MHRA introduces new procedures for Marketing Authorisation Applications

Giannis Tsogkas, Senior Manager, Regulatory Affairs, examines the changes and their implications.

Transition from previous procedures

The IRP replaces the European Commission Decision Reliance Procedure (ECDRP) and the Mutual Recognition/Decentralised Reliance Procedure (MRDCRP).

Applications submitted under ECDRP and MRDCRP before January 1st will continue to be processed under the superseded procedures.

Expanded Reference Regulators (RRs)

The IRP allows the MHRA to rely on assessments and MAA approvals the Applicant has received from specified Reference Regulators (RRs).

RRs approved by the MHRA[1] now include the EMA, individual EU member states including Norway, Iceland, and Lichtenstein (either national or MR/DC approved products), the Australian Therapeutic Goods Administration (TGA), the United States Food and Drug Administration (FDA), Health Canada, SwissMedic, the Singapore Health Science Authority (HSA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA).

This move expands the RRs beyond the previously accepted EMA and EEA member states.

Eligibility criteria for IRP

The IRP is available for new UK MAAs of the same product (having the same qualitative and quantitative composition, and the same pharmaceutical form) as authorized by the RR, and for Applicants belonging to the same company or group of companies as the Marketing Authorisation Holder (MAH) approved by the RR.

The Applicant must be established in the UK or the EU.

Furthermore, the reference Marketing Authorisation (MA) must have RR approval based on a full regulatory assessment. Assessments using other reliance pathways or applications for emergency approvals cannot be used to support an IRP.

Scope of applications

The IRP applies to full, generic, hybrid, biosimilar, and fixed combination applications. However, it cannot be used for well-established use applications, Homeopathic registrations, or Traditional Herbal medicines.

Post-authorization activities

Additionally, the IRP extends to post-authorization activities, including line extensions, variations, and renewals. The MHRA recommends using the same RR for product lifecycle activities, although more than one RR can be used where justified.

Recognition routes

The MHRA has established two recognition routes - Recognition A and Recognition B.

Both have specific eligibility criteria with different supporting documentation requirements and review/approval timetables.

• Recognition A: To be eligible for Recognition A, the manufacturing process in the MAA dossier must be the same as the one approved by the RR, all manufacturing sites must be GMP certified, the MAA approval by the RR was granted less than 2 years before the UK MAA and must not include any of the Recognition B criteria.

Recognition A will be concluded within 60 days. The process starts on the date the MHRA positively validates the Application, and no clock-stop option is available.

• Recognition B: This option is applicable if the MAA approval in the RR was granted less than 10 years before the UK MAA or where any of the Recognition B eligibility criteria apply. These criteria include:
  • Whether the UK MAA dossier details additional manufacturing sites or there are differences in the manufacturing process or analytical procedures compared to the reference dossier
  • Whether the UK application proposes a different shelf life or different storage conditions compared to the reference dossier
  • Whether the application refers to an Orphan drug or an ATMP.

Recognition B procedures will be concluded within 110 days, with an optional clock stop at Day 70 where the Applicant can address MHRA’s queries within 60 days. If by Day 110 there are still issues to be resolved, the IRP will then follow a national procedure timetable (210 days).

It should be noted that the Recognition B timetable will be applied to Recognition A procedures in cases where outstanding issues cannot be resolved within the Recognition A timetable.

Application Process

For initial MAAs only, the Applicant completes an electronic Eligibility Form, determining if the application meets Recognition A or B criteria or if the application requires a preliminary assessment from the MHRA before a decision can be made. The Eligibility Form and specific documents based on the chosen RR must be included in the eCTD dossier submitted to the MHRA.

At a minimum, these include the list of questions received and the responses provided, the approval letter, the approved Product Information, and summaries of any pre-submission or scientific advice meetings held during the assessment of the application by the RR.

Relevant UK national requirements must also be fulfilled (e.g., paediatric requirements, Risk Management Plan, Environmental Risk Assessment, Good Manufacturing Practice).

Considerations for Applicants

Reduced assessment timetables, lower fees for Recognition A and B compared to a purely national procedure, and the expanded list of acceptable RRs should be considered when planning the submission strategy to the MHRA.

For further details, refer to the International Recognition Procedure documentation.

References:

1. International Recognition Procedure
2. Supplementary Information
3. Eligibility Checker
4. eCTD Guidance
5. Current MHRA Fees

[1] RRs approved by the MHRA[1] as of January 5^th, 2024.