THE MDR TALE OR THE STORY OF TRANSITION FROM THE MDD

The countdown!

Here we are, a couple of months after the countdown has ended. And let’s be honest, we were all freaking out!

Since we got the draft at the end of 2012 and later the adopted version in 2017, we had all heard fifty shades of the MDR. We had been trying to decipher, to analyze, to implement… 

Few weeks after the “big jump” in this new era for the medical device sector, I’ve found necessary to pause and quickly revisit this transition from the MDD to the MDR.

Medical Technologies

For the past decade, we’ve witnessed, been confronted to, have contributed to the outbreak of “medical technologies” and how they’re transforming patients’ journeys, being more comprehensive, more precise, more digitalized (e.g., virtual reality, robot-directed surgery, precision medicine, healthcare wearables, artificial organs, 3-D printing, wireless brain sensors). 

Medical technologies are considered to be products, services or solutions intended to optimize healthcare pathways, and ultimately intended to save lives, providing innovative means for diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of diseases[i].

Three core categories of medical technologies are commonly defined:

• Medical devices (MDs) referring to products, services or solutions intended to prevent, diagnose, monitor, treat and support care for human beings by physical means (Vs. pharmacological, immunological, or metabolic means).
• in vitro diagnostics (IVDs) referring to non-invasive examinations performed on biological samples (e.g., blood, urine, or tissues samples) to inform on one’s health condition.
• Digital health and care referring to tools and services that use information and communication technologies (ICTs) to enhance prevention, diagnosis, treatment, monitoring and management of health and lifestyle.

Yet, for the sake of this article, medical technology shall be understood as medical devices and in vitro diagnostics exclusively.

How it started...

Making up about 27% of the world’s market, estimated at roughly €120 billion in 2018, EU competitive and innovative medical technology industry (MedTech) has been constantly and significantly growing for the past ten years, particularly thanks to very active small and medium-sized companies. 

This is clearly illustrated by the fact that the patents applications in the field of health technologies filed from European countries (EU28, UK, Norway, and Switzerland) went from around 8,5K to more than 14,2K between 2006 and 2020, culminating at 38 % of world’s patents applications in MedTech. Globally, the ratio of granted patents to patent applications in the medical technology sector has reached 73% in 2020 Vs. less than 45% in the pharmaceutical and biotechnology field.[ii]

The MedTech is thus undoubtfully key to the provision of an optimized, personalized, and more comprehensive healthcare, and it plays an important part in both the European and global economy.

In that prospective EU has been regulating MedTech for decades with a framework that aimed at easing commercial trade within the Union market, with a primary goal to guarantee the highest protection for patients and users.[iii]

This EU regulatory framework around medical technologies had its ground on three directives:

• Council Directive 90/385/EEC on Active Implantable Medical Devices (AIMDD) (1990)
• Council Directive 93/42/EEC on Medical Devices (MDD) (1993)
• Directive 98/79/EC of the European Parliament and of the Council on in vitro Diagnostic Medical Devices (IVDMD)

However, the intrinsic specificities of the legal instruments, and the liberty they allowed to Member States, led to issues with divergent interpretations of the current Directives, as well as to widely broadcasted incidents concerning product performance, highlighting the limitations and weaknesses in the legal system[iv]. Revision of the legislation was then crucial to:

• reinstall trust in the public opinion 
• reinforce high standards of product performance and safety and 
• consolidate the role of the EU as a global leader in MedTech. 

...How it's going

5 April 2017. Two new regulations on medical devices and in vitro diagnostic devices are adopted to provide an EU legislative framework more:

• adapted to the gigantic leap that technology and medical sciences have made over the previous 20 years, and the increasing investment of the governments toward medical devices (e.g., US expenditures on medical devices went from a little more than $1.4 in 2000 to $4.01 trillion in 2020)[v];
• robust and to ensure better protection of public health and patient safety;
• coherent among the EU.

They entered into force on 25 May 2017 to progressively replace the existing directives after a transition period:

• by 26 Mai 2021 for the Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC [referred to as “MDR”]

NOTE: Originally planned for 26 Mai 2020, the EU postpones the date of application for most MDR provisions by one year – until 26 May 2021, under the pressure of member states authorities, notified bodies, manufacturers and other actors pleading, in particular, other urgent priorities induced by the COVID-19 outbreak that has driven the world in an unprecedent crisis.[vi]

• by 26 Mai 2022 for the Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU [referred to as “IVDR”].

MDR: The Game Changer

Apart from being about four times longer, and containing five more annexes than the MDD, the MDR has set a challenge of a whole new level for many economic actors in MedTech through new or revised requirements. The significant evolutions in wording and in the level of expected evidence, require(d) for companies to perform an impact assessment of their core processes including the quality assurance, design and development, risk management, production / supply chain and post-market activities to identify, prioritize and plan the implementation of the measures necessary to meet new/update regulatory requirements for CE Marking and commercialization of their medical devices. The resulting actions of this assessment shall absolutely mean to consider huge documented review, planning and updating.

Let’s be honest, this exercise has led or shall lead some of organizations to rationalize their activities to keep providing products and services of quality in compliance with new requirements, while remaining agile and competitive!

Now let’s quickly review key considerations that we need(ed) to have while facing the transition from MDD to MDR:

The MDR now displays a broader scope expanding its application, particularly the requirement to demonstrate the performance of the device through clinical evaluation, to products that were not covered before, among which:

• groups of products without an intended medical purpose but similar to medical devices based on how they work and the type of risk they represent for patients and users;
• some products utilizing derivatives of non-viable or rendered non-viable human tissues or cells;
• products intended for cleaning, disinfection and sterilization of medical devices;
• software products that fall under the definition of a medical device (medical device software or MDSW).

