Terminal care research should be designed so that the benefits of research justify any burden, discomfort, or inconvenience to the participants; the prospect of benefit from research participation is not exaggerated; the needs and wishes of participants to spend time as they choose are respected; and the entitlement of those receiving palliative care to participate is recognized.

Participants Who May Be Involved in Illegal Activities

The G-NatlStmt provides specific requirements related to conducting research on participants who may be involved in illegal activities. Research that is intended to study or expose, or likely to expose, illegal activity should be reviewed and approved by an ethics committee (EC) (known as Human Research Ethics Committee in Australia). The investigator(s) should be satisfied that potential participants are aware that the research may discover illegal activity and do not have unrealistic expectations of benefit from their participation. Finally, this research should only be approved where the illegal activity bears on the discharge of a public responsibility or the fitness to hold public office, the risks are justified by the benefits, and the research meets the other requirements in the G-NatlStmt.

Aboriginal and Torres Strait Islander Peoples

The G-NatlStmt states that research involving Aboriginal and Torres Strait Islander Peoples must be reviewed and approved by an EC and include assessment and advice from: people who have networks with and/or knowledge of Aboriginal and Torres Strait Islander Peoples; and people familiar with the culture and practices of the relevant Aboriginal and Torres Strait Islander community(ies). In addition, the investigator should ensure the following:

  • Research methods are respectful and acknowledge the cultural distinctiveness of participating Aboriginal and Torres Strait Islander communities and groups
  • There is evidence of support for the research project from relevant Aboriginal and Torres Strait Islander communities or groups and the research methodology engages with their social and cultural practices
  • The research methods provide for mutually agreed mechanisms for recruitment, information provided about the research, notification of participants’ consent and of research progress, and final reporting
  • Procedures and actions have been taken to monitor and, where appropriate, minimize any potential negative consequences of the proposed research

For more information on research involving Aboriginal and Torres Strait Islander Peoples, see the G-AboriginalEthic, the G-EthicsRsrchTrackII, and the G-EthicsIndigenousStudies.

People in Other Countries

The G-NatlStmt states that research involving people in other countries must be reviewed and approved by an EC and comply with the G-NatlStmt. The research design, protocol, and consent process should take into consideration the local cultural values, yet still result in participants being treated with no less respect and protection than what is provided in the G-NatlStmt. Additional details are provided in the G-NatlStmt.

See the Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations.

1
Section 4 (Introduction, 4.1, 4.3, 4.4, 4.6, 4.7, and 4.8)
Informed Consent > Children/Minors
Last content review/update: December 17, 2021
Summary

Overview

AUS-35 indicates that under Australian law, the age of majority is 18. The age of consent for medical treatment differs across jurisdictions.

However, in accordance with the G-NatlStmt, when the research participant is a child or young person it is not possible to attach fixed ages to their capacity to consent. The informed consent form (ICF) must be signed by the child or young person whenever he/she has the capacity to make this decision, and either one (1) parent, except when the ethics committee (EC) (known as Human Research Ethics Committee in Australia) decides that the risks require the consent of both parents, or the child or young person’s legal representative(s) or guardian(s). The AU-ICH-GCPs and the G-NatlStmt state that children and young people should be informed to the extent compatible with their maturity and understanding, and if capable, they should sign and personally date the ICF.

In accordance with the G-NatlStmt, informed consent requirements for conducting clinical trials follow the general requirements listed in the Required Elements section.

In addition, as stated in the G-NatlStmt, children and young people who are not of sufficient maturity to consent should only participate in clinical studies when: the research is likely to advance knowledge about the health or welfare of, other matters relevant to, children and young people; or their participation is indispensable to the conduct of the research. When considering the inclusion of children and young people in research, the researchers and EC must consider their level of maturity to ensure adequate protections for his/her welfare.

As per the G-NatlStmt, if the child or young person has the capacity for consent, his/her affirmative consent is required to participate in a study according to his/her level of development and capacities. The following guidelines on maturity and corresponding capacity to consent are provided:

  • Infants, who are unable to take part in discussion about the research and its effects
  • Young children, who are able to understand some relevant information and take part in limited discussion about the research, but whose consent is not required
  • Young people of developing maturity, who are able to understand the relevant information but whose relative immaturity means that they remain vulnerable; the consent of these young people is required, in addition to consent from a parent or guardian
  • Young people who are mature enough to understand and consent, and are not vulnerable through immaturity in ways that warrant additional consent from a parent or guardian

The EC may approve research to which only the child or young person consents if it is satisfied that:

  • He/she is mature enough to understand the relevant information and give consent
  • The research involves low risk
  • The research aims to benefit children or young people
  • The child or young person is estranged or separated from his/her legal representative(s) or guardian(s) and the researcher ensures his/her safety, security, and well-being in the research conduct; or it would be contrary to the best interests of the child or young person to seek consent from his/her legal representative(s) or guardian(s), and the researcher ensures his/her safety, security, and well-being in the research conduct

Regarding dissent, the G-NatlStmt states that the researchers must respect the dissent of a child or young person who has the capacity to give consent.

4
Section 4 (4.2)
Country Reports: Australia
Informed Consent > Pregnant Women, Fetuses & Neonates
Last content review/update: December 17, 2021
Summary

Overview

As per the G-NatlStmt, studies involving pregnant women, fetuses, and neonates require additional safeguards to ensure that the research assesses the risks to the pregnant women, fetuses, and neonates.

In accordance with the G-NatlStmt, informed consent requirements for conducting clinical trials follow the general requirements listed in the Required Elements section. However, except for therapeutic innovative therapy cases, the process of providing information and obtaining consent for participating in research should be clearly separate from clinical care if the woman is pregnant and the fetus in utero.

The wellbeing and care of the woman who is pregnant and of her fetus always takes precedence over research considerations. Research involving a fetus or fetal tissue should be conducted in a manner that maintains a clear separation between the woman’s clinical care and the research. For requirements related to research on embryos and deceased fetuses, see G-EthicsART.

Further, the woman should be informed of the following:

  • That she should consider whether to seek consent to the proposed research from any other person (e.g., the other parent)
  • Whether it is possible to store the fetus or fetal tissues for later use in research
  • That she is free to withdraw her consent to the research at any time, whether before or after a termination or other loss of a fetus
  • Whether there is potential for commercial application of outcomes of the research, including the development of cell lines
  • That she will not be entitled to a share in the profits of any commercial applications
  • Whether fetal organs or stem cell lines developed from them will be exported to another country
Section 4 (4.1)
Informed Consent > Prisoners
Last content review/update: December 17, 2021
Summary

Overview

According to the G-NatlStmt, prisoners are considered vulnerable because incarceration, which may create a dependent or unequal relationship, could affect their ability to make voluntary decisions regarding participation in research.

Per the G-NatlStmt, a research study involving prisoners should, wherever possible, invite prospective participants to discuss their participation with someone who is able to support them in making their decision. If prospective participants are especially vulnerable, researchers should consider appointing a participant advocate.

Section 4 (4.3)
Informed Consent > Mentally Impaired
Last content review/update: December 17, 2021
Summary

Overview

According to the G-NatlStmt, the ethics committee (EC) (known as Human Research Ethics Committee in Australia) must approve the participation of research participants who are mentally incapable of giving consent. While the G-NatlStmt distinguishes cognitive impairment from intellectual disability and mental illness, the informed consent guidelines are similar. As delineated in the G-NatlStmt, the mentally impaired participant must consent if he/she has the capacity, or the participant’s legal representative(s) or guardian(s) must consent on behalf of the mentally impaired participant. Where a legal representative(s) or guardian(s) has given consent, the researchers still must explain to the participant what the research is about and what participation involves. If the participant recovers the capacity to consent, the researcher should offer him/her the opportunity to continue participation or withdraw. Dissent will preclude participation of a mentally impaired person.

If the participant’s mental impairment is temporary or episodic, researchers should seek consent when the condition does not interfere with his/her capacity to give consent. This consent should occur in the presence of a witness who is familiar with the participant, is independent from the research, and understands the research’s merits, risks, and procedures.

Section 4 (4.5)
Investigational Products > Definition of Investigational Product
Last content review/update: December 17, 2021
Summary

Overview

According to the AU-ICH-GCPs and the G-TrialsSOP, an investigational product (IP) is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when used or assembled (formulated or packaged) in a different way from the approved form; when used for an unapproved indication; or when used to gain further information about an approved use.

In Australia, IPs are also referred to as unapproved therapeutic goods. As per the G-CTHandbook and AUS-47, an unapproved therapeutic good includes:

  • Any medicine, biological, or medical device not entered on the Australian Register of Therapeutic Goods (ARTG) (AUS-22), including any new formulation, strength or size, dose, name, indications, directions for use or type of container of a medicine already in the ARTG
  • Any therapeutic good already in the ARTG to be used in a manner not covered by the existing ARTG entry
Determine if the product is ‘unapproved’
1
Terms
Investigational Products > Manufacturing & Import
Last content review/update: December 17, 2021
Summary

Overview

As specified in the TGAct, the TGR, and the G-CTHandbook, the Therapeutic Goods Administration (TGA) authorizes the manufacture of investigational products (IPs) in Australia. As per AUS-47 and AUS-49, the sponsor provides manufacturer and/or active ingredient information to the TGA in the clinical trial application under one (1) of the two (2) regulatory schemes—the Clinical Trial Notification (CTN) scheme or the Clinical Trial Approval (CTA) (formerly known as Clinical Trial Exemption (CTX)) scheme. Pursuant to TGManuf, Australia adopted the AU-PIC-S-GMP-Guide to guide the manufacture of therapeutic goods. The TGA also issued the AU-PIC-S-GMP-Guide-Intpn, a complementary guidance explaining the TGA’s interpretation and expectations for compliance. (See Submission Process and Submission Content sections for detailed application requirements).

