At the end of last May, the EMA released a new updated version of the "Q&A" addressed to applicants and marketing authorisation holders of medicinal products as well as to notified bodies, with specific regard to the implementation of the MDR (Regulation (EU) 2017/745) and the IVDR (Regulation (EU) 2017/745).
In the following paragraphs we summarise the main aspects of this new version of the Q&A, which is the result of the experience gained by the EMA in dealing with concrete cases following the entry into force of the 2 European Regulations on medical devices.
- Medical devices that form an integral product with a drug, (integral drug-device combinations such as, for example, prefilled syringes) and their management during their life cycle.
The EMA, in this new version of the Q&A, clarifies that if drugs and medical devices are placed on the market within the same package, they are not to be considered as integral combinations, but would rather fall under the umbrella of co-packaged drug-devices.
In addition, the EMA recommends contacting the national competent authorities on medicines and/or devices to obtain guidance from the individual Member State on the correct qualification/classification of drug-device combinations. This, above all, will help to clear doubts in the case of borderline products, i.e. those products for which it is not immediately obvious which regulatory framework might apply, whether that of medical devices or that of medicines
The Agency also offers detailed guidance on when a new/updated EU declaration or certification of conformity is required as a result of changes made to a device (or part thereof) after the initial marketing authorisation of the integral drug-device combination.
A further new opinion by the notified body regarding the device 'part' in an integral drug-device combination is required if a new device is introduced with an extension or line variation.
Similarly, an additional opinion is required if major changes are introduced to an existing device, such as: (i) change in design; (ii) addition or replacement of an integral device (or part thereof); (iii) change in performance characteristics; (iv) change in intended use, such as a different patient population and/or a new user (such as, for example, a home versus hospital environment) and/or a new usability study, and/or significantly different instructions for use, such as to have a potential significant impact on the supply or on the quality, safety or efficacy of the medicine.
Also in this context, EMA clarifies how so-called 'minor changes' to the terms of the marketing authorisation should be submitted for integral combinations resulting from changes made to the device (or a part thereof). In doing so, the European body gives practical examples of what it considers to be minor changes to the marketing authorisation, such as a change in the suppliers of a device, its size, its qualitative/quantitative composition or a change in the method of sterilisation of the device itself.
Furthermore, maintaining a 'case-by-case' approach, the EMA provides recommendations to MAHs on whether a new/updated opinion should be provided by the Notified Body for changes to the medicinal product (e.g. in the case of an extension of the indication, a new strength or a new pharmaceutical form or a new route of administration) in an integral drug-device combination. Indeed, changes to the medicinal product could have a major impact on the safety or performance of the device or its intended use, and in this regard, the European Medicines Agency advises that each case should be carefully and individually assessed
- Medicinal products that include a medical device in their packaging (referred to as co-packaged) and how to label them.
The EMA proposes precise guidance for those cases where 'co-packaged' Class I and IIa medical devices (such as dispensing devices) are supplied without individual packaging and when it is not technically possible to implement labelling requirements on the device itself. These devices are often supplied 'in bulk' by their manufacturer, without individual packaging and without their own packaging or IFU (this is permitted by Annex I, section 23.1 (d) of the MDR). These devices are small by nature and direct marking of any information on the device itself may be difficult or technically infeasible. The EMA, therefore, provides that the information on the medicinal product (such as the SmPC, labelling and package leaflet) should not include the information required for the device, proposing the following alternatives:
- Include a separate package leaflet containing the required information on medical devices within the packaging of the medicinal product. This leaflet should refer to the package leaflet of the medicinal product to avoid confusion.
- Attach the package leaflet of the medical device to the package leaflet of the medicinal product, forming a single folded component. The medical device section should be clearly differentiated, possibly as a tear-off section, and defined with a relevant subheading.
- Attach a folding sticker or sticker containing device-specific information directly to the device or its packaging, ensuring that the information is indelible, legible and understandable.
- Consultation procedure for medical devices containing an ancillary medicinal substance.
The European Medicines Agency recalls that MDs with an ancillary medicinal substance are those devices that incorporate as an integral part an element which, if used separately, would be considered a medicinal product. In doing so, the EMA is also concerned to provide guidance on the consultation procedure to be followed for an ancillary (or ancillary) medicinal substance on which there has already been a consultation under the Medical Devices Directive 93/42/EEC.
Pursuant to Art. 52 para. 9 of the MDR, as clarified by MDCG Guideline 2020-12, notified bodies are required to request a consultation with a competent authority for medicinal products as part of the conformity assessment under the MDR for ancillary medicinal substances on which there has already been a consultation under the Medical Devices Directive 93/42/EEC or 90/385/EEC. In each case, EMA proposes a table in the 'Q&A' from which it is possible to determine whether a full initial consultation or a follow-up consultation (variation) will be required.
- Consultation procedure for companion diagnostics.
The term 'companion diagnostic' is used to define those in-vitro diagnostic tests that are essential for the safe and effective use of a specific medicinal product to identify patients who will benefit from or are at risk for treatment. Annex II of MDCG 2020-16 presents a flow chart for determining whether an in vitro diagnostic test meets the definition of a complementary diagnostic under the IVDR.
Complementary diagnostics require a conformity assessment by a notified body and consultation with a medicinal product authority to assess the suitability of the device for the related medicinal product. The notified body will have to request a scientific opinion from the EMA insofar as the medicinal product will be subject to the new centralised authorisation procedure, whereas for medicinal products not subject to the centralised procedure, the notified body may alternatively consult a national competent authority or directly with the EMA in order to obtain a scientific opinion.