GovWire

Overview

Variations are either:

• an administrative change such as a change of company name and/or address
• a change to the characteristics of a product that can affect its quality, such as a change to its composition
• a change to the safety, efficacy or pharmacovigilance of the product

Changes are classed as major (type II) or minor. Minor changes are either type 1A or 1B.

You can apply for:

• a single change to one marketing authorisation (MA)
• multiple changes to one or more products and/or MAs

Marketing authorisation types

From 1 January 2021, the following market authorisation types are possible in the UK:

PL authorised for use in UK

• as a purely national UK-wide MA
• as part of an MR/DC procedure involving Northern Ireland as CMS, but a UK-wide MA

PLGB authorised for use in Great Britain only (England, Scotland and Wales)

• as a purely Great Britain national
• following conversion of a centrally authorised product (CAP)
• under the unfettered access route (MAH needs to be established in Northern Ireland and any product must access Great Britain via Northern Ireland as a qualifying Northern Ireland good)

PLNI - authorised for use in Northern Ireland only

• as a purely Northern Ireland national
• as part of an MR/DC procedure including Northern Ireland only

See our guidance on applying for a licence to market a medicine in the UK.

Variations procedures

The variation procedures follow for the different types of marketing authorisations from 1 January 2021 are essentially the same as before that date, where relevant, covered by the appropriate European or national legislation. The procedures depend on who is responsible for leading the assessment:

• MHRA for purely national variations
• RMS for MR/DC or Reference Authority for any worksharing variations

Centralised marketing authorisations are authorised for use in Northern Ireland only and any variations to these products will be managed by the EMA.

Until further notice the variations classification guideline, which is a fundamental component of the operation of the variations system, will continue to apply to all types of variations.

Reliance route

You can present variations to purely national MAs (PL, PLGB and PLNI) to the MHRA under the reliance route: following the acceptance of the same change(s) to a related or the same product as part of a European procedure. For example, a CAP variation or an MR/DC variation.

If you are taking this approach, you need to make it clear in the application and relevant evidence, declarations and supporting information. For example, where relevant, provide copies of assessment reports to support the submission. We will publish further in due course.

Minor variations

These are divided into 2 types: IA and IB.

Type IA change

Type IA changes have little or no impact on the quality, safety or efficacy of the product, for example administrative modifications such as:

• the manufacturers name
• a minor change to a control method
• deleting details of where the product is packaged

Type IA procedures are classed do-and-tell, where you should implement the change before you notify MHRA, ensuring that where relevant (non-immediate notification) you submit the application within 12 months. If the implementation period passes 12 months without a variation being made, you should submit a default Type 1B. The MHRA will take up to 30 days to process your application.

See the CMDh variations procedure guidance for the details of this type of change.

Type IAIN change (immediate notification)

Type IAIN is a sub-type of type IA and also classed a do-and-tell procedure where MHRA requires immediate notification within 2 weeks of the change being implemented. A minor change would usually be type IAIN if it interferes with MHRAs ability to continuously supervise the product.

All relevant conditions and documentation must be met for a Type IA/IAIN and confirmed in a copy of the classification guideline with either a tick or where not relevant, Not Applicable (N/A).

No requests for further information (RFIs) apply to Type IA procedures and there is no fee associated with a National Type IA/IAIN. A full fees list and further information about fees is available fees for licence variation applications.

See the CMDh variations procedure guidance for the details of this type of change.

Type IB change

If the change is more significant than a IA change but is not a type II change or an extension, it is considered a type IB change. MHRA must approve type IB changes before they are made to the product.

See the CMDh variations procedure guidance for the details of this type of change.

Once MHRA has all the necessary documents, it takes up to 30 days to process your initial application. You could be given a further 30 days to respond to any request-for-information letter, which for Type IB are called Notification with Grounds letters (NWG).

These are a conditional determination of a type IB variation, where the applicant has one opportunity to address any deficiencies or omissions.

There is a 30-day deadline to respond to an NWG. Otherwise, we will withdraw or refuse the variation. This also applies if we have received only a partial response by the 30-day deadline.

Major variations (type II)

These changes are more complex and may have a significant impact on the quality, safety and/or efficacy of the product.

MHRA needs to approve major variations before they are made. One example of a major change is adding a new therapeutic indication to a product or updating the current indication (the medical needs the product is used for).

See the CMDh variations procedure guidance for the details of this type of change.

Once MHRA has all the documents, it will take 30, 90 or 120 days to assess your application, depending on how urgent or complex the changes are, excluding time taken to answer questions.

Once MHRA has all the documents, it will take 22-days, (reduced timetable), 60-days (standard timetable) or 90-days (extended complex timetable) to assess your application depending on how urgent or complex the changes are, excluding time taken to answer questions.

With questions (RFIs), assessment timeframes become 30, 90 and 120 days respectively.

The below tabulates the various stages for each type II timetable

A reduced Type II procedure (reduced from 60 days to 30) is for variations concerning safety issues and is agreed between the MHRA and the Marketing Authorisation Holder (MAH) and in general will be changes to the SmPC, requested following the assessment of a Periodic Safety Update Report (PSUR) or at the request of the MHRA Pharmacovigilance Unit.

You should make requests for a reduced timescale to variationqueries@mhra.gov.uk.

All other forms of submission will be rejected.

Common invalidation errors and pre-submission checklist

We strongly advise you to use our 