Medical Device Regulation Research Articles

Information Disclosure, Medical Device Regulation, and Device Safety: The Case of Cook Celect IVC Filters

Information Disclosure, Medical Device Regulation, and Device Safety: The Case of Cook Celect IVC Filters

The application study of harmonization code in medical device adverse event reporting.

The reporting of adverse events in medical devices (MD) is a starting point of post-market surveillance and the most common source of initial safety signals. Because MD adverse events (AE) occur globally and involve high-profile international public health crises, international regulators implanted standard codes for MDAE reporting. This study aimed to assess the application of MDAE terminology and codes by providing examples of virtual events. An online survey was conducted among participants of the MD Training Program for Regulatory Authorities which provide International Medical Device Regulators Forum (IMDRF) adverse event terminology and codes, and six virtual MDAE cases. All 29 of the 72 participants were regulators. In all cases, most participants selected the broad (level 1) codes rather than the detailed (level 2 or level 3) codes. While responders selected a variety of codes for all annexes in case 1, over 50% of responders selected the intended codes in case 6. The codes for cause investigation were chosen more frequently than other annexes for device problem, components, and health effect. No differences were observed in code selection amongst different stakeholders. We identified the diversification in terminology and code selection for reporting MDAEs.

Cybersecurity Framework for Synthetic Data in Training Medical AI

Abstract The development of medical artificial intelligence is dependent on the availability of vast quantities of data, a considerable proportion of which is medical data containing sensitive information pertaining to the health and well-being of patients. The use of such data is subject to extensive legal regulation and is further hindered by financial and organisational constraints, which can result in limitations on accessibility. One potential solution to this problem is the use of synthetic data. This article examines the potential for their use in light of cybersecurity requirements derived from horizontal and sectoral EU legislation. The outcome of this analysis is that EU legislation does not contain specific regulations on the use of synthetic data. Consequently, it cannot be concluded that there is any prohibition on their use. Moreover, while the Medical Device Regulation (MDR) contains some general requirements for cybersecurity, these are further specified by the provisions of the AI Act. It is important to note, however, that the AI Act will not apply to Class I medical devices, which are subject only to the MDR. Furthermore, only indirect obligations within the scope under consideration can be derived from the horizontal regulations, which will apply in a limited number of cases.

PHSOR07 Presentation Time: 9:30 AM: In-House Developed Medical Device Software BiCycle for Automated BT Treatment Planning, Compliant with the European Medical Device Regulation (MDR)

PHSOR07 Presentation Time: 9:30 AM: In-House Developed Medical Device Software BiCycle for Automated BT Treatment Planning, Compliant with the European Medical Device Regulation (MDR)

AI Robotics in Healthcare Between the EU Medical Device Regulation and the Artificial Intelligence Act

AI Robotics in Healthcare Between the EU Medical Device Regulation and the Artificial Intelligence Act

Accessibility engineering in the mhealth industry - A multi-case study

Abstract Medical apps, i.e. apps that fall under the EU Medical Device Regulation (MDR), are increasingly becoming a relevant part of healthcare in European countries. This is particularly evident in the numerous partnerships between app vendors and insurers as well as in the launches of national reimbursement programs. However, when it comes to enabling as many patients as possible to benefit from the medical advantages associated with the use of these apps, funding is only one part of the equation. It is up to the app vendors to develop barrier-free user interfaces so that people - regardless of individual characteristics such as cognitive abilities, physical limitations or language skills - can interact successfully with the app. Little is known about how these companies approach the topic of accessibility, what challenges they face and how big the impact of medical device legislation and other regulations on accessibility is. Against this background, we are undertaking a case study in several companies offering apps on the German market that are certified as medical devices and targeted at patients. Through interviews with employees with various roles (e.g. business, engineering, design) we are aiming at reconstructing the development processes of the apps with a focus on accessibility. We plan to expand the results by interviews with experts, e.g., in the area of MDR conformity assessment. 20 interviews in four companies have revealed that accessibility only plays a minor role during development. As a result, the topic is not systematically addressed, but only a few features are implemented. The app’s compatibility with screen reader or voice control was not explicitly addressed in any of the companies. There was also no deliberate involvement of people with disabilities in user studies. The preliminary results also indicate that the influence of medical device legislation on the implementation of accessibility is negligible. Key messages • User interface accessibility has a very low priority in the mhealth companies we have examined so far. • The current regulations are not sufficient in enforcing the basic implementation of accessibility features requiring more guidance and detailed regulations, given our sample of companies.

