Last updated: 18 October 2024
To see updates, click the’+’ sign below:
| Date | Update(s) |
|---|---|
| 18 Oct 2024 | 1) Section What application types are suitable for Project Orbis? updated to add the last papagraph about the UK. 2) New section In the UK, are authorisations granted via Project Orbis limited to GB or are they applicable UK wide? added. |
| 18 Mar 2023 | Section Further information added. |
This post is an attempt to provide some basic information on Project Orbis, an FDA initiative to facilitate faster access to innovative cancer therapies.
An important limitation in the writing of this post has been that the information on Project Orbis provided on the regulatory agency websites of the Project Orbis Partners, appears not to be always complete or even consistent in instances where it should be consistent.
Project Orbis is an initiative of the FDA’s Oncology Centre of Excellence (OCE) 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 multiple countries.
Source: TGA
In addition to the US FDA, Project Orbis partners (POPs) include the regulatory agencies of:
- Australia – Therapeutic Goods Administration (TGA) –
- Brazil – Agencia Nacional de Vigilancia Sanitaria (ANVISA)
- Canada – Health Canada
- Israel Ministry of Health – See link
- Singapore – Health Sciences Authority (HSA)
- Switzerland – Swissmedic
- United Kingdom – Medicines & Healthcare Products Regulatory Agency (MHRA)
Interestingly, Israel is not currently mentioned as a POP on the MHRA website.
Currently, Brazil, Israel and Singapore appear not to have a specific page dedicated to Project Orbis on their regulatory agency websites.
For the UK, any authorisations granted under Project Orbis will only be applicable in Great Britain as oncology medicinal products fall within the mandatory scope of the European Medicine Agency (EMA) centralised procedure that applies in Northern Ireland.
Project Orbis is intended for high-impact and clinically significant applications. Applications are generally expected to meet the criteria for “FDA Priority Review”
Any/all other requirements stipulated by each participating Project Orbis Partner must also be met.
Source: FDA (for the first sentence.)
Project Orbis promotes collaboration amongst its partners. The US FDA OCE is the primary coordinator for Project Orbis application selection and review and develops a core review document to facilitate discussions. 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 authorization
- the content of the labelling
- the wording of the indications
- post-market surveillance requirements
The FDA coordinates the selection of applications for Project Orbis.
- Either the FDA or the U.S. sponsor can propose an application for Project Orbis. The sponsor does so via the respective Office of Oncologic Diseases review divisions.
- Projects selected for Project Orbis concern high-impact and clinically significant applications.
- The FDA then sends a proposal to the project partners to confirm their:
- interest
- availability to participate
- Sponsors can select the number of Project Orbis Partners (POPs)partners to be included in a Project Orbis submission. They must select at least two partners, including the FDA.
- Once the POPs are identified, FDA confirms the global submission plan (GSP) via the U.S. sponsor.
- The Project Orbis working group for each submission will consist of the FDA and he participating POPs.
Sources: Health Canada, FDA
Project Orbis currently accepts the following application types:
- New Drug Applications (NDA)
- Biologics License Applications (BLA)
- Supplemental applications (new indications for previously approved therapies)
Note that the above application types are US FDA specific. Essentially, it means that applications eligible for Project Orbis include oncology products that are either:
- new active substances (new chemical entity or new biological entity applications)
- new indication applications
Applications submitted to the MHRA within a Project Orbis procedure must be new marketing authorisation applications (MAAs) or new indication applications (variations) for oncology products.
| Orbis Type | Applications timeframes | Collaboration model |
|---|---|---|
| Type A (Regular Orbis) | Applications should be submitted to Project Orbis Partners (POPs) within 30 days of submitting it to the FDA. Applications submitted with a greater than 30-day delay or a regulatory action greater than 3 months of the FDA action are termed Type B Orbis (Modified Orbis).* | Type A Orbis allows for maximal collaboration during the review phase, including: · sharing of review documents · exchanging requests for information · observe and participate in multi-country discussions · possibility of concurrent action with FDA* |
| Type B (Modified Orbis) | Applications submitted to POPs more than 30 days after the submission to the FDA. | Type B Orbis allows Project Orbis partners to: · receive FDA review reports · exchange or receive requests for clarification · observe and participate in some multi-country meetings · allows the possibility of concurrent review with FDA but no concurrent action* |
| Type C (Written report only Orbis) | Applications submitted to POPs after the FDA has taken regulatory action. | The FDA shares their completed review documents with the POPs. The POPs will not have concurrent review or concurrent action with the FDA. |
The source of most of the information above is the TGA website.
