International Recognition Procedure Guidance – September 2023

The MHRA hosted a webinar relating to the International Recognition Procedure (IRP) on Thursday 14th September. This webinar expanded on the MHRA guidance published on 30th August, which can be found by clicking the link below.
link to MHRA Guidance

This post captures the key findings from both the webinar and guidance page to help clients who are considering utilising this procedure to make informed choices.

Key Features of the International Recognition Procedure (IRP)

The IRP is intended to increase speed to market for products and enhance the desirability of the UK market, whilst meanwhile providing predictability and reliability to IRP eligible marketing applications.

IRP will be open to applicants who have already received an authorisation for the same product from one of MHRA’s specified Reference Regulators (RRs). The ‘same product’ is defined as having the same composition and pharmaceutical form, submitted by applicants belonging to the same company or group of companies, or who are ‘licensees’.

IRP replaces the EC Decision Reliance Procedure (the reliance procedure for products granted in EU/EEA via the Centrally Authorised Procedure) from 1st January 2024. However, the Mutual Recognition/Decentralised Reliance Procedure (MRDCRP, for products granted via Mutual Recognition or Decentralised Procedure) will be incorporated under the umbrella of IRP.

Applications submitted and validated before the end of 2023 will continue to be assessed under the reliance procedures in place at the time of submission.

Reference Regulators

The MHRA have utilised guidelines and practises of existing reliance/recognition procedures globally, in particular Singapore, Switzerland and Australia, to develop the IRP.

The list of MHRA’s RRs is as follows:

Country or Jurisdiction Regulatory Authority
Australia Therapeutic Goods Administration (TGA)
Canada Health Canada
Switzerland SwissMedic
Singapore Health Science Authority Singapore (HSA)
Japan Pharmaceuticals and Medical Devices Agency (PMDA)
United States Food and Drug Administration (FDA)
European Union European Medicines Agency (EMA) and Member State Competent Authorities (This includes approvals through the centralised, MRP/DCP and individual member state national routes)
Eligibility

Not all applications approved by a RR will be eligible for the IRP. The eligibility criteria for medicines are as follows:

  • Full standalone review performed by RR (basis of approval cannot have been another reliance).
  • Same product as reviewed by RR (as per above definition).
  • Only one single RR can be utilised during initial Marketing Authorisation Application (MAA) submission.
  • The following types of MAAs can be used for IRP:
    • Regulation 50: chemical and biological new active substances and known active substances.
    • Regulation 51, 51A and 51B: generic applications
    • Regulation 52, 52A and 52B: hybrid applications
    • Regulation 53, 53A and 53B: biosimilar applications
    • Regulation 55: new fixed combination product applications

Traditional herbal registrations, homeopathic and well-established use (bibliographic) applications are excluded from IRP for now, but this may be reviewed in the future.

Medical device equivalent procedures are still being developed under IRP.

IRP can also be used for post-authorisation procedures including line extensions, variations and renewals, whether the product was initially approved via standalone national or via one of the reliance routes (MRDCRP, ECDRP or IRP). Conversely, it is also acceptable to submit standalone national post-authorisation procedures, including variations, for IRP licences.

Timings and Submission Process
Initial Marketing Authorisation Application (MAA)

There are two recognition timetables for initial MAAs:

Recognition A: 60-day timetable (calendar days post validation)

Recognition B: 110-day timetable (calendar days post validation)

The Recognition A route will be open to applications that meet the criteria for IRP and do not meet any of the Recognition B criteria. The key features of both routes are captured here:

Recognition route A                                     Recognition route B
The RR approval of initial MAA must have been within the previous 2 years. The RR approval of initial MAA must have been within the previous 10 years.
60 calendar day timetable

No clock stop

110 calendar day timetable

D70 clock stop if required

Issues not resolved – Switches to Route B timelines Issues not resolved – Switches to national timelines
Manufacturing process must be the same as that approved by RR Changes in manufacturing process or analytical methods from that approved by RR.
Evidence of compliance with Good Manufacturing Practice (GMP) is required. Product is an ATMP, orphan products, 1st in class biologic or over the counter product.
Environmental Risk Assessment has been assessed by RR Many other criteria listed: International Recognition Procedure – GOV.UK (www.gov.uk)
If one of these apply, then route B must be used.

