Medical Device Regulation Research Articles

Use of three-dimensional printing technology for supporting the hip reconstruction surgery in paediatric patients

The use of three-dimensional (3D) printed patient-specific anatomical models is nowadays a viable strategy for improving surgical outcome in medicine. In adult surgery, 3D printing technology is commonly studied, but its use in paediatric surgery is still under development. This work presents the implementation of 3D printing technology in Orthopaedic department of the paediatric hospital “Santobono-Pausilipon” in Naples by fabricating 3D printed anatomical models of paediatric patients. The 3D printed models fabricated were used for the training of the surgical team during the preoperative planning and for carrying out a surgical simulation. The anatomical models are designed in compliance with the current European Medical Devices regulation and following the already existing guidelines in literature. The impact of the 3D printed anatomical models used, a total of seven printed anatomical models based on four patients, is then evaluated throughout a questionnaire proposed to the surgical team, composed by eight paediatric orthopaedic surgeons. Surgeons answered to a total of ten questions, six scale-based questions and four free-text questions. Results obtained from the questionnaires highlighted how 3D printed anatomical models can lead to a better understating of the treated pathologies, carrying relevant improvements in both the surgical team training and the surgical outcome.

Digital Interventions and Their Unexpected Outcomes - Time for Digitalovigilance?

The application of digital interventions in healthcare beyond research has been translated in the development of software as a medical device. Along with corresponding regulations for medical devices, there is a need for assessing adverse events to conduct post-market surveillance and to appropriately label digital health interventions to ensure proper use and patient safety. To date unexpected consequences of digital health interventions are neglected or ignored, or at least remain undescribed in literature. This paper is intended to raise awareness across the research community about these upcoming challenges. We recommend that - together with developing a new research field of digitalovigilance - a systematic assessment and monitoring of adverse events and unexpected interactions be included in clinical trials, along with the reporting of such events and the conduct of meta-analyses on critical aspects.

Medical Device Regulations for custom-made devices: Answers to a further ten important questions

Medical Device Regulations for custom-made devices: Answers to a further ten important questions

Use of the ETV6/RUNX1 probe to verify the performance of the fluorescence in situ hybridization probe before clinical detection

Objective: To explore the standardized performance of a FISH probe before clinical detection. Methods: The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test. Results: The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001. Conclusion: For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

Approaching 3D printing in oral and maxillofacial surgery - suggestions for structured clinical standards.

With respect to the European Union 2017 amendment of the Medical Device Regulations (MDR), this overview article presents recommendations concerning medical 3D printing in oral and maxillofacial surgery (OMFS). The MDR were screened for applicability of the rules to medical in-house 3D printing. Applicable regulations were summarized and compared to the status of medical use of 3D printing in OMFS in Germany. Recommendations were made for MDR concerning medical 3D printing. In-house printed models, surgical guides, and implants fall under the category of Class I-III, depending on their invasive and active properties. In-house medical 3D printing for custom-made medical devices is possible under certain prerogatives: (1) the product is not being used in another facility, (2) appropriate quality systems are applied, (3) the reason for omitting commercial products is documented, (4) information about its use is supplied to the responsible authority, (5) there is a publicly accessible declaration of origin, identification, and conformity to the MDR, (6) there are records of manufacturing site, process and performance data, (7) all products are produced according to the requirements proclaimed before, and (8) there is an evaluation of clinical use and correction of possible issues. Several aspects must be addressed for in house medical 3D printing, according to the MDR. Devising MDR related to medical 3D printing is a growing challenge. The implementation of recommendations in OMFS could help practitioners to overcome the challenges and become aware of the in-house production and application of 3D printed devices.

Ala®sil chemical characterization and toxicity evaluation: an example of the need for the Medical Device Regulation 2017/745.

