Article 117

Article 117

There is a common practice in quality audit reports of listing issues in terms of priority or importance. Whichever issue is documented in the first and second point are generally viewed as the critical issues which the Auditor is particularly concerned about..

There is no legal or GxP reason for this approach and indeed sometimes all points raised are equally important. But it can be viewed as an unwritten understanding.

It is similar to when you are doing a presentation it is always a good idea to put your single most important point, that you want people to remember on Slide 1 but no later than Slide 2. On a side note, this can be a cultural issue when you are dealing with dispersed virtual teams. In some cultures it is expected that you give a good background or reason before you get to the SMIP and in others not so; this can lead to interesting culture clash if you are the person giving the presentation. But in general, it is a good idea to have all your important points up and centre.

Which brings me to Article One Hundred and Seventeen… yes 116 articles into MDR we have 117. And it is not even a big article, two or three paragraphs at most but it has had a massive , possibility unforeseen impact.

REGULATION (EU) 2017/745 

Perhaps at the time of drafting the concept of drug-device products was seen as limited field and the Article was just putting some meat on the bones of a similar requirement in the MDD which apparently was never enforced and maybe ignored or unknown to Pharmaceutical Competent Authorities. This has changed since the drafting and final text. In the last few years there has been an explosion of innovation in the pharmaceutical arena, particularly with biologics and also with delivery of drugs.

What Article 117 expects is that for drug device product where the intended action is pharmacological and the device and drug are integrated that one of the following options are met;

1. The device element is CE marked; may be possible if there is a partnership between a device manufacturer and pharmaceutical company.

2. There is an EU Declaration of Confirmity; this is a self declaration for some Class I devices.

3. A Notified Body Opinion is issued; perhaps the route established drug-device manufacturer’s may need to take.

For a number of pharmaceutical companies who have an integrated drug-device it is unlikely that the device element is CE marked and this will be the first time they have needed a Notified Body.

Let’s leave the headache of trying to get a Notified Body out of the equation and consider what is an Notified Body Opinion? Luckily the EMA have stepped into the breach and have issued guidance that indicates what the EMA requires from their viewpoint.

But there remains so many questions. The areas I am examining are how legacy products which require renewing will be dealt with and what involvement relationship a Notified Body will have after a Notified Body Opinion has been issued. There is also no clear indication if a manufacturer can seek NB Opinions from multiple Notified Body organisations. The relationship is between the MAH and NB. This may not be as. far fetched as you would think. The EMA are indicating that they would like a NB opinion on Day 0 (Zero) of the marketing authorisation submission and appear not interested in parallel tracks. If I am a drug company with a new product in the pipeline would it be a good business approach to reduce risk of a Notified Body Opinion delaying my launch day (particularly for a generic company!) by having at least two Notified Body organisations involved to ensure at least one will deliver in time.

For products which Market Authorization is being renewed it has been stated previously by the EMA that it is a review approach of product efficiacy and pharmacovigilence data. So will a NB Opinion be required when market authorisation is required or will it only be new products. I did hear on a recent podcast from Easy Medical Device who had Theresa Jeary as a guest that anecdotally it would appear Competent Authorities have now realised that even under the MDD there was suppose to have been a formal declaration of a device the MDD Essential Requirements and have requested this at renewal. It was not indicated if this was widespread or if it had an impact on renewal of a product.

Likewise is the NB Opinion a once off commercial activity during initial registration between the MAH and the NB. The EMA have indicated that it will be the MAH decision to decide if any changes require a new Opinion but there does not appear to be an actual legal requirement to engage a Notified Body in the lifecycle management of the device.

There are many unknowns here but in my opinion this is a transformation rather than a revolution of how drug-device products will be managed from a regulatory perspective going forward. The issue of patient treatment adherence is a significant industry problem especially with the development of expensive biologic drugs and drugs which can be adjusted to suit individual patients. The costs for such drugs are high leading to innovation in drug delivery systems to ensure proper medical treatment. These systems may be complex and the involvement of experienced and knowledgeable medical device assessors will be required

Therefore for current drug-delivery product manufacturers Article 117 may be just a slight additional regulatory requirement (with a significant headache of getting the attention of a Notified Body). For new innovative drug device products the NB Opinion may an essential aspect in the product lifecycle.