Suitability for Recognition A or B is determined by means of an eligibility form to be completed by the Applicant 6 weeks before the planned date of MAA submission.

A flowchart of the process can be found here:

Exact details of the eligibility form are yet to be provided.

During the first few months of the IRP, the MHRA will permit flexibility in switching to IRP from an existing national application, though in future, Marketing Authorisation Holders may be required to withdraw and resubmit their applications to IRP.

The submission should be aligned with the consolidated dossier as reviewed by the RR. For initial MAAs, the IRP submission should be as follows:

Dossier Format Electronic Common Technical Document (eCTD), EU Module 1 specification.
Language English.

Note, translated documents accepted but proof of acceptability of the translation required.

Cover Letter Additional information needs to be supplied in the cover letter or in the additional contents folder (full list available here)
Application Form EU electronic application form (eAF)
Product Information UK product information requirements still apply – the RR product information will need to be updated to suit MHRA format.

The final product information (or international equivalent) approved by the RR also needs to be included.

Orphan Note that if you have orphan designation in a RR you still need to apply separately to the MHRA for orphan designation.
Risk Management Plan (RMP) RMP following EU RMP template, GB/UK-specific annex can be supplied with approved EU RMP. (Note where the RR has not assessed the RMP or it is in a different format to the UK RMP, then recognition route B will apply.)
Paediatric Paediatric Investigation Plan (PIP) requirements still apply – compliance check needed at time of submission.
Responses The full responses of the applicant to RR questions during MAA procedure needs to be included.
Working Documents It is assumed that all iterations of RR assessment reports for the initial authorisation (and any major post-authorisation procedures approved by the RR e.g., significant variations, renewals) must be included in the working documents folder in English for the IRP, and apart from assessor’s name should be unredacted.

. The relevant MAA documents of the RR’s approval decision for each eligible RR are listed here. It is expected that these will also need to be filed in the working documents folder.

Product information texts also need to be included as per usual MAA submission requirements.

Nitrosamine Risk Assessment Required for each application.
Lifecycle Management

Lifecycle management (LCM) between the IRP and other reliance procedures remains similar, with only subtle differences. Unlike EC Decision Reliance Procedure (ECDRP), there is no deadline to submit a Lifecycle change within 5 days on RR approval. IRP can be used for line extensions, variations (Type IB, Type II), and all renewal applications. Normal published national timelines apply. However, for complex Type II variations (e.g., new indications), the IRP is expected to provide quicker timelines than the national route. It is recommended to use the same Reference Regulator (RR) as the original Marketing Authorisation Application (MAA) submission for variations, but it’s not a requirement if you can justify using another RR.

JensonR+ Assessment of IRP Guidance to Date

We welcome this detailed guidance ahead of the implementation of the IRP next year. There is clearly more information that needs to be published, but the information provided around eligibility criteria in particular is critical for strategic planning.

When considering utilising the IRP, the applicant should ensure that they have factored in the UK specific requirements we have detailed above. The application will need to be prepared by a team that is familiar with the UK medicines market and the documentation requirements needed for national applications.

We anticipate that the legal status of the medicine (Rx or OTC) will be a national decision by MHRA based on current market and treatment pathways and will not be influenced significantly by the RR’s opinion. However, the MHRA did not provide a clear position on this. It would be recommended to seek advice on possible legal status prior to applying if OTC status is key to your commercial success.

The exclusion of well-established use (bibliographic) applications from the scope of the IRP will concern a number of pharmaceutical companies that have utilised the European reliance procedures for these types of applications in the last few years. We also are concerned about how well-established use applications submitted under an existing reliance procedure that are pending assessment as of 1st January 2024 will be handled.

The current MHRA timelines for national applications (approximately 600 days at day of publication) will present a serious barrier for these type of applications in the future.

How JensonR+ can support you

We can support you by providing bespoke guidance and support with IRP. We will continue to keep on top of the latest regulatory intelligence to make sure you have the information needed to make informed choices.

If you are considering utilising the IRP, we can assess your product portfolio to ensure the candidates are eligible and identify any UK specific submission requirements that will need to be prepared ahead of submission. As an established regulatory consultancy in the UK we can prepare the application and represent you with all types of interactions with the MHRA.

Lauren Foster
Latest posts by Lauren Foster (see all)