Development of an assessment process for digital medical devices in Austria

Abstract Issue/problem Digital medical devices have experienced a rapid development in recent years and are playing an increasingly important role in healthcare. These devices offer numerous benefits and can improve patient care. However, despite their potential benefits, the use of digital medical devices also poses risks and regulation from governmental side is needed from a Public Health Perspective. This is why some countries already implemented assessment processes for Digital Medical Devices (e.g. Germany and France) leading to the question how such a process could be established in Austria too. Description of the problem While digital medical devices must fulfil requirements set by the medical device regulation to enter market, several other aspects are of interests when offering digital medical devices in routine care. These include e.g. medical effectiveness, data security and interoperability. The objective of the ongoing pilot project is to develop a process for the assessment of quality-assured digital medical devices in Austria in 2024. For this, a combination of literature research, interviews and workshops with relevant stakeholders is used in order to gain all necessary information. Process and assessment criteria will be tested and revised in a pilot phase with several digital medical devices. Results At the end of the project, an assessment framework as well as a potential evaluation process will be designed in accordance with relevant stakeholders. Moreover, legals aspects and the potential integration into the austrian health telematics infrastrucutur will be assessed. This will form a basis for implementing digital medical devices within the austrian healthcare system. Key messages • The result of this project aims to build the basis for implementing an evaluation process for digital medical devices in Austria. • The establishment of an evaluation process for digital medical devices supports the integration of quality assured digital medical devices in healthcare.

Quality evaluation of field safety notices of medical devices, across EU and non-EU countries

Abstract Introduction The EU Medical Device Regulation 2017/745 (MDR; article 87) requires device manufacturers to report to the relevant authorities any serious incident and any corrective action undertaken, through Field Safety Notices (FSN) whose content must be consistent in all Member States. Before MDR, due to the lack of harmonized global standards for reporting, FSNs were published independently by each country with different formats, styles, nomenclatures and languages. This heterogeneity makes it challenging to use such historical data for trend analysis in post-market surveillance (PMS). Purpose 1) To assess the quality of the FSNs issued by EU or non-EU national authorities for analysing historical trends. 2) To group countries based on such quality, and test for differences between EU and non-EU countries. Methods As part of the CORE-MD project coordinated by the ESC, all FSN information publicly available as HTML text (excluding linked PDFs) was retrieved automatically from national authorities’ websites, using the CORE-MD PMS tool [1]. For each FSN, a score was assigned to each field of interest (1 or 2, according to importance for building trends) (see Figure 1), and a Percentage Score (PS) computed as the % of the ratio between the scores’ sum and the maximum possible score (10). Based on PS, FSNs were categorized as Excellent (≥90), Very Good (80≤PS<90), Good (70≤PS<80), Medium (60≤PS<70), or Unqualified (<60). For each country, the distribution of FSN categories was computed. Hierarchical Agglomerative Clustering (HAC) was used to group countries based on their similarities, and differences between EU and non-EU countries were assessed by Mann-Whitney U test. Results 126,405 FSNs published before 31/12/2022 were retrieved and analyzed. The % of FSN in which each field was available is shown by country in Figure 1. Manufacturer and Device were clearly described, but more detailed device information was often absent. The Description, with the reason for publishing the FSN, and the Device Category, allowing nomenclature categorization, were provided only by a few countries. The % of FSNs in each quality category is reported in Figure 2: only Italy provided some FSNs (31%) classified as Excellent. The HAC analysis identified three clusters: "high-quality FSNs" (Czechia, Denmark, Italy, Sweden, the Netherlands, and the USA), "moderate-quality FSNs" (Australia, Canada, Greece, Ireland, Latvia, Slovenia, Spain, and the UK), and "low-quality FSNs" (Croatia, Estonia, France, Germany, Poland, and Portugal). There was no difference between EU and non-EU countries. Conclusions A significant discrepancy was observed in the quality of FSNs retrieved from different countries, highlighting the difficulty in using such data to analyse trends, for example in reports of cardiovascular devices. This study reinforces the need for a global minimum reporting standard, to facilitate more effective PMS.Figure 1Figure 2

