The MHRA’s International Recognition Procedure: new medicine approval in 2–4 months

by | Nov 17, 2023 | Regulatory Affairs

Your Questions

Question 1

How is the United Kingdom’s (UK’s) Medicines and Healthcare Products Regulatory Agency (MHRA) expediting approvals with the International Recognition Procedure (IRP)?

Question 2

What does this mean for United States (US)-based pharmaceutical and biotechnology companies?

Our Answers

In a nutshell, the IRP uses the approval granted by the US Food and Drug Administration (FDA) following review of a New Drug Application (NDA) or Biologics License Application (BLA).

With this route (IRP), it is possible to be granted a marketing authorisation (MA) in the UK in as little as 60 days.1

How can this be achieved?

The UK’s MHRA has created several initiatives to approve new medicines efficiently and effectively.

One such recent innovation is the IRP, which aims to streamline and accelerate approval of new medicines by recognising approvals given by seven international ‘Reference Regulators’ (RRs) – including the FDA. This article outlines some of the key steps involved and ‘must know’ information for you.

The IRP will impact how US-based medicine developers should approach their development plan. With early planning and expert advice, the IRP should run smoothly, reaping three main benefits in the process.

What are the benefits of the MHRA’s IRP?

Benefit 1: Fast-track drug approval.

A 60-day review procedure for IRP-Route A and 110 days for IRP-Route B submissions.

To put this into perspective, here are the standard review timelines of the European Medicines Agency (EMA), FDA and MHRA.

Regulatory authorityReview time*
FDA6–10 months2
EMA210 days3 (7 months)
MHRA (not via IRP)210 days1(7 months)
MHRA IRP Route A60 days1 (2 months)
MHRA IRP Route B110 days1(3–4 months)

*These do not include clock stops to address questions from the authority. In some cases, the authority may give a positive outcome sooner – for example, at Day 180 for the EMA.

There are two routes in the IRP and if you’re not eligible for the 60-day IRP evaluation (via Route A),1 your medicinal product will be evaluated through the 110-day IRP evaluation (via Route B).1

With either route, the evaluation relies on a prior approval from an RR and is therefore significantly shorter than the standard MHRA national Marketing Authorisation Application (MAA) timeline of 210 days.1

Benefit 2: You don’t need to create a new MAA submission dossier.

Submitting a marketing application is a significant undertaking, involving a whole team of people over a period of up to 2 years (if all goes to plan).

Navigating the regulatory processes in the lead-up to the submission can be challenging and planning for your MAA or NDA/BLA submission should start 2–3 years before you submit.

Conversely, because the IRP recognises your original FDA approval, Modules 2–5 can be refined and reused for the MHRA submission.

The MHRA has even published the list of documents they want to review from your original NDA/BLA submission and FDA approval:1

Medical reviewChemistry review
Pharmacology reviewStatistical review
Non-clinical reviewClinical pharmacology biopharmaceutics review
Risk assessment and risk mitigation reviewAdministrative document and correspondence
Cross discipline team leader reviewOffice Director memo
Final FDA labelSummary review
Post marketing reviewApproval letter
Summaries of meetings with the FDA

Benefit 3: Springboard for marketing authorisation with the EMA.

While Brexit separated the MHRA from the EMA, it didn’t drastically change the MAA submission process or requirements between the regulatory authorities, and the MHRA generally accepts European guidelines and templates, including in relation to Module 1.

This means that getting approval for your medicine in the UK through the IRP could streamline an EMA MAA, as a result of having already prepared an EU-compliant Module 1.

 This approach not only expedites time to approval but also lays the foundation for an easier transition to apply for marketing authorization in the European Union (EU).

When will the MHRA IRP start?

As of the 1st of January 2024,1 the IRP will replace the European Commission Decision Reliance Procedure (ECDRP) which is a similar approval recognition procedure initiative, but for medicinal products that received approval via the EMA’s centralised procedure.

Routes to IRP approval

Route A: 60 days to approval

  • The FDA approved your product within the past 2 years,1
  • You have the same manufacturing process as the one the FDA approved, and
  • You don’t meet ANY of the criteria in Route B.

Route B: 110-days to approval

The MHRA’s IRP Overview contains a list of all the Route B criteria, including:1

  • The FDA approved your product within the past 10 years,
  • The FDA granted accelerated approval,
  • You’re going to file an Exceptional Circumstances application,
  • You’ve added manufacturing sites or made substantial changes to manufacturing that the FDA hasn’t assessed,
  • One or more of your manufacturing sites is not Good Manufacturing Practice (GMP)-certified,
  • There are UK-specific risk management aspects to your development,
  • The FDA stipulated you must conduct Post Authorisation Safety Studies (PASS),
  • Your pivotal data is taken from single-arm trials or real-world data,
  • You’re developing an advanced therapy medicinal product /plasma product/novel-technology/first-in-class new active substance,
  • You’re applying for orphan designation status,
  • Your safety/efficacy data cut-off was available after those assessed by the FDA.

The ‘fine print’ for a pharmaceutical or biotechnology company in the US

Specific aspects of your development programme and documentation must meet MHRA requirements, and as a US-based medicine developer, these requirements will most likely involve adding components to your Common Technical Document (CTD)—an entire Module 1 in fact.

