Welcome to the Drug-Device Combination Products discussion group 2021!

Hi, we’ll be starting the discussion group again from tomorrow, 6pm CET and meeting once a month - unless there are any hot topics and we can add another meeting!
Please let us know if you have any specific questions for us to consider in advance.
To start with, we can maybe discuss:

3 Likes

Hi Janine, I do not have a meeting on my calendar. Can you please forward? I do have comments on the NMPA DDC announcement.

Thanks,
Susan

Hi Jasmine,
I have one question related to this article 117: I would like to have the point of view of the group about the pharmaceutical form PATCH. To consider the backing film and the release film the device part of the drug product.
Thanks

Hi All,

Following our discussion yesterday about the transdermal patch, I have found the rule 21 applicable to my case.
Rule 21
Devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body are classified as
• class III if they, or their products of metabolism, are systemically absorbed by the human body in order to achieve the intended purpose;
• class III if they achieve their intended purpose in the stomach or lower gastrointestinal tract and they, or their products of metabolism, are systemically absorbed by the human body;
• class IIa if they are applied to the skin or if they are applied in the nasal or oral cavity as far as the pharynx, and achieve their intended purpose on those cavities;
• class IIb in all other cases.

And so the patch manufactured by my client is classified as class IIa.

Dolores

Hi!
As mentioned in the meeting yesterday, I’m currently participating in the TOPRA Masterclass Module 18. We talked about transdermal patches delivering medicines in our interactive case study session yesterday and also today in relation to a presentation by a NB representative fro BSI. The person confirmed that when you have a DDC Art 117 product where the device constituent can be classified as a class I device (if the device was to be supplied separately), then you do not need a NBOp - submitting a GSPR Checklist with your MAA application would be sufficient. Based on the outcome of the discussions, the device constituent of a transdermal drug-delivering patch could theoretically be a class I device (class 1, 2 or 21). However, some NBs might argue that a medicinal product is not a substance (i.e. not rule 21), others might accept it. Also, the definition of whether it’s measuring or not might vary from NB to NB. It was recommended that if you’re in doubt about fundamental aspect of your regulatory strategy, you present your documentation strategy, including solid justifications, up front to your NB so that they can ‘discuss and understand your approach’.
Personally, I have good experience with presenting a strategy to a NB up front. It obviously mitigates the risk level in your regulatory strategy, but in this case you need to consider whether you want to involve a NB at all, if you think that you can justify that your ‘plaster’ is a class I device.
I got the feeling that this is one of the grey zone areas where we might see different ‘rulings’ depending on which NB is involved - at least for a while until EMA and NBs are more aligned on drug-device issues.
I can highly recommend TOPRA Masterclass Module 18. Great presenters and a brilliant opportunity to exchange experiences with other people working in the area.

Correction to the post above: Rule 21 is obviously not class I. It will trigger a NBOp and should have been in a separate sentence :slight_smile: Sorry.
Christina

1 Like

Hi Christina and Dolores, sorry for the late reply, but I’m really not sure that Rule 21 is applicable for transdermal patches - as I understand it, it was meant to be for self-care substance based devices like cough syrups, lubricating or protective nasal or throat sprays etc - and to address the issue of claims being made for things like cranberry juice being a medical device after absorption. I can definitely see why you read that it could apply though, without knowing the background.

Some examples given by AESGP at the TOPRA Symposium 2018 were:

  1. Nasal sprays
  2. Eye drops
  3. Anti flatulence products
  4. Laxative capsules
  5. Moisturizing cream
  6. Ultrasound gel
  7. Intimate lubricants
  8. Nail treatments
  9. Throat pastilles

It would be great to have clarification somewhere - maybe in the borderline document under development by the MDCG? In the meantime, @theresa.jeary maybe you could comment for us? Or if anyone else has experience of Rule 21 being applicable, that would be helpful.

From the EMA website, they may be asked to review if a substance based medical device is systemically absorbed:

Medical devices made of substances that are systemically absorbed

Some medical devices are made of substances that are absorbed by the human body to achieve their intended purpose.

These devices are normally introduced into the human body via an orifice or applied to the skin.

Role of EMA

Before it can issue a CE certificate, the notified body must seek a scientific opinion from EMA or a national competent authority on the compliance of the substance with the requirements laid down in Annex I to Directive 2001/83/EC.

EMA will provide further information on the consultation procedure between the notified body and a competent authority or EMA.

See the EMA medical devices page: Medical devices | European Medicines Agency

Hope this is helpful!
Janine

Hi All,

Sorry its taken me a few days to pick on this very interesting discussion, as always it is very beneficial to see other opinions and interpretations, so that we can work on ensuring any guidance that may be developed considers this type of information.

Firstly - Thanks Christina for the feedback on the Module 18 MasterClass, pleased that you found the sessions helpful and I do agree with you that it can be beneficial to discuss your plans and approach with your Notified Body so that internally we have visibility and can understand the rationale applied - as with so many things in life, it is good to have open communications.

Regarding the lengthy chain of thoughts - a few things did come to mind as I read through the points raised and some clarifications and pointers perhaps;

  1. The intention of this Rule is to cover a wide range of exclusively substance-based medical devices and as Janine indicated - Creams, Eye drops Gels, Nail Treatments, Anti-Obesity Tablets etc, To me Rule 21 is capturing those products that may look and feel more like a medicinal product than a physical / mechanical medical device, however these Rule 21 products meet the definition as a medical device based on the achievement of the principal intended action via physical means. If you think of Rule 21 in this way, it doesn’t apply to transdermal patches - they are more like MDR Rule 4 plasters.

  2. The EMA guideline on Article 117 which referenced the classification of the “device component” of the overall medicinal product when determining if a NB Opinion would be required or when a Declaration of Conformity could be submitted is quite pragmatic and beneficial to Companies involved in Article 117 products. However, if you are trying to then classify the device component you really need to fully understand how medical device classification is conducted and consider the full text within MDR Annex VIII, including all the definitions contained within. Device Classification does work really well, but it can take a little while to really understand what is meant by the rules and how to work through the determinations to make a final decision. In terms of available guidance on how to classify, currently available is MEDDEV Guidance - MEDDEV 2.4/1 Rev 9 which of course is based on the Medical device Directive Annex IX Classification rules, but I think it would provide a nice pointer to what needs to be considered when faced with trying to classify the device component. The MDCG Guidance on Classification of Medical devices according to MDR has gone through final comment stage and I anticipate that this shall be published by May so keep an eye out for that document on the Europa Website. Just be aware that when classifying a device you work through all the rules and identify those that are applicable to your particular product, more than 1 rule can apply as well with the highest risk class taken where several rules apply.

Hope this helps your discussions and clarifies a few aspects

Kind Regards

Theresa