medicaldeviceslegal

The MDR and the IVDR in paper now that they finally final, printed on both sides mind you

The fat lady has her lines and is about to sing. After the lengthy legal linguist revision process (remember, these texts have to be consistent in 24 languages) the Council published the text for its first reading for the MDR and IVDR.

First reading only, after such a lengthy process in which we arrived at a ‘general approach’ sufficient for starting the trilogue.

After the trilogue we had many interesting last ditch lobby mini battles about some of the things that came out of the translation process and legal linguist review.

So now everybody (Council and Parliament) still needs to formally vote on this text but that should be – well – a formality now. Aim for entry into force this summer.

Texts and compares, and no changes?

If you haven’t got them already, the first reading texts are here for your download and perusal:

• MDR
• IVDR

And here are the compares that I myself made versus the trilogue texts (warning: these are pdfs coming from a public Dropbox directory, so your security settings may not like this at all) – I hope they are useful:

• MDR compare
• IVDR compare

Although the institutional actors in the legislative process keep saying nothing changed that was not in the trilogue agreed texts, I believe there was a bit more detail to this and so did others. Here we go:

No design dossier review after all for the class IIb active devices that transport medicines to and from the body

One of the things that came out of the legal linguist review and looked like more than minor goalpost moving was the unhappy surprise that class IIb active devices that transport medicines to and from the body would also be subjected to design dossier review under article 52(4) MDR. This was a very bad surprise for manufacturers of these devices, many of which are very well understood and proven technology. An important group of devices affected would only fall in the scope of this clause because of the (in my view weird) practice of qualification of gases used in medical setting as medicinal products.

However, this has been taken out again of the first reading text, likely after a last minute targeted lobby. Water under the regulatory bridge now.

But some changes in the transitional regime with potentially big consequences

Another interesting development that lead to a true change was the adaptation to the transitional regimes in articles 120(3) MDR and 110(3) IVDR and the associated recital 99 in both regulations. While these articles are new they clarify the transitional system that remained the same in the basis, except that reliance on the grace periods for certificates overrunning the date of application became a lot less attractive as a result.

The new provisions clarify requirements that apply to devices that are relying on the grace period of 4 (MDR) respectively 2 (IVDR) years with respect to PMS, market surveillance etc (MDR/IVDR instead of the old directives, which was unclear).

They also provide that during the grace period (and that’s an important one) no significant design or intended purpose changes are allowed anymore. In other words, the device is locked in its status quo at the date of application of the MDR/IVDR (the end of the transitional period).

This is very important for the manufacturers that will miss the boat for an MDR/IVDR certificate during the transitional period and will be forced to rely on a grace period MDD/AIMDD/IVDD certificate or are betting on using the grace period because they know that they won’t be ready for an MDR/IVDR certificate by the date of application. The penalty (or trade-off) for relying on that regime is that these devices cannot be subject to any significant changes in design or intended purpose (unless of course when the changed device is placed on the market under an MDR/IVDR certificate) for that period.

Manufacturers stuck in a grace period will therefore not be able to make any significant innovations or extend the scope of the device’s intended purpose until their notified body will be able to issue an MDR or IVDR certificate for the device. This is crucial for manufacturers in relation to transition planning: if you’re late in the day and won’t obtain your MDR / IVDR certificate during the transitional period and you are lucky enough to be able to extend your existing certificate past the date of application, your device innovation is essentially frozen until your notified body is able to issue an MDR / IVDR certificate. This will affect your competitive position in the market – see this article in MedTech Insight for more details on potential consequences of the choice to rely on the grace period.

Also, manfufacturers relying on the grace period must realise that they will be in a situation of concurrent application of MDR/IVDR and MDD/AIMDD/IVDD certificates. That means that the market can choose between competing products with an MDR/IVDR certificate or a MDD/AIMDD/IVDD certificate. Different standards, same intended purpose.  But some certificates may be more equal than others – what will you prefer if you are a hospital issuing a tender, or country in the Middle East or Asia relying on CE certificates? Certificates under the regulations or certificates under the directives? It will be interesting to see if the EU Court’s Medipac judgment (every CE marked device on the market is equally good from regulatory perspective and tendering entities may not discriminate between them) also holds when a hospital prefers MDR / IVDR certificates over ‘old’ certificates in a tender, given that it can be argued that the conformity assessment for MDR /IVDR certificates was to a higher standard (the whole idea of the new regulations in the first place). Moreover, while the Medipac judgment applies in the EU, it does not apply to tendering and regulating entities outside it.

Finally, don’t forget that the grace period referred to above is available only for devices with a notified body issued CE certificate – so not for all self-certified devices (which constitutes the majority of CE marked IVDs currently on the market for example). All self certified devices have to be compliant by the date of application of the MDR/IVDR – no grandfathering.

