DEVICE REGULATIONS – Early Preparation Will Pay Big Dividends as EU Enacts New EU Device Regulations


In the medical device industry, it’s long been evident that European regulations dating to the mid-90s have not kept pace with progress in developing new products. Current directives, for example, require only a critical evaluation of published literature for approval of new products that are functionally similar to existing ones. Now, those directives are giving way to new regulations that require Class III and implantable devices to undergo clinical investigation to show that they are equal or superior to other products on the market.

The new regulations also expand the list of devices that fall under the Class III designation to include spinal implants, devices that monitor and control active implants, nanomaterials, apheresis machines, and combination products. The industry must now prepare for what will surely be significant impact.

Spurring these changes: a pair of high-profile product failures that resulted in widely publicized recalls, both occurring in 2010:

– A French manufacturer of breast implants substituted cheaper industrial-grade silicone for medical-grade material, subjecting hundreds of thousands of patients to a 500% greater risk of leakage or rupture.
– A US maker of orthopedic products said its metal-on-metal artificial hip joints would last about 15 years, but the devices experienced a high rate of very early failures. Patients endured extreme pain and complicated, costly replacement surgery, and more than 11,000 lawsuits are still pending.

These events underscore the reality that failure is a sometimes necessary companion of innovation, and product flaws — whether they occur in automobiles, consumer electronics, or medical devices — are part of the process. Stringent and thoughtful regulation is vital to protecting patients as technology evolves, ensuring that new products meet or, ideally, exceed the standard of care.


Following nearly 4 years of debate, the European Commission in mid-2016 approved plans to replace EU directives on active implantable medical devices (90/385/EEC) and on medical devices (93/42/EEC) with a single medical device regulation, and to replace a directive on in vitro diagnostic devices (98/79/EC) with a regulation on the same subject. The changes, which explicitly establish manufacturers’ responsibilities for device quality, performance, and safety, affect a wide range of products — from contact lenses and pregnancy tests to X-ray machines, hip implants, pacemakers, and HIV blood tests.

The changes affecting in vitro diagnostics are particularly significant, constituting a major overhaul of the rules that will require secondary legislation and best practice guidance that have yet to be enacted.

The rationale is to provide more robust evidence of product efficacy and patient safety prior to market approval. Because the implications are complex and far-reaching, both new regulations have extended phase-in periods — 3 years for the medical device rules and 5 years for in vitro diagnostics. These lengthy transitions are intended to give the device industry ample time to prepare for these and other significant changes.

Attention on Pathway Toward CE Mark
The transition to the new medical device and in vitro device regulations will require diligence on all existing CE marked certificates between 2020 and 2025, the effective date varying based on the product. That means all products will require recertification according to the new rules over a period of about 4 to 6 years.

Notified Body Recertification
Notified Bodies (NBs), organizations accredited by EU member states to assess products for market approval, must be recertified and re-designated under the new regulations. NBs also will face more stringent oversight by national authorities. The number of these entities has already been falling due to stricter accreditation requirements, leaving only about 60 overburdened NBs in existence today — and that number is expected to fall further. That means evaluations could take longer, driving up costs.

Unannounced Audits
Notified Bodies will be required to conduct unannounced audits of manufacturers and suppliers to ensure that all participants in the device development process are following the new regulations. This requirement also will mean higher costs for manufacturers.

Scrutiny Process
A new provision allows authorities to take a second look at technical documentation prior to CE approval of high-risk devices. Article 44 will require the NB to submit a new technical review report, allowing authorities to request further information — potentially delaying submissions by several months, thereby reducing the market advantage of introducing products in Europe first.

Classification Changes
There will be changes in product classification. The impact will be especially pronounced for in vitro diagnostic devices, which will be re-designated from Class A, signifying lowest risk, to Class D, highest risk — with NBs required to take part in evaluating all but Class A devices. That means NBs will participate in about 80% of IVD classifications versus 20% today. This accounts for the extended 5-year transition period for the new IVD regulations.

Companion Diagnostic Designation
Companion diagnostics will be assigned a new Class C designation under the new rule, and therefore will face regulation for the first time under the in vitro device regulation — a change that means mandatory involvement of competent authorities. Under the current regulatory system, most companion diagnostic tests are classified in the lowest risk category and are thus self-certified.