Recent regulatory developments in EU Medical Device Regulation and their impact on biomaterials translation

AbstractWe envision this work to assist researchers and medical device developers (beside other stakeholders) to better understand biomaterial‐based medical device development and its approval process proposed by the new MDR and IVDR in the European Union, as more complex biomaterials emerge, with the MDR reflecting the progress in biomaterial discoveries. Additionally, insufficient international harmonization in regulatory laws and poor‐quality data reporting contribute to the problem. This review describes the possible reasons for a slowing biomaterials translational trend observed over the past decades, focusing on the European Market, and suggests a feasible approach for biomaterials‐based medical device translation into the clinic. Suitable solutions to upgrade biomaterial translation to the clinic have not yet been provided by the field: no additional hurdles should be imposed for researchers, clinicians, the medical device industry, and insurance companies, which all should collaborate on bringing innovative solutions to patients. The new MDR and IVDR represent a substantial advancement in ensuring patient safety and reflect a major step forward in healthcare. However, they should not constrain innovation in biomaterials‐based medical device development. Incorporating reverse engineering from patient safety and a ‘safe by design’ (SbD) strategy early into medical device development might lead to a smoother and successful approval process. A solid R&D phase, with an emphasis on device safety and performance assessment, is fundamental to ensure an effective transition into the clinic. We offer an overview of the recently implemented regulations on medical devices and in vitro diagnostics across the EU, describing a shifting paradigm in the field of biomaterials discovery. As more complex biomaterials emerge, suitable regulations will be necessary to keep bringing safe and well‐performing medical solutions to patients.

Modernizing Medical Device Regulation: Challenges and Opportunities for the 510(k) Clearance Process.

Nearly all medical devices reviewed by the U.S. Food and Drug Administration (FDA) are authorized via the 510(k) clearance process. Established in 1976, this review pathway bases authorizations on the comparability of new devices to previously authorized devices ("predicates"). This evaluation usually does not require clinical evidence of safety and effectiveness. Advocates of the 510(k) clearance process tout its support for device innovation and rapid market access, and critics of the 510(k) clearance process express that it may inadequately protect patient safety. In September 2023, the FDA issued 3 guidance documents that, if finalized, would significantly change medical device regulation. This article provides clinical and regulatory context for the proposed guidance documents, which focus on predicate selection, clinical testing requirements, and implantable devices, and identifies opportunities for further reforms that promote transparency and patient safety.

Energy-Based Medical Devices in Plastic Surgery: A Comparison of FDA-Approved Indications to Advertised Claims.

Lasers and energy-based devices are commonly employed in aesthetic medicine. In the United States, the FDA regulates lasers as medical devices, restricting marketing to approved indications and making off-label claims illegal. Despite this, no comprehensive analysis of off-label marketing prevalence exists. The authors of this study aim to compare the FDA-approved indications for 2 popular aesthetic lasers to their online advertising claims. Additionally, they seek to educate aesthetic providers on the current regulatory restrictions surrounding off-label advertising. FDA-approved indications for 2 lasers-helium plasma dermal resurfacing and 2940 nm fractional erbium-doped yttrium aluminum garnet-were obtained from the publicly available Establishment Registration & Device Listings Database. Online advertisements regarding the capabilities of each laser were collected from practice websites in the United States. Our analysis of 100 online claims for each laser revealed that more than half of the websites advertising helium plasma (n = 59) and 44 websites advertising fractional lasers made at least 1 off-label claim. Both plastic surgeons and nonplastic surgeons made at least 1 off-label claim, with no statistically significant difference between the groups. Despite FDA regulation of medical devices, online advertising regarding the indications and capabilities of popular medical lasers varies widely. Patients who seek information regarding aesthetic laser treatments may encounter inaccurate and differing claims for these treatments, potentially leading to false expectations and poor patient outcomes.

