Referral Procedures: When Your Medicine Is Reviewed EU-Wide

A referral takes a medicine out of the hands of its marketing authorisation holder and puts it in front of the entire European regulatory network. The European Medicines Agency is asked to deliver a harmonised position on behalf of the EU, and the outcome — a restricted indication, a new contraindication, a suspension — travels to every market where the product is authorised. A referral that begins with a safety signal in another Member State can end in a Commission decision that EOF is obliged to implement in Greece.

Who can start one, and why

Referrals exist to resolve issues that no single national authority should settle alone: concerns over the benefit-risk balance of a medicine or a whole class, or disagreements between Member States on how a product should be used. They can be triggered by the European Commission, by any Member State, or in some cases by the company that markets the medicine.

The routing depends on the question. Safety-related referrals are assessed first by the Pharmacovigilance Risk Assessment Committee (PRAC), then by the CHMP for centrally authorised products or by the CMDh for nationally authorised ones. All other referrals on human medicines go to the CHMP alone.

The procedural map

• Article 107i — urgent Union procedure. Triggered by a Member State or the Commission when urgent action is needed on safety grounds: suspension or revocation, prohibition of supply, deleted indications, reduced doses, new contraindications. A marketing authorisation holder cannot trigger it.
• Article 20. Quality, safety or efficacy issues concerning centrally authorised products.
• Article 31. Quality, safety or efficacy concerns where the interest of the Union is involved — applicable to any medicine or class, however it was authorised.
• Articles 13 and 29(4). Disagreement between Member States on a type II variation, or on a pending application in a mutual-recognition or decentralised procedure, on the grounds of a potential serious risk to public health.
• Article 30. Harmonisation, where Member States have adopted divergent indications, contraindications or posology over the years.
• Article 5(3). A CHMP opinion on any scientific matter related to the evaluation of human medicines.

Several older routes — Articles 5(11), 6(12), 6(13), 36 and the original Article 107 — are no longer applicable, having been replaced by the framework above.

The clock is shorter than it looks

In an urgent Union procedure, PRAC has a maximum of 60 days to issue its recommendation after the published deadline for submission of data — a window EMA describes as three consecutive PRAC plenary meetings, and one the committee can shorten where urgency justifies it. Oral explanations, public hearings and input from a scientific advisory group all sit inside that same period; none of them buys extra time.

The CHMP opinion or CMDh position follows within 30 days of receipt of the PRAC recommendation. Where the CMDh reaches consensus, Member States implement on the timetable set out in the position itself. Where it goes to a majority vote, translations are finalised and sent to the Commission, which adopts a binding decision.

Re-examination is not a second chance to prepare. Intention to request it must be notified in writing within 15 days of receiving the opinion or recommendation, with the detailed grounds following within 60 days. Miss either deadline and the request is inadmissible — the opinion becomes final.

What holders consistently underestimate

• Scope is not negotiable. You cannot opt a product out; inclusion follows the safety concern defined in the notification, and the Agency can widen the scope mid-procedure.
• Being outside the scope is not immunity. Member States are expected to take the scientific conclusions into account for other affected products, including ones authorised later.
• Implementation is your problem. Once the decision or position lands, product information updates, translations, artwork and national roll-out fall to the holder — and that is where Greek timelines tend to bite.
• Fees apply, with reductions or waivers available to companies already qualified by EMA as small, medium or micro-sized enterprises.

How PQRA helps

We monitor PRAC and CHMP meeting highlights for procedures whose scope touches our clients’ portfolios, build rapporteur-ready response packages inside procedural timelines, prepare oral explanations and re-examination grounds, and manage the downstream work — SmPC and package leaflet updates, Greek translations, and implementation with EOF — so that an EU-wide decision does not become a national compliance gap.

If a referral touches a product in your portfolio, or you want to be ready before one does, get in touch with our regulatory team.