AUS-47 indicates that IPs may be imported and held under the direct control of the importer until the IPs are included in a notification made to the TGA through the CTN scheme. The IPs must be kept in a warehouse or other properly secured area. The importer does not require approval from the TGA prior to importation of the IPs, but the trial must be notified to the TGA through the CTN scheme prior to supply of the IPs to the trial sites. Importers are advised to contact other relevant agencies, as there may be further restrictions on importation imposed through other legislation.

As per AUS-48, the Exports area of the TGA is the appropriate area to contact for information regarding the exportation of IPs from Australia, or importation to Australia and subsequent exportation of IPs for trials taking place outside of Australia. For more information, contact the Exports area of the TGA at eps@tga.gov.au.

According to the TGR, the sponsor must provide a written assurance to comply with any trial-related requests by an authorized TGA officer(s), which includes allowing him/her to inspect clinical trial sites. The principal investigator is required to comply with requests and answer any questions the authorized officer(s) may have.

Schedule 1 (Part 1)
Chapter 3 (Part 3-2 (19) and Part 3-3 (34-38))
12AB and 12AC
The CTN and CTA schemes and Manufacturing
Investigational medicinal products (Annex 13)
Annex 13
FAQs
Creating a New CTN Form
Investigational Products > IMP/IND Quality Requirements
Last content review/update: December 17, 2021
Summary

Overview

According to the AU-ICH-GCPs, the sponsor is responsible for providing the investigators with an investigator’s brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs), including significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information. The sponsor must ensure that an up-to-date IP is made available to the investigator(s), and the investigator(s) must provide an up-to-date IB to the ethics committee.

Investigator's Brochure Content Requirements

According to the G-TrialsSOP, where the investigator contributes to the content and development of the IB, he/she must ensure the IB follows the outline in the AU-ICH-GCPs. The AU-ICH-GCPs requires the IB to cover the following areas:

  • Physical, chemical, and pharmaceutical properties and formulation parameters
  • Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
  • Effects of IP in humans (pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
  • Summary of data and guidance for the investigator(s)

See Section 7 of the AU-ICH-GCPs for detailed content guidelines.

The sponsor is also accountable for supplying the IP, which includes ensuring another designated or contracted party supplies the IP, including the comparator(s) and placebo, if applicable. As specified in the AU-ICH-GCPs, the sponsor must ensure that the products are manufactured in accordance with Good Manufacturing Practices (GMPs).

Certificate of Analysis

Pursuant to the AU-ICH-GCPs, the sponsor must maintain a Certificate of Analysis to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

5, 7, and 8
SOP 04
Investigational Products > Labeling & Packaging
Last content review/update: December 17, 2021
Summary

Overview

Investigational product (IP) labeling in Australia must comply with the requirements set forth in the G-CTHandbook, the AU-ICH-GCPs, the AU-PIC-S-GMP-Guide, and the AU-PIC-S-GMP-Guide-Intpn. The following information must be included on the IP label:

  • Sponsor’s name, address, and phone number. The main contact details for information on the product, clinical trial, and emergency unblinding must be an Australian contact.
  • Pharmaceutical dosage form, route of administration, and quantity of dosage units. For closed blinded trials, the labelling should include a statement indicating “placebo or [name/identifier] + [strength/potency]”.
  • The batch and/or code number to identify the contents and packaging operation
  • A trial reference code. The trial reference code used should identify the particular trial site, unless provided elsewhere or its absence can be justified.
  • The trial participant identification number/treatment number
  • Investigator’s name. The name of the principal investigator should appear on the label unless already included in a trial reference code or unless its absence can be justified.
  • Directions for use
  • “For clinical trial use only”
  • The storage conditions
  • The period of use
  • “Keep out of reach of children” except when the product is for use only in hospitals
  • Warnings and/or handling instructions

In addition, the AU-ICH-GCPs states that the IP must be coded and labeled in a manner that protects the blinding, if applicable. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

Additional details are provided in the G-CTHandbook, the AU-PIC-S-GMP-Guide, and the AU-PIC-S-GMP-Guide-Intpn.

Manufacturing
5
Investigational medicinal products (Annex 13)
Annex 13
Investigational Products > Product Management
Last content review/update: December 17, 2021
Summary

Overview

In accordance with the AU-ICH-GCPs, the sponsor is responsible for providing the investigators with an investigator’s brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs), including clinical and nonclinical studies, safety, marketing, physical, chemical, pharmaceutical, pharmacological, pharmacokinetic, metabolic, and toxicological information. The sponsor must ensure that an up-to-date IP is made available to the investigator(s), and the investigator(s) must provide an up-to-date IB to the ethics committee (EC). According to the G-TrialsSOP, where the investigator contributes to the content and development of the IB, he/she must ensure the IB follows the outline in the AU-ICH-GCPs.

