Devices Containing Ancillary Medicines Likely To Need ‘Near Full Review’ Under MDR
Latest EU guidance highlights the challenges ahead for class III, high-risk, device/drug combinations when preparing for compliance under the tougher requirements of the MDR.
Manufacturers of medical devices containing ancillary medicinal substances are likely to have a lengthy journey to conformity assessment under the Medical Device Regulation (MDR), according to the latest EU guidance.
This is even if the identical product has already been successfully audited by a notified body under the existing Medical Devices Directive (MDD) or Active Implantable Medical Device Directive (AIMDD).
While there is a similar requirement for the involvement of a medicinal product authority in the drug component under the MDD and AIMDD, which remain in force until 26 May 2021, the MDR requirements are stricter and more detailed which accounts for why some products may not have an easy passage onto the market under the MDR.
The deadline for compliance for totally new products would be 26 May next year, while other products will be able to benefit from the grace period and remain on the market until 26 May 2024 under the current medical device directives, if certain conditions are met, Medtech Insight notes. But by 26 May 2024, even established products will need to go through the new, more stringent processes.
This latest position is clarified in a new six-page guidance from the European Commission’s Medical Device Coordination Group (MDCG). The guidance covers transitional provisions for consultations of authorities on devices incorporating a substance that may be considered a medicinal product, and which has an action ancillary to that of the device, as well as on devices manufactured using transmissible spongiform encephalopathy (TSE)-susceptible animal tissues.
This guidance (MDCG 2020-12) also covers in its scope human blood derivatives which have an action ancillary to the device where the notified body is required to consult the European Medicines Agency.
The guidance states that “there may be changes in the documentation of the device due to the new requirements of the MDR, for example in clinical evaluation, which have a bearing on the quality, safety or usefulness of the ancillary substance. “
It also states that the notified body may change its the assessment of the device and documentation under the MDR, requiring a reassessment or the medicinal products authority may have new information on the substance, leading to a modified or different opinion.
This should include the last opinion of the medicinal products authority under the MDD/AIMDD (whether initial or supplementary), as well as a consolidated list of changes.
And it goes one step further than the MDD and AIMDD to clearly state that the notified body may not award the certificate if the medicinal products authority opinion is unfavorable.
Well Established Review Process
Medical devices containing ancillary medicinal substances are regulated among highest risk, class III medical devices. Not only will an expert panel be involved in reviewing the notified body’s clinical evaluation procedures for such combination devices under the MDR, but as with the MDD, the European Medicines Agency (EMA), or a medicinal products competent authority, “must assess the quality and safety of the substance… including the clinical benefit-risk profile of incorporating the substance into the device” before it is first placed on the market.
This medicinal products review has always had a 210-day time-frame, but with clock stops where it has been necessary for the authority to obtain additional information from the manufacturer. It should be no longer than 60 days for a supplementary consultation where there are any subsequent changes to the ancillary substances, particularly in relation to its manufacturing process.
Possibility To Change Medicinal Products Authority
The notified body can approach any of the medicinal products authorities authorized to assess the drug, and not necessarily the one consulted under the MDD/AIMDD, except in cases where the drug element must go through the European Medicines Authority (EMA).
This is important in the context of Brexit given the frequency with which the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has provided its opinions for the medicinal product elements of class III device/drug combinations, a role that looks set to be redundant at the end of the UK withdrawal agreement at the end of this year, Medtech Insight notes.
Discretionary Acceleration In Review
Where there are no changes to the medicinal product, nor to the medical devices element, this should be declared and, if many elements concerning the substance remain identical, then the medicinal products authority is “highly recommended to expedite its review,” the MDCG says.
Medical Devices Containing Animal Tissue
The guidance also covers in its scope medical devices containing animal tissue susceptible to TSE.
It was already mandatory through Regulation 722/2012, concerning active implantable medical devices and medical devices manufactured utilizing tissues of animal origin, for notified bodies, through their competent authority, to carry out a consultation of the other competent authorities and the commission on the safety of the animal tissue element. Under the MDR, this requirement remains unchanged.
Under the first certification under the MDR, the notified body is required to submit the full summary evaluation report as stated in Regulation (EU) 722/2012 to the competent authorities. If there have been no changes to the documentation required from the manufacturer, the summary evaluation report may be accompanied by a declaration by the notified body, stating elements that have remained identical. In addition, if there have been no changes to the assessment of this documentation by the notified body, this may also be included in the declaration.
As with medical devices containing ancillary medicinal products, the MDCG recommends an expedited review if many elements of the summary evaluation report for the MDR remain identical to the submissions under the MDD or AIMDD.