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Submitting a variation that impacts the SmPC, label and Patient Information Leaflet (PIL)

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Several variations have a direct or consequential impact on the product information of a Marketing Authorisation (MA), by introducing changes to the SmPC and fragments, labelling and Patient Information Leaflets (PILs); these variations have a range of submission requirements and processes to make sure the product information remains current and up-to-date on both the MHRA’s electronic systems and public website.

Changes which affect the SmPC require both clean and annotated versions of the revised SmPC document.  In addition,  clean versions of the relevant SmPC fragments that have been changed should be submitted  using the MHRA SmPC Word template; this is a  UK national requirement that applies to both eCTD and NeeS submissions. If the updated fragments are not included with the variation submission, the procedure is rejected.

For changes that affect the labels and PILs for marketed products both updated text and clean mock-ups are required.

If the product is not marketed, only text versions of the labelling and PIL need to be submitted.

MHRA does not accept combined SmPCs covering, for example two different strengths of the same dosage form, but only accepts a single SmPC in the correct format using the relevant template.  This enables the agency to meet its obligation to publish and upload on to the MHRA website the approved product information.

It is important to make sure product licences remain current and up-to-date, by promptly submitting appropriate variations, even if the MA may have pending procedures. For example, when a renewal application has been approved, documentation submitted as part of the National phase should be reviewed and finalised by the relevant Competent Authorities within a 30-day timeframe.  Delays finalising the national phase, should not prevent a Marketing Authorisation Holder (MAH) from submitting changes to the MA using the appropriate variation procedure.

QRD updates to the SmPC, PIL and labelling may be submitted at any regulatory opportunity when other changes are being made to these documents, under type IB and type II variations. No separate classification is required. If changes are proposed to the PIL and labelling only, these may be combined with changes that are being submitted for full assessment under Article 61.3 (categories P1-P4); this approach is applicable to national licences only.  For MR licences, these changes may be combined with other updates to the harmonised labelling and PIL text via a MR Art. 61.3 procedure. CMDh guidance can be found under Q. ‘3.16.  Under which classification category can editorial changes be submitted?’.   QRD updates may also be submitted independently as a type IB variation, under code C.I.z.

If you are uncertain about any of the above points that may impact the SmPC, label and patient information leaflet, please contact the Regulatory Information Service (RIS) at to discuss before submission of the variation application.

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