Project Orbis

Project Orbis is an initiative of the FDA's Oncology Center of Excellence that provides a framework for the collaborative review of promising new cancer treatments among international regulatory partners. It aims to give patients faster access to promising cancer treatments across the globe.

In addition to the US FDA, Project Orbis partners include the regulatory agencies of:

• Australia - Therapeutic Goods Administration
• Brazil - National Health Surveillance Agency (ANVISA)
• Canada - Health Canada
• Israel - Ministry of Health
• Singapore - Health Sciences Authority
• Switzerland - Swissmedic
• United Kingdom - Medicines and Healthcare Products Regulatory Agency (MHRA).

The TGA has been a partner in Project Orbis since its inception in May 2019, working with the FDA and Health Canada on the first Project Orbis submission to approve lenvatinib (Lenvima®) in combination with pembrolizumab (Keytruda®) for the treatment of certain patients with advanced endometrial carcinoma in September 2019.

As of 30 September 2023, the TGA has approved approximately 25 new medicines and 35 new indications through Project Orbis.  Well over half of these submissions have been approved through either the priority or provisional pathway, and approximately 15 submissions have been designated orphan drugs.

A consolidated list of all new medicines and new indications approved by the FDA and Project Orbis Partners (including the TGA) is available on the Project Orbis page of the FDA’s website - external site, under “Orbis Approvals”, and this is updated periodically.  This list contains the FDA’s approval dates, which do not necessarily reflect the approval dates of the Project Orbis Partners.

The TGA’s approvals through Project Orbis are also published in the Prescription medicines registrations database.

Applicant and application selection

Requirements for applications

The FDA coordinates the selection of applications for Project Orbis in collaboration with the US applicant.

Applications eligible for Project Orbis include oncology products that are either:

• new active substances (new chemical entity or new biological entity applications)
• new indications applications

Project Orbis is intended for high-impact and clinically significant applications. Applications are generally expected to meet the criteria for "FDA Priority Review".

Once the potential Project Orbis partners are identified, the FDA will send a proposal to the Project Orbis partners (POPs) to confirm their interest and availability to participate in a collaborative review process (see collaboration models below).

Australian applicants who have the opportunity to take part in Project Orbis should contact the TGA at PMABinternationalevaluations@health.gov.au to discuss the suitability of their application. Please include 'Project Orbis' in the subject line of your email.

TGA considerations for participation in Project Orbis

TGA does not have specific criteria to determine whether applications are suitable for Project Orbis. Applications may be submitted through the standard, provisional or priority review pathways.

Sponsors are encouraged to consider the Priority review pathway should they want a shorter target evaluation timeframe and flexibility of the priority review process.

Dossier requirements

The dossier should comprehensively address all Australian specific requirements, including Module 1 and the RMP (if applicable), and must be submitted using the electronic Common Technical Document format (eCTD).

In addition, sponsors should submit the 'Sponsor Authorization Letter' (SAL) submitted to the FDA and the 'Assessment Aid - external site' document in their dossier.

For Type A and B Orbis applications (see below), it is generally expected that the sponsor submits a 'global dossier', i.e. the same data set for Modules 2-5 (noting country-specific aspects) as submitted to the FDA and other participating agencies. Any differences should be clearly indicated in the application cover letter.

Types of Project Orbis collaborations

There are three types of Project Orbis collaborations based on the level of alignment between the submission to the FDA and the POPs. TGA will determine which type of collaboration is possible based on the Orbis types and our existing workload and priorities.

^[1] Regulatory action at the TGA is unlikely to occur immediately after FDA action and, particularly for Type B and C, will follow the relevant assessment pathway (ie. the standard, priority, or provisional pathway).

^{[2] Contact the TGA regarding optimal timing for submission of Type C dossier.}

*Note that Orbis application types (A, B, and C) are not related to the TGA's application types used for fees associated with applications which are also identified by a letter, for example, Type A new chemical entity etc.

**Note that in general, the TGA will only consider applications of exceptional clinical significance for Type A Orbis.

Pre-submission procedures

Pre-submission meetings

Sponsors may request a pre-submission meeting should they feel it would benefit their submission. Where a pre-submission meeting is requested, standard TGA pre-submission processes and timelines will apply.

