Medical device manufacturers will need to provide substantially more clinical evidence to support claims of safety and performance for many medical and in vitro diagnostic (IVD) devices marketed in the European Union (EU) as the result of two new regulations adopted by the European Parliament.

The reforms, which are among the most far-reaching changes to affect the industry in recent years, were developed to harmonize regulatory requirements across Europe and improve patient safety. Yet the new regulations are expected to cause higher costs and longer timelines for new product development. In addition, all devices sold in Europe—a number estimated at more than 500,000 today—must be recertified to comply with the rules, which will require new clinical monitoring and data collection for certain products to stay on the market.

Expected effects from the regulations include large organizations withdrawing devices from the market and smaller companies putting themselves up for sale as they begin to review their pipelines and portfolios to assess whether products are worth the investment needed to comply with the new requirements. Reforms will also force companies to re-think the long-held strategy of first launching new devices in Europe, where they could earn revenue while collecting clinical evidence needed to obtain FDA approval, as it becomes more costly to obtain a CE mark.

“It’s becoming more arduous and complicated to get on the market in Europe first,” said Michael Wienholt, founder and principal consultant of the North Carolina-based FDA Consulting, which specializes in submissions for medical devices and in vitro diagnostics. “There are increased requirements on clinical evidence, technical documentation and post-market clinical follow-up. All of that is an increase in regulatory burden.”

Negotiations to replace directives governing medical devices and in vitro diagnostics in the EU began nearly five years ago in response to differing interpretations of the existing rules among EU member states, demands for legislation that considered the most recent advances in technology and science and the need to ensure patient safety after high-profile problems with particular breast and metal hip implants.

While manufacturers have three years to comply with the new Medical Devices Regulation (MDR) and five years for the In Vitro Diagnostic Medical Devices Regulation (IVDR), consultants say companies may have difficulty completing necessary steps, which include developing a strategy to assess portfolios and creating an organizational structure to manage changes, to comply with the regulations within the tight transition period. For each product, companies need to determine its category under the new regulations and what additional testing or other changes will be required to conform. In addition, since the reforms cover products that previously didn’t require review, some organizations not accustomed to conducting clinical trials will need to establish an in-house clinical organization.

“There is a two-stage approach. Companies have to look at their portfolio of products and make a determination of the gaps for each program or product, how to prioritize and what type of evidence is needed. The second part is the execution of collecting the data, preparing the reports and being able to maintain market share by keeping their product on the market,” said Vicki Anastasi, global head, Medical Device & Diagnostics Research at Icon. “For companies that have a lot of products on the market or in their pipeline, two to five years is not that long.”

Consultants and CROs report seeing an increase in the number of request for proposals as organizations want to understand the new regulations, develop strategies and plan for remediation. While some large companies have already begun to perform gap analyses of product portfolios and systems in anticipation of the much-discussed regulatory changes, most have waited until the rules were finalized before beginning compliance work.

“We are seeing a lot of people scrambling. They have waited too long to do the initial planning and assessment of their portfolio,” said FDA Consulting’s Wienholt. “Many still don’t see what is coming at them or are in simple denial. They think they can worry about it after the transition period. But then it will be too late.”

The reforms also move some medical devices into higher risk classifications and require that a greater number of devices be submitted to a regulatory body for approval.

Because of reclassifications, some medical devices, such as spinal implants and surgical meshes, will require certification for the first time or recertification under different rules, which means companies will need to conduct new clinical studies for some devices. The new regulations make it more difficult for companies to demonstrate clinical safety or performance by showing a product was equivalent to another device, which was a common practice under the previous directives for medical devices.

“The way trials are executed won’t change. But a lot more studies will be required. Because of that, companies need to be more innovative and creative with their study design. They need to minimize the amount of time they are in studies, the cost of studies and try to efficiently use all of the data they collect,” said Icon’s Anastasi.

The most significant changes will affect manufacturers of in vitro diagnostics, such as genetic tests for cancer or blood glucose monitors, due to the introduction of a new risk-based classification system. The proportion of IVDs that will require the involvement of a Notified Body, which is an organization that reviews product submissions in EU countries and helps enforce the new regulations, will increase from 10% today to about 90%. Only IVDs in the lowest risk category, which includes laboratory instruments and specimen receptacles, will be exempted from the regulatory review.

“Manufacturers will have to produce a lot more evidence for IVDs. They will have to conduct performance evaluations that demonstrate the scientific validity of the test as well as the analytical and clinical performance. All that data will have to be reviewed by Notified Bodies in a majority of cases for IVDs. It’s a big change for those manufacturers and it will impact their development timelines,” said Karen Hill, senior manager of Regulatory Affairs at Icon.

In addition, all Notified Bodies will be re-designated by the European Commission to certify specific classes and types of medical and IVD devices, which could result in fewer NBs available to review submissions and extend review timelines.

The new rules have implications for U.S. companies that contract with authorized representatives in the EU. While manufacturers must have liability insurance for their products, the new regulations require that the company’s authorized representative in Europe also verify the insurance is adequate or take out additional insurance.

“That pool of available services is shrinking because some of the authorized representatives, by definition, are now economic operators and have specific liabilities and requirements to obtain and retain the appropriate insurance coverage,” said Wienholt. “This is pushing some of the smaller authorized representatives out of the market and contracts have to be re-negotiated to reflect the new requirements, so the prices are going up.”

This article was reprinted from Volume 21, Issue 33, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »