UK MHRA Guidance: Medicines-Apply for a Variation to Your Marketing Authorisation
Marketing authorisation variations allow changes to an authorised medicine, including administrative changes, changes affecting product quality, and changes that may affect safety, efficacy or pharmacovigilance requirements. The Medicines: apply for a variation to your marketing authorisation guidance explains the UK procedures for Type IA, Type IB and Type II variations, extensions, grouping and bulk submissions, product information changes, fees and application requirements.
Overview
Variations may involve administrative changes, changes to product characteristics that can affect quality, or changes that may affect safety, efficacy or pharmacovigilance requirements.
Changes are classified as major Type II variations or minor variations, with minor variations divided into Type IA and Type IB. Applicants can submit a single change to one marketing authorisation or multiple changes to one or more marketing authorisations.
Marketing Authorisation Types
From 1 January 2025, UK marketing authorisations include UK-wide marketing authorisations and Northern Ireland-only MAs. UK-wide MAs may be purely national or may have originated through earlier Mutual Recognition or Decentralised procedures involving Northern Ireland as a Concerned Member State.
Centralised marketing authorisations and subsequent variations ceased to be valid in Northern Ireland on 1 January 2025.
UK Variations Procedures
The procedures for variations to purely national UK marketing authorisations were incorporated into UK law and continue under the Human Medicines Regulations 2012. The revised Variations Regulation became applicable on 1 January 2025, and new guidance on procedures and variation categories applies from 15 January 2026. The procedure depends on the authority responsible for leading the assessment, which may be the MHRA, the Reference Member State or the Reference Authority for relevant procedures.
UK Variations Classification
The variations classification guideline explains the categories of changes, including Type IA, Type IAIN, Type IB, Type II and Extension.
The updated EU Variations Guidelines on variation categories and documentation apply in the UK from 15 January 2026, except for strain or sequence changes to authorised COVID vaccines. Changes requiring a marketing authorisation extension are handled through extension procedures.
Minor Variations
Minor variations are divided into Type IA and Type IB changes.
Type IA Variations
Type IA changes have little or no impact on the quality, safety or efficacy of the product. Examples include changes to the manufacturer's name, minor changes to a control method, and deletion of an unused packaging site. Type IA variations follow a “do-and-tell” procedure. The change is implemented before notification, normally within 12 months. Certain Type IA changes, known as Type IAIN, require immediate notification after implementation. Type IA changes may be grouped and submitted as annual updates. Annual submission timing depends on implementation dates, with specific exceptions allowing earlier submission.
Type IAIN Variations
Type IAIN variations are a subtype of Type IA and must be submitted immediately after implementation, with a period of 2 weeks considered reasonable. They may be included in grouped submissions or annual updates where the submission is not delayed. The applicable conditions and documentation requirements must be met, and applications are accepted or rejected without requests for further information.
Type IB Variations
Type IB changes are more significant than Type IA changes but do not qualify as Type II changes or extensions. MHRA approval is required before implementation. Many Type IB changes relate to manufacturing or testing procedures. Once all necessary documents are available, the variation may take up to 30 days to process, with a further period available for responses to Notification with Grounds letters where deficiencies or omissions are identified.
Major Variations (Type II)
Type II variations are more complex and are expected to have a significant impact on the quality, safety or efficacy of a product. MHRA approval is required before implementation. Adding a new therapeutic indication is an example of a Type II variation. Such applications are assessed under a 120-day extended procedure because of the clinical data required to support safety and efficacy and demonstrate a positive benefit-risk balance.
Variations to Add a New Therapeutic Indication
Applications for a new therapeutic indication follow specified submission deadlines and assessment stages, including procedure start dates, Commission on Human Medicines meetings and approval or requests for further information.
In certain circumstances, a variation for a new indication may result in a conditional marketing authorisation where comprehensive data are not yet available. This may apply where the benefit-risk balance is positive, further comprehensive data are expected, the indication addresses an unmet medical need and immediate availability provides greater benefit to patients than the risk associated with the outstanding data.
Type II procedures may use reduced, standard or extended assessment timelines depending on the nature and complexity of the change.
Changes to COVID Vaccines
Seasonal strain or sequence changes to existing licensed COVID vaccines should be submitted through a line extension application rather than a Type II variation. Additional strengths, pharmaceutical forms or presentations for the new strain should also be submitted as separate line extensions. Where a strain or sequence change has been authorised elsewhere through a Type II variation, the supporting data and relevant assessment reports may be used through the International Recognition Procedure, but the UK application remains a line extension.
Common Invalidation Errors and Pre-Submission Checklist
The MHRA is developing a pre-submission checklist for variations. Common areas of invalidation include incorrect reference product information for certain Type IB changes, missing IRP submission checklists, incomplete Active Substance Master File documentation, incorrect SmPC fragments and unacceptable grouped Type IB or Type II variations.
Marketing authorisation holders are responsible for ensuring that all relevant conditions and documentation are met and that submitted dossiers are current and complete. Deficient or incorrect documentation may result in invalidation or rejection.
Extension Applications
Where a proposed product change is sufficiently significant, it must be submitted as a line extension through a new marketing authorisation application. Examples include changes to the active substance, including its salt, ester, isomer or biological active substance; changes to strength or pharmaceutical form; and changes to the route of administration, including different parenteral routes.
Revised Labels, Leaflets and/or Packaging
Where a variation affects product labels, leaflets or packaging, updated versions must be included with the variation submission for assessment. A variation is not required where there is no product change and only style changes are proposed for the labels, leaflets or packaging.
Submitting Multiple Changes
Multiple directly related changes to a single marketing authorisation can be submitted using the grouping format. The procedure type, assessment timeframe and applicable fee are determined by the highest classification within the group. Where a proposed grouping is not already covered by the relevant guidance or examples, applicants should obtain confirmation of its acceptability before submission.
Same Variations to Multiple Products
The same Type IB or Type II change, or group of changes, may be submitted to multiple marketing authorisations held by the same marketing authorisation holder as bulk applications.
Type IA variations may also be included where they are consequential or related. Bulking does not affect the procedure timescale and may reduce duplication for both applicants and the MHRA.
Supergrouping of Type IA and IAIN Variations
A single application may be used for the same Type IA or Type IAIN variation or group of variations across multiple UK marketing authorisations where the relevant marketing authorisation holders belong to the same parent or group of companies or are licensees.
Where products do not share a single eCTD lifecycle, the changes must be submitted as a super-grouped application and must be identical across the collection.
Composite Coordination Collection
The Composite Coordination Collection procedure can be used for changes affecting product information for one or more purely national marketing authorisations.
It can cover consolidated mock-ups of leaflets and labels, mixtures of variations and Article 61(3) applications, and single or grouped Type IB and Type II changes. It is not intended for urgent safety variations, standalone Type IA notifications, changes that do not affect product information or products with a centralised licence.
Variations to MAs Where Northern Ireland Is a Concerned Member State
For Northern Ireland-only MAs granted through Mutual Recognition or Decentralised procedures, and UK-wide MAs where Northern Ireland remains a Concerned Member State, variation procedures are led by the Reference Member State and managed through the relevant Mutual Recognition procedure.
These MAs may also be included in EU work-sharing procedures led by the Reference Authority. UK-wide nationally authorised marketing authorisations cannot be submitted as part of an EU work-sharing procedure.
Supporting Documents
For Type IA and IB applications, applicants need to provide the cover letter, information on grouped variations where applicable, supporting information required for the specific variation, present and proposed product details where necessary, and a contents page.
Type II applications require the same information together with relevant supporting information such as publications and cited references and updated quality, clinical and non-clinical overviews.
Summary of Product Characteristics
Where relevant, SmPC fragments must be submitted in the required format using the specified templates. The templates should not be altered other than by inserting the relevant information.
The required documents cover sections of the SmPC including product name, composition, pharmaceutical form, therapeutic indication, administration, contraindications, warnings, interactions, undesirable effects, pharmacodynamics, pharmacokinetics, shelf life, packaging and other applicable information.
Recent Updates
The page was last updated on 21 September 2026. The update included the publication of guidance on Type IA annual update variations. Earlier updates in 2026 clarified the assessment process for 120-day Type II variations for new therapeutic indications, including Day 90 decisions and the use of a single request for further information, and added deadlines for new therapeutic indication variations.
Comments