Introduction: Ala®sil infusion was on the market for clinical use under the Medical Devices Directive (MDD) 93/42/EEC as an irrigating solution based on polydimethylsiloxane (PDMS). The product was withdrawn in 2016, and to the best of our knowledge, it did not cause any health damage. Methods: A bibliographic review and experimental analysis were conducted to evaluate whether this CE-marked product could have been used in patients under the current Medical Device Regulation (MDR) 2017/745. Analytical results from gas chromatography-mass spectrometry (GC-MS) and matrixassisted laser desorption ionization (MALDI) were performed. Citotoxicity studies were also carried out. Results: Only one study related to Ala®sil clinical use was found, describing a pilot series of five patients. The authors rated the product as not helpful in three out of the five cases for internal searching of retinal breaks and in four out of the five cases for drainage of subretinal fluid. No other scientific papers or documentation was found regarding Ala®sil's safety. Nevertheless, the product was introduced in the market after achieving the CE marking. GC-MS and MALDI showed that the polymer has a low molecular weight of 1,000g/mol. Several linear and cyclic low-molecular-weight components (LMWCs) were identified as impurities ranging from L3 to D8, with a molecular weight below 600g/mol. The Ala®sil sample was found to be cytotoxic after 24h of cell culture but non-cytotoxic after 72h, probably due to the cellular regeneration capacity of an immortalized cell line. Tissular cytotoxicity revealed an increased apoptosis rate but without morphological modifications. Discussion: Although Ala®sil cannot be classified as cytotoxic, this substance appears to increase retinal cell death processes. This study supports the notion that the MDDwas not functioning adequately to ensure the safety of medical devices. However, the current MDR 2017/745 imposes stricter standards to prevent the commercialization of medical devices without high-quality preclinical and clinical information, as well as precise clinical verification for their use, information not available for Ala®sil infusion.

Finding our way in the In Vitro Diagnostic Medical Devices Regulation: a discussion paper from the European Bioanalysis Forum.

Finding our way in the In Vitro Diagnostic Medical Devices Regulation: a discussion paper from the European Bioanalysis Forum.

Mapping the Regulatory Framework for Telemedicine in Zambia: A Content Analysis

This paper explores the regulatory framework for telemedicine in Zambia. Telemedicine, involving remote clinical services using technology, is a rapidly evolving field intersecting with legal, ethical, and professional domains. The primary aim is to understand Zambia's telemedicine regulatory framework through an analysis of key documents namely the Zambia E-Government Interoperability Standard (eGIF), Zambia Digital Health Strategy 2022-2026, HPCZ Guidelines for the Quality Assurance of Telemedicine Services, and Statutory Instrument 43 of 2023 (SI 43 of 2023). The study addresses the challenge of comprehensively understanding and effectively implementing telemedicine in Zambia, considering the evolving nature of technology and healthcare services. Mapping the regulatory framework is a critical exercise for ensuring legal compliance, maintaining high standards of service, protecting patients, and making informed strategic decisions in the telemedicine sector. The study conducts a detailed exploration and content analysis of the aforementioned documents. This includes examination of their contributions to establishing a strong telemedicine landscape in Zambia, focusing on aspects like interoperability, data security, and healthcare service delivery. Findings reveal each document's significant, yet varied, contributions to the telemedicine framework in Zambia. The eGIF ensures integrated, standardized, and secure digital telemedicine services. The Zambia Digital Health Strategy 2022-2026 promotes telemedicine via digital technology and global alignment, while the HPCZ Guidelines provide a detailed framework focusing on ethical and legal standards. SI. 43 of 2023 emphasizes data security, quality assurance, and collaboration in telemedicine. Comparatively, Zambia's framework, as shaped by the four documents, aligns with global standards but differs in its centralized regulation and strategic focus, lacking extensive coverage on medical device regulations and reimbursement issues seen in other countries. The study suggests the need for a unified approach to telemedicine, emphasizing standardization, legal compliance, accessibility, and inclusivity. Recommendations include improving interoperability, ensuring data security, and fostering user-centric telemedicine services for enhanced healthcare outcomes.

AI in imaging: the regulatory landscape.

Artificial intelligence (AI) methods have been applied to medical imaging for several decades, but in the last few years, the number of publications and the number of AI-enabled medical devices coming on the market have significantly increased. While some AI-enabled approaches are proving very valuable, systematic reviews of the AI imaging field identify significant weaknesses in a significant proportion of the literature. Medical device regulators have recently become more proactive in publishing guidance documents and recognizing standards that will require that the development and validation of AI-enabled medical devices need to be more rigorous than required for tradition "rule-based" software. In particular, developers are required to better identify and mitigate risks (such as bias) that arise in AI-enabled devices, and to ensure that the devices are validated in a realistic clinical setting to ensure their output is clinically meaningful. While this evolving regulatory landscape will mean that device developers will take longer to bring novel AI-based medical imaging devices to market, such additional rigour is necessary to address existing weaknesses in the field and ensure that patients and healthcare professionals can trust AI-enabled devices. There would also be benefits in the academic community taking into account this regulatory framework, to improve the quality of the literature and make it easier for academically developed AI tools to make the transition to medical devices that impact healthcare.