The word "safety" appears seven times more in the MDR than in the late MDD, and that itself illustrates the profound willingness of the European Counsel to emphasize the absolute need to demonstrate device safety for patients and users, prior to making it available and during its entire life on the market.

In the same prospective, the “General Safety and Performance Requirements” annex (Annex I of the MDR), identifies new conditions that will need to be addressed for most legacy devices (CE marked under the MDD). Notwithstanding the “grace period” until 2024 during which legacy devices meeting specifics conditions will still be allowed on the Union market, these products shall be re-certified in accordance with the new regulations.

The annex I and the overall new rules regarding evidence of safety and performance disseminated throughout the MDR require from many (not to say most) companies to update or even generate in-depth clinical data to prove safety and performance and support the claims, as well as to update technical documentation, including updates of instructions for use and the labeling. Here is one big thing (among so many others some will say!): the MDR established more constraints when using similar or equivalent devices for clinical evaluation as manufacturers now must establish contracts with the concerned other manufacturers to get access to sufficient relevant data to support their demonstrations. The objective is here to “force” transparency, to ensure a proper analysis of available data to adequately assess risks related to the use of the devices and to avoid false / incomplete claims.

This quest for transparency is also supported by the (re)establishment of a European database on medical devices (EUDAMED) and of the Unique Device Identification (UDI). 

The UDI is implemented[vii], throughout the economic operator involved in the supply chain, intended to allow a more robust and common traceability system for devices on the market. This requires for manufacturers to define the appropriate nomenclature considering:

• Basic UDI-DI, static code identifying a group of devices within the same category (intended purpose, risk class, essential design, manufacturing characteristics). It’s only intended to be used for administrative purpose.
• UDI-DI, static code identifying a specific device on your portfolio.
• UDI-PI, dynamic code informing about lot number, serial number, manufacturing date, expiration date.

Manufacturers had to/will have to adapt their production to design and affix on-all labels mentioning UDI-DI and UDI-PI.

The MDR also brought a renewed EUDAMED concept[viii], for which a first version had already been defined in the MDD. The European data base for medical device will be composed of several electronic platforms for operators’ identification, UDI, certificates and more, and including one platform that will require from the manufacturers to report all incidents, injuries and deaths into the EU portal. The intent here is to centralize relevant data for an overall access (to users and economic operators) to more safety-related information. The module on Actor registration has been made available back in December 2020, and a release of more modules (on UDI/device registration and on Certificates and Notified Bodies) are expected for September 2021viii.

“Extended scope”, previously mentioned, also means potential reclassifications. For the past few years, many companies have reached for help as their products will now be considered as medical devices or as their medical devices are now of higher risk class, hence are subjected to more / different regulatory constraints. Moreover, numerous software products utilized for patient care now fall under the definition of a medical device (MDSW) switching from “not regulated” to “requiring notified body oversight to get and maintain CE mark”! That’s indeed a game changer!

Last consideration but far from being the least: the IVDs. As per IVDR, in vitro diagnostics are now classified into four risk classes versus the old “list A, list B or others”. This implies a required notified body oversight for roughly 90% of the in IVDs, up from the current 10%.

Now... what?

As manufacturers, distributors, counsels… we have experienced and are still experiencing this major evolution with different perspectives: as a regulatory burden, as a challenge, as a chance for new competitive advantages… It has enriched our perceptions of the industry and sharpened our expertise, whether we realize or not.

Next time, we’ll go “real” with lived experiences of companies in MedTech, throughout their testimony on the hurdle they went through and how they now face the fresh entry in application of the MDR.

MedTech story is being shaped for the better. Important matters take times… but we’re getting there, and regulatory bodies are doing an immense work to support that (e.g., Decisions 2021/1182 and 2021/1195 listing harmonized standards for MDs and IVDs, including of 5 which aim to cover requirements set out in the MDR – 4 of them also cover IVDR) and to ensure understanding and optimal application of this new regulatory framework (e.g., 2 published MDR corrigenda, MDCG guidance).

As the saying goes “it’s not an ending, it’s merely the point in the story where you turn the page”. 

[i] Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC

Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU

[ii] “The European Medical Technology Industry in figures” 2019 and 2020. MedTech Europe

[iii] European Commission; Medical devices sector: https://ec.europa.eu/health/md_sector/overview_en#new_regulations

[iv] « Le scandale des prothèses ses mammaires PIP » : https://pages.rts.ch/la-1ere/programmes/on-en-parle/2928013-le-scandale-des-protheses-mammaires-pip.html

[v] “Estimates of Medical Device Spending in the United States” Gerald Donahoe and Guy King, S.A., M.A.A.A.;July 2012

“National Health Expenditure Projections, 2019–28: Expected Rebound In Prices Drives Rising Spending Growth” Sean P. Keehan, Gigi A. Cuckler, John A. Poisal, Andrea M. Sisko, Sheila D. Smith; March 24, 2020

[vi] “Commission postpones application of the Medical Devices Regulation to prioritise the fight against coronavirus” European Commission press release of April 3, 2020

[vii] “UDI Beginners Guide: Unique Device Identification (EU MDR and IVDR)” Monir El Azzouzi; August 8, 2020

[viii] European Commission Medical Devices - EUDAMED: https://ec.europa.eu/health/md_eudamed/overview_en