We set out in a previous post that the UK Medicines and Healthcare products Regulatory Agency (MHRA) intends to introduce a new international recognition procedure (IRP) for medicinal products, whereby decisions taken in certain countries could be recognised by the MHRA to fast-track approval in the UK.
On 30 August 2023, the MHRA published detailed guidance on how it will use the IRP for medicinal products. The IRP will be open to applicants who have already received an authorisation for the same product from one of the MHRA’s specified Reference Regulators (RRs) in Australia, Canada, the European Union, Japan, Switzerland, Singapore and the United States. However, the MHRA retains the right to reject the IRP and conduct a full assessment if considered necessary.
This procedure will operate in parallel to the MHRA’s current national procedures, including the shortened 150-day timetable, offering applicants a range of authorisation routes depending on the status in other countries and type of application. The hope is that this will allow the MHRA to be able to use the decisions in other countries, while still being able to conduct its own assessment where necessary for the UK market.
The IRP will be available from 1 January 2024. However, until the Windsor framework is in place on 1 January 2025, discussed here, products falling within the scope of the EU Centralised Procedure can only be authorised in Great Britain (England, Scotland and Wales).
Applications eligible for IRP
The IRP can be used for the following types of marketing authorisation applications (MAAs):
- chemical and biological new active substances and known active substances
- generic applications
- hybrid applications
- biosimilar applications
- new fixed combination product applications
- the following are excluded: traditional herbal registrations, homoeopathic registrations, homeopathic national rules authorisations and bibliographic applications
The IRP can also be used for post-authorisation procedures such as line extensions, variations and renewals. However, variations that impact patient safety will be assessed in the context of UK clinical trials and an assessment through a national route may be required if there are UK-specific considerations.
It is not necessary to keep the licence aligned with the authorisation approved via the RR, and it is possible to use different RRs for different variations to the UK authorisation. However, this may need to justified to the MHRA, and the MHRA recommends that the same RR is used.
Eligible reference products
The reference product must have undergone a full and standalone review by the RR, and be authorised in the relevant country. The UK authorisation will therefore be necessarily behind that of the RR. The MHRA guidance sets out the list of documents that comprise a complete assessment for each RR and which must be included in the IRP application.
The IRP applicant should be the same company (or belong to the same group of companies) as the marketing authorisation holder (MAH) of the RR procedure to ensure the submission requirements are met as well as the MAH’s legal obligations.
Recognition procedure and timetables
There will be two recognition routes with a different (calendar day) timeline that starts once the IRP submission has been validated by the MHRA:
Recognition A: 60-day timetable from validation
- The RR approval must have been granted within the last 2 years.
- The manufacturing process in the UK must be the same as that approved by the RR, with evidence of compliance with Good Manufacturing Practice (GMP) at the time of IRP submission.
- Recognition A procedures will not include a clock stop. However, if major objections arise that cannot be resolved within 60 days, the timetable may change to a Recognition B route.
Recognition B: 110-day timetable from validation
- The RR approval should have been granted within the last 10 years.
- IRP applications will follow Recognition B if any of the additional criteria applies, whereby the application contains additional considerations meaning a longer period of assessment is required. For example, Recognition B will apply if the RR was granted an MA under conditional or exceptional circumstances (or international equivalent) or if a conditional or exceptional circumstances MA is sought in the UK. In addition, IRPs that include GB orphan drug designation applications, advanced therapy medicinal products and plasma products are only eligible for the Recognition B procedure. This procedure should also be used for applications to switch the legal status of a medicinal product.
- Recognition B procedures will include one clock stop at day 70, allowing the applicant up to 60 days to respond to any issues. If there are outstanding major objections at day 110, the timetable may revert to the standard national 210-day timetable.
The medicinal product must be classified as a medicinal product under the UK Human Medicines Regulations and the standard MHRA requirements for a UK marketing authorisation apply. Further national requirements include, for example:
- Paediatric requirements: if paediatric requirements are triggered, applicants will need to include the latest UK Paediatric Investigation Plan (PIP) or waiver, and the compliance check outcome documents in the IRP application.
- Nitrosamine risk assessment: applicants must provide a nitrosamine risk assessment in line with MHRA guidance before a new product can be approved.
- Generic and biosimilar applications: proposed indications and posology must be in line with the UK Reference Product, and applicants must ensure data and market exclusivity is not infringed. In the case of generic or hybrid medicines, if the comparator product used in the bioequivalence or therapeutic equivalence study was not sourced from the UK/EU/EEA market, the relevant MHRA guidance should be referred to.
The IRP will replace the current European Commission Decision Reliance Procedure, and the Decentralised and Mutual Recognition Reliance Procedures, both of which were introduced post-Brexit to allow the MHRA to rely on a decisions taken in the EU to grant a new marketing authorisation in the UK.