More information is available at:

• Pre-submission meetings with TGA

Priority review and provisional applications

Project Orbis applications do not automatically qualify for one of the TGA's expedited pathways. Separate applications for priority or provisional determination are required. Where applicable, sponsors should submit their priority review or provisional determination request at least 3 months in advance of filing. A valid determination must be held in order to access these pathways.

Sponsors are required to follow the existing guidance where a priority review or provisional determination is required.

More information is available at:

• Priority registration process
• Provisional approval pathway: prescription medicines

Application submission and assessment

Submission of applications

To maximise collaboration opportunities with the FDA, Type A and B Orbis applications will not be batched and the submission phase will generally align with the Priority registration process as follows:

• sponsors must use the PPF-only pre-submission phase option (the PPF-only option)
• TGA will process the PPF when it is received
• sponsors can submit their dossier at any time after lodging their application and will be encouraged to align submission dates as closely as possible with the submission to the FDA

Type C Orbis will follow the usual Prescription medicines registration process.

Assessment process

For Type A and B Orbis applications, POPs will collaborate on the assessment in response to the sponsor's position in the Assessment Aid documents.

For Type C Orbis applications, the TGA may undertake an assessment similar to that undertaken for the COR report-based process, however the target timelines for the evaluation process will follow the appropriate standard, priority, or provisional pathways.

In general, the FDA's Multidisciplinary Assessment Aid (and when applicable, the CMC Assessment Aid) will be used in lieu of a TGA evaluation report(s). The TGA will not provide these documents to the sponsor.

The TGA may prepare supplementary reports that summarise the review and cover Australia-specific aspects, particularly for Module 1 (including the Risk Management Plan) and Module 3. These reports will be provided to the Australian sponsor in the usual manner.

Process for handling regulator information requests

Project Orbis partners, including the TGA, will prepare their own Information Requests (IRs) for modules covered by the Orbis procedure based on their evaluation of the dossier.

For Type A and Type B Orbis applications:

• IRs will be shared with the participating agencies for review and comment before they are sent to the local applicant.
• The Australian sponsor will be requested to provide complete responses to all IRs from the FDA and other participating agencies as soon as possible via email to streamlinedsubmissions@health.gov.au and eSubmissions@health.gov.au
• The TGA will provide a proposed approach for the sponsor to submit consolidated sequences incorporating all responses to the IRs ('catch up sequences’) during the assessment phase.

For Type C Orbis applications:

• For IRs issued by the Project Orbis partners during the review, the Australian sponsor will be asked to follow a similar approach to that outlined above.
• Additionally, the Australian sponsor is asked to provide relevant IRs and responses from the FDA’s completed review (and the ongoing/completed reviews of the participating Orbis agencies) in Module 1.0.3 of the initial dossier. Please title and structure the documents according to Module, Regulator etc, as appropriate.

It is common for Project Orbis partners to issue 'rolling questions' throughout the assessment phase. Given the nature of the Project Orbis evaluation process, it is not possible to predict in advance when IRs will be issued during the evaluation period.

TGA will forward their Australian-specific IRs on Modules 1-5 to the Australian sponsor for response. The timing of this request and response period will follow the evaluation plan outlined in the Milestone 2 letter.

More information is available at:

• CTD Module 1: Administrative information and prescribing information for Australia - Applicable to applications received by the TGA from 9 February 2018

Role of each regulatory authority in the review process and decision phase

Project Orbis promotes collaboration amongst its partners. However, each participating regulatory authority remains fully independent with regard to the regulatory decision-making for each application under their jurisdiction.

This may result in differences in:

• the approval or rejection of marketing authorisation
• the content of the Product Information document
• the wording of the indications
• post-market surveillance requirements

The TGA will follow the usual decision phase as outlined in the Prescription medicines registration process. This may include seeking advice from the Advisory Committee on Medicines or other independent specialist advice.

Publication of regulatory decisions

Submissions reviewed under Project Orbis are subject to TGA's transparency initiatives. As with all other qualifying submissions, we will:

• add it to the list of prescription medicines applications under evaluation
• publish an Australian prescription medicine decision summary and Australian Public Assessment Reports for prescription medicines (AusPAR) when applicable.