Project Orbis

1.Overview

The programme provides a framework for concurrent submission and review of oncology products among international partners. It aims to deliver faster patient access to innovative cancer treatments with potential benefits over existing therapies.

Project Orbis is coordinated by the US Food and Drug Administration (FDA).(FDA). Alongside MHRA,Alongside MHRA, it involves the regulatory authorities of:

• Australia (Therapeutic Goods Administration (TGA))(TGA))
• Canada (Health Canada)
• Singapore (Health Sciences Authority (HSA))(HSA))
• Switzerland (Swissmedic)
• Brazil (Agência Nacional de Vigilância Sanitária (ANVISA))(ANVISA))
• Israel (Ministry of Health)

Project Orbis Partners (POPs) may propose products for inclusion in the scheme. Each country remains fully independent on their final regulatory decision.

2. Products eligible for Project Orbis

Applications submitted to the MHRA withinthe MHRA  within a Project Orbis procedure must be new marketing authorisation applications (MAAs) or new indication applications (variations) for oncology products. 

WhenAuthorisations the Windsor Framework comes into force from 1 January 2025[1] authorisations granted through this programme will be applicable UK-wide. in Until that date authorisations are limited to Great Britain only becauseas oncology 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. 

You can find out more fromon our the UK-wideEMA licensing guidancewebsite.. 

The FDA coordinatesThe FDA  coordinates the selection of products that will be included. Initial enquiries that MHRA receive the MHRA receive will be referred to the FDA.the FDA. Submissions do not require an Innovation Passport designation for inclusion in the Project Orbis programme, though applicants can also apply for the Innovation Passport within the Innovative Licensing and Access Pathway (ILAP)(ILAP) if they wish to.  

You can find out more in our  our  guidance about ILAPabout ILAP. 

Submissions will need to meet the FDA’sthe FDA’s clinical criteria for priority review. 

If you wantwant MHRA to the MHRA to submit a product or new indication for the Project Orbis programme, email email  Orbis-MHRA@mhra.gov.ukOrbis-MHRA@mhra.gov.uk  with  with a summary of the product explaining how you meet the eligibility criteria. Thecriteria. MHRA  will arrange a meeting with you to discuss eligibility. 

3.Types  Types of submissions

There are three different types of submission depending on the timelines between the FDA and thethe MHRA.FDA and MHRA.

Type A

Applications should be submitted concurrently or near-concurrently (within 30 days) to the FDA andFDA the MHRA.and MHRA. These are termed Type A Orbis (Regular Orbis) and allow for maximal collaboration during the review phase and the possibility of concurrent action with thewith FDA.FDA.

Type B

Applications submitted with a greater than 30-day delay or a regulatory action greater than 3 months of the FDA actionthe FDA action are termed Type B Orbis (Modified Orbis) and allow the possibility of concurrent review with FDA butwith FDA but no concurrent action.

Type C

If the FDA hasthe FDA has already taken regulatory action, a Type C Orbis (Written Report Only Orbis) will allows the FDA tothe FDA to share their completed review documents with the MHRA but there is no concurrent review or action with the FDA.FDA.

Table 1:

Project Orbis Types

Orbis Type	Type A	Type B	Type C
Submission Timeline	Application submission to POPs ≤ 1 month of FDA submissionof FDA submission	Application submission to POPs > 1 month of FDA submissionof FDA submission	Any time after FDAafter submission[2]FDA submission2
Submission overlaps with FDAwith FDA	Expected	Expected	Permitted[2]Permitted2
Sharing of FDA reviewsof FDA reviews	Yes	Yes	Yes
Multi-country review meetings (POP TCONs)	Yes	Yes	No
POP Attendance at FDA reviewat FDA review meetings	Yes	Yes	Unlikely
Concurrent review with FDAwith FDA	Expected	Possible	Unlikely
Near concurrent action with FDAwith FDA	Possible[3]Possible1	No[3]No1	No[3]No1

[2] Dependent¹ onRegulatory Projectaction Orbisin Partnerother (POP)jurisdictions guidelines.is Contactunlikely specificto POP(s)occur regardingimmediately optimalafter timingFDA foraction submissionand ofwill Typefollow Crespective dossier.health authority timelines.

[3]²Dependent Regulatoryon actionProject inOrbis otherPartner jurisdictions(POP) isguidelines. unlikelyContact tospecific occurPOP(s) immediatelyregarding after FDA actionoptimal andtiming willfor followsubmission respectiveof healthType authorityC timelines.dossier.

4.Inclusion  Inclusion of the MHRA inthe MHRA in a Project Orbis Procedure

Once a product or new indication has been identified for inclusion in Project Orbis, FDA willOrbis, FDA will contact the MHRA tothe MHRA to request their interest in involvement. If the request is provisionally accepted by the MHRA,the MHRA, the parent US Company will be advised and should provide details of the local UK affiliate to the MHRA.  to MHRA.  

MHRA participationMHRA participation is contingent on agreement with the UK affiliate.

5.  FeesFees

You will need to pay the relevant national authorisation fee for any applications made to Project Orbis.

