USR: urgent safety restriction
An urgent safety restriction (USR) is a provisional change to a medicine's product information imposed at once because of a risk to public health.
Article 22 of Commission Regulation (EC) No 1234/2008 lets a marketing authorisation holder take provisional urgent safety restrictions on its own initiative where there is a risk to public health, and lets the competent authorities impose them. A USR is an interim change to the terms of the marketing authorisation, typically a new contraindication, a reduced dose, a new warning or a restriction of the indication, that takes effect before the usual variation assessment. It is used when waiting 60 days for a Type II variation would leave patients exposed.
The holder informs the relevant authorities at once: EMA for centrally authorised products and each national competent authority for national, MRP and DCP products, with the RMS taking the lead in the latter. If the authority raises no objection within 24 hours of receiving the information, the restriction is deemed accepted and the holder implements it within the time agreed with the authority. The USR then has to be converted into a proper variation; the holder submits the corresponding variation application within 15 days of the start of the restriction. The authority can also impose a USR directly, in which case the holder must submit the variation in the same way.
USRs are rare compared with ordinary safety variations, because most safety changes can be handled by a standard Type II or an accelerated 30-day assessment. They appear mainly for serious new risks found through signal detection or a clinical study, and they often travel with a DHPC that tells prescribers what has changed. Where several holders market the same substance, the authorities usually coordinate so that all products are restricted at the same time.
What goes wrong: holders that implement an urgent change without telling every authority concerned, so one Member State finds out from the press; the 15-day variation that is filed late or as the wrong type; packaging and leaflets printed with the old text long after the SmPC changed, because the artwork process was not started on the day of the restriction; and confusion between a USR and a product recall or withdrawal, which follow different procedures and different legal bases.
Timing
The holder notifies the authorities and may implement the restriction if no objection is raised within 24 hours of receipt. The resulting variation application must be submitted within 15 days of the initiation of the restriction, and it is then assessed under the usual Type II timetable, which can be shortened to 30 days for urgent safety issues. Labelling and leaflet changes follow as soon as the variation is approved, and in practice artwork should start on the day of the restriction.
Used in
When a USR changes the product information, check reprinted leaflets and packs against the restricted text in Print Proofreader before release.
Related terms
- DHPC: direct healthcare professional communicationA direct healthcare professional communication (DHPC) is a letter agreed with authorities that alerts prescribers and pharmacists to urgent safety issues.
- Type II variation: major change requiring prior approvalA Type II variation is a major change that may significantly affect a medicine's quality, safety or efficacy and needs approval before implementation.
- Signal detection: identifying new safety information from pharmacovigilance dataSignal detection is the process of finding information that suggests a new or changed causal link between a medicine and an adverse event.
- PRAC: Pharmacovigilance Risk Assessment CommitteeThe PRAC is the EMA committee that assesses the safety of human medicines in the EU, from risk management plans and PSURs to signals and safety referrals.
- SmPC: summary of product characteristicsThe summary of product characteristics (SmPC) is the approved document that tells healthcare professionals how to use a medicine safely and effectively.
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