Postmarket Surveillance of Neuroendovascular Devices

Endovascular devices have catalyzed a global industry for advanced technologies such as flow diverters and stent retrievers. Though adoption of these devices has skyrocketed over the past 30 years, the regulatory landscape for real‐world monitoring is constantly under revision. Postmarket surveillance is an area of Medical Device Regulation that monitors how devices perform in the real world after regulatory approval. This area of research is underdeveloped globally, with most surveillance relying on passive adverse event data collection from health care systems. The US Food and Drug Administration has not yet established a comprehensive postmarket surveillance strategy for neuroendovascular devices. Postmarket clinical surveillance data are rare; only 4 mandated 522 postmarket neuroendovascular trials exist, and 4 of 14 endovascular registries have published results per ClinicalTrials.gov. The European Union 2017 Medical Device Regulation describes a comprehensive regulatory strategy to address postmarket surveillance, yet it has faced difficult implementation due to resource constraints and concerns such as increased costs and reliance on foreign devices and regulators. More than 50% of manufacturers are planning portfolio reductions, with 33% of the devices from these manufacturers planned for discontinuation. As of April 2022, &gt;85% of 500 000+ previously certified devices were without new certification. In this article, we describe the current regulatory landscape for postmarket surveillance and support the need for a comprehensive, cost‐efficient postmarket strategy for neurovascular devices while proposing several solutions and considerations. An effective postmarket strategy has numerous benefits, such as promoting patient safety, expanding real‐world data collection, and increased efficiency for approving future devices.

Patient-Reported Outcome Measures in High-Risk Medical Device Registries: A Scoping Review.

Abstract Little is known about the methods and outcomes of patient-reported outcome measure (PROM) use among high-risk medical device registries. The objective of this scoping review was to assess the utility and predictive ability of PROMs in high-risk medical device registries. We searched Ovid Medline, Embase, APA PsychINFO, Cochrane Library, and Scopus databases for published literature. After searching, 4323 titles and abstracts were screened, and 262 full texts were assessed for their eligibility. Seventy-six papers from across orthopedic (n = 64), cardiac (n = 10), penile (n = 1), and hernia mesh (n = 1) device registries were identified. Studies predominantly used PROMs as an outcome measure when comparing cohorts or surgical approaches (n = 45) or to compare time points (n = 13) including pre- and postintervention. Fifteen papers considered the predictive ability of PROMs. Of these, 8 treated PROMs as an outcome, 5 treated PROMs as a risk factor through regression analysis, and 2 papers treated PROMs as both a risk factor and as an outcome. One paper described PROMs to study implant survival. To advance methods of PROM integration into clinical decision-making for medical devices, an understanding of their use in high-risk device registries is needed. This scoping review found that there is a paucity of studies using PROMs to predict long-term patient and clinical outcomes in high-risk medical device registries. Determination as to why PROMs are rarely used for predictive purposes in long-term data collection is needed if PROM data are to be considered suitable as real-world evidence for high-risk device regulatory purposes, as well as to support clinical decision-making. Level of Evidence: 4

Medical device regulation and its impact on the industry: A case study of Czech companies

The implementation of regulations is often seen as a necessary tool to mitigate market failures and safeguard consumer interests. The Medical Device Regulation (MDR) is a recent regulation specifically designed for the production of medical devices, aiming to ensure their safety and effectiveness. This article focuses on Czech companies and seeks to examine and quantify the effects of the MDR on their operations, considering both economic and procedural impacts. Through the analysis of primary and secondary data, this study endeavors to shed light on the repercussions of the MDR on the companies in question. The findings suggest that the MDR will have a negative impact on the profitability of these companies, consequently influencing their operational strategies. One key factor contributing to this negative outcome is the inability of the companies to transfer the increased costs resulting from regulatory requirements to their customers. As a result, affected companies are forced to make adjustments to their product portfolios, reducing their range of offerings. The research reveals that the perception of the MDR among the companies is predominantly negative. This negative sentiment arises primarily due to the financial burdens imposed by the regulation and the other associated impacts discussed in the article. Furthermore, the MDR is not perceived as a catalyst for innovation within the industry. By quantifying the effects of the MDR on Czech companies, this article provides valuable insights into the real-world implications of this regulatory framework. The findings highlight the challenges faced by companies in adapting to and complying with the MDR, particularly in terms of its impact on profitability and product offerings. This research serves as a reminder of the complex interplay between regulations, economic outcomes, and industry dynamics. Ultimately, it emphasizes the importance of considering the potential ramifications of regulations and their effects on businesses and markets.