Investigational Product Supply, Storage, and Handling Requirements

As defined in the AU-ICH-GCPs, the AU-PIC-S-GMP-Guide, and the AU-PIC-S-GMP-Guide-Intpn, the sponsor must supply the investigator(s) with the IP(s), including the comparator and placebo, if applicable. Under the Clinical Trial Notification (CTN) scheme, the sponsor must notify the Therapeutic Goods Administration (TGA) of the intent to supply the IP(s).

The AU-ICH-GCPs specifies that the sponsor must ensure the following:

  • Timely delivery of the IP(s)
  • Records maintained for IP document shipment, receipt, disposition, return, and destruction
  • A system for retrieving or disposing of IP(s) and documenting this retrieval or disposal
  • Written procedures including instructions for IP handling and storage, adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor
  • IP product quality and stability over the period of use
  • IP manufactured according to any application of the Good Manufacturing Practices (GMPs)
  • Proper coding packaging, and labeling of the IP(s)
  • Acceptable IP handling and storage conditions and shelf-life

Refer to the AU-ICH-GCPs for detailed sponsor-related IP requirements.

As per the G-TrialsSOP, responsibility for IP management and accountability at the trial site rests with the principal investigator (PI). However, the PI may delegate responsibility for IP management to the site pharmacist or, where a pharmacist is not available or involved, to an appropriately qualified person. The site pharmacist or the appropriately qualified person will undertake IP management at the primary site and/or the satellite site in a teletrial. The investigator, pharmacist, or appropriately qualified non-pharmacist must ensure the IP is used only in accordance with the approved protocol and confirm IP certification and all relevant trial approvals/notifications are in place before releasing the IP for dispensing to participants. Refer to the G-TrialsSOP for detailed investigator-related IP requirements.

Record Requirements

According to the G-TrialsSOP, the investigator, pharmacist, or appropriately qualified non-pharmacist must maintain records of all IP management aspects. These records at a minimum should include: shipping documents; date of each transaction; quantities; batch/serial numbers; expiration dates/retest dates (if applicable); temperature logs showing the storage conditions of the IP throughout the trial period; the set of unique code numbers assigned to the IP and to the trial participant; and record of destruction/return.

As set forth in the AU-ICH-GCPs, the sponsor must retain essential documents for 15 years following completion of the trial. The sponsor should inform the investigator(s) and institution(s) in writing when record retention is needed and when the trial-related records are no longer needed.

5 and 7
SOPs 04 and 11
Investigational medicinal products (Annex 13)
Annex 13
Specimens > Definition of Specimen
Last content review/update: December 17, 2021
Summary

Overview

In Australia, a specimen is referred to as a “biological” or a “human biospecimen.” According to the TGAct, a biological is made from, or contains, human cells or human tissues that are likely to be taken to:

  • Treat or prevent disease, ailment, defect, or injury
  • Diagnose the condition of a person
  • Alter the physiological processes of a person
  • Test the susceptibility of a person to disease
  • Replace or modify a person’s anatomy

The G-NatlStmt defines human biospecimen as any biological material obtained from a person, including tissue, blood, urine, sputum, and any derivative from these including cell lines.

Legislation in Australian states and territories does not use standard terminology, but generally refers to human biospecimens as “human tissue.”

Chapter 3 (Part 3-2A)
Section 3 (3.2)
Specimens > Specimen Import & Export
Last content review/update: December 17, 2021
Summary

Overview

Per the G-NatlStmt, if a human biospecimen will be, or has been, imported for research, investigators must establish whether the human biospecimen was obtained in a manner consistent with the requirements of the G-NatlStmt and relevant Australian legislation. If this cannot be established, then the human biospecimen should not be used for research in Australia. Further, a human biospecimen obtained in Australia may be sent overseas for research if its exportation is consistent with the original consent and ethics committee (EC) (known as a Human Research Ethics Committee in Australia) approval is obtained.

Per the G-SpecExport and AUS-24, a permit to export human body fluids, organs, and other tissue, or a substance derived from human blood, must be obtained from the Therapeutic Goods Administration (TGA). The application form requires the reason for the request, which can include research purposes. See AUS-24 for the application forms.

Per the G-CTHandbook, restrictions may be imposed on the importation and exportation of therapeutic goods for clinical trials through other legislation:

  • Customs (Prohibited Imports) Regulations 1956 and Customs (Prohibited Exports) Regulations 1958 – a license and/or permit to import or export may be required for substances controlled under the Customs legislation
  • Biosecurity Act 2015 – permission may be required from the Department of Agriculture and Water Resources prior to importing any material of biological origin (human, animal, plant, or microbial)
  • Environment Protection and Biodiversity Conservation Act of 1999 – permission may be required from the Department of the Environment and Energy prior to importing endangered species
  • Gene Technology Act 2000 – permission may be required prior to importing genetically modified organisms
  • State and territory requirements
  • Requirements of the originator or destination country

