Medical Devices Coordination Group Archives - European Industrial Pharmacists Group (EIPG)

Some perspectives on green pharmaceuticals


by Giuliana Miglierini The central role the green agenda plays within the EU Commission’s transformative policies impacts also on the development and availability of pharmaceutical products characterised by a improved sustainability. The concept of “Pharmaceuticals in the environment” (PiE) is Read more

European Council’s conclusions on the European Innovation Agenda and research infrastructures


by Giuliana Miglierini The European socio-economic framework is undergoing a profound transformative moment, as a result of the new vision impressed by the von der Leyen Commission, with its goals in the field of the Digital and Green transitions. The Read more

EMA’s new Quality Innovation Expert Group (QIG)


by Giuliana Miglierini Innovative approaches to the development manufacturing and quality control of medicines are becoming the new paradigm to be faced both from an industrial and regulatory perspective. Not only innovative technologies for delivery, such as mRNA vaccines, many Read more

MDCG, a position paper on the capacity of notified bodies

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by Giuliana Miglierini

The lack of a suitable capacity of notified bodies (NBs) is one of the main issues still pending after the entry into force of the new Medical Device Regulation (MDR) (EU) 2017/745 and In Vitro Diagnostic Regulation (IVDR) (EU) 2017/746. The Medical Devices Coordination Group (MDCG) discussed some suggestions on how to address the problem within a position paper published in August 2022.

Even if the document does not represent an official guideline, it describes some critical points to be considered by manufacturers and notified bodies in order to face the great challenge of the re-certification of medical devices and in vitro diagnostics according to the new rules. Should this not occur in time, many products may exit the market at the end of the transition period, potentially leading to a supply crisis greatly impacting on the health of patients and the normal functioning of healthcare institutions.

The MDCG position paper answers the request of EU Health ministers advanced during the EPSCO Council meeting on 14 June 2022 to figure out some immediate measures to face the problem. The final goal of the document is to improve the efficiency in the application of the current regulatory framework, with no reduction of requirements to be fulfilled by manufacturers. Waivers from applicable conformity assessments procedures should be considered only in relation to an interest of public health, patient’s safety, or health.

The position paper consists of nineteen points addressing the issue under its different perspectives, the first eleven of which refer to the increase of notified bodies’ capacity. The MDCG calls on all stakeholders to collaborate in order to smoothly implement the suggested actions, a process that will be monitored by the MDCG itself.

How to increase the capacity of NBs

Hybrid audits should be the elective tool notified bodies may use where appropriate to timely and efficiently run conformity assessment. Duplication of activities should be also avoided. To this instance, the suggestion is to “develop a framework for leveraging evidence, or components thereof, from previous assessments” run according to previous Directives. A pre-condition to activate this possibility is that the previous assessment has been judged “valid and properly substantiated also with regard to the MDR/IVDR requirements and the device” by a duly qualified notified body personnel.

A flexible approach may also apply to the combination of audits for legacy devices and actions needed to guarantee their ‘appropriate surveillance’. Combined audits may be used particularly for legacy devices whose application for MDR/IVDR certification is under review by a NB, thus moving the focus more towards the assessment of compliance with the new rules. To this instance, the MDCG also announced the intention to produce a specific guidance on ‘appropriate surveillanceunder Article 110(3) IVDR and to update MDCG 2022-4.

Already existing guidance may also be reviewed to reduce the administrative burden for NBs, and remove limitations related to the scope of documentation not required by MDR/IVDR.

A fundamental piece of the new European infrastructure for medical devices and IVDs is represented by the centralised Eudamed database, which should be timely fed by NBs with all relevant information using machine-to-machine procedures. Double registrations should be avoided as much as possible.

New notified bodies are essential in order to increase capacity. To this instance, the MDCG suggests supporting training, coaching and internship activities for their personnel. The rationalisation of internal administrative procedures is also deemed important.

Time for re-assessment of NBs is undergoing a review by the European Commission, which is expected to result in the publication of new Delegated Acts. The proposal is to move from the current first re-assessment at three years after notification (and then every 4th year) to up to five years after notification, on the basis of a flexible approach. There are currently ten re-assessments planned in 2022, twelve in 2023 and 11 in 2024. According to the MDCG, the new timeframe for re-assessment would allow national designating authorities to free resources to assess new NBs, while existing ones could process higher numbers of first MDR/ IVDR certifications.

Assessment, designation and notification of conformity assessment bodies (including the European Commission) are also called to reduce their timeframes and improve the efficiency of their processes, keeping unaltered the requirements to be met. The possibility to add specific codes to the designation of NBs shall be also explored by the MDCG. The Group is also committed to prioritise some ongoing actions which may impact on NB’s capacity (i.e. revision of section III.6. of MDCG 2019-6 revision 3).

