Update of the EMA Q&A document on Combination Products

Combination products (the combination of a medicinal product and a medical device) are increasingly "on the rise". However, the regulation governing these combination products is very complex. On the one hand, the pharmaceutical legal requirements regarding marketing authorization and GMP must be complied with. Inspections are then carried out by GMP supervision authorities. On the other hand, the legal requirements for medical devices must also be taken into account. This means orientation towards the Medical Device Regulation (MDR) and compliance with harmonized standards. A notified body may also be involved. Things are different in the USA, where there exist specific GMP regulations for combination products. For the EU area, assistance is provided in the EMA Q&A document Questions & Answers for applicants, marketing authorization holders of medicinal products and notified bodies with respect to the implementation of the Medical Devices and In Vitro Diagnostic Medical Devices Regulations ((EU) 2017/745 and (EU) 2017/746).

The document was originally published in 2019 and is intended for applicants, marketing authorization holders and notified bodies to provide guidance on the involvement of the European Medicines Agency (EMA) with regard to combination products. The first revision took place in 2019, followed by a further, very extensive revision in 2021. The relevant passages are highlighted in the document with the year. The document was revised again at the end of 2023.

What is new?

Question 2.10 has been updated and deals with the influence of the MDR and its Article 117 on the submission of a combination product (or drug-device combination, DDC, as referred to here in the document) for marketing authorization as part of a mutual recognition procedure (MRP) from 26 May 2017. The MDR came into force on 26 May 2017. The revision of this issue clarifies that the documentation for the MRP procedure/repeated use procedure (RUP) is accepted in accordance with the former Medical Device Directive (MDD) in its existing form. However, there must not have been any significant changes to the combination product since the MDR came into force. In the event of significant changes, however, the essential safety and performance requirements in accordance with the MDR and Annex I of Directive 2001/83/EC point 12, section 3.2 must be taken into account. In addition, the supporting documentation such as the certificate of conformity or a notified body opinion must be included in the dossier. A design change, a change in the intended purpose of the medical device or a new medical device are given as examples of a significant change.

Further details can be found in the document itself.