Manufacturers of self certified devices (class I MDD/self certified IVDs) also have to pay additional attention to whether their device remains self certified or not (not for most of the IVDs) in which case they have to be ready to deal with the bottlenecks at the end of the transitional period. For these manufacturers it will be sink or swim, because no MDR/IVDR certificate by date of application is no more placing of products on the market and off of the regulatory cliff you go.

IVD conformity assessment changes

Some amendments were made to conformity assessment for IVDs with respect to the procedures for companion diagnostics and class D devices – nothing shocking.

For companion diagnostics it was clarified that the notified body must consult a competent authority for medicines (makes sense for a companion diagnostic), as is set out in the new paragraph in article 48 (3):

“In addition to the procedures referred to in the first and second subparagraphs, for companion diagnostics, the notified body shall consult a competent authority designated by the Member States in accordance with Directive 2001/83/EC of the European Parliament and of the Council1 or the EMA, as applicable, in accordance with the procedure set out in Section 5.2 of Annex IX.”

It was further clarified that companion diagnostics need to go through the Assessment of the technical documentation procedure in Annex IX, 4.1-4.8 (see addition to Annex IX, 5.2 (a)).

None of this was new, but now it has been written down more clearly.

For class D devices it was clarified that:

“Manufacturers of class D devices, other than devices for performance study, may, instead of the conformity assessment procedure applicable pursuant to paragraph 3, choose to apply a conformity assessment as specified in Annex X coupled with a conformity assessment as specified in Annex XI.”

This is also not stunning new logic, as type examination combined with production quality assurance is a normal combination as alternative to full quality system based conformity assessment procedure for high risk devices (see article 52 (3) MDR in relation to class III devices, but also article 11 (1) (b) MDD provided this already – obviously the IVDD did not have this logic yet as it relied on another conformity assessment logic).

Other (little) details

I haven’t been able to go through both of the texts in complete detail but I spotted the some things that may be worth mentioning for each regulation – more may be forthcoming in future blogs. You will see that the numbering of articles and sections and even whole annexes has changed compared to the trilogue text, so we all will have to learn new numbering.

MDR

• New recital 18 added that “this Regulation should include requirements for devices’ safety and performance characteristics which are developed in such a way as to prevent occupational injuries, including protection from radiation.”
• Free nomenclature for use of Eudamed (recital 45)
• Scientific advice is possible for the IIb devices that are also subject to the clinical  (recital 57 and article 61 (2) MDR)
• “directly or indirectly” was taken out of rule 11 (classification of software) in Annex VIII – not sure what that means yet.
• Article 52 (9), (10) and (11) conformity assessment procedures for device-drug combinations, devices incorporating tissues and cells and substance-based devices have been clarified
• Article 78 (14) is new, giving member states more room not to apply the coordinated assessment procedure for multi-jurisdiction clinical trials yet.
• New recital 73 stating that “the principles of replacement, reduction and refinement in the area of animal experimentation laid down in the Directive 2010/63/EU of the European Parliament and of the Council should be observed. In particular, the unnecessary duplication of tests and studies should be avoided.”, which is well and good except that this recital is not operationalised in the MDR.
• New recital 99 reflecting the changes to article 120 (3) transitional regime described above.

IVDR

• New recital 16 that “this Regulation should include requirements for devices’ safety and performance characteristics which are developed in such a way as to prevent occupational injuries, including protection from radiation.”
• Additional recital language on home brew IVDs (recitals 28 and 29)
• Free nomenclature for use of Eudamed (recital 42)New recital 73 stating that “the principles of replacement, reduction and refinement in the area of animal experimentation laid down in the Directive 2010/63/EU of the European Parliament and of the Council should be observed. In particular, the unnecessary duplication of tests and studies should be avoided.”, which is well and good except that this recital is not operationalised in the MDR.
• New recital 74 stating that “the principles of replacement, reduction and refinement in the area of animal experimentation laid down in the Directive 2010/63/EU of the European Parliament and of the Council should be observed. In particular, the unnecessary duplication of tests and studies should be avoided.”, which is well and good except that this recital is not operationalised in the IVDR.
• Article 78 (14) is new, giving member states more room not to apply the coordinated assessment procedure for multi-jurisdiction clinical trials yet.
• Changes to recitals 98 and 99 reflecting the changes to article 110 (3) transitional regime described above.

Full steam ahead!

So, now it’s full steam ahead to publication, entry into force, the implementation circus and the mother of all bottlenecks towards the end of the transitional period when the newly notified MDR/IVDR notified bodies will need to push as many devices already on the market as they can through certification, with the additional burden of the new devices entering the market towards the end of the transitional period. This will not look nice, especially not for the manufacturers that are not well-prepared. More about that in a next blog!