Stricter Requirements for Comparative Evaluation
It will be much more challenging to demonstrate product safety and performance using equivalence data. The new rules require more data, and it will be more rigorously interpreted. Additionally, a manufacturer performing a comparative evaluation must obtain agreement from the company whose device it is using as the basis of comparison, further complicating the process.

Technical Documentation
Until now, there was no prescribed way of providing data to NBs, leaving each device maker to produce technical files to its own standards. The new rules are much more specific concerning the content and format of technical files, so it’s likely that all product and product family files will require some conversion.


Challenges aside, industry groups have embraced the changes. “The European medical device industry recognizes that Europe’s regulatory framework needs an overhaul to strengthen the system that has been, up until this point, the world’s fastest in providing life-saving technologies without compromising safety,” the trade association MedTech Europe said in a statement on its website.

“The rules must be fit for purpose, more transparent, and better adapted to scientific and technological progress,” the organization continued. “MedTech Europe supports revised legislation that speeds up approval processes, strengthens harmonized standards, and creates an integrated approach that is better coordinated and managed.”

Likewise supportive is GS1 UK, part of the global non-profit organization GS1, which develops and maintains global standards for business communication. Manufacturers will use GS1 global standards to implement the new EU system of Unique Device Identification, which aims to support patient safety and supply-chain security.

“Using GS1 standards for UDI benefits patients, the healthcare system, and the medical device industry,” said Glen Hodgson, Head of Healthcare for GS1 UK. “We’re working with healthcare organizations to help them identify medical devices, which will help make recalls quicker and more efficient — particularly compared to the often incomplete paper-based systems often used today.”

GS1 standards for UDI provide the foundation for a secure global healthcare supply chain by recording accurate data for adverse events and documenting the use of medical devices in electronic health records and clinical information systems, Hodgson said. “This is a huge step forward for patient safety in the U.K.”


OK, but these regulations are phasing in over a period of years, so there’s lots of time to prepare — right? Wrong! In fact, it would be hard to overstate the importance of early, thorough, and careful preparation. Close attention to preparation and planning are essential, starting now, because in some cases, time is shorter than it might appear. For example, all NBs need to be reaccredited, a process than can start 6 months after the official texts are published — a process that’s planned to take about a year. That means NBs won’t be ready for auditing until 2019, cutting roughly in half the 3-year transition period.

We’re advising our customers to make full use of the 3- and 5-year transitions, avoiding the temptation to conduct business as usual and play catch-up as the final implementation dates draw closer. In particular, companies that are in the process of  improving an existing device must perform a gap analysis to determine if a literature-based clinical evaluation will suffice, or if the revised product will require evidence derived from a clinical investigation.

There are many other things to start considering:

– If you don’t already have them, develop standard operating practices and processes to support successful inspections and audits
– Train staff to conduct mock audits and provide tools for ad hoc preparation. This will go a long way to instill in your organization a culture of attention to detail that’s essential to maintaining an audit-ready environment
– Makers of CE-marked devices will need to update some processes and procedures, especially concerning post-market surveillance and clinical follow-up, between now and 2020
– As discussed, the new rules require recertification of all NBs. Will your current NB still be appropriate for your needs? With the number of NBs expected to decline, finding an organization that’s up to the task could be difficult.
– Longer evaluations dictated by the new regulations will drive up assessment costs, possibly delaying product release. That will, at minimum, affect cash flow — and for small and virtual pharma and biotech companies, it could be an existential threat.
– New technical documentation standards will affect nearly everyone. What’s involved, and how long will it take? Will you need additional staffing?
– If you’re required to conduct clinical studies in place of the literature reviews that previously sufficed, are you equipped to do so? Would engaging a contract research organization be more effective than undertaking this lengthy and costly process on your own?

Through its new approach to device regulation, the EU has taken laudable and prudent steps to acknowledge that patient outcomes and safety are our primary goals — but the transition will not be an easy one for device makers. The phase-in clock has just started ticking, and manufacturers should make good use of the next few years to embrace the new regulations for the good of the device industry, and ultimately for the benefit of the patients it serves.

Joanne Emmett is VP, Medical Devices, at Premier Research, overseeing teams around the world, ensuring that each of the company’s teams is made up of the right people at the right time with the right skills to advance new and creative drug and device development practices. Working with Premier Research resources and customers, she makes certain that their personalities and work styles are thoroughly compatible with those of the client. Her past operational experience within large and small CROs brings to Premier Research a strong and diverse skill set focused on customer service.