UK MHRA Guidance: Apply for a Variation to your Marketing Authorisation

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) updated the section 3.1: 'Implementation of new guidelines' through its official guidance titled Medicines: Apply for a Variation to your Marketing Authorisation — a key reference for MA holders operating in the UK regulatory ecosystem.

A variation is any change to the terms of an existing marketing authorisation, from simple administrative updates to changes that may affect quality, safety or efficacy.

These changes must be formally assessed and approved (except for certain “do‑and‑tell” minor changes) so that the authorised product always reflects current manufacturing, control and clinical information.​

Variations are grouped into minor changes (Type IA and IB), major changes (Type II), and extensions where the impact is so great that a new MA (line extension) is required. The classification drives the data needed, the fee, the assessment timeline and whether the change can be implemented before or only after MHRA approval.

• Type IA variations are minor changes expected to have minimal or no impact on quality, safety or efficacy, such as simple administrative updates or certain minor quality changes. They follow a “do‑and‑tell” model, where the change is implemented first and then notified to MHRA, usually within 12 months unless an immediate notification is required.​

• Type IAIN (“immediate notification”) is a sub‑class of Type IA for changes that must be reported promptly after implementation, with about two weeks regarded as reasonable for submission. Many non‑urgent Type IA changes are bundled into an annual update per MA, submitted within a defined window after first implementation.​

• Type IB variations are minor but not clearly Type IA and are also not major (Type II) or extensions. They often cover quality‑related changes such as adjustments to manufacturing processes or testing that need prior assessment but are not expected to fundamentally alter benefit–risk.​ MHRA usually has up to 30 days to assess a valid Type IB variation, excluding applicant response time to questions. If MHRA issues a Notification with Grounds and the MAH fails to address all points within 30 days, the variation can be refused.​

• Type II variations are major changes that could significantly affect quality, safety or efficacy, for example new indications, key manufacturing changes or important safety updates to the SmPC. These require comprehensive supporting data and must be approved before the company implements the change.​

  Assessment timelines range from accelerated 30‑day procedures for agreed urgent safety changes to standard 60‑ or 90‑day schedules for more complex cases, not counting the MAH’s response time. Urgent safety‑related Type II variations often follow Periodic Safety Update Report assessments or specific pharmacovigilance requests

The UK has embedded the EU Variations Regulation (EC) No 1234/2008, as amended, into the Human Medicines Regulations 2012, so the core variation framework remains aligned but applied under UK law. Updated EC guidance on variation categories and documentation starts to apply from 15 January 2026, with transitional arrangements until then.

Until mid‑January 2026, MAHs continue to use the existing EU variations classification guideline to decide whether a change is Type IA/IAIN, Type IB, Type II or an extension, and to identify the applicable conditions and documents. From 15 January 2026, new variation guidelines on categories and documentation come into effect, except for certain COVID‑19 vaccine changes that follow dedicated rules.

For licensed COVID‑19 vaccines, seasonal strain or sequence changes are treated as line extension applications with new product licences, not as standard Type II variations. Additional strengths, forms or presentations linked to a new strain are also handled via extensions, though these may be submitted in grouped packages.​

Even if a strain change has been approved elsewhere as a Type II variation, in the UK it still needs to be submitted as a line extension, potentially using international recognition routes to leverage external assessments.

The guidance allows MAHs to group related variations affecting a single MA, with the overall procedure type defined by the highest category change in the group. The Composite Coordination Collection (CCC) procedure lets companies combine certain variations and Article 61(3) notifications that impact product information into one coordinated application for purely national MAs. CCC is not suitable for urgent safety variations, standalone Type IA notifications, or changes that do not affect SmPC, labels or leaflets.

For more details check the MHRA guidance Medicines: apply for a variation to your marketing authorisation, which remains the definitive reference for UK requirements, definitions, categories and procedures for variations to marketing authorisations.