Euro Convergence: Navigating changing regulation of drug-device combination products

| 28 October 2020 |  By 

As European regulators prepare to implement new requirements for drug-device combination products under the upcoming Medical Device Regulation (MDR), manufacturers and notified bodies are grappling with some of the lingering questions.

“There are still some gaps… and some areas where we’d like to see more certainty, but until then we will continue to keep the dialogue going,” Jonathan Sutch, PhD, senior medicinal specialist at the notified body BSI Group, said during a drug-device combination-focused session at Euro Convergence 2020 virtual meeting.
Coming up with guidance related to drug-device combinations under the MDR has been an iterative process with a lot of feedback from stakeholders, said Armin Ritzhaupt, PhD, scientific administrator at the European Medicines Agency (EMA).

“What has been key and quite critical, and I think it’s still an element that we can improve on, is the communication and collaboration,” Ritzhaupt said.

Under the MDR, which takes full effect on 26 May 2021, various types of drug-device combinations will face new regulatory hurdles. (RELATED: “Combination Products and MDR: EMA Offers New Draft Guideline” Regulatory Focus 03 June 2019)
Devices to administer medicines
The first category of drug-device combinations are devices that administer medicines, including co-packaged devices.

New MDR requirements for co-packaged devices include General Safety and Performance Requirements (GSPR) 10.3, which is similar to requirements under the Medical Devices Directive (MDD), Sutch explained. However, the wording has been changed to clarify that a medical device cannot be used with a licensed medicine in an off-label fashion.

“Labeling, however, remains a sticky issue for co-packaged products,” Sutch said.

Under GSPR 23, there is a lengthy list of requirements for labels for device use. However, these requirements are different from the medicinal product labeling requirements. This presents a challenge for the manufacturer of a co-packaged product, who will need to comply with both, Sutch explained. Currently, a draft guidance document from the EMA clarifies that the medicinal product directive labeling takes precedence, but it’s unclear if that guidance should be interpreted as superseding the MDR.

“It’s not clear for us as notified bodies if we can ignore the elements of GSPR 23” when assessing a co-packaged product, Sutch said. “This is something that we’re pushing for a little more clarity on because notified bodies, and particularly manufacturers, are stuck between the requirements of the two regulations.”

Ancillary Devices
The next category of combination devices includes products where the primary action is physical, but which contain an ancillary medicine, such as a drug-eluting sent. These products are regulated as devices and fall under Rule 14 of the MDR.

Under this framework, the notified body needs to assess the usefulness of the ancillary medicinal substance in the device and then seek a scientific opinion from the Competent Authority. As part of this assessment, the sponsor needs to provide a medicinal dossier in CTD format.

“A medicinal dossier is often a challenge for smaller device companies,” Sutch said. “But, as I said, there is good guidance out there.”

The most significant change under Rule 14 may be the removal of the phrase “liability to act” upon the body, which was present in the MDD’s Rule 13. Recent guidance from the Medical Device Coordination Group (MDCG 2020-12) says that if the device did not fall under Rule 13 of the MDD due to liability to act, it must have a consultation under Rule 14.

“This is a very bold statement and may have implications for many manufacturers, and we’re urgently seeking clarification from the European Commission on this,” Sutch said.

Until there is additional guidance, manufacturers falling into this “hole” will need to go through an arbitration process with the Competent Authority and the MDCG over classification. “Obviously this is not ideal,” he said.
The MDCG 2020-12 also requires that combination devices that had a consultation under Rule 13 also receive a new consultation under Rule 14. The document requirements include a statement about all the changes to ancillary medicinal substances over the lifetime of the MDD certification. But one open element in the process is timing. A full consultation takes 210 days, as it did under the MDD. But for products that had a consultation under MDD and are transitioning to MDR, the MDCG is advising the Competent Authorities to expedite the review. “What this means in practice is not known,” Sutch said.

Integral Devices
The third type of combination device is a device whose main purpose is to deliver medicine, but the medicine and the device form a single integral product, such as a pre-filled syringe or inhaler. These devices are regulated as a medicine but the device must also show conformity under MDR Article 117.

For any marketing application of this type of integral drug-device combination, the device should either have a CE certificate, a declaration of conformity, or a notified body opinion on the relevant safety and performance requirements.

Required documentation for a notified body opinion includes a GSPR checklist, top level summary reports, and detailed supporting data and reports.

“The notified bodies don’t take the reports on trust. We need to verify the data in order to verify compliance of the device part to the GSPRs,” Sutch said.

Euro Convergence 2020


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy