Therapeutic Goods Administration

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 allows 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 and Aged Care. According to the G-TrialsSOP and AUS-32, the TGA regulates the supply, import, export, manufacturing, and advertising of therapeutic goods. Per AUS-31, therapeutic goods include prescription medicines, vaccines, sunscreens, vitamins and minerals, medical devices, blood, and blood products.

Per AUS-22, the TGA manages the Australian Register of Therapeutic Goods (ARTG) (AUS-22), a public database of therapeutic goods that can be legally supplied in Australia. According to the TGAct, the TGA grants exemptions from inclusion in the ARTG for unapproved therapeutic goods to be supplied in clinical trials.

Contact Information

Per AUS-23 and AUS-47, the contact information for the TGA is as follows:

Postal Address:
P.O. Box 100
Woden ACT 2606
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) or +61 2 6289 4614
Fax: +61 2 6232 8112
E-mail: clinical.trials@health.gov.au

Overview

In accordance with the G-CTHandbook, the G-TrialsSOP, and AUS-47, the Therapeutic Goods Administration (TGA) allows 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) scheme. The G-CTHandbook specifies that the scope of the TGA’s assessment includes all clinical trials (Phases I-IV).

Under either regulatory scheme, per the TGR, the G-NatlStmt, the G-CTHandbook, the G-TrialsSOP, and AUS-47, an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) must approve the research protocol.

According to AUS-43 and the G-TrialsSOP, all participating institutions must also authorize any research in accordance with their research governance frameworks, including site-specific assessments (SSAs) for public health institutions. The SSA and ethics review (incorporating 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) of each participating institution before institutional authorization is granted.

For summaries of the clinical trials regulatory environment, legislation, and guidance, see AUS-40 and AUS-42.

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. 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.

CTN Scheme

As per the G-CTHandbook, the G-TrialsSOP, and AUS-47, under the CTN scheme, the sponsor must notify the TGA of its intention to sponsor a clinical trial involving an unapproved therapeutic good. The TGA does not assess any data relating to the proposed trial 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/authorization. However, it is the sponsor’s responsibility to ensure that all relevant approvals and authorizations are in place before commencement of the trial.

The G-CTHandbook indicates that a clinical trial is deemed to be notified as soon as the online CTN form (AUS-36) has been submitted and the relevant fee has been paid. If there are any changes to the trial details notified to the TGA (such as a change in the details of the principal investigator (PI), the address of the site, or the therapeutic good), the sponsor must update the relevant fields on the online CTN form.

The G-CTHandbook further states that the TGA may request additional information if the trial raises any concern, or ask specific questions to address any deficiencies. Specifically, the TGA can request certain information or documents from the sponsor relating to the supply and handling of the goods, as well as the monitoring and results of the supply of the goods. If the TGA directs a trial notified under the CTN scheme not to be conducted or becomes aware that conducting or continuing the trial would be contrary to the public interest, then the goods used in the trial would no longer be exempt from inclusion in the Australian Register of Therapeutic Goods (ARTG) (AUS-22) and cannot be lawfully supplied. This may occur if the TGA becomes aware that allowing the trial to proceed or continue carries an unacceptable risk of death, serious illness, or serious injury.

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. Some class IV biologicals must be submitted under the CTA scheme.

AUS-47 indicates that the CTA scheme consists of a two (2)-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. In addition, the TGA can request certain information or documents from the sponsor about therapeutic goods approved under the CTA scheme relating to the supply and handling of the goods, as well as the monitoring and results of the supply of the goods.

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.

The G-CTHandbook further states that the TGA can revoke an approval of a clinical trial under the CTA scheme where the conditions of approval are not met.

Other Considerations

The Department of Health and Aged Care’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 PI’s ability to supervise associate investigator(s) conducting 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 (COSA)’s Australasian Tele-trial Model (AUS-2).

Therapeutic Goods Administration

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) scheme for evaluation. Per the G-FeesCharges, the fees are as follows:

• $410 Australian dollars for unapproved medicines CTN, and for each notification of one (1) or more additional trial sites
• $1,954 Australia dollars for unapproved medicines CTA (30-day evaluation)
• $537 Australian dollars for unapproved medicines CTA - variation (30-day evaluation)
• $24,285 Australian dollars for unapproved medicines CTA (50-day evaluation)
• $6,628 Australian dollars for unapproved medicines CTA – variation (50-day evaluation)
• $410 Australian dollars for unapproved biologicals CTN, and for each notification of one (1) or more additional trial sites
• $29,574 Australian dollars for unapproved biologicals CTA
• $8,069 Australian dollars for unapproved biologicals CTA – variation

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.

Payment Instructions

AUS-66 indicates that regulatory fees and charges may be paid online, by cheque (made payable to the “Therapeutic Goods Administration”), or by direct deposit (electronic funds transfer (EFT)). 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 the payment has been successful. The user may request an email confirmation. Certain payments, including a CTN fee and a variation to a medicine, may be made online without an invoice. See AUS-25 for more information.

AUS-66 further indicates that to ensure all payments are correctly allocated, the TGA Client Number and the full invoice number of the relevant invoice should be included in EFTs. The TGA’s account details are as follows:

Bank: Commonwealth Bank of Australia
BSB: 062-909
Account Number: 10215498

Payments from overseas can only be accepted in Australian denominations. Payers must ensure that their payment covers any international banking fees. The TGA’s international banking details are as follows:

IBAN: 06290910215498
Swift Code: CTBAAU2S

Overview

As indicated in the TGAct, the TGR, the G-CTHandbook, the G-NatlStmt, and AUS-47, Australia has a decentralized process for the ethics review and approval of clinical trial research. According to the TGR, the G-NatlStmt, the G-CTHandbook, the G-TrialsSOP, and AUS-47, Australia requires human research protocols to be reviewed by an institutional-level ethics committee (EC). (Note: Institutional ECs are referred to as Human Research Ethics Committees (HRECs) in Australia.)

Per the TGAct and AUS-20, 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. According to the TGR, the G-NatlStmt, 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.

For summaries of the clinical trials regulatory environment, legislation, and guidance, see AUS-40 and AUS-42.

Ethics Committee Composition

As stated in the G-NatlStmt, an EC must be composed of at least eight (8) members in the following categories:

• A chairperson
• 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
• One (1) person with knowledge of and current experience in the professional care, counseling, and/or treatment of people
• One (1) person who performs a pastoral care role in the community
• One (1) lawyer
• Two (2) people with current research experience relevant to the research proposals under consideration by the EC

ECs may also include other members with the above areas of expertise or with additional areas of expertise. To the extent possible, ECs should be composed of equal numbers of men and women, one third of whom are from outside the institution. Institutions may also establish (or share) pools of individuals who can serve as EC members as necessary or desired. ECs may also obtain ad-hoc input from non-member experts whenever additional expertise is considered appropriate.

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. Members should be appointed to an EC using open and transparent processes, and institutions should consider reviewing appointments to the EC at least every three (3) years.

The G-NatlStmt states that as far as possible, each EC meeting should be arranged to enable at least one (1) member in each composition category noted above to attend. Meeting papers should be provided enough in advance to enable members to be fully informed. An EC’s decision about whether a research proposal meets the requirements of the G-NatlStmt must be informed by an exchange of opinions from each of those who constitute the minimum membership. The exchange should, ideally, take place at a meeting with all those members present. Where there is less than full attendance of the minimum membership at a meeting, the chairperson should be satisfied, before a decision is reached, that the views of those absent who belong to the minimum membership have been received and considered. The EC should attempt to reach decisions by general agreement, but not necessarily unanimity.

According to the G-NatlStmt, ECs may invite researchers, and researchers may request, to be present for discussion of their proposed research. In addition, ECs may seek advice from experts to help in considering a research proposal. Communication between the sponsor and the EC should be avoided where it may, or may be perceived to, influence the ethical review and approval of the project. ECs 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.

Overview

According to the G-NatlStmt, the institutional ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) is responsible for protecting the interests of research participants and for promoting good research by ensuring adherence to the values of research merit and integrity, beneficence, justice, and respect for persons throughout the conduct of the research project. The EC must review the recruitment and consent processes, weigh the benefits and risks of the research, and consider the impact of the research on certain groups of participants deemed to merit special consideration.

Pursuant to the G-NatlStmt, the EC is responsible for conducting a 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 privacy and confidentiality safeguards.

Role in Clinical Trial Approval Process

According to the G-CTHandbook, the G-TrialsSOP, and AUS-47, 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) scheme—prior to the sponsor initiating a trial. As per AUS-43 and the G-TrialsSOP, the institution must also authorize any research in accordance with its research governance framework, including a site-specific assessment (SSA) for public health institutions. The SSA and ethics review (incorporating 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) of each participating institution before institutional authorization is granted.

The G-CTHandbook states that a CTN scheme is a notification scheme under which the Therapeutic Goods Administration (TGA) does not review or evaluate any data relating to the clinical trial. The EC is responsible for assessing the scientific validity of the trial design, the balance of risk versus harm of the therapeutic good(s), and the overall ethical acceptability of the trial. Per AUS-47, EC and institutional review and approval/authorization 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 and authorizations are in place before commencement of the trial.

Under the CTA scheme, as delineated in the G-CTHandbook, the TGA reviews relevant, but limited, scientific data, while the EC is responsible for considering the scientific and ethical issues of the proposed trial protocol.

Per the G-CTHandbook, the sponsor determines whether to conduct a clinical trial under the CTN or CTA scheme. Consulting the EC responsible for protocol approval may assist the sponsor in making the decision. One of the determining factors for an EC is whether the committee has access to appropriate scientific and technical expertise in order to assess the safety of the product. If an EC feels that it requires additional expertise to review a CTN, it may seek advice from external authorities or it may seek to collaborate with another EC that has the required expertise. An EC may also determine that it does not have access to the appropriate scientific and technical expertise to review the proposed trial under the CTN scheme and recommend review under the CTA scheme.

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.

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

• G-NatlStmt
• Declaration of Helsinki (AUS-52)
• AU-ICH-GCPs
• Any relevant Commonwealth and/or state/territory laws

According to the G-CTHandbook and 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.

As stated in AUS-20, ECs also consider the protection of privacy for humans participating in research and their data. ECs do this by considering whether the research proposal conforms to relevant legislation, principles, and guidelines, including federal and/or state/territory legislation as well as the G-PrivacyAct95 and G-PrivacyAct95A guidelines. See the Personal Data Protection section for more information.

Per the G-NatlStmt, an EC may approve, request amendment of, or reject a research proposal on ethical grounds. The EC must clearly communicate its decision to the researcher(s):

• Where a proposal is approved, communication must be in writing (which may include email) and should include an explicit statement that the proposal meets the requirements of the G-NatlStmt.
• Where amendments are requested, communication may be written or, where appropriate, informal. Reasons should be given for the requested amendments.
• Where a proposal is rejected, communication of the rejection must be in writing (which may include email) and should include reasons linked to the G-NatlStmt.

