Effects of the MDR on medical devices with medicinal products
29.04.2025
We have already explained what „combination products“ are in our „Combination products/medical device & medicinal products“ article. There we considered the regulatory requirements for the various categories of combination products (1. medical device with medicinal product as an integral component; 2. medical device with additional medicinal product component and 3. medical device & medicinal product (co-packaged or cross-labeled).
Read our blog post „Combination products/medical device & medicinal products“ here.
As questions repeatedly arise, particularly in the category "medical device with medicinal product as an integral component", e.g. with regard to Article 117 of the MDR, we will take a closer look at these combination products in the following article.
What are "medical devices with medicinal products as an integral part"?
The term "medical devices with medicinal product as integral component" ("integral drug device combinations" - iDDC) is used when the main effect of the overall product is attributed to the medicinal product and the medicinal product and medical device are combined. A distinction can be made between the following subcategories in accordance with Article 1(8) second section and 1(9) second section of the MDR:
- Products which, when placed on the market, contain as an integral part a substance which, taken separately, would be considered a medicinal product, provided that the principal action of the product as a whole is exerted by that substance. An example of this sub-category would be an ingestible sensor embedded in a medicinal product.
- Products that are intended to deliver a medicinal product, where the components form a single inseparable product that is intended solely for use in that compound and is not reusable. These include, for example, prefilled syringes, autoinjectors and ready-to-use powder inhalers that are not intended for reuse once all doses have been used.
This is to be distinguished from "medical devices with an ancillary medicinal product component" in accordance with Article 1(8), first section of the MDR, where the main effect of the overall product comes from the medical device component.
What regulatory requirements apply and what should the according documentation look like?
As the main effect of the overall product is attributed to the medicinal product, it is regulated and authorized in accordance with the Medicinal Products Directive 2001/83/EC or Regulation (EC) 726/2004. For this purpose, relevant information on the medical device component must be included in the medicinal product dossier (see "A. Medicinal product dossier requirements relating to the medical device").
At the same time, however, the conformity of the medical device component with the safety and performance requirements according to Annex I of the MDR must also be demonstrated. Depending on the risk class of the medical device component, it may be necessary to obtain an opinion from a notified body on the relevant safety and performance requirements ("Notified Body Opinion" - "NBOp" for short) in accordance with Article 117 MDR. This applies to devices for which the involvement of a Notified Body would be required for the conformity assessment of the medical device part alone (classes Is/m, IIa, IIb, III). For this purpose, the GSPR checklist (GSPR = General Safety and Performance Requirements) and the relevant information and documents associated with it must be submitted to the notified body (see "B. Notified Body Opinion-required documentation"). Proof of conformity with the safety and performance requirements according to the MDR can alternatively be provided by a declaration of conformity / CE certificate.
A. Medicinal product dossier requirements regarding the medical device
- Modul 1:
- Information for healthcare professionals: name of the medical device, product description, instructions for use, shelf life, storage conditions and materials of the individual components
- Package insert: Instructions for use with "Handling instructions"
- Labeling:g. relevant symbols relating to the medical device on the outer packaging but no CE mark; this should only be affixed to the medical device itself.
- Modul 3.2.P:
Product description of the medical device and its suitability for the combination product including sterilization, if applicable, specifications, relevant aspects of the container closure system, manufacturing process including its development, validation and monitoring, and stability - Modul 3.2.A.2:
Information regarding the use of materials of human or animal origin and corresponding risk assessment (e.g. regarding TSE pathogens and viral safety) - Modul 3.2.R:
- Summarized information on studies conducted (including user studies)
- Proof of compliance with the requirements of the MDR, Annex I:
- Class I: (Class Is/m are not included): EU declaration of conformity or declaration by the applicant that the relevant safety and performance requirements (GSPR) are fulfilled
- Class Im, s, r, IIa, IIb, III: EU declaration of conformity / CE mark or opinion by a notified body on the relevant safety and performance requirements ("Notified Body Opinion" - NBOp) in accordance with Article 117 MDR
- Modul 5:
Study data (including user studies)
The required information listed above varies depending on the type of medical device component or combination product. Evidence of compliance with the relevant safety and performance requirements of the MDR (EU Declaration of Conformity, CE mark or Notified Body Opinion "NBOp") should, if possible, be submitted directly as part of the Marketing Authorization Application ("MAA") to the competent medicinal product authority as described above. They can also be submitted later in the course of the procedure, but this may result in additional procedural delays.