A Blueprint for Clinical-Driven Medical Device Development: The Feverkidstool Application to Identify Children With Serious Bacterial Infection

Clinical decision rules (CDRs) integrated into applications enhance diagnostic and treatment prediction support for clinicians, necessitating CE-mark certification to enter the European market. We describe the development of a CDR as a medical device, focusing on challenges from a physician's perspective exemplified by the Feverkidstool (FKT), a validated CDR for febrile children. We pursued a local process, aligned with the CE-marking process, to develop the FKT as in-house developed device. We aim to provide a blueprint for colleagues.Medical device development, conform the Medical Device Regulation and performed by a multidisciplinary team, encompassed five stages: market scan, design, production, verification and validation and conformity assessment. Regulatory processes were continuously updated. The market scan identified a need for the FKT compared to existing applications. A prototype was designed in stage 2, further adjusted and improved based on the qualitative and quantitative results of stage 2-4. Lastly, stage 5 confirmed FKT's performance and safety. Medical device development presents challenges for physicians, requiring collaboration for technical, regulatory, and financial expertise. Multidisciplinary teamwork also poses challenges, including uncertainties regarding responsibility and timelines. After CE-certification, adapting to evolving needs and ensuring data privacy highlights the ongoing nature of medical device development.

Raman Spectroscopy for Instant Bladder Tumor Diagnosis: System Development and In Vivo Proof-Of-Principle Study in Accordance with the European Medical Device Regulation (MDR2017/745).

This work reports on an in vivo Raman-based endoscopy system, invaScope, enabling Raman measurements of healthy and tumor bladder tissue during an endoscopic procedure in the operating theatre. The presented study outlines the progression from the initial concept (validated through previously performed ex vivo studies) to the approval and implementation of a clinical investigational device according to the requirement within the framework of the European Medical Device Regulation (MDR2017/745). The study's primary objective was to employ the invaScope Raman system within the bladder, capturing in vivo spectroscopic Raman data followed by standard histo- and cytopathological examinations of urological tissue (considered the gold standard). The collected data were analyzed and correlated with histopathological findings post-procedure. Additionally, the study aimed to assess the feasibility of using diagnostic equipment, probes, and software for application in a clinical setting, evaluating usability aspects that are important during surgical procedures. This research represents a pivotal step toward advancing Raman spectroscopy for routine clinical use in characterizing bladder lesions.

Research Into Digital Health Intervention for Mental Health: 25-Year Retrospective on the Ethical and Legal Challenges.

Digital mental health interventions are routinely integrated into mental health services internationally and can contribute to reducing the global mental health treatment gap identified by the World Health Organization. Research teams designing and delivering evaluations frequently invest substantial effort in deliberating on ethical and legal challenges around digital mental health interventions. In this article, we reflect on our own research experience with digital mental health intervention design and evaluation to identify 8 of the most critical challenges that we or others have faced, and that have ethical or legal consequences. These include: (1) harm caused by online recruitment work; (2) monitoring of intervention safety; (3) exclusion of specific demographic or clinical groups; (4) inadequate robustness of effectiveness and cost-effectiveness findings; (5) adequately conceptualizing and supporting engagement and adherence; (6) structural barriers to implementation; (7) data protection and intellectual property; and (8) regulatory ambiguity relating to digital mental health interventions that are medical devices. As we describe these challenges, we have highlighted serious consequences that can or have occurred, such as substantial delays to studies if regulations around Software as a Medical Device (SaMD) are not fully understood, or if regulations change substantially during the study lifecycle. Collectively, the challenges we have identified highlight a substantial body of required knowledge and expertise, either within the team or through access to external experts. Ensuring access to knowledge requires careful planning and adequate financial resources (for example, paying public contributors to engage in debate on critical ethical issues or paying for legal opinions on regulatory issues). Access to such resources can be planned for on a per-study basis and enabled through funding proposals. However, organizations regularly engaged in the development and evaluation of digital mental health interventions should consider creating or supporting structures such as advisory groups that can retain necessary competencies, such as in medical device regulation.

