Impact of new legislation on the availability of paediatric medical devices in the European Union with an emphasis on paediatric gastroenterology, hepatology and nutrition

1. NOVELTIES INTRODUCED BY A NEW EUROPEAN UNION REGULATION ON MEDICAL DEVICES

In the year 2017, the European Union (EU) introduced a new regulatory framework for medical devices (MD), ¹ which are defined as ‘products or equipment intended for a medical purpose’ and classified according to their invasiveness and risks for the patient into four risk categories (I, IIa, IIb and III) among which the categories IIb and III notify high‐risk implantable devices such as pacemakers and stents, or active delivery systems such as insulin pumps. ² This new Medical Devices Regulation (MDR) became applicable on May 26, 2021, with a transition period until May 26, 2024. To comply with it and to receive a ‘conformité européenne’ (CE) stamp necessary for marketing in the EU, each MD irrespective of whether already available in the market or newly introduced, must undergo a ‘conformity assessment’ by reputable notified bodies, created for that purpose.

In comparison to the first EU MD legislation ³ determined to unify requirements and conditions across EU countries and to facilitate trade by creating a single market, the new MDR regulates the MD's quality, security and efficacy, aiming at improving healthcare for patients and protecting public health. It is therefore not surprising that for the successful conformity assessment, the 2017 EU regulation introduced the requirement for clinical evidence documenting efficacy and safety. Besides that, several other novel barriers may halt the (re)certification of MDs by the manufacturers such as the very long process (18–24 months) and exceptionally high costs (>200,000 EUR) incurred by the notified bodies which are private enterprises and therefore free to decide on the final costs of the assessment procedures. To put it into a wider perspective, both the costs and the duration are 10–100 times higher/longer compared to other markets such as those in Canada or the United States. Furthermore, an insufficient number of notified bodies, responsible for the MD conformity assessment, have been formed, and their members require training. It is therefore not surprising that a huge backlog of unresolved applications was created, which, coupled with widespread concerns raised by various stakeholders, were a driving force for the EU to introduce regulatory amendments in March 2023. ⁴ The most important amendment is the extension of the transition period up to December 2027 for high‐risk devices and until December 2028 for medium and low‐risk devices, which means that an extra 3–4 years are provided to finalise the (re‐)certification.

2. A NEW LANDSCAPE FOR MD USERS AND PRODUCERS

Irrespective of the markedly prolonged transition period, the barriers described above could have profound negative implications for the EU market. Manufacturers may abolish the production and selling of their products in EU countries and turn to more open markets such as Canada, the United States and other parts of the world, where the legislation is less restrictive. Furthermore, the current situation could also halt new developments in the area of MDs and create a lack of the best new products on the EU market that will ultimately have a damaging impact on the health of the population. For the paediatric population, the risk is even higher given the fact that generally, there are fewer MDs available for children than for adults. And this is not just a potential problem but one that already exists. The recent survey of the Biomedical Alliance in Europe, representing 36 medical and research societies, detected that 53% of 314 respondents who were primarily clinicians and laboratory specialists were already facing the disappearance of certain MDs in their clinical practice. Furthermore, 29% of them did not have an alternative MD, and 59% of respondents implied that the nonavailability reduced the quality of patient care. ⁵ Concerning producers and manufacturers, in December 2022 the European Society of Gastrointestinal Endoscopy (ESGE) circulated an online questionnaire among 15 endoscopy‐device producers. Almost all of the 10 responding endoscopy manufacturers do plan to spend more resources on the EU device‐application process and also to sponsor more clinical trials. However, 70% of them either plan to withdraw or have already withdrawn a device from the EU market, while 60% are prepared to reduce the number of new devices submitted for certification in Europe. ⁶ With respect to paediatric gastrointestinal endoscopy, it is of paramount importance that novel concepts and procedures, such as sedation‐free endoscopy in children aged 5 years and above will be also explored in Europe as it already is in the United States.

3. NEGATIVE IMPLICATIONS FOR PAEDIATRIC AND ORPHAN MDS (TABLE 1)

Table 1.

Types of medical devices recorded as missing—results of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) online survey.

Medical device	Number of times recorded as missing
Tunnelled central venous catheters	4
Gastro‐jejunal tubes & PEG/PEJ & Buttons	3
ERCP neonatal scope	2
Endoscopes & accessories for endoscopy	2
I.v. systems for delivering PN solutions	1
Enteral‐feeding pumps	1
Variceal banding devices for children ≤10 kg	1
Equipment for measuring cytokine sweet profile	1
Anal manometry probes	1
Pain sensors	1

For paediatric and orphan MDs the implications of the new MDR could be even more devastating for several reasons. Per definition, many conditions occur infrequently in children, and the costs of developing the products are higher. Therefore, companies producing them may have limited manpower and financial resources, and slower returns on investment. Examples of off‐label use are widespread for both paediatric and orphan MDs. Given also the long duration of the process, and the exceptionally high costs, many manufacturers of paediatric MDs currently marketed in the EU may not even apply for recertification, and the same is true for the development of novel products.

The disappearance of essential high‐risk paediatric/orphan MDs is already having serious clinical implications. Almost every second participant of the survey by the Biomedical Alliance had a problem with devices that are used for small subsets of patients such as children and patients with orphan diseases. ⁵ Among the first to express concerns were paediatric cardiologists referring to the nonavailability of expandable renal stent systems used off‐label for interventions such as coarctation of the aorta in newborns, and balloons for the Rashkind procedure. ⁷ To anticipate the extent of the problem in paediatric gastroenterology, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recently made an online survey among its members. Although the response rate was low, the problem with the lack of previously marketed MDs was reported by 56% of the 54 respondents from 14 different countries (8/14 from the EU), and in 74% of them, the missing device was a paediatric one. The MDs reported as missing were central venous catheters and banding devices, ERCP endoscopes, and various endoscopic equipment—most of them of paediatric dimension, to mention just the commonest examples, while the full list is provided in Table 1. The most named reasons for the shortages were new EC MDR, problems with delivery and cessation of manufacturing for unclear reasons.

An example of another recently described dramatic shortage of paediatric MDs is the unavailability of highly specialised small‐dimension devices for retrograde cholangiopancreatography, which directly increases the need for invasive diagnostic or therapeutic surgery in infants. ⁸

4. IS THERE A WAY(S) OUT?

Investigators of the EU Horizon 2020 funded project ‘Coordinating Research and Evidence for Medical Devices’ (CORE‐MD) joined with experts from various paediatric specialties, and representatives of regulatory agencies and authorities published very recent recommendations for clinical evaluation of high‐risk paediatric MDs and suggested pathways for resolving the incurred problems. ⁹ Among the suggested initiatives, the group recommended the establishment of a paediatric expert panel to help designate devices as paediatric and/or orphan, to provide clinical guidance on the scope of required clinical studies, and to be a source of expertise to all parties involved—notified bodies, regulators and manufacturers. Development of novel paediatric/orphan regulatory pathways with expedited timelines and lower and/or EU‐subsidised costs was also advised. Finally, the group also recommended transition solutions, for example, automatic permission for continuous marketing for MDs with the evidence of several years of safe use on the EU market, or those with approval under the US Humanitarian Device Exemption regulation. ⁹

Most of the listed recommendations will require changes to the current MDR and the involvement of the EU Commission and the EU Parliament. Therefore, the crucial initiative to follow is to create a network of interested stakeholders including paediatric experts, patients' organizations, and manufacturers that will jointly, with the members of Parliament, formulate the amendments, and raise sufficient awareness required for their acceptance.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.