Richard,
I absolutely love the great advice, assistance and information that you provide in the forum. However, on this topic Combination Products or in the EU Drug Device Combinations DDC), I do not agree.
In this case I believe we are discussing a device that is used to deliver a drug, as address in Article 1 (9) of the MDR and not a device that has an ancillary medical product as addressed in Article 1(8).
For this situation, the MDR states:
"Any device which is intended to administer a medicinal product as defined in point 2 of Article 1 of Directive 2001/83/EC shall be governed by this Regulation, without prejudice to the provisions of that Directive and of Regulation (EC) No 726/2004 with regard to the medicinal product.
This would address devices that are separately provided or co-packaged with the Medicinal product. As such, these must be fully compliance with this regulation (MDR) which means DOC, CE Marking, etc.
The exception to this requirement is addressed in the following paragraph, which states:
However, if the device intended to administer a medicinal product and the medicinal product are placed on the market in such a way that they form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single integral product shall be governed by Directive 2001/83/EC or Regulation (EC) No 726/2004, as applicable.....
This means that these products are NOT medical devices subject to the MDR regulation but are ONLY subject to the Medicinal Product Directive.
Article 117 is somewhat confusing, first, it is ONLY describing what the marketing authorization (which is submitted under the medicinal product directive) is to contain, as these products are ONLY regulated under that Directive (per Article 1). Second it combines both the to the second paragraph to Article 1(8) and the second paragraph of Article 1(9). I have not had experience with Products in Article 1 (8), but products that are Described in Article 1(9) have never been required, allowed or accepted to be certified by a Notified Body to the directive (or now the Regulation) and CE marked under the MDD or the MDR. Declarations of Conformity (to the MDD or MDR) were not required as these products did not need to conform to the Directive and are not required to conform to the regulation.
The only requirement in the regulation is that the "If the dossier does not include the results of a conformity assessment referred to in the first subparagraph (which as I have asserted, has never been provided for integrated drug delivery devices but possible could be relevant for products that meet the requirements under Article 1(8)) and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with Regulation (EU) 2017/745 (this excludes class 1 devices that do not require a NB), the authority shall require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements set out in Annex I to that Regulation issued by a notified body designated in accordance with that Regulation for the type of device in question. Please note the use to the term "that Regulation" twice in the last part of this Article. This is stated as a requirement as part of the Medicinal Product Directive referring to "that" regulation, which is the MDR.
There surely may be some flaws in this analysis, as the construction of this Article is not the best, but it would seem that these products do not require any Declaration (such as a DOC) and only need an opinion from the NB as to whether these is sufficient evidence that the "Device Part", if it were able to be used separately, would comply with the GSPRs in Annex 1. Even this is not clear, as, since the device and medicinal product are inseparable, separating the device "safety and function" from the drug "safety and efficacy" is sometime problematic. However, that was not the crux of the original question.
I believe the original question was regarding the situation where the integrated device, if used separately, would be class 1 and not require a NB. As in the past, this would fall to the Marketing Authorization Holder (MAH) to make the case that the device part meets the applicable Annex 1 GSPR requirements in the Marketing Authorization Application. This has always been provided as a "checklist" or table, which includes, or references as available in the technical file, the supportive information and data. This could, in some cases be considered a Declaration of Conformity, but it is not the same as is described in the MDR.
I hope that this at least generates some good discussion.
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Lee Leichter RAC
President
Fort Denaud FL
United States
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Original Message:
Sent: 10-Feb-2023 05:14
From: Richard Vincins
Subject: MDR Article 117 Annex I
Hello Anon,
There are still quite a few unanswered questions or intent of approach under Article 117 which by 2023, 6 years after the EU MDR was published, would have hoped there would have been some guidance by now. With that, these statements are my opinion or how I believe should be handled, but there may be differing opinions or thoughts on how Article 117 is approached. I have seen two or three presentations on Article 117 in the last few years and there is definitely no consistency on the approach.
The first thought I will provide is any medical device, defined as a medical device, whether combined with medicinal products, used on their own, or such, would need to comply with all of the necessary requirements of the EU MDR (and EU IVDR). This means requirements such as Declaration of Conformity (DofC) Annex IV or General Safety and Performance Requirements (GSPR) Annex I or placing of CE Mark Annex V are applicable to any medical device, regardless of class. The second thought in regard to Article 117 and GSPR, basically has to show conformance to Annex I. Many believe this is just submitting a GSPR Matrix (or checklist, but I do not like to use that phrase now), but in fact when needing to meet Annex I, basically will be putting together a complete Technical Documentation index/file under Annex II.
To answer your questions:
1) Not following completely the question, but under Article 117 there needs to be a Declaration of Conformity or a CE Certificate issued by a Notified Body. However, again going back to Articles in the regulation, Annex IV, any medical device would have a Declaration of Conformity (DofC), so a DofC would be needed. There is the word 'or' in the text which seems to indicate either a DofC or a CE Certificate. I view it as 'and/or' meaning if regardless of Class of device there is a DofC, and for those applicable Class I, and Class IIa and greater can also obtain a CE Certificate.
2) I do not read the text in the regulation this way. If the product is a medical device, regardless of Class and regardless of co-packed/integral device, then there would be a DofC. Again, there are a lot of differences around application of this Article. Primarily, would need to understand exactly what type of 'integral device' is being discussed and how this would fit into a review under Article 117; maybe seek further expert advice.
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Richard Vincins ASQ-CQA, MTOPRA, RAC
Vice President Global Regulatory Affairs
Original Message:
Sent: 09-Feb-2023 09:30
From: Anonymous Member
Subject: MDR Article 117 Annex I
This message was posted by a user wishing to remain anonymous
Article 117. When you have a 1(9) integral device. The marketing authorisation dossier shall include, where available, the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements set out in Annex I to that Regulation contained in the manufacturer's EU declaration of conformity. (Your device is a Class I device, NBop is not required).
1) if the manufacturer of the Device doesn't have a Declaration of Confirmity (DoC) and if it is not registered as Legal manufacturer under MDR. It will be correct for the MAH to sign the Annex I without any DoC to refer to?
2) For definition then you will not be a medical device Class I ( as there is not a DoC). You will be a integral Device in compliance with Annex I. This was correct for MDD but is it enough to comply with what is required in the MDR?
Thank you