Today was a big day with a half hour press conference by Commissioner Dalli (for Twitter summaries see here and here) to festively launch the two much anticipated EU medical devices regulation proposals (one for general medical devices, including active implantables, and one for IVDs).
The generalities of the proposals, as you can read in the press release and the Commission’s communication on the subject, are not a surprise given what we already know. However, the devil is in the details and there are some significant changes in specific matters. For those not interested in details: see the ultra short summary by Reuters. For those that are interested in some gems already unearthed, check Robert van Boxtel’s timeline on twitter.
I hope you will forgive me that the below analysis is not comprehensive: the entire proposal for the general medical devices regulation alone is 194 pages and I am sure I have missed a few points. I won’t discuss the new IVD regulation proposal in this post, but I could establish that my earlier blog on what I expected it to be was pretty accurate and will discuss that at a later occasion.
I am planning to do a series of blogs to discuss distinct parts of the regulation, so this is just a first and very personal impression of what jumped out at me in the proposal for the general medical devices regulation (MDR).
In a nutshell the aim of the MDR is that supervision of notified bodies, conformity assessment procedures, clinical investigations and clinical evaluation, vigilance and market surveillance are significantly reinforced, whilst provisions ensuring transparency and traceability regarding devices are introduced. Eucomed is happy with it because much stays the same (no PMA) except for the scrutiny procedure (see below), but their worst fears may still come true in the legislative process that the proposal has now entered.
The political dimension is quite apparent. The Commission makes a big point of referring to its eHealth strategy in the explanatory memorandum to the MDR proposal, as well as referring to international harmonization via the GTHF and contributing indirectly to public health under its new Lisbon Treaty competences acquired by integrating clinical trials rules into the regulation (now that they did not make it to the proposal for the revised clinical trial directive). And of course there is the fact that the Commission is quite done with the member states’ sometimes really different way of looking at things and make a mess of the internal market that way, and therefore forces everyone in line now with a directly applicable regulation.
The non-viable human tissue gap is closed by stipulating that substantially manipulated tissues and cells that are not covered by the ATMP regulation are in scope of the MDR, just like finished products from cells and tissues covered by the EU Tissues and Cells Directive. Human tissues and cells that are not substantially manipulated and products derived from such tissues and cells, should not be covered by the MDR. Anyone (including me) that has worked with the ATMP regulation knows what a bone of contention and disagreement the “substantially manipulated” criterion is and how different member states apply it to the detriment of innovative therapies, so brace for stubborn persistence of the current borderline problems here.
Also added to the scope are implantable or other invasive products without a medical purpose that are similar to medical devices in terms of characteristics and risk profile (e.g. non corrective contact lenses, implants for aesthetic purposes).
Demarcation provisions for products that contain or consist of viable biological substances (e.g. living microorganisms) and food have been included.
A special regime has been added for products that cause real borderline headaches, i.e. products composed of substances or combinations of substances that are intended to be ingested, inhaled or administered rectally or vaginally and that are absorbed by or dispersed in the human body, such as the lactic acid tampons. In short, they are classified in the highest risk class and should comply with the relevant requirements of Annex I of Medicinal Products Directive 2001/83/EC.
The producers of software, handhelds and other devices that, whilst not being medical devices, can be used in combination with them should beware that the accessory definition has been significantly expanded by adding the word “assist” in the definition (“an article which, whilst not being a medical device, is intended by its manufacturer to be used together with one or several particular medical device(s) to specifically enable or assist the device(s) to be used in accordance with its/their intended purpose(s)”). Obviously, “assist” is something different than “enable”, signifying that the accessory does not need to be a conditio sine qua non (as “enable” would suggest) for intended purpose but merely being helpful in some way might be enough for the product to be regulated as medical device.
Entry into force
It applies from three years after entry into force (entry into force being moment T for what follows, which I postulate two years from now based on normal duration of the legislative procedure). However, the requirements for manufacturers and importers to submit devices to Eudamed for registration and for notified bodies to enter certificate details in Eudamed apply from 18 months after date of application (i.e. as of T plus three years plus 18 months). Furthermore the section on designation of notified bodies and the establishment of the Medical Device Coordination Group (MDCG) shall apply from six months after entry into force (so as of T plus 6 months). However, prior to T plus three years , the obligations on notified bodies emanating from the accreditation provisions shall apply only to those notified bodies which submit an application for notification, so the newly notified notified bodies.
Apart from to the EU countries the MDR also applies to the countries that have entered into international agreements with the EU which confer on that country the same status as a Member State for the purpose of application of this Regulation, as it is currently the case with the EEA (Norway, Liechstenstein, Iceland), the Agreement between the European Community and Switzerland on mutual recognition in relation to conformity assessment and the Agreement of 12 September 1963 establishing an association between the European Economic Community and Turkey from 1963.
The proposal provides for a legal basis for the MDGC to remedy the lack of democratic foundation for currently operating committees such as CMC and MDEG in which member states cooperate with respect to certain aspect of the current MDD. The MDGC consist of member state representatives chaired by the Commission and will have as tasks:
(a) to contribute to the assessment of applicant conformity assessment bodies and notified bodies;
(b) to contribute to the scrutiny of certain conformity assessments under the scrutiny procedure;
(c) to contribute to the development of guidance aimed at ensuring effective and harmonised implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of the general safety and performance requirements and conduct of the clinical evaluation by manufacturers and the assessment by notified bodies;
(d) to assist the competent authorities of the Member States in their coordination activities in the fields of clinical investigations, vigilance and market surveillance;
(e) to provide advice and assist the Commission, at its request, in its assessment of any issue related to the implementation of this Regulation;
(f) to contribute to harmonised administrative practice with regard to medical devices in the Member States.