MDCG’s guidance documents should be seen as an aid “to apply the legal requirements in a harmonised way, providing possible solutions endorsed by the MDCG”. Nevertheless, demonstration of the compliance to requirements should always benefit of a certain flexibility. A reasonable time should also be granted to integrate the new guidance in the relevant systems and/ or to apply them, suggests the MDCG.

Suggestions for the manufacturers

Under the perspective of manufacturers of MDs and IVDs, costs to access NBs may play an important role, especially for small-and-medium companies (SMEs). The MDCG position paper recalls NBs to the obligation to make their standard fees publicly available, possibly in a way that might be easily compared. Specific access schemes should be also in place to make available some capacity to SMEs and other first-time applicants for conformity assessment.

Manufacturers should also refer to notice MDCG 2022-11 to ensure timely compliance with MDR requirements. IVDs should not left behind, even if this category of products benefits of one more year for the transition to new rules compered to medical devices.

Structured dialogue is the suggested tool to improve the collaboration between manufacturers and notified bodies along the entire process of conformity assessment aimed at regulatory procedures, should this approach turn to be useful in order to improve the overall efficiency and predictability.

A timely communication to manufacturers by mean of webinars, workshops, targeted feedback and informative sessions is also deemed important in order to allow for a better preparedness, with a particular attention to SMEs and first-time applicants. The MDCG also suggest NBs to develop common guidelines for manufacturers to assist them in the application phase, containing explicative examples of typical non-conformities and details on he preparation and content of technical documentation. National authorities and industry associations are called as well to contribute to the dissemination of relevant information across their stakeholders.

Specific guidance should be issued by the MDCG to support a simpler conformity assessment of some aspects of legacy and orphan devices denoted by a demonstrable track record of safety. The development of a specific definition of “orphan devices” is also planned.

An improved dialogue between NBs and medicines authorities, and cases where expedited review would be possible is also supported in order to speed up consultations on medical devices incorporating an ancillary medicinal substance and companion diagnostics.


IVD regulation in force: new MDCG guidelines and criticalities for innovation in diagnostics

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by Giuliana Miglierini

The new regulation on in vitro diagnostic medical devices (IVDR, Regulation (EU) 2017/746) entered into force on 26 May 2022. The new rules define a completely renewed framework for the development, validation and use of these important tools supporting the diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of a disease, in line with technological advances and progress in medical science. “Diagnostic medical devices are key for lifesaving and innovative healthcare solutions. Today we are marking a big step forward for the patients and the diagnostics industry in the EU. The COVID-19 pandemic has underlined the importance of accurate and safe diagnostics, and having stronger rules in place is a key element in ensuring this is the case for EU patients.”, said Stella Kyriakides, Commissioner for Health and Food Safety

The European Commission also published a Q&A document to facilitate the comprehension of the new framework.

The main contents of the IVDR

The risk-based approach for the classification and development of in vitro diagnostics is at the core of the IVDR. There are four different classes of IVDs: class A (low individual risk and low public health risk), class B (moderate individual risk and/or low public health risk), class C (high individual risk and/or moderate public health risk) and class D (high individual risk and high public health risk). The assessment of the quality, safety and performance of IVDs by independent notified bodies shall be based on more detailed and stringent rules. Higher-risk categories will also be subject to further assessment by newly created scientific bodies acting under the auspices of the European Commission, such as the expert panels and the network of EU reference laboratories. Twelve expert panels have been established up to now.

Each single IVD will be associated to a Unique Device Identifier (UDI), so to facilitate its traceability along the entire life cycle. The identifier will also serve to locate the relevant information about a diagnostic marketed in the EU within the European database of medical devices (EUDAMED), where also a summary of safety and performance will be publicly available for medium- and high-risk devices. The database will also contain information about all economic operators and provide a repository for the certificates issued by notified bodies.

The new regulation strengthened the framework for post-marketing surveillance of IVDs, asking for a closer coordination of the vigilance activities by all member countries. The IVDR also introduced reinforced rules on clinical evidence and performance evaluation, including an EU-wide coordinated procedure for authorising multi-centre performance studies, and a specific regime for devices manufactured and used in the same health institution (in-house devices).

Difficulties in the timely implementation of the (EU) 2017/746 regulation may still be possible due to the lack of a sufficient number of notified bodies, as only seven have been designated up to now, established in only four countries (Germany, France, the Netherlands and Slovakia), while eleven other applications were pending in May 2022. To solve this issue, Regulation (EU) 2022/112 was adopted. A transition period up to May 2025 applies to devices that require a notified body certificate already under the previous Directive (around 8%, vs about 80% according to the IVDR); other classes of IVDs benefit of different transition periods (May 2025 for class D, May 2026 for class C and May 2027 for class B and A sterile).

Q&As on the interface with the Clinical Trial regulation and UDI

The Medical Devices Coordination Group (MDCG) published a Q&A document (MDCG 2022-10) to provide guidance on the interface between Regulation (EU) 536/2014 on clinical trials for medicinal products for human use (CTR) and the IVDR.

The guideline addresses the requirements for assays used in clinical trials, that may include IVDs carrying a CE mark for the intended purpose, IVDs developed in-house and devices for performance studies. Only the devices falling on the definition of an IVD with regards to their intended purpose are subject to the IVD legislation. The guideline also provides suggestions on assays likely to be considered IVDs, as they are used for medical management decisions of trial subjects within the trial.

Another Q&A guideline (MDCG 2022-7) provides clarifications on how to apply the Unique Device Identification system to both medical devices and in vitro diagnostics.

Topics covered by the document include the need for a new UDI-DI assignment in case the number of items in a device package changes or for single-use reprocessed devices, the requirement for economic operators to maintain a registry of all UDIs of the devices which they have supplied or with which they have been supplied, or the requirement of a new UDI-DI for substance-based medical devices, in case of formula quantity changes or additional claims.

The MDCG also addressed the assignment and use of the Basic UDI-DI and the determination of the ‘grouping’ for design or manufacturing characteristics, including the case of devices comprising a patient and a physician facing module, and the contents of the Declaration of Conformity (DoC). Labelling is also addressed, as well as rules for systems and procedure packs (SPPs) and configurable devices, as well as those applying to retail point of sale, promotional packs and marketing related samples.

The impact of the IVDR on innovation

The issues linked to the IVDR implementation and their impact on innovation and diagnostic laboratories, including the development and use of in-house devices, have been analysed by the BioMed Alliance In Vitro Diagnostics Task Force, and published in HemaSphere.

The Task Force identified two main challenges to be faced by the academic diagnostic sector. The first one impacts on the possibility to use in-house IVDs, based on the demonstration that no equivalent CE-IVD kit is present on the market or when the specific needs cannot be met at the appropriate level of performance by an equivalent CE-IVD. The strict exemptions applying to in-house IVDs (e.g. prohibition of transferring to other legal entities, compliance with EN ISO 15189 and justification of use, etc.) may impact also on the potential for innovation in the diagnostic sector.

The second challenge refers to the not so clearly defined boundaries between CE marked-IVDs, modified CE-IVDs, Research Use Only (RUO) tests, and in-house IVDs. The Task Force recalls the immediate applicability of the General Safety and Performance Requirements specified in Annex I of the IVDR, as they have not been included in the approved amendment of the implementation timeline.

Furthermore, only tests meeting economic viability may in the future be transferred from the academia to the industry, while rare or complex tests would probably remain excluded. According to the paper, the cost of diagnostics shall likely increase, and the academa should carefully consider how to support further research into rare or complex diagnostics in order to ensure their availability to patients.

Following the results of a survey among medical societies on current diagnostic practices, several suggestions are made to better support the implementation of the IVDR, namely by mean of the availability of diagnostic equivalents of the European Reference Networks for rare diseases and a concerted action involving all stakeholders. A joint biomarker-to-test pipeline between the IVD industry and research/academic labs would also be useful to facilitate the initial development and local application of innovative diagnostics within healthcare institutions or diagnostic reference networks with specific expertise, to then transfer them to manufacturers above a certain production volume.


Joint implementation plan for the IVDR regulation

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by Giuliana Miglierini

Regulation (EU) 2017/746 (IVDR), establishing the new legislative framework for in vitro diagnostic medical devices (IVDs), will entry into force on 26 May 2022. The Medical Device Coordination Group (MDCG) has published an updated version of the Joint implementation and preparedness plan, discussing the priority actions to be implemented and monitored at the level of member states, Commission and MDCG.

The implementation of the IVDR is highly complex, as it requires a strict coordination between all the different stakeholders, including manufacturers, notified bodies, authorised representatives and laboratories. The IVD regulation has introduced a completely new device classification system for in vitro diagnostics, as well as a greater involvement of notified bodies in conformity assessment and new regulatory structures such as the EU reference laboratories and expert panels.

The Joint implementation plan is aimed to support the harmonised implementation of the new framework, a process led by the Commission and where member states are called to ensure the new provisions are effectively applied and enforced at national level.

Ongoing actions and future goals

As of January 2022, six notified bodies were already designated and the examination of other applications is undergoing. The Unique Device Identifier system that will support the punctual tracing of the devices has also been set up, while the Eudamed database is still under development. From the regulatory perspective, a number of new common specifications are being drafted; some guidance documents are already available while others are under development.

To smooth the impact of the transition and to prevent disruption in the supply of essential IVDs, Regulation (EU) 2022/112 has established the calendar for the transition of different classes of devices, i.e. 26 May 2025 for IVDs that fall in class D under the IVDR, 2026 for class C, 2027 for class B and A sterile.

The Joint implementation plan identifies two sets of priorities to be tackled by the stakeholders, on the basis of public health’s goals, patient safety and transparency. Set A includes essential actions to enable IVDs to maintain access to the market. Set B includes the development of other new pieces of legislation and guidance documents needed to better support the transition and the designation of EU reference laboratories for high-risk IVDs.

Set A, essential actions

Contingency planning and monitoring are the first priority to be met under Set A essential actions, in order to anticipate possible risks of IVDs’ shortages arising from the transition to the new framework. The MDCG will closely follow this process to monitor its progress and identify systemic risks and mitigation actions, with a particular attention to the availability of particularly critical IVDs.

Regular updates are also expected from the industry and notified bodies to inform member states and the Commission about the need of specific actions. This type of activity would also support the identification of barriers that could result in shortages of devices, e.g. with reference to the designation of notified bodies or the certification process. Stakeholders are also requested to be ready to manage some uncertainty in areas where guidance is still not available, thus requiring the provision of sound justifications to maintain critical IVDs on the market.

The second highest priority is the availability of a sufficient number of notified bodies to support the expected very high volume of applications for the certification of medium and high-risk IVDs. The plan indicates the need to make available national experts for the joint assessment of notified bodies. Member states should also address the need to improve the notified body capacity, discussing this issue within the MDCG and its specialised working groups as well as with the Commission. According to the Joint plan, the percentage of IVDs requiring certification under the new IVDR will rise up to 80-90%, from approx. 10% devices requiring involvement of a notified body under Directive 98/79/EC.

To facilitate this part of the transition, Regulation (EU) 2022/112 establishes that certificates issued under the Directive 98/79/EC are valid, under certain conditions, until May 2025. Renewals of existing certificates by a set of nineteen notified bodies designated under the current Directive is possibile, if necessary, up to 26 May 2022.

The plan also takes into consideration the possible occurrence of new Covid-19 restrictions, that may highly impact the work of the notified bodies (for example, due to the need to run first-time audits of many manufacturers). The Commission and the MDCG are thus called to consider how notified bodies can perform conformity assessment activities in such circumstances.

Set B, high priority actions

Actions included in set B are not essential for manufacturers to market their IVDs, but their implementation would support a smoother transition.

The EU reference laboratories are a new type of independent scientific body designated by the Commission to carry out additional tests on the performance and compliance with any common specifications of class D devices, before placing them on the market. If the Commission would not designate a EU reference laboratory for a particular device in class D, those requirements are not applicable. According to the Joint plan, a call for application to member states and the Joint Research Centre shall be issued by the Commission to nominate candidate laboratories. New implanting acts on tasks and criteria and on fees to be levied by the EU reference laboratories are also expected.

According to the IVDR, the adoption of common specifications (CS) is optional; nevertheless, the Joint plan indicates the intention of the Commission to propose some sets of common specifi cations and reach an agreement on the text that should enter the first adoption round. This should also lead to the adoption of the first implementing act containing the common specifications. This round should include common specifications relative to Kidd and Duffy blood grouping, Chagas and syphilis, and cytomegalovirus/Epstein-Barr virus devices, for which the drafting process is at an advanced phase.

New common specifications should be targeted to class D devices and will be developed by the IVD sub-group of the MDCG. Already existing CS under the old Directive should be transposed without major modifications.

A new implementing act on the MDR/IVDR standardisation request should be adopted by the Commission and accepted by relevant bodies (CEN/Cenelec). The Commission should also adopt the implementing acts on the publication in the Official Journal of references of harmonised European standards in support of the IVDR requirements.

Set B of actions include also the drafting and endorsement of a guidance on notified body designation codes, as well as of guidance on batch testing for notified bodies. New guidance may be also developed on significant changes and on appropriate surveillance, as referred to in Article 110(3) of IVDR. The MDCG should also complete the issuing of a new guidance on clinical evidence for IVDs, which is part of the documents needed to support the evaluation of the devices’ performances and the work of expert panels.

To this instance, the plan also indicates the need for a clarification on what constitutes a “type of device” and on the process to be followed by notified bodies in context of views of the expert panel. A template for summary of safety and performance should be also released, together with a template for the application/notification of performance studies. The issuing of an IVDR-specific guidance on harmonised administrative practices and alternative technical solutions until Eudamed is fully functional is also planned.

The joint plan also includes sections on actions required in the field of companion diagnostics, legacy devices and in-house devices.