The G-TrialsSOP indicates that to ensure the integrity of biological samples has been maintained, there should be evidence of the chain of custody from their point of collection through processing, storage, transport, through to disposal, with evidence of appropriate storage and transit conditions. Equipment used for processing and storage of samples (e.g., centrifuges, fridges, and freezers) should be maintained by suitably qualified persons and periodically inspected, cleaned, and calibrated to the relevant International Organization for Standardization (ISO) standard according to local policy and manufacturer’s manuals. Additionally, the investigator must ensure all study staff, who have cause to handle or ship biological substances, hold a current certificate in the International Air Transport Association (IATA) Approved, Civil Aviation Safety Authority (CASA) Certified Dangerous Goods Packaging Course. The investigator must also ensure that documentation (e.g., receipts, shipping records, order forms, and proformas) related to handling and shipment of biological specimens is maintained and filed in the respective site file.

Additional details are provided in the G-CTHandbook, the G-TrialsSOP, the G-SpecExport, AUS-24, and AUS-11.

Importing and exporting
About this Guidance and Applying for a TGA Export Permit
SOP 10
Section 3 (3.2)
Specimens > Consent for Specimen
Last content review/update: December 17, 2021
Summary

Overview

In accordance with the G-NatlStmt, prior to collecting human biospecimens, consent must be obtained from the participant and/or his/her legal representative(s). The general requirements for consent must be met, including the investigator(s) obtaining ethics committee (EC) (known as Human Research Ethics Committee (HREC) in Australia) review and approval of the proposed consent, collection, processing, storage and distribution, and disposal. This requirement pertains to human biospecimens that are collected for a specific clinical research project or are placed into a biobank for future research use.

In addition, the investigator must provide potential participants with information about:

  • The research for which their biospecimens will be used and, where extended or unspecified consent is sought, and sufficient information is provided to meet the general requirements of consent
  • How their biospecimens will be stored, used, and disposed of, including any processes to be adopted that respect their personal or cultural sensitivities
  • The extent to which their biospecimens will be reasonably identifiable, and how their privacy and confidentiality will be protected
  • Whether the biospecimen research is likely to provide information that may be important to their health or to the health of their blood relatives or their community; and, if such information is likely to be revealed, whether they have the choice to receive this information, whether they have the choice for it to be provided to their relatives or their community, and how these will be managed
  • Whether their biospecimens and associated data may be distributed to other researchers, including those outside Australia
  • Their right to withdraw consent for the continued use of their biospecimens or associated data in research, and any limitations that may be relevant to their withdrawal of consent
  • Any relevant financial or personal interests that those engaged in the collection, processing, storage and distribution, and use of their biospecimens may have
  • Any potential for commercial application of any outcomes of the research and how this will be managed and to whom the benefits, if any, will be distributed

Human biospecimens that were previously obtained for clinical purposes and have been retained by an accredited clinical pathology service may be used if the identity of the donor is not needed. If the donor’s identity is needed, a request for the waiver of the consent requirement to use existing collections of human biospecimens can be submitted to an EC.

Where proposed research involving the use of human biospecimens may reveal information that may be important for the health of the donors, their relatives, or their community, researchers should prepare an ethically defensible plan to describe the management of any proposed disclosure or non-disclosure of that information. An EC must approve this plan.

With regard to biospecimens post-mortem, any wish expressed by a person about the use of their biospecimens post-mortem should be respected. If no such wish is discovered, researchers seeking to obtain human biospecimens post-mortem should obtain consent from the person(s) authorized by relevant legislation.

Human Genetic Research Consent Requirements

The G-NatlStmt indicates that research results and information collected for genomic research may be significant for relatives of research participants. Research including genomics will generally require review by an EC. However, if no information that can identify an individual is used and no linkage of data is planned, the research may be considered low risk.

Researchers must prepare and follow an ethically defensible plan to manage the disclosure or non-disclosure of genomic information of potential importance for the health of participants or their relatives. An EC must approve the plan. Where researchers consider that the results of the research must be provided to participants, the project should be designed to include the mandatory return of results and this condition should be clear in any informational materials.

In considering the appropriate form and scope of consent, as well as the most appropriate process for obtaining consent, researchers should consider:

  • What information will be generated by the research
  • What may be discovered by the research
  • What will be deliberately excluded from the scope of the research
  • Which, if any, of the findings of the research will be communicated to participants and, if so, how
  • What the health implications are of the information for participants and their relatives
  • Whether there are any other implications for participants and their families by being given this information
  • The potential for the information generated by or used in the research to result in participants being re-identified
  • Whether information generated by the research will be shared with other research groups
  • Potential future use of information and biospecimens, including commercial applications

Consent specific to the research may not be required, or a waiver of the requirement for consent may be considered by an EC, if:

  • The data or information to be accessed was previously collected and either aggregated or had identifiers removed
  • Prior consent for the use of the data or information was provided under the scope of a research program that encompasses the proposed research project
  • Prior consent for the use of the data or information was provided in the clinical context for research that encompasses the proposed research project
  • Unspecified consent has been provided

In addition, researchers should consider how genomic research data or information will be stored in the event it is needed for future analysis/testing and disclosure to participants.

Section 2 (2.2 and 2.3), and Section 3 (3.2 and 3.3)
Sources > Requirements
(Legislation) National Health and Medical Research Council Act 1992 (No. 225, 1992 as amended) (NHMRCAct) (Amended July 1, 2014)
Office of Parliamentary Counsel
(Legislation) Privacy Act 1988 (No. 119, 1988, Compilation No. 84) (PrivacyAct) (Amended September 4, 2021)
Office of Parliamentary Counsel
(Legislation) Therapeutic Goods (Manufacturing Principles) Determination 2020 (TGManuf) (September 30, 2021)
Office of Parliamentary Counsel
(Legislation) Therapeutic Goods Act 1989 (No. 21, 1990, Compilation No. 77) (TGAct) (Amended September 1, 2021)
Office of Parliamentary Counsel
(Legislation) Therapeutic Goods Regulations 1990 (Statutory Rules No. 394, 1990, Compilation No. 96) (TGR) (Amended October 29, 2021)
Office of Parliamentary Counsel
(Guidance) National Principles for Teletrials in Australia (G-TeletrialPrncpls) (Last Updated March 4, 2021)
Department of Health
(Guidance) Australian Clinical Trial Handbook: Guidance on Conducting Clinical Trials in Australia Using ‘Unapproved’ Therapeutic Goods (G-CTHandbook) (Version 2.4) (August 2021)
Therapeutic Goods Administration, Department of Health
(Guidance) Australian Code for the Responsible Conduct of Research (G-CodeConduct) (2018)
National Health and Medical Research Council, Australian Research Council, and Universities Australia
(Guidance) Data Safety Monitoring Boards (DSMBs) (G-DSMB) (2018)
National Health and Medical Research Council
(Guidance) Ethical Conduct in Research with Aboriginal and Torres Strait Islander Peoples and Communities: Guidelines for Researchers and Stakeholders (G-AboriginalEthic) (August 2018)
National Health and Medical Research Council
(Guidance) Ethical Guidelines on the Use of Assisted Reproductive Technology in Clinical Practice and Research (G-EthicsART) (April 20, 2017)
National Health and Medical Research Council
(Guidance) Export of Human Substances (G-SpecExport) (Version 1.1) (January 2020)
Therapeutic Goods Administration, Department of Health
(Guidance) Fees and Charges: Summary - From 1 December 2021 (G-FeesCharges) (Version 2.0) (November 2021)
Therapeutic Goods Administration, Department of Health
(Guidance) Good Practice Process for Site Assessment and Authorisation Phases of Clinical Trial Research Governance (GPP-SiteAssess) (Version 2.3) (2018)
National Health and Medical Research Council
(Guidance) Guide to Managing and Investigating Potential Breaches of the Australian Code for the Responsible Conduct of Research (G-CodeBreaches) (2018)
National Health and Medical Research Council, Australian Research Council, and Universities Australia
(Guidance) Guidelines for Ethical Research in Australian Indigenous Studies (G-EthicsIndigenousStudies) (2012)
Australian Institute of Aboriginal and Torres Strait Islander Studies
(Guidance) ICH Guideline for Good Clinical Practice, Annotated with TGA Comments (AU-ICH-GCPs) (June 25, 2018)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Therapeutic Goods Administration, Department of Health
(Guidance) Indemnity and Insurance Arrangements for Clinical Trials in the Public and Private Sectors in Australia (G-CTInsurance) (May 2014)
National Health and Medical Research Council
(Guidance) Keeping Research on Track II (G-EthicsRsrchTrackII) (August 2018)
National Health and Medical Research Council
(Guidance) Management of Data and Information in Research: A guide supporting the Australian Code for the Responsible Conduct of Research (G-DataInfoMgt) (2019)
National Health and Medical Research Council, Australian Research Council, and Universities Australia
(Guidance) National Standard Operating Procedures for Clinical Trials, including Teletrials, in Australia (G-TrialsSOP) (Last Updated March 15, 2021)
Department of Health
(Guidance) National Statement on Ethical Conduct in Human Research 2007 (G-NatlStmt) (Updated 2018)
National Health and Medical Research Council, and Australian Research Council, and Universities Australia
(Guidance) Note for Guidance on Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (CPMP/ICH/377/95), Annotated with TGA Comments (G-SafetyDataMgt) (July 2000)
Therapeutic Goods Administration, Department of Health
(Guidance) Payment of Participants in Research: Information for Researchers, HRECs and Other Ethics Review Bodies (G-ResearchPayment) (2019)
National Health and Medical Research Council
(Guidance) PE009, the PIC/S Guide to GMP for Medicinal Products: TGA Interpretation and Expectations for Demonstrating Compliance (AU-PIC-S-GMP-Guide-Intpn) (Version 2.1) (September 2020)
Therapeutic Goods Administration, Department of Health
(Guidance) PIC/S Guide to Good Manufacturing Practice for Medicinal Products, PE009-14, 01 July 2018 (AU-PIC-S-GMP-Guide) (July 23, 2020)
Therapeutic Goods Administration, Department of Health
(Guidance) Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for Trials Involving Therapeutic Goods (G-RptBreachGCP) (2018)
National Health and Medical Research Council
(Guidance) Research Governance Handbook: Guidance for the National Approach to Single Ethical Review (G-GovHndbk) (December 2011)
National Health and Medical Research Council
