Euro Convergence: EMA won’t delay drug approval of combo product if diagnostic part doesn’t have CE mark

AMSTERDAM – European regulators will not prevent approval of a drug if the device part of the combination product is delayed in getting certification from a notified body, an European Medicines Agency (EMA) official assured delegates at RAPS Euro Convergence.

During a town hall meeting on 12 May with European regulators and notified body representatives, Marina Belonogova, associate director for diagnostics and digital health at Janssen Pharmaceutical, asked that if companies are putting themselves at risk if their drug and device components are not reviewed in parallel when trying to gain market authorization in the EU.

She noted that in theory, drug and device components are supposed to be reviewed in parallel, but in practice, that’s not happening as notified bodies are still ramping up capacity. She added that notified bodies are currently focusing on class D in-vitro diagnostics (IVD). On average, it takes about 18 months to certify class C IVDs, so there is a substantial delay in certifying certain diagnostic products. By comparison, she said, EMA approves drugs much faster.

Belonogova asked the EMA panelists if a company submits a marketing authorization application (MAA) for a combination product, but a notified body fails to seek scientific advice from regarding the diagnostic component, would that pose a risk to the medicinal component of the product.

Christelle Bouygues, an EMA regulatory affairs senior officer, pointed out that they are not legally required to synchronize the review of a combination product's drug and device components. However, she said that not being able to review the products in parallel can be a challenge and hoped that the system eventually evolves so that constituent components can be reviewed in parallel.

“The reality of what’s happening is that we will not block the approval of a medicinal product while the companion diagnostic is not yet certified,” said Bouygues.

However, she noted that as part of the review of the medicinal product, regulators would look at the diagnostics product used in the clinical trial. While it may not be the final diagnostic used for the marketed combination product, she added that it is meant to give reviewers minimal information about the kind of diagnostic that will be used.

The product description needs to include a statement that an appropriate certified IVD is meant to be used with the medicinal product, which is the wording EMA has come to in agreement with the European Commission (EC), Bouygues said.

Marta Carnielli, head of certification for IVDs at the notified body TUV SUD, said they have received a handful of cases where a companion diagnostic has been submitted for conformity assessment to receive CE marking and they’ve mostly been for legacy products.

“As we gain practice with this process, I think we also need to synchronize so there are no delays, but we would only step in when a manufacturer is ready to get a CE marking,” she said.

Ilona Reischl, an assessor at the Austrian Medicines Agency (AGES MEA), said that sponsors need to study the diagnostic component of their combination early on to ensure they are as prepared as possible for the certification process. She reminded attendees that ensuring that the different components of a combination product are reviewed timely and in parallel starts during the clinical trial phase where researchers can ask what is lacking in their development plan.

Reischl also noted that if a diagnostic is not CE marked for its intended purpose during the clinical trial, it is not only a clinical trial but should be seen as a performance study of the diagnostic product.

"You have to start much earlier in thinking about this," she emphasized.

RAPS Euro Convergence

Euro Convergence: EMA won’t delay drug approval of combo product if diagnostic part doesn’t have CE mark

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