The regulatory status of health apps that employ gamification

Smartphone applications are one of the main delivery modalities in digital health. Many of these mHealth apps use gamification to engage users, improve user experience, and achieve better health outcomes. Yet, it remains unclear whether gamified approaches help to deliver effective, safe, and clinically beneficial products to users. This study examines the compliance of 69 gamified mHealth apps with the EU Medical Device Regulation and assesses the specific risks arising from the gamified nature of these apps. Of the identified apps, 32 (46.4%) were considered non-medical devices; seven (10.1%) were already cleared/approved by the regulatory authorities, and 31 (44.9%) apps were assessed as likely non-compliant or potentially non-compliant with regulatory requirements. These applications and one approved application were assessed as on the market without the required regulatory approvals. According to our analysis, a higher proportion of these apps would be classified as medical devices in the US. The level of risk posed by gamification remains ambiguous. While most apps showed only a weak link between the degree of gamification and potential risks, this link was stronger for those apps with a high degree of gamification or an immersive game experience.

LEGAL ANALYSIS OF EU ARTIFICIAL INTELLIGENCE ACT (2024): INSIGHTS FROM PERSONAL DATA GOVERNANCE AND HEALTH POLICY

Background: This study correlates the up-to-date ethical, functional and legal evaluations related to the management and governance of artificial intelligence (AI) under European Union (EU) law, particularly impacting the health data sector and medical standards as provided by the Artificial Intelligence Act within the Regulation adopted by the European Council in May 2024. The initial proposal for the management and governance of the AI sector was submitted in April 2021. Three years later, on 13 March 2024, the European Union Artificial Intelligence Act (EU AIA) was adopted by the European Parliament. Subsequently, on 21 May 2024, the Council adopted an innovative legislative framework that harmonises the standards and rules for AI regulation. This framework is set to take effect in May 2026, with the central objective of stimulating and motivating a fair, safe, legal single market that respects the principles of ethics and the fundamental rights of the human person. Methods: The current legal analysis focuses on the European Union’s new institutional governance involving a multistage approach to managing health data, ethical artificial intelligence, generative artificial intelligence and classification of types of AI by considering the degree of risk (e.g. artificial intelligence systems with limited risk and systems with high risk) and medical devices. It outlines the legal framework for AI regulation and governance in the EU by focusing on compliance with the previously adopted legislation in the Medical Devices Regulation (2017) and the In-Vitro Diagnostic Regulation (2017). The paper also examines the application of the newly adopted EU Artificial Intelligence Act in relation to national justice systems, previous EU regulations on medical devices and personal data protection regulation, and its correlation with the European Court of Human Rights jurisprudence. This opens up complex discussions related to judicial reform and access to justice. For this purpose, as a research objective, the legal analysis includes an innovative perspective following an integrative discussion on the latest legal reforms and regulations of the AI sector in Eastern Europe launched in 2024 with a special focus on the latest developments in the EU Candidate Countries namely Ukraine and the Republic of Moldova. Results and conclusions: The present research facilitates the exploration of the real benefits of managing innovative AI systems for medical data, research, and development, as well as within the medical technology industry.

How to advance from minimally invasive coronary artery bypass grafting to totally endoscopic coronary bypass grafting: challenges in Europe versus United States of America.

Robotic coronary and intra-cardiac surgery has been available for more than 25 years. In this period, multiple studies have demonstrated the beneficial effects of robotic surgery over conventional open surgery. Throughout the years, technical developments have enabled us to perform totally endoscopic coronary artery bypass (TECAB) grafting. But these techniques remained in the hands of a small group of pioneers because of a lack of structured training programs and the absence of long-term results at that time. Currently, a renewed interest and a wide dispersion of robotic platforms, thanks to use of robotics in other disciplines, has led to an exponential increase in robotic cardiac centers both in Europe and USA. Nonetheless, this increase was slowed down in Europe as a result of the uncertainty introduced by the implementation of a revised regulatory framework for medical devices [Regulation 2017/745, 'Medical Device Regulation' ('MDR')]. The MDR was introduced with the goal of increasing patient safety and supporting innovation. Implementing the MDR has proven to be exceptionally challenging and risks to the supply of essential devices have been identified. Changes to both regulatory and market dynamics led to a circumstance where the only available robotic platform for cardiac surgery decided to cease marketing of essential accessories for conducting surgery. This resulted in the disappearance of dedicated tools such as the Endowrist stabilizer, essential for TECAB, and the atrial retractor which is essential for intra-cardiac surgery. In the mean-time, further clinical evidence was published demonstrating the superiority of robotic cardiac surgery over other minimally invasive approaches. This has demonstrated the need to better define the clinical evidence requirements for regulatory purposes to ensure that dedicated tools for evidence-based interventions in robotic coronary surgery remain available such that TECAB can continue in Europe.

