Medical devices new rules: the clock is ticking
It’s a familiar scenario: a product failure or other high-profile event imperils public safety, prompting new, more stringent government regulations. The refreshed and timely medical device regulation and in vitro diagnostic regulation create the improved opportunity to plan and avoid recalls:
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 orthopaedic products said its new 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.
Failure is an unavoidable byproduct of innovation, and product flaws—whether they occur in automobiles or home appliances or medical devices—are part of the process. Thoughtful, stringent regulation is vital to protecting patients as technology evolves, ensuring that new products meet, or ideally exceed, the standard of care.
In the device industry, it’s become clear that existing European regulations, dating to the mid-1990s, have not kept pace with progress. For example, current directives require only a critical evaluation of published literature for approval of new products that are functionally similar to existing ones. In May, those directives gave way to new regulations that require CE class III (the highest risk) and implantable devices to undergo a clinical investigation to show that the new device is 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 impact on the industry will be significant, to say the least.
What’s changing?
Following nearly four years of debate, in mid-2016 the European Commission 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 medical devices (98/79/EC) with a regulation on the same subject. The changes affect a wide range of devices, from contact lenses and pregnancy tests to X-ray machines, hip implants, pacemakers, and HIV blood tests.
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—three years for the medical device rules and five 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:
Notified body recertification
Notified bodies, organisations accredited by EU member states to assess products for market approval, must be recertified and redesignated under the new regulations. The number of these entities has been falling due to stricter accreditation requirements, leaving only about 60 overburdened notified bodies in existence today—with that number 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 notified body 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.
CE marks becoming obsolete
If your product has a CE mark and is on the market, it must be reassessed. Current CE marks will become obsolete, with no grandfathering.
Classification changes
There will be changes in product classification. The impact will be especially pronounced for in vitro diagnostic devices, which will be redesignated from class A, signifying lowest risk, to class D, highest risk—with notified bodies required to take part in evaluating all but class A devices. That means notified bodies will participate in about 80% of in vitro diagnostics classifications versus 20% today. This accounts for the extended five-year transition period for the new in vitro diagnostics regulations.
Companion diagnostics
Companion diagnostics will be assigned class C designation under the new rules, a change that will mean 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 data 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 notified bodies, and each device maker produced 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.
What should you do now?
These regulations are phasing in over a long period—so there’s lots of time to prepare, right? Wrong.
We’re advising our customers to make full use of the three- and five-year transitions, avoiding the temptation to chug along 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 whether 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 now:
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.
As discussed, the new rules require recertification of all notified bodies. Will your current notified body still be appropriate for your needs?
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 clinical research organisation be more effective than undertaking this lengthy and costly process on your own?
In designing the new regulations, EU regulators have taken laudable and prudent steps to acknowledge that patient outcomes and safety are our primary goals—but the transition will not be easy 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.
Jo Emmett is vice president of medical devices at Premier Research. She can be contacted at: info@premier-research.com