The G-CTHandbook further indicates that 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). ECs have a high level of independence and are responsible for establishing their own processes for reviewing research proposals.

Per the G-NatlStmt, if the EC finds reason to believe that continuance of a research project would compromise participants' welfare, it should immediately seek to establish whether ethical approval for the project should be withdrawn.

National Mutual Acceptance Scheme

As described in AUS-21 and AUS-41, the National Mutual Acceptance (NMA) scheme supports the acceptance of a single scientific and ethical review of multicenter research conducted in publicly funded health services. All Australian states and territories are a part of the NMA scheme.

Per AUS-68, in order for ethics reviews of human research to be accepted under NMA, the EC conducting the review must be certified under the National Health and Medical Research Council (NHMRC) National Certification Scheme of Institutional Processes Related to the Ethical Review of Multi-centre Research (National Certification Scheme), and also be a “Certified Reviewing HREC” under the NMA scheme.

For more information on submissions to ECs under the NMA scheme and the National Certification Scheme, see the Submission Process and Oversight of Ethics Committees sections.

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

Overview

As per the TGAct, the G-TrialsSOP, and the G-CTHandbook, the National Health and Medical Research Council (NHMRC) is responsible for receiving applications from ethics committees (ECs) (Human Research Ethics Committees (HRECs) in Australia) to be registered. The NHMRC was established by the NHMRCAct. Per the NHMRCAct, the NHMRC’s activities are designed to raise the standard of individual and public health throughout Australia; to foster the development of consistent health standards between the various states and territories; to foster medical and public health research and training throughout Australia; and to foster consideration of ethical issues relating to health.

Registration, Auditing, and Accreditation

Per AUS-20, registration means that the EC has notified the NHMRC of its existence and declared that it meets the requirements of the G-NatlStmt. In order to review and monitor clinical trials of unregistered therapeutic goods, an EC must be notified to the NHMRC, and constituted and operating in accordance with the G-NatlStmt. Forms for registering an EC, notifying the NHMRC of changes to the EC, or terminating an EC’s registration are available at AUS-20.

Per AUS-20, registered ECs must 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.

See AUS-20 for more information and a list of registered ECs.

National Certification Scheme

According to AUS-21, the NHMRC developed the National Certification Scheme of Institutional Processes Related to the Ethical Review of Multi-centre Research (National Certification Scheme) to enable the single ethics and scientific review of human research occurring at multiple institutions in Australia. Under this scheme, certified institutions can have their ethics review accepted by other institutions participating in the research project, so that researchers only need to submit an ethics application to one (1) EC. Acceptance of another EC’s ethics review is not mandatory under the National Certification Scheme, so it is up to individual institutions participating in the research project to decide whether they will accept the review outcome from a certified institution’s EC, or conduct their own review.

AUS-21 states that as part of the National Certification Scheme, certified institutions and their ECs are required to self-report to the NHMRC on their multicenter research activities.

As per AUS-21, the NHMRC assesses each institution’s interest for certification on a case-by-case basis. Certification respects institutional decisions about research governance matters, including whether research should be conducted at a given site. Before commencing steps to apply for certification, institutions should contact HREC.admin@nhmrc.gov.au.

As stated in AUS-68, EC certification under the National Certification Scheme is required in order for ethics reviews of human research to be accepted under the National Mutual Acceptance (NMA) scheme. The NMA scheme facilitates single scientific and ethical review of multicenter research conducted in publicly funded health services. See the Scope of Review section for more information on NMA.

Overview

In accordance with 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) scheme.

Under either regulatory scheme, per the TGR, the G-NatlStmt, the G-CTHandbook, the G-TrialsSOP, and AUS-47, an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) must approve the research protocol. AUS-47 indicates that the review and approval/authorization 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 and authorizations are in place before commencement of the trial.

According to AUS-43 and the G-TrialsSOP, the institution must also authorize any research in accordance with its research governance framework, including a site-specific assessment (SSA) for public health institutions. The SSA and ethics review (incorporating 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) of each participating institution before institutional authorization is granted.

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

Regulatory Submission

CTN Scheme

According to AUS-47 and AUS-30, CTN forms are submitted online through the TGA Business Services (TBS) webpage (AUS-36). The sponsor must have or obtain a TGA Client Identification Number.

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.

See AUS-30 and AUS-49 for additional information on using and submitting the online form. Per AUS-47, any further questions can be directed to the TBS Helpdesk at ebs@tga.gov.au or 1 800 010 624.

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.

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

Ethics Review Submission

AUS-46 indicates that the National Health and Medical Research Council (NHMRC) developed the Human Research Ethics Application (HREA) form (AUS-9) as a concise application to facilitate timely and efficient ethics review for research involving humans. The HREA assists researchers in considering the ethical principles of the G-NatlStmt in relation to their research and is accepted by institutions that participate in the National Mutual Acceptance (NMA) scheme, which facilitates single ethics review for most human research within the public health context.

According to the G-CTHandbook, trial sponsors and researchers should use the HREA unless advised otherwise. AUS-19 contains resources for using the HREA.

Per AUS-46, research proposals should be submitted to ECs associated with public health institutions in New South Wales, Queensland, South Australia, Australian Capital Territory, and Victoria, as well as Mater Research, via the Research GEMS system (AUS-55), the Ethical Review Manager (ERM) website (AUS-8), and/or the Research Ethics and Governance Information System (REGIS) (AUS-10), depending on which jurisdictions are involved. For research in the Northern Territory, Tasmania, or Western Australia, the EC should be contacted for their local submission requirements.

