The International Recognition Procedure (IRP): Does it offer a post-Brexit boost for speedier drug approvals in the UK?

Following Brexit, the UK introduced several regulatory schemes to address access challenges after leaving the EU's Centralised Procedure.

These include Project Orbis, the ACCESS Consortium, ILAP, and the EC Decision Reliance Procedure (ECDRP). From 1st January 2024, the International Recognition Procedure (IRP) replaced the ECDRP, incorporating the Mutual Recognition/Decentralised Reliance Procedure (MRDCRP) into its framework. How does this change impact manufacturers, and can the IRP truly streamline access to the UK market by leveraging approvals from global Reference Regulators (RRs)?

The IRP is designed for applicants who have already obtained a Marketing Authorisation (MA) from one of the MHRA’s designated Reference Regulators (RRs). By leveraging the expertise and decisions of these regulators, the MHRA conducts a targeted assessment, streamlining its review and approval process.

Recognised RRs include the Therapeutic Goods Administration (Australia), Health Canada, SwissMedic, the Health Sciences Authority (Singapore), the Pharmaceuticals and Medical Devices Agency (Japan), the FDA (USA), and the EMA (European Union).

There are two possible recognition pathways for the new IRP marketing authorisation application (MAA):

How does the IRP compare with other schemes in the UK?

The IRP significantly accelerates the approval process with timelines of 60 days for Route A and 110 days for Route B, much faster than the MHRA's traditional 210-day schedule for MAAs, thereby enhancing the availability of new medicines in the UK by swiftly assessing and determining their approvability.

Additionally, the UK participates in international collaborative initiatives such as Project Orbis and the Access Consortium. Project Orbis allows simultaneous reviews by agencies like the FDA and MHRA, speeding up and harmonising decisions, particularly in oncology. The Access Consortium facilitates shared responsibilities among member countries for safety, efficacy, and quality evaluations, aiming to shorten approval times and enhance patient access to new medications. The effectiveness of these pathways in terms of faster MAAs can, however be variable and difficult to predict.

The Innovative Licensing and Access Pathway (ILAP) integrates discussions on the route to marketing authorisation and reimbursement, focusing on early dialogue and possible parallel processes with both regulatory and HTA bodies.

The Early Access to Medicines Scheme (EAMS) grants patients access to unlicensed medicines for severe or life-threatening conditions when no adequate treatments exist, providing early access to promising new therapies without fixed timelines before formal approval.

Compared to other regulatory frameworks in the UK, the IRP offers a notably faster route for drug approvals, enabling manufacturers to achieve regulatory approval within 110 days if the drugs have already been approved by any of the recognised RRs.

Can the IRP indeed be a pathway for accelerating regulatory approval in the UK compared to the EU?

The UK government states that the IRP, in collaboration with global regulators including the FDA, is designed to expedite the introduction of life-saving medicines in the UK, capitalising on Brexit freedoms. Since Brexit, the UK has progressively moved away from the EMA's regulatory framework. The IRP presents a new opportunity for manufacturers, enabling them to secure regulatory decisions within 110 days after obtaining FDA approval. With this expedited timeline, the MHRA has the potential to grant marketing authorisation ahead of the EMA.

This was demonstrated with leniolisib, a treatment for a rare condition, which received FDA approval in March 2023 and was subsequently approved by the MHRA on 25th September 2023 via the IRP. This marked the first instance of the MHRA granting approval following FDA endorsement. Meanwhile, the EMA has been reviewing the submission for leniolsib since 27th October 2022 and has yet to make a final decision. Another case example is givinostat, which obtained regulatory approval in the US in March 2024 and in the UK in December 2024 via the IRP, whereas the EMA is still reviewing the submission, with a CHMP opinion anticipated in the first half of 2025.

The 110-day IRP timeline enables innovative drugs to be launched in the UK faster than the typical difference in review times between the EMA and FDA

The FDA is often the first to approve innovative drugs, with manufacturers typically choosing to submit their applications to the FDA initially. According to research by FRIENDS of Cancer Research, from January 2003 to December 2024, out of 152 novel oncology drugs approved by both the FDA and EMA, 112 were submitted first to the FDA - typically about two months prior to their submission to the EMA. Notably, 94% (143 out of 152) of these drugs received FDA approval before EMA approval.

The earlier approval of innovative drugs by the FDA compared to the EMA is not just because manufacturers often submit their applications first to the FDA, but also due to differences in review periods between these agencies. In the research conducted by FRIENDS of Cancer Research, the FDA's median review time was significantly shorter, averaging 207 days, while the EMA's average review time was about 422 days, although the agency typically aims for a 210-day approval process. This discrepancy in review times contributes to the faster approval rate observed with the FDA.

When manufacturers choose to submit their IRP applications after obtaining FDA approval, they generally undergo assessment under Procedure B. This procedure allows up to 110 days for the MHRA to make a decision, and may include the possibility of a time clock pause, which can extend the review process to the standard national 210-day timetable.

Despite this potential delay caused by the clock pause, the IRP has proven effective since its launch on 1st January 2024. By January 2025, the MHRA had approved 453 IRP submissions, comprising 273 Type IB and 180 Type II applications, with 98-100% of these approvals granted within the statutory timeframe (Type II IRP variations and Type IB IRP variations, respectively). This indicates that the MHRA has efficiently managed most IRP applications within the planned 110-day period.

The IRP’s potential 110-day review timeline suggests that innovative drugs could be approved in the UK before the EMA (see figure below). Given the significant difference in average review times between the FDA and EMA, which exceeds 200 days, this could position the UK as a faster alternative for getting innovative treatments to market compared to the EU/ EMA.