Find out more about about our fees.

6.Assessment  Assessment process and expert advice

The multidisciplinary assessment teams will carry out the assessment of the application.

The assessment process will include consultation with the MHRA Expertthe MHRA Expert Advisory Groups and the Commission on Human Medicines, as required.

7.  PublicationPublication

The granting of a Great Britain marketing authorisation or new indication through Project Orbis will lead to publication of a Great Britain Public Assessment Report.

8.Overview  Overview of Orbis Project approvals

Table 2

Product	Type of Project	New Indication	Grant Date
Tagrisso	Variation to add a new therapeutic indication	Tagrisso as a monotherapy is indicated for the adjuvant treatment after complete tumour resection in adult patients with non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations	06/05/2021
Trovdelvy	Initial licence application	TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior lines of systemic therapies, at least one of them given for unresectable locally advanced or metastatic disease (see section 5.1).	08/09/2021
Lorviqua	Variation to add a new therapeutic indication	Lorviqua as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor.	23/09/2021
Lumykras	Initial licence application	LUMYKRAS is indicated as monotherapy for the treatment of adult patients with KRAS G12C mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), who have progressed on, or are intolerant to, platinum-based chemotherapy and/or anti PD-1/PD-L1 immunotherapy.	08/09/2021
RYBREVANT	Initial licence application	RYBREVANT as monotherapy is indicated for treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) Exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy.	15/11/2021
TEPMETKO	Initial licence application	TEPMETKO is indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations.	24/09/2021
Tecentriq	Variation to add a new therapeutic indication	Tecentriq as monotherapy as adjuvant treatment following complete resection for adult patients with Stage II to IIIA (7th edition of the UICC/AJCC-staging system) non-small cell lung cancer (NSCLC) whose tumours have PD-L1 expression on ≥ 50% of tumour cells (TC) and whose disease has not progressed following platinum-based adjuvant chemotherapy.	27/01/2022
Jakavi	Variation to add a new therapeutic indication	Graft versus host disease (GvHD) - Jakavi is indicated for the treatment of patients aged 12 years and older with acute graft versus host disease who have inadequate response to corticosteroids. Jakavi is indicated for the treatment of patients aged 12 years and older with chronic graft versus host disease who have inadequate response to corticosteroids. (see Section 5.1)	23/03/2022
EXKIVITY	Initial licence application	EXKIVITY as monotherapy is indicated for the treatment of adult patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutation-positive locally advanced or metastatic non-small cell lung cancer (NSCLC), who have received prior platinum-based chemotherapy	17/03/2022
Welireg	Initial licence application	Welireg is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for VHL associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumours (pNET), and for whom localised procedures are unsuitable or undesirable.	31/05/2022
Kimmtrak	Initial licence application	KIMMTRAK is indicated as monotherapy for the treatment of human leukocyte antigen (HLA)-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.	07/06/2022
REZUROCK	Initial licence application	Rezurock is indicated for the treatment of patients aged 12 years and older with chronic graft-versus-host disease (chronic GVHD) who have received at least two prior lines of systemic therapy.	07/07/2022
OPDIVO	Variation to add a new therapeutic indication	Neoadjuvant treatment of NSCLC OPDIVO in combination with platinum-based chemotherapy is indicated for the neoadjuvant treatment of resectable (tumours ≥ 4 cm or node positive) non-small cell lung cancer in adults	16/08/2022
NUBEQA	Variation to add a new therapeutic indication	metastatic hormone‑sensitive prostate cancer (mHSPC) in combination with docetaxel (see section 5.1)	22/11/2022
IMFINZI	Variation to add a new therapeutic indication	IMFINZI in combination with gemcitabine and cisplatin is indicated for the first line treatment of adults with locally advanced, unresectable, or metastatic biliary tract cancer (BTC).	25/01/2023
Tabrecta	Initial licence application	Tabrecta, as monotherapy, is indicated for the treatment of adult patients with unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) with a MET exon 14 skipping mutation.	27/03/2023
Jemperli	Variation to add a new therapeutic indication	JEMPERLI is indicated in combination with platinum-containing chemotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/ microsatellite instability high (MSI H) primary advanced or recurrent endometrial cancer (EC) and who are candidates for systemic therapy.	02/10/2023
Opdualag	Initial licence application	Opdualag is indicated for the first line treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older.	27/12/2023
Truqap	Initial licence application	Truqap is indicated in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative (defined as IHC 0 or 1+, or IHC 2+/ISH-) locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations following recurrence or progression on or after an endocrine based regimen (see section 5.1).	17/07/2024

Further details on the approval can be found on the the Public Assessment Report.

The page will be updated on each Orbis project approval.

9.Find Furtherout informationmore

ForIf you would like any more information or have any questions pleaseyou email can email Orbis-MHRA@mhra.gov.ukOrbis-MHRA@mhra.gov.uk.

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[1] Subject to the UK providing written guarantees to the European Commission as provided for in Article 8 of EU Regulation 2023/1182 and following the entry into force and application procedure provided for in Article 14