Module 1 of the electronic CTD (eCTD) contains all the country-specific documentation relating to your medicinal product and the MHRA has stipulated—quite clearly—that specific aspects of your product’s development must comply with UK and/or EU guidelines, including:

Module 1 documents 4-6

  • The application form with Annexes,
  • Evidence of compliance with paediatric requirements,
  • Manufacturing authorisations,
  • GMP certificates,
  • Transmissible Spongiform Encephalopathies certificates,
  • Scientific advice correspondence,
  • Orphan application,
  • Invented name(s),
  • New active substance justification,
  • Batch release certification from the Qualified Person,
  • Summary of Product Characteristics + patient leaflet mock ups,
  • User testing documentation,
  • Risk Management Plan,
  • Environmental risk assessment, and
  • Pharmacovigilance system summary.

You may also need to revise some of the clinical modules (2.5, 2.7.3 or 2.7.4) to incorporate updates such as new data cuts and discussion, or discussion of UK-specific aspects of clinical practice. The quality (2.3 and 3) modules may require updates to align the content with the UK supply chain and the relevant pharmacopoeia, and to include the nitrosamine risk assessment.

Another component included in the Module 1 documents listed above, and similar to the EU, is a paediatric compliance check, which is a necessary component of validating your MAA.

You must include the outcome of a positive compliance check with an agreed Paediatric Investigation Plan (PIP) or a PIP waiver in Module 1 of the submission. This is a critical step in the submission of a UK MA, and you should plan this as early as possible.

Pediatric Study Plans (PSPs) required by the FDA may be similar in breadth and depth of content to a PIP. However, it will be necessary to establish whether more information is needed to address the requirements of the PIP. Additionally, the PIP must include UK-specific information regarding disease prevalence and incidence, as well as UK-specific diagnostic and treatment paradigms.

Our experts at Somerville Development Partners have over 20 years of experience compiling and submitting Module 1 of the CTD in the UK and EU.

How do you apply for the IRP?

Your company must be established as a legal entity in the UK, EU or the European Economic Area and the medicinal product must be the same as the medicinal product you had approved by the FDA.

However, you can apply for the IRP through a third party, so long as you can adequately demonstrate that all the legal obligations can be met.

MHRA International Recognition Procedure application process
MHRA International Recognition Procedure application process

The MHRA recently published more detailed supplementary information on different aspects of the IRP.

Summary

The MHRA’s IRP offers significant advantages for US-based pharmaceutical and biotechnology companies to fast-track an MA in the UK. As an initiative based on recognising your existing FDA approval, the IRP streamlines the approval process, saving you time and resources.

However, there are caveats.

The 60-day evaluation procedure is subject to strict eligibility criteria, meaning you’re more likely to find yourself on the 110-day evaluation timeline.

Also, there are UK-specific requirements for some aspects of the CTD, and this requires an understanding of the UK and EU regulatory landscape, approved precedents and treatment paradigms.

How Somerville Development Partners can help

We will:

  • Review your NDA/BLA submission package and identify documents that require UK-specific amendments,
  • Review your PSP and identify the changes required to satisfy a UK PIP submission,
  • Write and submit your PIP,
  • Write and collate all necessary Module 1 documents, and
  • Plan your UK and EU-specific regulatory strategy, including the MA submission strategy and agency interactions.

To ensure we support you effectively, we will build a foundational understanding of your product and data, so that we are able to act as a strategic partner and proactively look out for your best interests.

Get in touch

We welcome the opportunity to discuss scientific advice and regulatory strategy with you!

Nicole

Author

Nicole Brooks, Regulatory Consultant / Copywriter
Nicole@somerville-partners.com

References

1. Medicines and Healthcare Products Regulatory Agency (2023). International Recognition Procedure. Guidance. Available at: https://www.gov.uk/government/publications/international-recognition-procedure/international-recognition-procedure

2. Food and Drug Administration (2018). The Drug Development Process. Step 4: FDA Drug Review. Available at: https://www.fda.gov/patients/drug-development-process/step-4-fda-drug-review#:~:text=Directions%20for%20use-,FDA%20Review,whether%20to%20approve%20the%20drug

3. European Medicines Agency (2023). The Evaluation of Medicines, Step-by-Step. Available at: https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/evaluation-medicines-step-step#:~:text=The%20assessment%20of%20a%20marketing,of%20a%20marketing%20authorisation%20application

4. European Medicines Agency (2023). Module 1: Administrative Application Form. User guide for the electronic application form for a Marketing Authorisation. CMDh/332/2017, Rev.4. Available at: https://www.ema.europa.eu/en/documents/template-form/application-form-user-guide-electronic-application-form-marketing-authorisation_ma.pdf

5. European Medicines Agency (2021). EU Module 1 eCTD Specification. Version 3.0.4. Available at: https://esubmission.ema.europa.eu/eumodule1/EU%20M1%20eCTD%20Spec%20v3.0.4.pdf

6. Medicines and Healthcare Products Regulatory Agency (2023). Marketing Authorisation Pre-submission Checklist. Available at: https://assets.publishing.service.gov.uk/media/5a7eefdfed915d74e33f35c5/Pre-submission_checklist.pdf