Embracing industry in the development of robotic coronary bypass grafting-the sun rises in the East.

The introduction of robotic surgical devices nearly two decades ago led to a significant reduction in the invasiveness of cardiac procedures. The further worldwide implementation of robotic surgical devices in cardiac surgery, especially coronary artery bypass grafting and mitral valve repair or replacement, has, however, been stalled by numerous challenges. First, there is the high complexity of the procedures that involve a significant learning curve; second, there is the significant cost of robotic surgical devices. Furthermore, significant changes in the medical device regulation have occurred in recent years, hindering further technological development and the emergence of new players on the market. Finally, clinical evidence regarding the benefits of robotic-cardiac procedures remains scarce at this time. We invited all players active in or planning to throw themselves into robotic-assisted cardiac surgery to discuss these challenges in a semi-structured interview. Two promising and ambitious companies showed interest in participating in this project: Medicaroid and SS Innovations. The main conclusions from the interview are that both companies aim (I) to launch an affordable alternative compared to the current robotic surgical devices, (II) to further develop their robotic devices based on the opinion of physicians, and (III) to engage in overcoming the steep learning curve correlated with robotic-assisted cardiac procedures.

Medical device similarity analysis: a promising approach to medical device equivalence regulation

ABSTRACT Background This study aims to facilitate the identification of similar devices for both, the European Medical Device Regulation (MDR) and the US 510(k) equivalence pathway by leveraging existing data. Both are related to the regulatory pathway of read across for chemicals, where toxicological data from a known substance is transferred to one under investigation, as they aim to streamline the accreditation process for new devices and chemicals. Research design and methods This study employs latent semantic analysis to generate similarity values, harnessing the US Food and Drug Administration 510k-database, utilizing their ‘Device Descriptions’ and ‘Intended Use’ statements. Results For the representative inhaler cluster, similarity values up to 0.999 were generated for devices within a 510(k)-predicate tree, whereas values up to 0.124 were gathered for devices outside this group. Conclusion Traditionally, MDR equivalence involves manual review of many devices, which is laborious. However, our results suggest that the automated calculation of similarity coefficients streamlines this process, thus reducing regulatory effort, which can be beneficial for patients needing medical devices. Although this study is focused on the European perspective, it can find application within 510(k) equivalence regulation. The conceptual approach is reminiscent of chemical fingerprint similarity analysis employed in read-across.

Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders

Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders Abstract: As a vulnerable group, minors require special protection in studies. For this reason, researchers are often reluctant to initiate studies, and ethics committees are reluctant to authorize such studies. This often excludes minors from participating in clinical studies. This exclusion can lead to researchers and clinicians receiving only incomplete data or having to rely on adult-based findings in the treatment of minors. Using the example of the study "Computer-Assisted Risk Evaluation in the Early Detection of Psychotic Disorders" (CARE), which was conducted as an 'other clinical investigation' according to the Medical Device Regulation, we present a line of argumentation for the inclusion of minors which weighs the ethical principles of nonmaleficence (especially regarding possible stigmatization), beneficence, autonomy, and fairness. We show the necessity of including minors based on the development-specific differences in diagnostics and early intervention. Further, we present specific protective measures. This argumentation can also be transferred to other disorders with the onset in childhood and adolescence and thus help to avoid excluding minors from appropriate evidence-based care because of insufficient studies.