On 30 August 2023, the UK’s Medicines and Healthcare products Regulatory Agency (“MHRA”) published detailed guidance on its recently announced new International Reliance Procedure (“IRP”) (see our prior blog and audiocast). The IRP will apply from 1 January 2024 and will replace and significantly expand on existing EU reliance procedures to apply to authorizations from 7 key international regulators. As such, the “IRP will allow the MHRA to take into account the expertise and decision-making of trusted regulatory partners for the benefit of UK patients.” The IRP has obvious implications for a company’s international regulatory filing strategy and will potentially fast-track the approval and access of innovative medicinal products in the UK
What is the IRP?
From 1 January 2024, the European Commission (“EC”) Decision Reliance Procedure will be replaced by, and the Mutual Recognition/Decentralized Reliance Procedure rolled-up into, the new IRP. The IRP is a new procedure that will allow medicinal products approved in other jurisdictions that meet certain criteria to undergo a fast-tracked MHRA review to obtain and/or update a marketing authorization (“MA)” in the UK or GB.
Applicants that have received an authorization for the “same product” from one of the following specified international “Reference Regulators” (“RRs”) can use the IRP:
- Therapeutic Goods Administration (“TGA”) (Australia)
- Health Canada (Canada)
- Swiss Medic (Switzerland)
- Health Science Authority Singapore (“HSA”) (Singapore)
- Pharmaceuticals and Medical Devices Agency (“PMDA”) (Japan)
- Food and Drug Administration (“FDA”)
- European Medicines Agency (“EMA”) and national competent authorities (European Union).
The UK, Australia, Canada, Singapore and Switzerland participate in an “Access Consortium,” which share work during scientific advice and application processes. Access Consortium approvals that did not include the MHRA can also be used in the IRP.
The RR authorization must be based on a full and standalone assessment of the relevant medicinal product to support the IRP. However, conditional and exceptional circumstances MAs (or international equivalents) can support IRP applications.
What types of MAAs can applicants submit under the IRP?
The IRP is broad in scope; applicants can submit the following types of marketing authorization applications (“MAAs”):
- new active substances and known active substances;
- generic applications;
- hybrid applications;
- biosimilar applications;
- new fixed combination product applications
The IRP is also not limited to initial MAAs. The procedure can be used throughout the lifecycle of a product for post-authorisation procedures including line extensions, variations and renewals. An applicant also has the flexibility to obtain an initial MA using the IRP and then use national post-authorization procedures.
Excluded from the scope of the IRP are: bibliographic applications; traditional herbal registrations; homoeopathic registrations (Simplified Registration Scheme); and homeopathic national rules authorisations (National Rules Scheme).
How long will the IRP take?
There are two mutually exclusive Recognition Routes in the IRP applicable to initial MAAs:
- Recognition A is a 60-day timetable with no clock-stops. To use this route the RR approval must have been granted in the last two years, the manufacturing process must be the same as approved by the RR and there must be evidence of GMP compliance. Also, the application must not meet any criteria of Recognition B. If there are any unresolved major objection at day 60, the timetable may revert to Recognition B.
- Recognition B is a 110-day timetable. It has one clock-stop at day 70. If there are any major objections that are unresolved at 110-days, then the application will revert to the standard MHRA 210-day timetable. Recognition B applies if the RR approval was granted in the last 10 years and the IRP application meets any one of the listed 24 criteria in the MHRA guidance. These include, for example: that the RR granted a conditional or exceptional circumstances MA (or equivalent); the applicant is seeking a conditional or exceptional circumstances MA in the UK/GB; the product contains a first-in-class new active substance; the pivotal clinical data are from single arm studies and/or including real world data; and/or where an IVD is required for correct use, the IVD is not CE/UKCA marked.
The guidance also highlights that certain products will only be eligible for Recognition Route B, including: orphan medicinal products, advanced therapy medicinal products, products where the Environmental Risk Assessment has not been assessed by the RR, products where any manufacturing site is a new site (i.e., not reviewed by the RR) and fractionated plasma products. These align with the listed Recognition B criteria.
Are there any Applicant eligibility criteria?
An applicant using the IRP must be established in the UK or EU/EEA and should be the same company or part of the same group as the holder of the authorization obtained from the RR. The MHRA will allow a third party, where written assurance is provided that they can meet the requisite legal obligations.
Six weeks before the intended submission date, an applicant should submit an online eligibility form to confirm suitability for Recognition Route A or B. This form should be submitted with the dossier. Applicants should submit their applications via the MHRA’s online Human Medicines Portal. The MHRA’s guidance details the documentation that has to be included, including a cover letter and the mandatory documents for each RR.
Are there any additional UK-specific requirements?
A medicinal product subject to an IRP application must satisfy the definition of a medicinal under the UK’s Human Medicines Regulations 2012. Additionally, generic and biosimilar applications must be consistent with the UK Reference Product’s indication and posology. However, applicants should refer to the MHRA’s guidance on comparator products in bioequivalence and therapeutic equivalence studies, if the comparator was not sourced from the UK/EU/EEA.
Applicants also need to comply with UK-specific requirements, for example, requirements relating to UK paediatric requirements, risk management plans, nitrosamine risk assessments, compliance with British Pharmacopoeia or European Pharmacopoeia monographs (unless justified) and having an Active Substance Master File if full information on the active substance is not otherwise included in Module 3.
In addition, generic and hybrid MAs that use comparator products sourced outside of the UK/EU/EEA can only obtain a UKMA(GB) until new provisions of the Windsor Framework concerning medicinal products take effect on 1 January 2025.
Will the IRP apply in Northern Ireland?
The IRP will apply for Northern Ireland. Currently, pursuant to the Windsor Framework products that have an EU central authorization can only be authorized in Great Britain (i.e., obtain a UKMA(GB), which is only valid in Great Britain). Once new provisions of the Windsor Framework concerning medicines take effect on 1 January 2025, recognition of an EU MA would result in an MA valid throughout the UK.
 “Same product” is defined as products having “the same qualitative and quantitative composition (active substance(s) and excipients), and the same pharmaceutical form, from Applicants belonging to the same company or group of companies or which are ‘licensees’.”