B. Notified Body Opinion-required documentation
If it is necessary to obtain a Notified Body Opinion (according to Article 117 MDR) to demonstrate the conformity of the medical device component with the safety and performance requirements of the medical device part according to Annex I of the MDR, the Notified Body must be provided with relevant information / documents for its assessment. These can be, for example
- Rationale that helps the reviewer to classify the product in regulatory terms
- Product description including intended purpose and user group, risk classification of the medical device component and description of the individual components and materials
- Instructions for use
- GSPR checklist (GSPR = General Safety and Performance Requirements) and corresponding associated documents:
- Information from the manufacturer of the medical device component, such as QMS certification, specifications, certificates of analysis for materials used, technical data, test reports, risk management documentation, sterilization validation
- Relevant product information for the overall product such as specifications, design verification, packaging information, risk management documentation, biocompatibility studies, stability studies, user studies, transportation studies.
It must be determined on a case-by-case basis which documents should be submitted to support the GSPR checklist. While complete technical documentation is not required, the relevant documents must be well-structured and easily searchable. In most cases, summary reports are sufficient, as raw data is typically not necessary.
It should also be noted that data collected by the manufacturer of the medical device component (e.g. user studies) may not be transferable to the overall product. Ultimately, the responsibility for this lies with the applicant for the marketing authorization application for the overall product.
The Notified Body Opinion is duly taken into account by the competent medicinal product authority in its assessment of the overall product. However, once approval has been granted by the medicinal product authority, the Notified Body has no further monitoring function, e.g. in the form of audits.
What requirements apply to products already on the market?
The conformity of the medical device component with the safety and performance requirements according to Annex I of the MDR does not have to be demonstrated retroactively and for devices already on the market.
However, it should be noted that as soon as changes are made to the medical device component, an assessment of "significant change" must also be carried out for these products in accordance with Art. 120(3) of the MDR. This may mean that the required new or updated EU Declaration of Conformity, the CE certificate or the Notified Body Opinion must be submitted or the respective change must be notified to the competent medicinal product authority in accordance with the Variation Regulation and associated Variation Guidelines.
But when are changes "significant"? This question is often difficult to answer. An assessment must be made as to whether the quality, safety or performance of the combination product is affected by this change. This includes, in particular, changes to the design or intended purpose of the medical device component or the introduction of a new medical device. If there is no clear answer to the question of whether or not a significant change has occurred, the relevant competent medicinal product authority should be consulted.
What can be the biggest challenges?
The above-mentioned requirements pose a major challenge for many manufacturers of this type of combination product. For many, this process starts with the hurdle of finding a suitable Notified Body in time. Once this is found, further delays can occur as in most cases feedback from both the Notified Body and the competent medicinal product authority must be taken into account.
If the applicant for the market authorization application is not also the manufacturer of the medical device component, it is very important to maintain constant communication between the applicant and the manufacturer or to ensure this by contract. This applies not least to information regarding changes to the product and adjustments to the documentation.
The question is often asked whether it is not redundant for both the medicinal products authority and the notified body to assess certain information/data. However, this should not be the case with a well-structured submission, as the medicinal products authority focuses primarily on the medicinal product component and only assesses any interactions between the medicinal product and the medical device, while the notified body assesses the medical device component primarily from a technical perspective.
qtec as your partner
The regulatory requirements for "medical devices with medicinal products as an integral part" in Europe have been presented here in a very simplified form. They can be very complex in individual cases and different issues arise for each overall product, not least with regard to the required documentation. We will be happy to help you implement these comprehensive requirements.
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Are you also facing similar challenges with your combination product? Feel free to give us a call!
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