The G-CTHandbook further states that ECs have a high level of independence and are responsible for establishing their own processes for receiving research proposals.

Research Governance

According to the G-NatlStmt, institutions should use and promote clearly formulated, documented, accessible, and current policies and procedures for research governance.

AUS-43 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 ERM website (AUS-8) is used for SSA form submission for Mater Research, Queensland, and Victoria. New South Wales and the Australian Capital Territory use REGIS (AUS-10) for site governance applications.

Regulatory Authority Requirements

Clinical Trial Notification (CTN) Scheme

As delineated in AUS-49, the following documentation must be submitted to the Therapeutic Goods Administration (TGA) in the CTN online 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
• Ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) name and contact information

Clinical Trial Approval (CTA) Scheme

AUS-47 states that the CTA scheme application consists of two (2) forms – Part 1: the application (AUS-56), and Part 2: Notification of the conduct of a trial under the CTA scheme (AUS-57).

The Part 1 CTA application form (AUS-56) requires general information (sponsor name, data details, and sponsor declaration) and details on the medicine (active ingredient)/biological be submitted to the TGA.

The Part 2 CTA application form (AUS-57) requires trial sponsor information (name and client ID code), the IP or biological, and the notification type, as well as trial and trial site details (title of study and trial type). The form also requires signed certifications from the sponsor, the principal investigator (PI), the EC, and the authority approving the conduct of the trial.

Ethics Committee Requirements

Per the G-CTHandbook, the EC and the institution are responsible for establishing what information should be provided in support of an application. The EC should request any additional information that it believes is necessary to undertake review of the proposed research. Unless advised otherwise, trial sponsors and researchers should use the Human Research Ethics Application (HREA) for submitting proposals for research involving humans to ECs.

AUS-46 indicates that the HREA assists researchers in considering the ethical principles of the G-NatlStmt in relation to their research. The G-NatlStmt requires that those who conduct and approve human research to consider:

• how the research question/theme is identified or developed
• the alignment between the research aims and methods
• how the researchers and the participants will engage with one another
• how the research data or information are to be collected, stored, and used
• how the results or outcomes will be communicated, and
• what will happen to the data and information after the project is completed

For more information on the HREA, see the Submission Process section.

Research Governance

According to the G-NatlStmt, institutions should use and promote clearly formulated, documented, accessible, and current policies and procedures for research governance. See the Research GEMS system (AUS-55), the Ethical Review Manager (ERM) (AUS-8), and the Research Ethics and Governance Information System (REGIS) (AUS-10) websites for public health organization site-specific assessment (SSA) forms, which may differ between institutions and states or territories.

Clinical Protocol

The G-TrialsSOP indicates that where the investigator is responsible for the protocol development, the investigator must ensure the protocol follows the outline in the AU-ICH-GCPs. Specific content of a protocol will vary depending on the research area, 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

Overview

In accordance with the G-CTHandbook, the G-TrialsSOP, and AUS-47, the Therapeutic Goods Administration (TGA) is responsible for authorizing 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) scheme. According to the TGR, the G-NatlStmt, the G-CTHandbook, the G-TrialsSOP, and AUS-47, under either regulatory scheme, an ethics committee (EC) (Human Research Ethics Committee (HREC) in Australia) must approve research protocols. AUS-47 indicates that the review and approval/authorization 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 and authorizations are in place before commencement of the trial.

Per AUS-43 and the G-TrialsSOP, the institution must also authorize any research in accordance with its research governance framework, including a site-specific assessment (SSA) for public health institutions. The SSA and ethics review (incorporating the scientific review) may occur in parallel.

Regulatory Authority Approval

AUS-47 states that the TGA’s target time to process online CTNs is five (5) to seven (7) working days, but the agency tries to process the notification as soon as possible. This timeframe does not include the time taken for TGA finance to match the payment (if required) to a submission. For information on how to check the status of a CTN, see AUS-69.

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. The G-GovHndbk and AUS-43 indicate that 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 G-TrialsSOP further specifies that EC approval must be obtained and submitted to the research governance officer (RGO) of each participating institution before institutional authorization is granted.

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

The G-GovHndbk further indicates that in the national approach to single ethical review, site assessment and project authorization are the responsibility of each institution participating in a multicenter human research project while ethical review is provided by a single EC using certified ethical review processes. Each institution collaborating in a multicenter project utilizing the outcome of a single ethical review must individually authorize the commencement of research at their institution. To avoid unnecessary delays in research commencing at all collaborating centers and sites, each institution should consider relevant local matters prior to or in parallel with ethical review.

See the G-GovHndbk for additional National Health and Medical Research Council (NHMRC) guidance on best practices in the governance of multicenter human research as part of the national approach to single ethical review.

The NHMRC also 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.

Overview

In accordance with the G-TrialsSOP, 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) scheme. According to the G-GovHndbk, the G-TrialsSOP, and AUS-43, under either scheme, both institutional ethics committee (EC) (Human Research Ethics Committees (HRECs) in Australia) approval and research governance authorization are required before a research project can commence at a site.

Research Governance

As described in AUS-43, research governance refers to the processes used by institutions 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 site-specific assessment (SSA) to evaluate whether the site has the capacity to conduct the research (e.g., physical resources, staff, and insurance). For more information on institutional responsibilities, see the Site/Investigator Selection section.

