Euro Convergence: Mind the gap in MDR's treatment of combo products

Regulatory NewsRegulatory News | 11 May 2021 |  By 

Navigating the re-consultation process for drug-device combination products under EU’s new Medical Device Regulation can be tricky business, said panelists during a session at Euro Convergence 2021.
Speakers at the combination products-focused session shared experiences and highlighted gaps where manufacturers still need clarity from competent authorities, who themselves are feeling the strain of implementing new regulations while they continue to sort out post-Brexit changes.
Janine Jamieson, of Jcombinations and International Pharmaceutical Quality in Sweden and the US, gave a high-level view of the issue, explaining that drug-device combination products incorporating ancillary medicinal substances will require a new consultation procedure under Medical Device Regulation (MDR) even if the product had previously had a successful consultation under the Medical Device Directive (MDD). The MDR is set to take full effect on 26 May 2021. (RELATED: “Euro Convergence: Navigating changing regulation of drug-device combination products” Regulatory Focus 28 October 2020)
A notified body and the manufacturer can choose a competent authority together, and while they “can in theory go to any competent authority,” not all competent authorities do consultations, Jamieson said. The consultation concerns the drug substance aspect on its own and how it functions inside the device. However, Jamieson noted that there are “variable procedures and timelines” across Europe depending on which competent authority is chosen for the consultation. A consultation with the European Medicines Agency (EMA) is also mandatory if a product is derived from human blood such as albumin and thrombin, or if the product is determined by MEDDEV and EMA to be derived from biotechnology.
High risk devices that incorporate a medical substance which previously fell under Rule 13 of the MDD now fall under Rule 14 of the MDR. Guidance on whether the product can be defined through pharmacological means, immunological means, or metabolic means to determine whether an ancillary substance is classified as a medicinal product or a medical device “has been incredibly useful in describing the consultation process” for MDD, and is currently under review for MDR, Jamieson explained.
Industry concerns for MDR include lack of published guidance, how to handle legacy devices, and scarcity of resources; in some cases, notified bodies are still waiting for their MDR designation. Resource limitations from medicines competent authorities are also worrisome. Additionally, there has been a lack of clarity in the level of assessment and detail of report, and handling of changes, such as when a critical supplier under MDD changes under MDR.
Don’t use MDD arguments for MDR
Jonathan Sutch, senior medicinal technical specialist, at BSI in the United Kingdom, provided more detail on the MDCG 2020-12 guidance, which concerns the consultation process from MDD to MDR as well as the removal of the “liable to act on the body” clause in the MDR. Specifically, the new MDCG 2020-12 guidance states that if a manufacturer used the “liable to act on the body” as a justification that their device doesn’t fall under Rule 13 of the MDD, the manufacturer of that device must undergo a consultation under Rule 14 of the MDR.
It is “a really bold statement,” Sutch said, “and not a very helpful statement.” He noted it may have implications for many manufacturers moving forward, and clarity is being sought from the European Commission on this guidance. While some competent authorities have indicated they would be “pragmatic” in assessing drug-device combination products under Rule 14 of the MDR, “it doesn’t quite go far enough,” Sutch said. For instance, “different designating authorities can interpret this ruling slightly differently, leading again to this uneven playing field for notified bodies and manufacturers.”
He advised manufacturers attempting to determine whether their device falls under Rule 14 to consider whether the ancillary substance in a device can be used as a medical product outside the device, and if it has an “ancillary action in the device.” Manufacturers should look at the wording of Rule 14 of the MDR and see how it applies to their device, rather than using claims they would have made under Rule 13 of the MDD. Any disputes between the notified body and the manufacturer will need to go through the Article 51 classification dispute process.
“Manufacturers really need to understand their products and the regulation when arriving at a classification determination,” Sutch said.
Julia Frese, director of medical and health service at TÜV SÜD Japan, echoed Sutch’s comments on how competent authorities would examine a drug-device combination product under MDR. For actions ancillary to the device, “the question is, ‘Is the risk overriding the benefit when you include such kind of an ancillary substance towards a medical device?’”
“This is actually what also competent authorities will look on,” she said. “I know from current cases which have been performed under the consultation of MDD, this is exactly also the questions which competent authorities are asking.”
MEB as a competent authority
Waldo Weijers, Senior Advisor of the NL Medicines Evaluation Board Utrecht in Utrecht, Netherlands, highlighted and provided an update some of the concerns the Medicines Evaluation Board (MEB) has with the MDR in 2021. To address problems with “peak loads” of drug competent authorities as a result of re-consultation under MDR and post-Brexit transfers of medical devices from to another drug competent authority, MEB has performed pipeline meetings with three notified bodies so far, Weijers said.
In total, MEB anticipates 50 products will need re-consultation under MDR, a number that is piled on top of transfer requests for products where MHRA was the drug competent authority, as well as consultations for new products under MDR.
“We’re doing our best,” Weijers said. In offering a transfer for MHRA products, MEB “did it for the patient, of course, to maintain a form of pharmacovigilance for the products where MHRA would not be in a position to do that anymore, but we are also reaching our limit.”
Euro Convergence 2021


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