Assessing operational readiness: Regulatory landscape and compliance in zimbabwe for medical devices and in vitro diagnostic medical devices.

The regulation of medical devices and In Vitro Diagnostic (IVD) medical devices have lagged significantly, especially in low- and middle-income countries. Disparities in regulating medical and IVD medical devices in Africa are below the global average. This may translate to poor access to quality-assured medical and IVD devices, resulting in undesirable health outcomes. Operational readiness to regulate medical and IVD devices at the Medicines Control Authority of Zimbabwe (MCAZ) was assessed. The aim was to determine the strengths and gaps and propose an action plan that can be monitored and evaluated to assess progress over time. We used the World Health Organization (WHO) Global Benchmarking Tool for medical devices and IVDs methodology to evaluate regulatory oversight of these products. Purposive sampling was used for data collection using researcher-administered global benchmarking tool factsheets and document reviews to evaluate the implementation of the regulatory functions. The regulatory functions assessed were the National Regulatory System, Registration and Market Authorization, Vigilance, Market Surveillance and Control, Licensing Establishment, Regulatory Inspection, Laboratory Testing, and Clinical Trials Oversight. The MCAZ attained maturity level 1, with a regulatory system score of 79%, registration and market authorization 44%, vigilance 27%, market surveillance and control 40%, licensing establishment 62%, regulatory inspection 68%, laboratory testing 88%, and clinical trials 18%. Condoms and gloves were the only regulated medical devices in Zimbabwe. IVDs were not regulated by the MCAZ. This review showed that the regulatory system is not robust, fit for purpose, responsive, transparent, or proportionate to the risk classification of medical devices and IVDs. It is crucial to amend the Medicines and Allied Substance Control Act to incorporate the definition and classification of medical devices and IVDs, regulatory authority establishment, licensing and registration, quality management system, conformity assessment, post-market surveillance, labeling and instructions for use, capacity building and training, and international harmonization.

A dual analysis of bougie and stylet development trend and impact of Chinese regulations on medical devices innovation.

Medical device research and development are characterized by high costs, extended timelines, inherent risks, and the necessity for interdisciplinary knowledge and skills. It is significantly influenced by policies, making the understanding of medical device innovation both important and challenging. This paper takes a dual approach to analyze medical device innovation. We reviewed representative clinical product of bougie and stylet and summarized the common characteristics and trend of these product. Innovations in these products often involve adding depth markings, replacing material and design structure, enhancing visualization, deciding between reusable or disposable designs, and integrating multi-functional features. This underscores the delicate balance between technological advancements and medical costs for widespread clinical applicability. We explored the guiding role of policy in medical device innovation, emphasizing its impact through an analysis of medical device regulations and policies in China. By offering insights from the perspectives of medical device companies and regulators, this paper aims to elucidate the critical aspects of medical device innovation, assisting researchers in mitigating risks during product development.

Medical Device Regulations: A Comparative Study of India with European Union

Medical Device Regulations: A Comparative Study of India with European Union

Integration of Cutting-Edge Technologies such as Internet of Things (IoT) and 5G in Health Monitoring Systems: A Comprehensive Legal Analysis and Futuristic Outcomes

The convergence of cutting-edge technologies such as the Internet of Things (IoT) and 5G has given rise to innovative applications in various sectors, notably in healthcare. The integration of cutting-edge technologies, notably the Internet of Things (IoT) and 5G, into health monitoring systems has brought forth a transformative paradigm in healthcare. This comprehensive legal analysis explores the intricate intersection of these technologies and the legal landscape governing their application in health monitoring. Delving into the realms of ethics, regulation, and privacy, this study examines the multifaceted challenges and opportunities that arise from this convergence. By scrutinizing patient data protection, medical device regulations, and liability concerns, the analysis offers insights into crafting effective legal frameworks. Additionally, it contemplates the futuristic outcomes of these advancements, considering the potential for enhanced patient care, remote monitoring, and seamless healthcare delivery. This study envisions a harmonious integration of technology and law that not only ensures the rights and privacy of patients but also paves the way for an innovative and patient-centric healthcare future. This research paper critically examines the integration of IoT and 5G technologies in health monitoring systems and analyzes the legal implications arising from their deployment. With a focus on the ethical, regulatory, and privacy concerns associated with these technologies, the paper aims to provide a comprehensive legal analysis that addresses the challenges and opportunities presented by their integration in the healthcare domain.

Physicians' Perspectives On FDA Regulation Of Drugs And Medical Devices: A National Survey.

Physicians' knowledge of Food and Drug Administration (FDA) approval processes is important in informing clinical decisions and patient discussions. Among a randomly selected national sample of 509 internists, cardiologists, and oncologists, 41percent reported moderate or better understanding of the FDA's drug approval process, and 17percent reported moderate or better understanding of the FDA's medical device approval process. Nearly all physicians thought that randomized, blinded trials that met primary endpoints should be very important factors required to secure regulatory approval. Also, nearly all physicians thought that the FDA should revoke approval for accelerated-approval drugs or breakthrough devices that did not show benefit in postapproval studies. Our findings suggest that physicians commonly lack familiarity with drug and medical device regulatory practices and are under the impression that the data supporting FDA drug and high-risk device approvals are more rigorous than they often are. Physicians would value more rigorous premarket evidence, as well as regulatory action for drugs and devices that do not demonstrate safety and effectiveness in the postmarket setting.

NEMECYS: Addressing Challenges to Building Security Into Connected Medical Devices

The European health care system is moving toward personalised, distributed, and home-based services. This is made possible via new and improved connected medical devices (CMDs), and will benefit health care providers in terms of reduced cost and improved service. Patients will see improved quality of life in terms of reduced travel time and reduced stress via treatment at home or where they want it. However, for these benefits to be fully realised, the cybersecurity of CMDs needs to be ensured. This paper presents a brief survey of challenges to building security into CMDs, and introduces NEMECYS, an EU-funded project which will help practitioners to (a) comply with Medical Device (MD) regulations; (b) be able to apply proportionate MD cybersecurity, and (c) build in cybersecurity by design for both MDs and the connected scenarios they operate in.

The influence of biomedical engineering in India

This comprehensive analysis delves into various crucial facets of biomedical engineering, covering cutting-edge technologies, creative methodologies, and ethical dilemmas. Quality Management Systems (QMS) play a pivotal role in maintaining precision, safety, and efficacy in lab experiments and biomedical product development, ensuring adherence to strict quality standards through guidelines like Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP). Advancements in medical imaging, from X-ray CT to molecular imaging, are revolutionizing disease diagnosis and treatment across multiple medical fields. Biomaterials and tissue engineering hold immense potential in regenerative medicine, addressing challenges like immune rejection and implant wear to meet diverse healthcare needs. Biomechanics and rehabilitation engineering merge biomechanical principles with assistive technologies to empower individuals with disabilities and improve their daily autonomy. Biomedical sensors, devices, and nanotechnology are driving personalized healthcare solutions, enhancing disease management through wearable and implantable technologies. Regulatory policies in India underscore the importance of strict regulations for medical devices and therapeutics to ensure safety and efficacy. Overall, this review highlights the transformative impact of biomedical engineering on healthcare advancements and societal well-being through responsible innovation and ethical practices.

Additive manufacturing for orthopedic implants: morphological and material characterization of SLM thin Ti6Al4V samples

In the last decades, the orthopedic industry has increasingly adopted Additive Manufacturing (AM) technologies, such as selective laser melting, to produce custom devices. Given their novelty with respect to discrete-size implants, New 2017/745 Medical Device Regulation introduced the need for safety and quality demonstration of such unique devices, a non-trivial task since no defined criteria state how to test them. In this scenario, numerical analyses can be a robust tool for the intended purposes as long as the reliability of the numerical models is verified in terms of geometry reconstruction and material assignment. The latter need has to deal with the peculiarities of AM in the production of lattice structures, distinctive features of this new generation of devices conceived to mimic bone morphology. Indeed, the struts of such structures have diameters of hundreds of microns, which approach AM accuracy limit. If, on the one hand, the issues related to AM production are well-known, on the other hand, it is not yet fully understood how to deal with them if thin struts are manufactured. Given the still questionable research area and starting from the few literature findings, this study aims to provide an exhaustive morphological and material characterization of Ti6Al4V thin struts produced by selective laser melting, supporting experimental activities with numerical analyses. The importance of investigating together their morphology and mechanical behavior will be highlighted: morphological analyses will constitute the first step to assess the quality of the manufactured samples and to correctly interpret the experimental results of static and fatigue tests. In this light, the differences with respect to the mechanical properties of both machined samples and thick AM samples will be outlined. The outcomes of this research will be fundamental for the development of reliable FE models of lattice-based devices.