The G-TrialsSOP states that in the case of a teletrial, the principal investigator (PI) must ensure that a robust site assessment is undertaken that fully quantifies the capabilities of each satellite site to inform the extent to which trial related activities can be delegated to the site. This may include a pre-commencement assessment before a specific trial is proposed so that the process of trial start up is expedited when a suitable trial is identified.

Per the G-TrialsSOP, prior to a study’s commencement, the PI must:

• Submit the primary site's Clinical Trial Research Agreement (CTRA), EC approval, the SSA form, evidence of any relevant good clinical practice (GCP) training, and any other required documentation to the institution’s research governance officer (RGO)
• Ensure all documentation and correspondence pertaining to the submission and approval processes is filed in the study master file (SMF) (see Appendix 8 of the G-TrialsSOP)
• Ensure each satellite site completes a clinical trial sub-contract and a SSA form, and submits to their RGO
• Await site specific RGO authorization before any study related activity can occur at that site
• Ensure the satellite site files all documentation in the satellite site study file (SSSF)

The G-TrialsSOP further states that prior to the initiation of a study, the investigator must also 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 for primary and satellite sites.

Clinical Trial Agreement

As delineated in the AU-ICH-GCPs, the sponsor must sign an agreement between all involved parties, including investigators, institutions, contract research organizations, and others for documentation purposes. Further, the sponsor should obtain the investigator’s/institution's agreement:

• To conduct the trial in compliance with good clinical practice, with the applicable regulatory requirement(s), and with the protocol agreed to by the sponsor and given approval/favorable opinion by the EC
• To comply with procedures for data recording and reporting
• To permit monitoring, auditing, and inspection
• To retain the trial-related essential documents until the sponsor informs the investigator/institution these documents are no longer needed

The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

For the purposes of the G-TrialsSOP, the CTRA for the primary site and the sub-contract for each satellite site constitute part of a research governance application, which is submitted to the RGO. The CTRA covers matters such as confidentiality, intellectual property, ownership of data, insurance and indemnity. The Medicines Australia CTRA (see AUS-38) is the recommended standard form. According to AUS-43, standard templates for CTRAs and indemnities should be used wherever possible in order to minimize the need for legal review.

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) (AUS-67). Per AUS-15, the Australian and New Zealand Clinical Trials Registry (ANZCTR) (AUS-12) is one (1) of the primary registries in the WHO Registry Network (AUS-33). To achieve prospective registration, the ANZCTR recommends applying for registration at the same time as ethics submission.

Safety Reporting Definitions

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 hospitalization or prolongation of existing hospitalization, 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

Safety Reporting Requirements

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 principal investigator (PI) must ensure that study staff, including those at teletrial satellite sites, are trained in the protocol, investigator’s brochure (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 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 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 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)

Per AUS-3, the Blue Card form may be emailed to adr.reports@tga.gov.au; mailed to Pharmacovigilance and Special Access Branch, Reply Paid 100, Woden ACT 2606; or faxed to 02 6232 8392. More information about reporting to the TGA may be found at AUS-7.

Interim and Annual Progress Reports

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 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 (ARTG) (AUS-22), 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. AUS-58 indicates that upon completion, the form may be emailed to the TGA at clinical.trials@tga.gov.au (preferred) or faxed to 02 6232 8112.

The AU-ICH-GCPs and the G-TrialsSOP 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.

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, the role of trial sponsor is assumed. 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.

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. 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.

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 (IP), 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 PI must also have sufficient time to properly conduct and complete the research within the specified period, as well as an adequate number of qualified staff and adequate facilities for the foreseen duration of the research. 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. 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.

See AUS-44 and AUS-64 for additional clinical trial and researcher resources.

Research Governance

The G-NatlStmt indicates that institutions must ensure that any human research they conduct or for which they are responsible is designed and conducted in accordance with the G-CodeConduct and ethically reviewed and monitored in accordance with the G-NatlStmt. Each institution needs to be satisfied that its human research meets relevant scholarly or scientific standards, and those conducting the research (i) are either adequately experienced and qualified, or supervised; (ii) understand the need to assess risks to their own safety and that of participants; and (iii) are free to withdraw from research on conscientious grounds. Institutions must also be satisfied that processes are in place for managing conflicts of interest, monitoring research, handling complaints, and ensuring accountability. Clearly formulated, documented, accessible, and current policies and procedures for research governance and ethical review should be used and promoted.

Per AUS-63, the Australian Commission on Safety and Quality in Health Care developed the National Clinical Trials Governance Framework (AUS-63), which embeds clinical trials into routine health service provision and strengthens the clinical and corporate governance arrangements for parties that deliver clinical trials. All jurisdictions have agreed to implement the framework in health service organizations, meaning the organizations will be assessed concurrently for clinical and corporate services and clinical trial service provision. For more information, including implementation timing, see AUS-63.

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

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

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 Therapeutic Goods Administration (TGA) (if required), and that was approved by the ethics committee (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

Insurance

The AU-ICH-GCPs and the G-NatlStmt 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-CTInsurance-AUS indicates that in the private sector, sites that conduct clinical trials will usually purchase clinical trials insurance from a commercial insurer. In the public sector, each state or territory provides indemnity or insurance coverage in relation to its clinical trial activities. The G-CTInsurance-AUS provides more details for each state and territory scheme.

Compensation

Injury or Death

According to the G-NatlStmt, institutions must ensure that sponsors have indemnity and compensation arrangements in accordance with applicable regulatory 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.

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

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.