*Information as stated on the UK MHRA website.
- The FDA review team notifies the OCE global team about the proposed Project Orbis application.
- The OCE global team will then reach out to the Project Orbis Partners (POPs) to consider whether they would like to collaborate on the review of a particular application under Orbis
- Upon agreement by a POP to collaborate on the review of a particular application under Orbis, the FDA team will notify the sponsor company regarding their acceptance into Project Orbis and indicate which POPs will be involved.
- The sponsor company should then send the Sponsor Authorization Letter (SAL) for those countries.
- Although SALs are not be required for and POPs not participating in Project Orbis, if the sponsor company plans to submit future applications to these other agencies, having an SAL on file would allow FDA to release minimally redacted reviews to the non-participating POPs.
Source: FDA
Whilst the FDA encourages submission of an application to all interested Project Orbis Partners/agencies, the final decision remains with the sponsor.
Source: FDA
The sponsor would have to work with each participating POP to:
- determine whether pre-submission meetings are required
- confirm the regulatory requirements for each agency
- negotiate pre-submission and submission timelines.
Source: FDA
Project Orbis Partners have regularly scheduled conference calls to collaborate and discuss evaluation of the application. Ultimately, each agency conducts their own review and retains independence of their final regulatory decision, labeling negotiations, and timelines.
Source: FDA
- Each agency can issue information requests (IRs) to the sponsor company and/or local affiliate, but in order to minimise duplication, the Project Orbis Partners (POPs) share the IRs for comment and review prior to sending to the sponsor company/local affiliate.
- The sponsor teams should send the IR response(s) to all HAs that have received the application.
- Responses to POPs IRs, should be submitted to the FDA in Module 1.11 as a single file.
- Partner country regulatory agencies that have yet to receive the application should confirm if and how they would like to receive the IR responses that were submitted to the POPs participating in an application, prior to the dossier submission in that country(ies).
Source: FDA
- The U.S FDA together with the Australian Therapeutic Goods Administration (TGA) and Health Canada (HC) took part in the first Project Orbis collaborative review.
- In September 2019, the FDA announced the conclusion of a review conducted simultaneously with Australia and Canada.
- The review was for lenvatinib (Lenvima) in combination with pembrolizumab (Keytruda) for the treatment of patients with advanced endometrial carcinoma meeting certain criteria and disease progression following prior systemic therapy who were not candidates for curative surgery or radiation.
- The three regulatory agencies collaboratively reviewed this application, allowing for simultaneous review decisions in all three countries. The aim of this collaborative review was to identify any regulatory divergence across the review teams.
- While the product labelling differed in format for each country, only minor differences were noted across the labels.
- In Canada, the approved indication was slightly different than the approved indication in the United States and Australia.
- This was an FDA accelerated approval. Health Canada approved the application under conditional approval with conditions and TGA used its provisional approval with conditions of registration.
Source: FDA
When the Windsor Framework comes into force from 1 January 2025, authorisations granted through this programme will be applicable UK-wide. Until that date authorisations are limited to Great Britain only because medicinal products containing new active substances for the treatment of cancer fall within the mandatory scope of the European Medicine Agency (EMA) centralised procedure that applies in Northern Ireland.
Source: MHRA
Yes, there is a list available on the FDA website. It can be downloaded here. The list is updated quarterly.
On the UK MHRA website, a list of approvals in GB is provided under the heading ‘Publication’.
Other Project Orbis Partners also publish approvals information on their respective websites.
The US FDA updated the information available on Project Orbis on its website in March 2023. You can view it here.
Please share any comments or suggestions on this post via the feedback form.