Supervision of notified bodies
Unsurprisingly in the light of the PIP scandal and the subsequent Commissioner Dalli Plan to improve market surveillance, the MDR includes much beefed up requirements for the accreditation and supervision of notified bodies. One important one is quality control for outsourced auditing work.
Classification and conformity assessment
This includes procedures for resolving classification disputes between manufacturer and notified body by member states, overseen by the Commission, the dreaded scrutiny procedure for applications for conformity assessments for devices classified as class III, with the exception of applications to supplement or renew existing certificates. The procedure will delay the grant of certificates but there does not seem to be an outright veto by the MDCG, as the notified body shall give due consideration to any comments received and It shall convey to the Commission an explanation of how they have been taken into consideration, including any due justification for not following the comments received, and its final decision regarding the conformity assessment in question. The Commission may define other categories of devices than class III to which the scrutiny procedure will apply during a predefined period of time.
A requirement has been introduced that within the manufacturer’s organization a ‘qualified person’ should be responsible for regulatory compliance. Similar requirements exist in EU legislation on medicinal products and in the national laws transposing the AIMDD/MDD in some Member States. A similar requirement applies for authorized representatives.
The Commission seems to be planning to set up a parallel system for devices clinical trials including database (why not use the existing EudraCT medicinal products database?). Because the new clinical trail directive proposal does not include medical devices, the Commission has mirrored that directive in the MDR, including provisions for international multi-centre trials. The MDR includes a procedure for post marketing clinical follow up trials within the scope of the CE mark. However, there remains a lot to be addressed, which the Commission reserves the right for to do in implementing acts. That it nothing to look forward to because this has not spelled good news for the ATMP regulation and never worked under the current MDD. If the implementing acts are not finalized well before the date of application, clinical trial planning and execution will be at risk as these require long term planning.
Vigilance and marketing surveillance
As was to be expected, there will be a regulation 765/2008 type supply chain control mechanism as we have already seen in the new Toy Directive that obliges each link in the chain to verify that the previous one was compliant. Each link will have their own regulatory responsibility for compliance related to their role in the supply chain.
Much of the vigilance MEDDEV is taken on board into the MDR.
A lot of procedural rules are added in which the member states authorities play a crucial role. Given that the lack of resources for medical devices market surveillance on national level is one of the big points that the MDR will not solve, you can see where this is going: market surveillance may well not improve as long. The good (ahem) news is that member states get the express competence to levy fees for their work to implement the MDR, so they might use this to levy some additional resources for much needed additional FTEs.
Device/drug combinations are addressed with an amended procedure with as big novelty that the EMA/competent authority can now veto a certificate being provided by the notified body, which is not currently the case.
The MDR also amends the medicinal products regulation with a procedure for drug/device combinations, to the effect that “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 of Annex I of that Regulation contained in the manufacturer’s EU declaration of conformity or the relevant certificate issued by a notified body allowing the manufacturer to affix a CE marking to the medical device. If the dossier does not include the results of the conformity assessment referred to in the first subparagraph and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with [the MDR], 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 of Annex I of that Regulation issued by a notified body designated in accordance with that Regulation for the type of device in question, unless the authority is advised by its experts for medical devices that involvement of a notified body is not required.”
There is a new essential requirement section for software, both incorporated and standalone. There is even a requirement for software intended to be used in combination with mobile computing platforms: that shall be designed and manufactured taking into account
the specific features of the mobile platform and the external factors related to their use. There is no definition of “mobile computing platform”, contrary to the draft FDA guidelines for mobile medical apps that – although heavily criticised in the US – did a much better job in this respect. Also, software is explicitly taken into account in design and risk management rules.
And there is of course the new accessory definition to take into account, because accessories have to meet all device requirements. Any software that “assists” a medical device might become regulated as a medical device itself.
Single use and reprocessing
Reprocessing of single-use devices is considered as manufacture of new devices so that the reprocessors must satisfy the obligations incumbent on manufacturers. The reprocessing of single-use devices for critical use (e.g. devices for surgically invasive procedures) will be prohibited.
There are a number of measures to improve the rightly criticized lack of transparency of the EU system:
• a requirement that economic operators must be able to identify who supplied them and to whom they have supplied medical devices;
• a requirement that manufacturers fit their devices with a Unique Device Identification (UDI) which allows traceability. The UDI system will be implemented gradually and proportionate to the risk class of the devices;
• a requirement that manufacturers/authorised representatives and importers must register themselves and the devices they place on the EU market in a central European database (likely Eudamed);
• an obligation for manufacturers of high-risk devices to make publicly available a summary of safety and performance with key elements of the supporting clinical data;
• and the further development of Eudamed, which will contain integrated electronic systems on a European UDI, on registration of devices, relevant economic operators and certificates issued by notified bodies, on clinical investigations, on vigilance and on market surveillance. A large part of the information in Eudamed will become publicly available in accordance with the provisions regarding each electronic system.
So… why not ask if me if you’re not sure
This is my first impression. I’m sure you’ll find lots of other first impressions that focus on different things. As announced, I am planning to write about the respective elements of the proposal in a lot more detail in future posts so you can expect those in the near future.
For the moment, if you have questions or just want to test a hypothesis, my firm has now implemented Question Time on the website, a feature that allows you to plan a 15 minute telephone, Skype or FaceTime meeting in our calendars to talk to us about whatever subject in EU medical device law (or pharmaceuticals, or biotech, or food law), at completely no cost. We figured we would try this as experiment to allow companies to have a sense of whether something might really be an actual problem that needs lawyer attention before they start paying fees. Mind you, some necessary terms apply, e.g. to manage possible conflicts of interest. If you are interested in this experiment, why not book yourself a slot to try it out. My colleagues and I are looking forward to speak with you.