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

Trial Participation

The G-NatlStmt states that it is generally appropriate to reimburse participants for the costs associated with taking part in research including travel, accommodations, and parking. Sometimes participants may also be paid for time involved. However, payment may not be disproportionate to the time involved, or include other incentives that encourage participants to take risks. Further, payment or reimbursement decisions should consider customs and practices of the community in which the trial will be conducted.

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.

According to the AU-ICH-GCPs, payments to a participant should be prorated and not wholly contingent on completion of the trial by the participant.

Post-Trial Access

Per the G-NatlStmt, 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.

Quality Assurance/Quality Control

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. Australian institutions must establish and maintain good governance and management practices for responsible research conduct. In addition, researchers must comply with the relevant laws, regulations, disciplinary standards, ethics guidelines, and institutional policies related to responsible research conduct. Compliance with the G-CodeConduct 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.

Monitoring 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 its own SOPs and that the auditor’s observations are documented.

Per the G-TrialsSOP, the principal investigator (PI) must ensure audit/inspection readiness throughout the study, have oversight of any audit or inspection of the trial at both primary and satellite sites, and ensure any deficiencies identified through audit or inspection are actively managed to ensure continuous improvement.

According to the G-GCP-Inspect, clinical trials of medicines and biologicals regulated under the Clinical Trial Notification (CTN) or Clinical Trial Approval (CTA) schemes are subject to the TGA’s GCP Inspection Program. See the G-GCP-Inspect for more details on how the TGA prioritizes and schedules GCP inspections, the kinds of inspections the TGA might conduct, the inspection process, and how the TGA reports and follows up on inspection.

The TGR further states that the sponsor must provide a written assurance to comply with any trial-related requests by an authorized TGA officer(s), which includes allowing inspection of clinical trial sites. The PI is required to comply with requests and answer any questions the authorized officer(s) may have.

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, 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

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 its established requirements for completeness, accuracy, reliability, and consistent intended performance, and that SOPs are maintained 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.

Responsible Parties

Per AUS-70, the PrivacyAct regulates how certain health service providing organizations collect and handle personal information, including health information. It also includes provisions that generally allow an individual to access information held about them.

According to the PrivacyAct, agencies and organizations as defined in the PrivacyAct must comply with the Act and the Australian Privacy Principles (APP), found in Schedule 1, and are referred to as APP entities.

Data Protection

Per the PrivacyAct’s APP, an APP entity must have a clearly expressed and up‑to‑date policy about the management of personal information by the entity. Individuals must have the option of not identifying themselves or of using a pseudonym, and an APP entity must not collect sensitive information about an individual unless the individual consents to the collection of the information.

The APP outline further requirements for the consideration of personal information privacy; the collection of personal information; dealing with personal information; the integrity of personal information; and access to, and correction of, personal information. For the full list of APP, see Schedule 1 of the PrivacyAct.

Consent for Processing Personal Data

The PrivacyAct’s APP indicate that if an APP entity holds personal information about an individual that was collected for a particular purpose, the entity must not use or disclose the information for another purpose unless consent is obtained from the individual. There are limited exceptions to this requirement, which can be found in Schedule 1 of the PrivacyAct.

AUS-70 notes that in certain circumstances, the PrivacyAct permits the handling of health information and personal information for health and medical research purposes, where it is impracticable for researchers to obtain individuals' consent, recognizing: the need to protect health information from unexpected uses beyond individual healthcare, and the important role of health and medical research in advancing public health. To promote these ends, the Office of the Australian Information Commissioner (OAIC) approved the National Health and Medical Research Council (NHMRC)’s legally binding guidelines, G-PrivacyAct95 and G-PrivacyAct95A, which researchers must follow when handling health information for research purposes without individuals' consent. The guidelines also assist ethics committees (ECs) (known as the Human Research Ethics Committees in Australia) in deciding whether to approve research applications. The guidelines are:

• G-PrivacyAct95, which sets out procedures that ECs and researchers must follow when personal information is disclosed from a federal agency for medical research purposes
• G-PrivacyAct95A, which provides a framework for ECs to assess proposals to handle health information held by organizations for health research (without individuals' consent). It ensures that the public interest in the research activities substantially outweighs the public interest in the protection of privacy

See the PrivacyAct, the G-PrivacyAct95, and the G-PrivacyAct95A for more information.

Obtaining Consent

In all Australian clinical trials, valid 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) (referred to as a participant information and consent form (PICF) in Australia) 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 institutional authorization, 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 the legal representative(s) or guardian(s). The ICF content should be as non-technical as practical and understandable to the participants and/or the 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 the 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 Emergencies, Children/Minors, Prisoners, and Mentally Impaired sections for additional information about these populations.

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 the legal representative(s) and/or guardian(s) to waive or to appear to waive their 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.

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 the 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.

Documenting Consent

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 the 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 the 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 the legal representative(s) and/or guardian(s)

• The participant and/or the 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 the 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.

Waiver of Consent

The G-NatlStmt specifies that although voluntary 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 opt-out approach is a method used in the recruitment of research participants where information is provided to the potential participant regarding the research and their involvement, and where their participation is presumed unless they take action to decline to participate. 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

Based on the AU-ICH-GCPs and the G-NatlStmt, the informed consent form (ICF) (referred to as a participant information and consent form (PICF) in Australia) 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 the 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
• The likelihood and form of dissemination of the research results, including publication

• Other relevant information, including research-specific information required under the G-NatlStmt

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

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) (referred to as a participant information and consent form (PICF) in Australia).

The Right to Participate, Abstain, or Withdraw

As stated in the AU-ICH-GCPs and the G-NatlStmt, the participant and/or the legal representative(s) or guardian(s) should be informed that participation is voluntary, that the participant 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 the 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.

See the Personal Data Protection section for more details on personal information collection and handling requirements.

The Right of Inquiry/Appeal

The AU-ICH-GCPs and the G-NatlStmt state that the research participant and/or the legal representative(s) or guardian(s) should be provided with contact information for the individual responsible for addressing trial-related inquiries and/or rights. AUS-45 guides the participant and/or the 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 protection of 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.

The AU-ICH-GCPs states that in emergency situations, when prior consent of the participant is not possible, the consent of the legal representative(s) or guardian(s), if present, should be requested. When prior consent of the participant is not possible, and the legal representative(s) or guardian(s) is not available, enrollment of the participant should require measures described in the protocol and/or elsewhere, with documented approval/favorable opinion by the ethics committee (EC) (known as the Human Research Ethics Committee in Australia), to protect the rights, safety, and well-being of the participant and to ensure compliance with applicable regulatory requirements, including the G-NatlStmt. Per the AU-ICH-GCPs, the participant and/or the 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.

The G-NatlStmt recognizes that in emergency care research, recruitment into a research project often must be achieved rapidly. Where the research involves emergency treatment and meets the G-NatlStmt’s requirements for research involving people highly dependent on medical care, consent for the research may be waived. See the Documentation Requirements section and the G-NatlStmt for more details on waiver of consent.

Overview

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

According to the G-NatlStmt, research involving people who are highly dependent on medical care may be approved where:

• It is likely that the research will lead to increased understanding about, or improvements in, the care of this population
• The requirements of relevant jurisdictional laws are taken into account
• Either 1) any risk or burden of the proposed research to this particular participant is justified by the potential benefits, or 2) where participants have capacity to consent, any risk or burden is acceptable to them and justified by the potential benefits of the research

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 states that when neither the potential participant nor the legal representative(s) or guardian(s) can consider the proposal and give consent, an ethics committee (EC) (known as the Human Research Ethics Committee in Australia) may, having taken account of relevant jurisdictional laws, approve a research project without prior consent if:

• There is no reason to believe that, were the participant or the legal representative(s) or guardian(s) to be informed of the proposal, the participant would be unwilling to consent
• The risks of harm to individuals, families, or groups linked to the participant, or to their financial or social interests, are minimized
• The project is not controversial and does not involve significant moral or cultural sensitivities in the community

And, where the research is interventional, these additional conditions apply:

• The research supports a reasonable possibility of benefit over standard care
• Any risk or burden of the intervention to the participant is justified by its potential benefits
• Inclusion in the research project is not contrary to the interests of the participant

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.

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-AIATSISCode.

Persons in Dependent Groups

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.

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.

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 EC. The investigator(s) should be satisfied that participants who are subject to criminal justice processes are aware that the research may discover illegal activity and do not have unrealistic expectations of benefit from their participation. Finally, research designed to expose illegal activity 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.

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.

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

According to AUS-71, children under 16 cannot give legal consent, which must be given by a legal representative(s) or guardian(s), but they can and should be involved in the decision. Young people over 16 can give legal consent to medical treatment; however, they usually cannot provide legal consent to participate in research until they are 18. Nonetheless, some ethics committees (ECs) (known as Human Research Ethics Committees in Australia) do allow mature young people under 18 to give their consent for some kinds of research.

The AU-ICH-GCPs states that minors should be informed to the extent compatible with their maturity and understanding, and if capable, they should sign and personally date the informed consent form (ICF) (referred to as a participant information and consent form (PICF) in Australia). In accordance with the G-NatlStmt, consent requirements for conducting clinical trials follow the general requirements listed in the Required Elements section.

The G-NatlStmt states before including a child or young person in research, researchers must establish that there is no reason to believe that such participation is contrary to that child's or young person's best interest. Furthermore, a child or young person's refusal to participate in research should be respected wherever he/she has the capacity to give consent to that same research. Where a child or young person lacks this capacity, his or her refusal may be overridden by the judgement of the legal representative(s) or guardian(s) as to what is in the child's best interest.

The G-NatlStmt indicates that an 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 the legal representative(s) or guardian(s) and the researcher ensures the child or young person’s 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 the legal representative(s) or guardian(s), and the researcher ensures the child or young person’s safety, security, and well-being in the research conduct

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 their welfare.

Assent Requirements

As stated in AUS-71, assent should be obtained when the child is considered to have sufficient maturity to be able to express a view on whether they would like to take part in the research. Both informed consent and assent require that children understand the research process and are informed about what they are expected to do or what will happen to them during the trial. Children should always be given information in a form that they can understand.

Furthermore, the G-NatlStmt states that except in cases involving standing parental consent, specific consent must be obtained from the child or young person whenever he/she has the capacity to make this decision, and either one (1) parent, except when the EC decides that the risks require the consent of both parents, or the child or young person’s legal representative(s) or guardian(s).

Per the G-NatlStmt, researchers must respect the developing capacity of children and young people to be involved in decisions about participation in research. The child or young person's particular level of maturity has implications for whether consent is necessary and/or sufficient to authorize participation. However, it is not possible to attach fixed ages to each level of maturity, which may vary from child to child. 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

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. The wellbeing and care of the woman who is pregnant and of her fetus always takes precedence over research considerations, and 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. Additionally, research should be designed to minimize pain or distress for the fetus, include steps for monitoring for signs of fetal pain or distress, and include steps for suspending or ceasing the research if necessary.

