As a medicinal expert at one of the leading notified bodies of the EU, I’ve been involved in the assessment of medicinal files of many different device-drug combination products. These are devices that include ancillary medicinal substances, in which the device has the primary mode of action, and the medicinal substance has an additional beneficial effect. The ancillary medicinal substances range from small molecules to human blood derivatives and recombinant products. Depending on the nature of the ancillary medicinal substance a consultation with a national competent authority or the EMA is required. Human blood derivatives and recombinant products are higher risk products and therefore require assessment by EMA. The consultation process for medical devices is comparable to filing a market application.
The notified body acts as liaison between the manufacturer and the competent authority, the consultation process is conducted by the notified body and therefore the aim of the notified body review is to ensure that the dossier complies with the requirements of the competent authority. These requirements are similar to the requirements of dossiers for medicinal substances (CTD format) and additionally, the notified body includes a usefulness report. This usefulness report gives a summary on the risks and benefits of the inclusion of the ancillary medicinal substance and will only be generated if the benefit is considered to outweigh the risk.
When there are changes to the device that affect the ancillary medicinal substance a supplementary consultation (variation) may be required. The classification of the change on the ancillary medicinal substance is assessed using the EMA classification guideline for human medicines. Based on the type of change and the competent authority that is used for the initial consultation a judgement is made if a supplementary consultation (variation) is required. In some cases, a change would be reviewed in-house and the outcome of the review would be shared with the competent authority to check if they agree with the assessment and agree that this change can be approved without a supplementary consultation.
Some drugs use devices, such as syringes or nasal sprays for example, as administration tools. Since the implementation of the medical device regulation in May 2021 a notified body opinion (NBOp) is required in the market application dossier for devices that are integral to drugs. This is an assessment which provides a statement on the conformity of the device part with the relevant GSPRs as set out in Annex I of the MDR. As a medicinal expert, I was involved in reviewing the article 117 applications from a medicinal perspective to identify the risks/hazards associated with administration of the drug that needed to be addressed in the documentation of the device. In summary, I have extensive experience in interacting with the major EU competent authorities and EMA. I know what is expected to be included in the medicinal dossiers for medical devices that include ancillary medicinal substances. And additionally, I have experience in performing reviews for drug-device combinations that fall under article 117 of the MDR, and therefore will be able to advise what needs to be included in the technical file for the device of the drug-device combination.