(Guidance) Risk-based Management and Monitoring of Clinical Trials Involving Therapeutic Goods (G-RBMgmtMntring) (2018)
National Health and Medical Research Council
(Guidance) Safety Monitoring and Reporting in Clinical Trials Involving Therapeutic Goods (G-SftyRpt) (November 2016)
National Health and Medical Research Council
Sources > Additional Resources
(Document) Australasian Tele-Trial Model: Access to Clinical Trials Closer to Home Using Tele-Health (AUS-2) (Version 7.0) (September 19, 2016)
Clinical Oncology Society of Australia (COSA) Regional and Rural Group
(Document) Children’s Rights (AUS-35) (August 2007)
The Library of Congress
(Document) OECD Recommendation on the Governance of Clinical Trials (AUS-1) (2012)
Organisation for Economic Co-operation and Development
(Document) Research Governance Policy (AUS-5) (June 8, 2021)
Department of Health, Government of Western Australia
(International Guidance) Declaration of Helsinki (AUS-52) (October 19, 2013)
World Medical Association
(Not Available Online) NIAID Communication with Australia Therapeutic Goods Administration (November 2021) (AUS-54)
(Webpage) About the TGA - Structure (AUS-28) (Last Updated October 16, 2020)
Therapeutic Goods Administration, Department of Health
(Webpage) About the TGA - What the TGA Regulates (AUS-31) (Current as of December 16, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) About the TGA - Who We Are & What We Do (AUS-32) (Current as of December 16, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) Application for a Permit to Export Human Substances (AUS-24) (Last Updated December 18, 2019)
Therapeutic Goods Administration, Department of Health
(Webpage) Australian Clinical Trial Sites (AUS-62) (Current as of December 16, 2021)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) Australian Clinical Trials - For Researchers (AUS-64) (Last Updated September 13, 2021)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) Australian Commission on Safety and Quality in Health Care - National Clinical Trials Governance Framework (AUS-63) (Current as of March 10, 2022)
Australian Commission on Safety and Quality in Health Care
(Webpage) Australian New Zealand Clinical Trials Registry (AUS-12) (Current as of December 16, 2021)
National Health and Medical Research Council
(Webpage) Australian Register of Therapeutic Goods (AUS-22) (Last Updated October 29, 2019)
Therapeutic Goods Administration, Department of Health
(Webpage) Clinical Trial Ethics & Governance (AUS-18) (Last Updated September 2020)
Office for Health and Medical Research, New South Wales Government, Australia
(Webpage) Clinical Trial Research Agreements (AUS-38) (Current as of December 16, 2021)
Medicines Australia
(Webpage) Clinical Trials (AUS-47) (Last Updated May 12, 2022)
Therapeutic Goods Administration, Department of Health
(Webpage) Clinical Trials Toolkit (AUS-40) (Last Updated November 26, 2021)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) Contact the TGA (AUS-23) (Current as of December 16, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) CTN Form - User Guide (AUS-49) (Version 1.2) (August 2020)
Therapeutic Goods Administration, Department of Health
(Webpage) Electronic Submission of Individual Case Safety Reports (AUS-26) (Last Updated October 18, 2019)
Therapeutic Goods Administration, Department of Health
(Webpage) Ethical Review Manager (ERM) Applications (AUS-8) (Current as of December 16, 2021)
Queensland Government, Australia, State Government of Victoria, Australia, and Mater Research
(Webpage) Ethical Review Process for Each Australian State and Territory - National Mutual Acceptance of Ethics Review for Multi-centre Clinical Trials (AUS-41) (Last Updated September 13, 2021)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) Good Clinical Practice (GCP) in Australia (AUS-14) (Last Updated December 1, 2020)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) How to Talk to Potential Participants (AUS-65) (Last Updated February 19, 2015)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) Human Research Ethics Application (HREA) Login Page (AUS-9) (Current as of December 16, 2021)
National Health and Medical Research Council
(Webpage) Human Research Ethics Application (HREA) Resources (AUS-19) (Current as of December 16, 2021)
National Health Medical Research Council
(Webpage) Human Research Ethics Committees (AUS-20) (Current as of December 16, 2021)
National Health and Medical Research Council
(Webpage) Import/Export of Unapproved Therapeutic Goods for Experimental Purposes (AUS-48) (Last Updated September 25, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) Importing Therapeutic Substances, Foods and Dietary Supplements (AUS-11) (Last Updated September 28, 2020)
Department of Agriculture and Water Resources
(Webpage) Indemnity and Compensation Guidelines (AUS-39) (Current as of December 16, 2021)
Medicines Australia
(Webpage) Information and Notices about TGA Fees and Payments (AUS-25) (Current as of December 16, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) Login to TGA Business Services (AUS-36) (Current as of December 16, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) Make an Online Payment (AUS-16) (Current as of December 16, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) National Certification Scheme for the Ethics Review of Multi-centre Research (AUS-21) (Current as of December 16, 2021)
National Health and Medical Research Council
(Webpage) National Mutual Acceptance (AUS-50) (Current as of December 16, 2021)
Department of Health & Human Services, State Government of Victoria, Australia
(Webpage) Payment Options (AUS-66) (Last Updated March 7, 2017)
Therapeutic Goods Administration, Department of Health
(Webpage) Report a Problem or Side Effect (AUS-51) (Current as of December 16, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) Research Ethics and Governance Information System (REGIS) (AUS-10) (Current as of December 16, 2021)
The Government of New South Wales, Australia and the Government of Australian Capital Territory, Australia
(Webpage) Research GEMS (AUS-55) (Current as of December 16, 2021)
Government of South Australia
(Webpage) Research Governance (AUS-43) (Last Updated February 15, 2019)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) Research Governance Applications (AUS-34) (Current as of December 16, 2021)
Department of Health & Human Services, State Government of Victoria, Australia
(Webpage) Resources for Clinical Trials in Australia (AUS-44) (Last Updated July 27, 2020)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) Sponsorship (AUS-13) (Last Updated February 19, 2015)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) TGA Business Services: Getting Started with the TGA (AUS-30) (Last Updated June 30, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) TGA Business Services (AUS-29) (Current as of December 16, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) TGA Online - Adverse Event Reporting (AUS-7) (Current as of December 16, 2021)
Therapeutic Goods Administration, Department of Health
(Webpage) The Department of Health - Clinical Trials (AUS-61) (Last Updated June 14, 2022)
Department of Health
(Webpage) The Human Research Ethics Application (HREA) (AUS-46) (Current as of December 16, 2021)
National Health and Medical Research Council
(Webpage) The National Teletrials Compendium (AUS-60) (Last Updated March 11, 2021)
Department of Health
(Webpage) The Regulatory Environment (AUS-42) (Last Updated November 10, 2020)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) The WHO Registry Network (AUS-33) (Current as of December 16, 2021)
World Health Organization
(Webpage) Trial Registration (AUS-15) (Last Updated June 29, 2016)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) Unimutual (AUS-6) (Current as of December 16, 2021)
Unimutual Limited
(Webpage) What to Do if You Have a Concern About a Clinical Trial? (AUS-45) (Last Updated June 30, 2020)
National Health and Medical Research Council and Department of Industry, Innovation and Science
(Webpage) Which Clinical Trial Scheme Should I Choose? (AUS-27) (Last Updated November 6, 2020)
Therapeutic Goods Administration, Department of Health
Sources > Forms
(Form) Blue Card Adverse Reaction Reporting Form (AUS-3) (June 2018)
Therapeutic Goods Administration, Department of Health
(Form) CIOMS Form I (AUS-4) (Data Unavailable)
Council for International Organizations of Medical Sciences
(Form) CTA Clinical Trial Completion Advice (AUS-58) (Date Unavailable)
Therapeutic Goods Administration, Department of Health
(Form) Supply of Unapproved Therapeutic Goods under the Clinical Trial Approval (CTA) Scheme - Part 1: The CTA Application (AUS-56) (November 2020)
Therapeutic Goods Administration, Department of Health
(Form) Supply of Unapproved Therapeutic Goods under the Clinical Trial Approval (CTA) Scheme - Part 2: Notification of the Conduct of a Trial under the CTA Scheme (AUS-57) (November 2020)
Therapeutic Goods Administration, Department of Health
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Details on the most recent Australia updates are available here.

New GCP Inspection Program

On April 26, 2022, Australia's Therapeutic Goods Administration (TGA) announced that it is implementing the ongoing risk-based Good Clinical Practice Inspection Program. Clinical trials of medicines and biologicals regulated under the CTN and CTA schemes are subject to TGA's GCP Inspection Program. For more information, see the corresponding guidance. ClinRegs will review the guidance and update the profile where appropriate.

Australian Commission on Safety and Quality in Health Care Update

In February 2022, all jurisdictions agreed to implement the Australian Commission on Safety and Quality in Health Care’s National Clinical Trials Governance Framework in health service organizations. The anticipated implementation of the framework is the second half of 2022. For more information, see the National Clinical Trials Governance Framework webpage. ClinRegs will monitor this development and incorporate any updates into the profile when the framework is finalized.

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This message was reviewed on June 2, 2022
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