EMA revises Q&A guidance on drug-device combination products

The European Medicines Agency and the Co-ordination Group for Mutual Recognition and Decentralized Procedures (CMDh) have issued a revised guidance that clarifies the information manufacturers should submit in new and existing applications for drug-device combination products. The guidance, which is in a question-and-answer format, incorporates major changes compared to a previous version issued in November 2023.

The guide should be read in conjunction with the revised Medical Devices Regulation (MDR), the In Vitro Diagnostic Medical Devices Regulation (IVDR) and Medical Device Coordination Group (MDCG) guidance documents. The MDR went into effect on 26 May 2021 while the IVDR came into force on 26 May 2022; both allow a transitional period for certain devices.

EMA announced that the guidance is “based on the experience gained since the implementation of the new regulations and actual cases encountered.” 

The guidance also complements EMA’s guideline on quality documentation for medicinal products when used with a medical device. (RELATED: EMA adopts guideline on quality documentation for drug-device combination products, Regulatory Focus 26 July 2021)

The guidance is the fourth revision since the original document was issued in 2019. It contains multiple new sections, while existing sections contain minor revisions.

There is a new question 1.3 on how to obtain advice on the classification of drug-device combination products, especially for borderline products. It addresses who has the final word on the classification of drug-device borderline products; these decisions reside with the national competent authority.

There is a new question 2.4 on whether applicants and marketing authorization holders (MAHs) can obtain a notified body opinion if they partially comply with the General Safety and Performance Requirements (GSPR). The answer is no. The guidance states that “a notified body opinion concluding on partial compliance cannot be accepted as the CHMP and the NCAs do not have the remit of assessing compliance of the device part with the General Safety and Performance requirements (GSPR).

A new question 2.7 addresses the submission of minor changes for “integral” drug-device products. Examples of minor changes include changing suppliers of a device part, modifying the device’s dimension, changing the qualitative or quantitative composition of a device part, or changing the sterilization method.

The guidance states that it is up to the MAH to determine whether the change is major and can impact the delivery, quality, safety or efficacy of the products or is a minor change. For major changes, manufacturers would need to submit a variation application. However, “if the change does not impact the registered information but the MAH concludes that there is an impact on the device’s delivery, quality, safety or efficacy of the iDDC, a variation application must also be submitted.”

A new question 2.8 addresses whether manufacturers need to obtain a new notified body opinion to extend a product’s indication or add a new strength for an integral drug-device combination. The answer is yes.

The guidance states that “while the change to the medicinal product can be the trigger of the variation or line extension, this procedure might need to include a new or updated EU declaration of conformity/EU certificate/notified body opinion in case of impact to the safety or performance of the device or to its intended purpose.”

A new question 3.2.1 addresses co-packaged class I and class IIa medical devices that are not supplied with individual packaging, and a new question 5.1 addresses the consultation procedure for companion diagnostics.

EMA