Notified bodies will need to clear a few more hurdles when recommending a CE Mark for a drug-device combination in the UK.
The UK’s Medicines and Healthcare products Regulatory Agency issued updated guidance for notified bodies to evaluate drug-device combination products. The new guidance refers to medical devices incorporating an ancillary medicinal substance, such as drug-eluting stents, catheters coated with heparin or antibiotics and wound dressings with antibacterial agents.
Information addressing the safety, quality and usefulness of the medicinal substance should be submitted to the notified body and then forwarded to the MHRA. The notified body must first verify the “usefulness” of the medicinal substance as part of the medical device, taking into account the intended purpose of the device.
The notified body must seek a scientific opinion from one of the competent authorities on the quality and risk of the drug/biologic, including the clinical benefit/risk profile of the incorporation of the medicinal substance into the device.
The medicines competent authority should review the data available on the medicinal substance as it is incorporated into the device. The competent authority will then inform the notified body of its opinion, “taking into account the manufacturing process and the data related to usefulness of incorporation of the ancillary medicinal substance,” the guidance says.
The notified body should consider the opinion of the competent authority and use its judgment to either approve or reject the drug/device combination. The notified body should have a preliminary opinion before approaching the MHRA regarding the suitability of the device incorporating the medicinal substance.
The EU Medical Device Directive requires the notified body to prepare an assessment of the usefulness of the drug/biologic as incorporated into the device before submitting the consultation application to the competent authority. A copy of this assessment should be included with the submission.
The guidance notes that the notified body may choose which competent authority to consult with, and the European Medicines Agency may be consulted when the drug has been authorized through the centralized procedure. The EMA must be consulted for all medical devices incorporating ancillary human blood derivatives.
The MHRA strongly recommends a pre-submission notification and meeting to prevent delays to the assessment process.
After considering the submission, the MHRA will send its report to the notified body on the safety, quality and usefulness of the medicinal substance in relation to the intended purpose of the device. Following receipt of the final decision notification, the notified body should communicate its decision to the MHRA using Form NB202.
For devices incorporating a known ancillary medicinal substance, the target assessment time is 100 days. Otherwise, the target assessment time is 150 days.
A new consultation form should be completed if there is any change in the design or manufacture of the device that could influence the quality, safety or usefulness of the drug substance in the device. A supplementary consultation may be required in cases of a change to the supplier, a change to the formulation or manufacturing process or a change in packaging or sterilization.