The European CE marking rule changes have been a source of constant dialog and scrutiny in the regulatory community and among device manufacturers for several months. To shed some light on the changes, insight on what they mean for manufacturers and regulatory procedures, and what's next for the industry, Dr. Basil Akra, TUV SUD's global director of the Clinical Centre of Excellence, and Dr. Royth von Hahn, vice president of TUV SUD America's Medical and Health Services, conducted a joint webinar. For the specifics on exact regulation changes, be sure to listen to the webinar or download the slides - Drs. Akra and von Hahn go into extensive detail. This virtual event lays out their assessment.
What is happening in Europe?
There are four separate processes happening in Europe:
- New medical device regulation
- New in-vitro diagnostic regulation
- New medical device documentation
- New ISO 13485 standard
That's a lot to keep track of. Each of these items are related but require separate consideration. Drs. Akra and von Hahn broke down each area one by one.
The EU's new medical device regulation (MDR)
This new regulation is really the result of a process that began in 2008, when the EU Commission launched consultation on medical device framework. From 2012 through 2015, the EU Commission, Council and Parliament released and discussed a series of proposals and positions. By June 2016, the three bodies had signed off on the MDR proposals (along with in-vitro diagnostic regulations), according to the Regulatory Affairs Professionals Society. The transition period from the old regulations to the new ones should last until 2019.
What do these new regulations mean? A few things:
- Regulations are more streamlined, but also more rigorous, with consistent oversight of all medical devices.
- More devices are now required to undergo pre-market review and Notified Body approval.
- Post-market documentation maintenance requires more money, time and effort for investigations and reports - like an annual safety and performance report.
- Notified Bodies now review skills and ability of Qualified persons to make sure they possess the necessary competence.
- The European Databank on Medical Devices (Eudamed) will be expanded to improve access to medical device information.
That's not all. Certification times may lengthen due to fewer Notified Bodies, more devices and more involvement from third parties. Device manufacturers will be subject to product testing and they will have three years to comply with the new standards. Additionally, new Common Specifications defining "State of the Art" will exist alongside the Harmonized Standards.
The EU's new in vitro medical device regulation (IVDR)
The process surrounding the new IVDR mirrored that of the new MDR, with the exception that it began in 2010, not 2008, with the launch of a consultation aimed at revising the IVD directive. Additionally, after the three EU regulatory bodies approved the new standards in June, the adoption period will take five years instead of three - IVD manufacturers are expected to align with the new regulations by 2021.
The upshot of the new IVDR also follows that of the new MDR. Notably, the IVDR scope includes far more devices than previous guidelines, meaning many additional manufacturers will have to follow the EU's prescribed standards. Moreover, over 70 percent of IVDs will be subject to pre-market scrutiny and approval by Notified Bodies. Only Class A (low-risk) devices are exempt. Like the new MDR, these changes will require a greater investment of time, resources and money, more review of qualified persons, and the expansion of Eudamed.
It's worth noting that these requirements will be equally enforced throughout the EU, so every device manufacturer will be on a level playing field.
Guidance document as an immediate act of member states
MEDDEV 2.7.1 Rev 4, released in June 2016, is 19 pages longer than its predecessor, released in 2009, reported EmergoGroup. The new guidance requires a more detailed approach to gathering clinical data. MEDDEV 2.7.1 Rev 4 updates nearly all of the circumstances for collecting clinical data, including when and how, the role of equivalent devices, the need for transparency and other elements. Let's look at a few of these changes:
Equivalence approach: Manufacturers will need to take biological, clinical and technical characteristics into account. Additionally, equivalence can only be based on a single device, the device cannot show significant difference in safety or performance, it must be manufactured through some special treatment, and the manufacturer should make an effort to measure clinically relevant specifications in both devices. That means it might be impossible to demonstrate equivalence in scenarios where there is limited access to the technical documentation for the device acting as the basis for comparison.
Scientific validity: There are numerous conditions that might tag a report as scientifically invalid. These transgressions might be basic and unintentional, like a lack of information on elementary aspects, a statistically insignificant sample size, or inadequate statistical methods. On the other end of the spectrum are items like misinterpretation of the data or even illegal activity on the part of the authors.
Devices for unmet medical needs: When patients experience a condition for which currently approved devices are inadequate, there is a process by which manufacturers can provide patients with access to a medical device that has not made it to market. Essentially, the manufacture must provide clear benefits and statistical support to gain clearance to conduct a study and include patients in that study.
When to update a clinical evaluation: There are occasions that justify updating a device's clinical evaluation. Those include: new information from post-market surveillance, annually if the device carries significant risk, every two to five years if there are few risks, or with any outside justification.
The first push to revise ISO 13485 began in 2012. However, in 2015, that process accelerated: The second draft of a revision was released in February that year, followed by the final draft in October, which ISO and CEN passed and revised in early 2016. The new version comes with numerous changes, which include:
- All quality management system processes must be based on a risk assessment, including those that are outsourced
- Any software used as part of the quality system must also be validated and documented
- Manufacturers should maintain a comprehensive master file containing technical information for each device, including relevant specifications and records
- Anyone involved in maintaining the quality management system must have defined skills and experience
- A new clause for contamination control, designed to address issues with sterile medical device manufacture
For the full scope of each of these items, reference Drs. Akra and von Hahn's full webinar. Additionally, it's worth pointing out the Great Britain's exit from the EU will undoubtedly have some effect on the regulatory procedures for both manufacturers in the U.K. and Notified Bodies located in the U.K. providing CE regulatory approval for vendors in the EU. TÜV SÜD will have more on that change in future content, including more roadshows and webinars, so remember to check back.