One Application, One Decision, Many Member States

Part of Regulatory Affairs and the Jurisdiction Map: The European Union under CTR 536/2014.

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Why this matters

Before Regulation (EU) No 536/2014, a trial across eight European countries meant eight applications, eight assessments, eight sets of questions, and eight decisions that could disagree with each other. Sponsors routinely received an approval in one member state and a refusal in another for the same protocol, and had no mechanism to reconcile them.

The Regulation replaced that with a single submission producing a single coordinated decision on the scientific part, while leaving genuinely national questions national. Understanding exactly where that line falls is the whole of European regulatory work.

Twenty seven member states operate under it, and CRLN's register records all twenty seven as verified against the Regulation as the governing instrument.

The structure: Part I and Part II

The application divides in two, and the division is the Regulation's central design decision.

Part I covers what should not differ between member states. The therapeutic and public health benefits and the risks. The protocol's scientific soundness. The quality of the investigational medicinal product, its manufacture and labeling. Compliance with the requirements for the Investigator's Brochure.

Part I is assessed jointly. One member state takes the lead as reporting member state, drafts the assessment, and the other member states concerned review and comment. The outcome is a single conclusion that applies across all of them.

Part II covers what legitimately differs by country. Informed consent arrangements. Rules for rewarding or compensating participants and investigators. Recruitment arrangements. Data protection compliance. The suitability of individuals and facilities. Rules on the collection, storage and use of biological samples.

Part II is assessed nationally, by each member state for its own territory, against its own law and its own ethical framework.

What this means operationally

The consequences follow directly from the structure, and they are not always intuitive.

A single Part I conclusion binds all concerned member states, with a narrow exception allowing a member state to disagree on specified grounds. You do not get a scientific approval in one country and a scientific refusal in another for the same protocol.

A member state can still refuse on Part II grounds alone. The science can be accepted across all of them and one country can decline because its national consent requirements are not met. Part I succeeding does not mean the trial runs everywhere.

The consent form is a Part II document. This catches teams out constantly. A sponsor that prepares one consent form and expects it to clear centrally has misread the structure. Each member state assesses consent against its own requirements, and national differences in what must be disclosed, in what language, and at what reading level are real.

Choosing the reporting member state is a genuine decision. Any concerned member state can be proposed as reporting member state, and the choice affects who drafts the assessment. Practical considerations include that authority's experience with the therapeutic area and the product type, and its current workload.

Where Articles 30 to 35 live

The Regulation addresses several consent situations that the global baseline does not, and these are Part II questions assessed nationally.

Article 30 addresses simplified consent in cluster trials. Article 31 addresses trials on incapacitated subjects and consent by a legally designated representative. Article 32 addresses trials on minors, including assent proportionate to age and understanding. Article 33 addresses pregnant and breastfeeding women. Article 35 addresses clinical trials in emergency situations, where consent may be obtained after the decision to include the participant.

A protocol relying on any of these is relying on provisions that each member state assesses for itself, which means the answer can legitimately differ across the member states in a single application.

In practice

A sponsor submits one application naming nine member states. Part I is assessed jointly with one acting as reporting member state.

Part I concludes acceptable. All nine accept the science, the product quality and the benefit risk assessment. That is one assessment where there would previously have been nine.

Part II produces three different outcomes. Six member states accept as submitted. One requires the consent form rewritten at a lower reading level and a specific national statement about data rights added. One asks for the participant compensation arrangements to be revised, because the amount proposed is considered capable of acting as an inducement under its national framework.

The sponsor now has one scientific position and three national conversations. The study team hears "approved" from the Part I conclusion and wants to start everywhere. The regulatory lead's job is to be precise: seven member states may proceed, two may not yet, and the reason has nothing to do with the science.

What this looks like when it goes wrong

A sponsor treats the Part I conclusion as the authorization and instructs all nine countries to begin site activation.

Two of them have no Part II decision. The trial is not authorized in those two, and any participant screened there is screened without authorization.

The error is structural rather than careless. The team read "single decision" as meaning one decision covering everything, when the Regulation's design is one decision on the shared questions and a national decision on the national ones. Both must exist before a site in a member state may start.

Key takeaways