EMA updates Question and Answer Document on Combination Products

Combinations of medicinal products and medical devices (medicinal product/drug-medical device combinations) are a challenging regulatory issue. After all, these products have to comply with both medicinal product regulations (e.g. GMP) and medical device and IVD regulations (e.g. ISO 13485). For this reason, guidance on these products from the authorities is very helpful. A Q&A document published by the European Medicines Agency (EMA) on this topic is updated continuously. It focuses on quality-related issues relating to these products in the context of authorisation. Below are some notes on the latest update.

The latest additions date from summer 2024 and are already revision 4 of the original document. Changes are labelled as 'Rev' or 'New'. And there are a lot of them.

The changes concern:

• The introductory text, whereby more or less only editorial changes apply here (e.g. title adjustment etc.) 
• 1.1 The question of which regulatory framework applies to products that contain a medicinal product and a medical device 
• 2.2 Article 117 (Medical Device Regulation, MDR) and its influence on medicinal products 
• 2.3 Provision of the Notified Body Opinion in the context of the marketing authorisation of the combination product 
• 2.5 How Article 117 of the MDR influences an integral combination device (iDDC).
• 2.6 Possible updating of the declaration of conformity in the event of changes to the medical device or parts thereof after authorisation of an integral combination product 
• 2.7 Submission of minor variations within the scope of the authorisation for integral combination products in the event of changes to the medical device or parts thereof 
• 2.8 Submission of questions on the opinion of the notified body in the case of changes to the medicinal product for an integral combination product 
• 2.9 Question on the submission of a Notified Body Opinion for devices that were placed on the market under the previous regulations (Medical Devices Directives 90/385/EEC or 93/42 EEC) with regard to compliance with Article 117 
• 2.11. Impact of the MDR and Article 117 on applications for authorisation of an integral combination product after 26 May 2021 in the context of a mutual recognition procedure 
• 2.13. Applicability of the UDI (unique device identifier) requirements to a medicinal product that contains a medical device as an integral part 
• 3.1 Impact of the MDR on co-packaged medical devices 
• 3.2 Requirements for the labelling of medical devices to which a medicinal product is added 
• 3.2.1 Alternatives to the labelling of individually packaged Class I and IIa medical devices 
• 3.3 Possible updating of the declaration of conformity in the marketing authorisation for co-packed medical devices 
• 3.4 Dealing with co-packed medical devices that have been classified higher and require the opinion of a Notified Body for the first time 
• 4.1 Dealing with the consultation procedure for an ancillary medicinal product that has already undergone a consultation procedure under the former Medical Devices Directive 
• 5.1 What type of consultation procedure is necessary for a companion IVD to a medicinal product

The amendments should be read in conjunction with the respective basic documents for medical devices (Medical Device Regulation, MDR, Regulation 2017/745 and the In Vitro Diagnostics Regulation, IVDR, 2017/746). And, of course, with the EMA guideline on quality requirements for medicinal products containing medical devices.

Conclusion: Eighteen of the 23 questions have been changed in revision 4. That's quite a lot!

The entire document can be viewed on the EMA website. As a special service, the EMA also offers a version with change tracking so that you can follow the changes directly. However, due to the many changes to the previous version, the document is difficult to read.

With regard to the design process, the ECA is organising the Live Online Training Design Controls for Drug-Device Combination Products on 15/16 October.