In accordance with the G-NatlStmt, 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 is in utero. Further, per the G-NatlStmt, 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

In addition, the G-NatlStmt states that if, for research purposes, fetal cells are to be derived from the fetal tissue and stored or propagated in tissue culture, or tissues or cells are to be used in human transplantation, the woman's consent is required. Others whom the woman identifies may also need to be involved in decisions about these matters.

For requirements related to research on embryos and deceased fetuses, see G-EthicsART.

The G-NatlStmt refers to prisoners and prison authorities as an example of people who may be in dependent or unequal relationships.

Per the G-NatlStmt, a research study involving people in dependent or unequal relationships (such as 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.

Cognitive Impairment, Intellectual Disability, or Mental Illness

The G-NatlStmt discusses the requirements for research involving participants with cognitive impairment, intellectual disability, and mental illness together, noting that many of the ethical issues they raise about research participation are similar. An ethics committee (EC) (known as Human Research Ethics Committee in Australia) must review and approve research involving such participants, except where the research uses collections of non-identifiable data and involves negligible risk.

Per the G-NatlStmt, the research design should take into account factors that may affect the capacity to receive information, to consent to the research, or to participate in it. Additionally, care should be taken to determine whether the participant’s cognitive impairment, intellectual disability, or mental illness increases the susceptibility to some forms of discomfort or distress. Ways of minimizing effects of this susceptibility should be described in the research proposal.

As delineated in the G-NatlStmt, the 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 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 the opportunity to continue participation or withdraw. Refusal or reluctance to participate in a research project should be respected.

The G-NatlStmt states that if the participant’s impairment, disability, or illness is temporary or episodic, researchers should seek consent when the condition does not interfere with the 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.

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.

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

Manufacturing

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) 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.

The AU-PIC-S-GMP-Guide-Intpn notes that the manufacture of IPs differs from the manufacture of commercial products in various aspects, requiring additional consideration and oversight to manage the risks associated with IP manufacture. Manufacturers of IPs must have a clear and documented understanding of the nature of the products, so that a pharmaceutical quality system can be developed to manage ongoing communication with the sponsor and effectively manage the IP manufacturing process.

See the AU-PIC-S-GMP-Guide and the AU-PIC-S-GMP-Guide-Intpn for detailed manufacturing requirements.

Import

The G-CTHandbook and AUS-47 indicate that IPs may be imported and held under the direct control of the sponsor (importer) until the IPs are the subject of a notification to the TGA under the CTN scheme or an approval under the CTA scheme. The IPs must be kept in a warehouse or other properly secured area. There is no requirement for the CTN or CTA process to have been completed prior to importation of the clinical trial goods.

Per AUS-47, importers are advised to contact other relevant agencies, as there may be further restrictions on importation imposed through other legislation.

Other Considerations

AUS-47 states that Australian clinical trial product importers/manufacturers are not required to provide the TGA with six (6) monthly reports under regulation 47B of the TGR. However, the TGA can require information or documents relating to the supply (including quantity) of therapeutic goods that are exempt under the CTN scheme or approved under the CTA scheme.

Per the AU-PIC-S-GMP-Guide-Intpn, there is an increased emphasis on the importance of sampling and testing of IPs, since processes for IP manufacture may not be validated to the extent required for a commercial product. Manufacturers should therefore implement robust sampling and testing procedures in order to generate and collate data that supports the suitability of the manufacturing process and the products manufactured. The sampling and testing system should consider:

• Increased sampling plans and test plans for starting materials, in-process materials, intermediates, and finished goods
• Comprehensive test method validation for all methods used in the analysis of materials and products
• Robust laboratory controls for data integrity required - particularly when data annotation tools are needed, which may be common for products in development (e.g., where quantification of related substances/impurities requires manual integration)
• Product specification file outlines agreed testing program and specifications

Investigator’s Brochure

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 IB is made available to the investigator(s), and the investigator(s) must provide an up-to-date IB to the ethics committee.

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.

Quality Documentation

As specified in the AU-ICH-GCPs, the sponsor must ensure that the products are manufactured in accordance with Good Manufacturing Practices (GMPs). Furthermore, 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.

Per the AU-PIC-S-GMP-Guide and the AU-PIC-S-GMP-Guide-Intpn, manufacturers should maintain documentation including specifications and instructions; the IP order; the product specification file; manufacturing formulae and processing instructions; packaging instructions; and processing, testing, and packaging batch records. See the AU-PIC-S-GMP-Guide and the AU-PIC-S-GMP-Guide-Intpn for more details on quality documentation requirements.

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 (Note: The regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• 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, which 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

The G-CTHandbook and the AU-PIC-S-GMP-Guide-Intpn recognize that in exceptional circumstances, it may not be possible to meet the requirements of Annex 13 of the AU-PIC-S-GMP-Guide for labelling IPs. In this case, the sponsor must contact the Therapeutic Goods Administration (TGA) (see AUS-72) if they wish to request a departure from the requirements of Annex 13.

In addition, the AU-ICH-GCPs states that the IP must be coded and labeled in a manner that protects the blinding, if applicable.

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

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 investigational product(s) (IPs)), including the comparator and placebo, if applicable. The G-CTHandbook and AUS-47 indicate that Therapeutic Goods Administration (TGA) approval through the Clinical Trial Approval (CTA) scheme or notification through the Clinical Trial Notification (CTN) scheme must occur prior to supplying the IP(s) to the trial site(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

In addition, the AU-ICH-GCPs states that the IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage. 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.

• 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-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 on import and export requirements are provided in the G-CTHandbook, the G-TrialsSOP, the G-SpecExport, and AUS-24.

• 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