New Clinical Data Requirements Could Discourage EU Market Entry

The U.S. could become a more attractive place than the EU to introduce new medical devices given the more stringent premarket clinical data requirements under the EU’s new Medical Device Regulation (MDR).

Maria Donawa, M.D., president of Donawa Lifescience Consulting in Rome, Italy, said in an interview that until recently, manufacturers often preferred to bring new medium- and high-risk devices to the EU before the U.S. because of the clinical data requirements required for 510(k)s.

However, she said the EU’s new MDR that will come into force next year has a significantly more stringent clinical evaluation process and numerous other mandates that could change this equation.

Sweeping new medical device regulations in the EU are expected to be finalized in December or early 2017, although medical device manufacturers will still have three to five years to comply. The new MDR will require risk management and quality management systems, the use of unique device identifiers, major changes to clinical evidence requirements, and tighter control over distribution chains.

Donawa said the MDR’s new premarket clinical data requirements will be especially relevant to market entry decisions. “The clinical evaluation process is already important under the current directives, but its prominence is significantly increased in the MDR,” she said.

Although current EU regulations require premarket data regarding usability, design, manufacturing, packaging, and other factors, many data requirements will be more detailed under the MDR.

Clinical Evaluations

In addition, revised guidelines on clinical evaluations (MEDDEV 2.7/1 Rev. 4) devote 56 of their 65 pages to describing how clinical evaluations should be performed. Although MEDDEVs are technically non-binding guidance documents, most EU regulators require manufacturers to follow them.

Among other things, the guidelines call for significantly more information in clinical evaluation documents and provide detailed instructions to EU notified bodies on how to evaluate these documents. Moreover, to use clinical data for a device to justify access to the EU market, a company will have to own the data or have a legal agreement to access it, rather than merely compiling data from competitive equivalent products.

“Many companies had problems with the previous version [of the MEDDEV], so the new one will be a significant challenge for some companies,” she said. “Preparing data in accordance with the MEDDEVs and the MDR requires detailed documents that can take considerable time and specialized resources.”

Many of the clinical data that will be required under the new MDR and MEDDEVs are not required by the FDA for 510(k)s.

“Although clinical data are sometimes required for 510(k)s, this is generally in the form of relatively small clinical studies to provide evidence of substantial equivalence on safety and effectiveness of a new device that differs technologically from a predicate device,” Donawa said. “Most 510(k)s do not require clinical studies, and FDA does not require the type of clinical information that will be necessary under the MDR.”

Additional Requirements

The upshot is that it could take six to 12 months to generate the extensive clinical data needed for CE marking — up to twice as long as it takes to obtain a 510(k) clearance.

Beyond clinical data requirements, the MDR has an expanded scope that covers not only the manufacturer and authorized representative, but also the importer and distributor. It adds new requirements related to managing and labeling hazardous substances, designating a person responsible for regulatory compliance, post-market planning and reporting, and providing implant cards to certain patients.

Moreover, the MDR identifies numerous areas where either “delegated acts” or “implementing acts” will be adopted by the European Commission to supplement or amend certain regulatory provisions or resolve differences in interpretation and application, Donawa said. It is uncertain what new requirements the delegated and implementing acts will impose.

All of this could make bringing some new devices to the EU market more of a hassle than it is worth. “History supports the increase and not the decrease in regulations, so it is difficult to see any trend in the future that would make life easier for manufacturers,” she said. — Jeff Kinney