Digital Therapeutics and Medical Device Regulation: What Evolve for Manufacturers? 

Not only are there 100 new articles and 4 new rules, the MDR has 125 more pages than the MDD. This underscores how more precise and detailed the new regulation is.

There are a number of key changes worth mentioning:

• MDR has created a Unique Device Identification (UDI) for the European market. This number is attributed to each medical device available on the European market. The UDI already exists in the United States.
• MDR establishes of a comprehensive EU database, known as EUDAMED, which integrates different electronic systems to collate and process information about medical devices and their manufacturers. It will improve transparency, provide better access to information for the public and healthcare professionals, and facilitate coordination among the Member States.
• The definition of “medical device” has been broadened to include devices were previously not regulated, such as contact lenses and cosmetic devices.
• There is a new classification for Software as a Medical Device as described in Rule 11, which we will discuss below.
• MDR reinforces rules related to clinical evidence. There are stricter rules for demonstrating equivalence and requirements to plan and implement a post-market clinical follow up.
• The regulation strengthens post market surveillance requirements for manufacturers.
• The Essential Requirements from the MDD have been updated to become the General Safety and Performance Requirements with additional details and a longer list of requirements.
• Each medical device manufacturer must appoint a Person Responsible for Regulatory Compliance. The PRRC’s qualifications must meet the criteria defined in the regulation.
• The responsibilities of the stakeholders involved in the medical

Preparation for MDR started in 2019 with a gap analysis and the creation of an action plan that had to be in place to ensure compliance as of May 2021. In total, we identified 186 actions to take to ensure that our products currently available in Europe followed the new regulation.

Our main project concerned the updating of our internal processes. For example, we re-evaluated the risk classification of our products and updated our manufacturing processes to comply with the new class requirements. We also adopted a process for creating a Unique Device Identification number to each of our digital therapeutics in Europe, and we updated out post market surveillance and vigilance processes. Finally, we assigned a PRRC: Raffi Krikorian, who is our Senior Vice President of Quality Assurance & Regulatory Affairs.

In addition, the MDR introduced a new rule to specify the classification for Software as Medical Device. The SaMD classification looks at two important criteria: A software’s intended use (providing information, monitoring physiological processes, monitoring vital physiological parameters and so on) and the risks for the patient (irreversible deterioration of state of health, serious deterioration, immediate danger, or death). As with medical devices, SaMD is classified based on the inherent risk, and all SaMDs are required to undergo clinical evaluation and ongoing assessment.

Our notified body evaluated the work done during our most recent annual audit in October 2021. It was a successful audit, as our ISO 13485 and Medical Device Single Audit Program (MDSAP) certifications for the United States and Canada were renewed gives us confidence that we will receive our next European clearances – the CE Mark – meaning that we have meet the safety and health requirements necessary to be sold in Europe. This also shows that our notified body trusts and values our work as a manufacturer.

Articles 83 to 90 of the MDR describe what is expected in terms of post-market activities. Concretely, the European Union asks the medical device manufacturer to report activities by completing specific report. These include the Periodic Safety Update Report, the Trend Analysis led by the Complaint Handling Unit, and the Post Market Clinical Follow-Up conducted by Medical Affairs.

Per article 88 of the MDR, manufacturers should perform a “trend analysis” to identify statistically significant increases in the frequency or severity of incidents that could have a significant impact on the benefit-risk balance, and that have led or may lead to unacceptable risks to health or safety of patients. If a negative trend is observed, we are responsible for reporting it.

At Voluntis, the Complaint Handling Unit performs the trend analysis every six months. The Risk Management and the Medical Affairs teams then reviews this analysis. This helps to ensure that we have done a thorough analysis and identified all trends in increased incidents.

MDR was written to ensure four things:

• The strengthening of health security.
• The improvement of traceability and transparency.
• The harmonization of the rules within the members of the EU.
• The adaptation to significant technological and scientific progress made in the past 20 years.

For medical device manufacturers, the MDR details precise evaluation criteria and references to guide us in evaluating our product to make sure they are 100% safe. We have been studying the MDR for three years now, and we are comfortable with and ready to meet the EU’s expectations and do business under the new regulations.