Global Perspective on Software as a Medical Device (SAMD): Development Process, Associated Risks, and Legislative Aspects

Continual learning in medical devices: FDA's action plan and beyond

Software as a Medical Device (SaMD) has become indispensable in diagnostics, treatment planning, and patient monitoring. While high-income countries have introduced clear regulatory frameworks, Bangladesh and many low- and middle-income countries (LMICs) still lack tailored pathways for medical software approval (IMDRF. Software as a Medical Device (SaMD): Key Definitions (IMDRF/SaMD WG/N10FINAL:(2013)); IMDRF. Software as a Medical Device (SaMD): Clinical Evaluation (IMDRF/SaMD WG/N41FINAL:(2017)); U.S. Food and Drug Administration (FDA). Software as a Medical Device (SAMD): Clinical Evaluation Guidance for Industry and FDA Staff (2017)). The current reliance on manual processes designed for physical devices leads to inefficiencies, inconsistent decisions, and potential risks to patient safety. This Comment proposes a semi-automated, risk-based intake roadmap for Bangladesh's Directorate General of Drug Administration (DGDA). Drawing on IMDRF, EU MDCG, and U.S. FDA frameworks, it presents a tangible workflow showing which submissions can be automatically triaged, which require human review, and where human override is maintained (European Commission (MDCG). Guidance on Qualification and Classification of Software in Regulation (EU) 2017/745 (MDCG 2019-11) and World Health Organization (WHO) Global Model Regulatory Framework for medical devices including IVDs (draft; WHO) (n.d.)). Key intake fields, escalation rules, and measurable performance indicators are defined. Anchored to Bangladesh's current DGDA and national digital health context, the proposal identifies specific legal and infrastructural gaps and outlines steps for phased modernization that may guide other LMICs.

IntroductionAustralians are adjusting to mobile health (mHealth) applications (apps) being used in clinical care. The nature of apps presents unique challenges (e.g. rapid lifecycle) to mHealth regulation. The risks they pose are mainly through the information they provide and how it is used in clinical decision-making. This study explores the international regulation of mHealth apps. It assesses whether the approach used in Australia to regulate apps is consistent with international standards and suitable to address the unique challenges presented by the technology.MethodsA policy analysis was conducted of all nine member jurisdictions of the International Medical Device Regulator's Forum (IMDRF), to determine if their regulatory agencies addressed the IMDRF recommendations relevant to the clinical evaluation of mHealth apps. Case-studies (submission to regulatory agencies) were also selected on varying types of regulated apps (standalone, active implantable, etc.) and assessed relative to the principles in the IMDRF's software as a medical device (SaMD): Clinical evaluation (2017) guidance document.ResultsAll included jurisdictions evaluated the effectiveness of mHealth apps, assessing the majority of the key sub-categories recommended by SaMD: Clinical evaluation. The submissions and jurisdictional regulatory bodies did not address the IMDRF safety principles in terms of the apps’ information security (cybersecurity). Furthermore, by failing to use the method recommended by the IMDRF (risk-classification), none of the submissions or jurisdictions recognized the potential dangers of misinformation on patient safety.ConclusionsNone of the approaches used by global regulatory bodies adequately address the unique challenges posed by apps. Australia's approach is consistent with app regulatory procedures used internationally. We recommend that mHealth apps are evaluated for cybersecurity and are also classified using the IMDRF risk-categories so as to fully protect the public.

The aim of this study is to determine whether the approach used in Australia to regulate mobile medical applications (MMA) is consistent with international standards and is suitable to address the unique challenges of these technologies. The policies of members of the International Medical Device Regulator's Forum (IMDRF) were analyzed, to determine whether these regulatory bodies address IMDRF recommendations for the clinical evaluation of software as a medical device (SaMD). Case-studies of varying types of regulated MMAs in Australia and the United States were also reviewed to determine how well the guidance in the IMDRF's SaMD: Clinical Evaluation (2017) document was operationalized. All included jurisdictions evaluated the effectiveness of MMAs and addressed the majority of the key sub-categories recommended in the IMDRF guidance document. However, safety principles concerning information security (cybersecurity) and potential dangers of misinformation (risk-classification) were generally not addressed in either the case-studies or in the policy documents of international regulatory bodies. Australia's approach was consistent with MMA regulation conducted internationally. None of the approaches used by global regulatory bodies adequately addressed the risk of misinformation from apps and the potential for adverse clinical consequences. The risks posed by MMAs are mainly through the information they provide and how this is used in clinical decision-making. Policy in Australia and elsewhere should be adjusted to follow the IMDRF risk-classification criteria to address potential harms from misinformation. Australian regulatory information should also be updated so the harm posed by cybersecurity and connectivity can be comprehensively evaluated.

BackgroundArtificial intelligence (AI) technology has the potential to transform medical practice within the medical imaging industry and materially improve productivity and patient outcomes. However, low acceptability of AI as a digital healthcare intervention among medical professionals threatens to undermine user uptake levels, hinder meaningful and optimal value-added engagement, and ultimately prevent these promising benefits from being realised. Understanding the factors underpinning AI acceptability will be vital for medical institutions to pinpoint areas of deficiency and improvement within their AI implementation strategies. This scoping review aims to survey the literature to provide a comprehensive summary of the key factors influencing AI acceptability among healthcare professionals in medical imaging domains and the different approaches which have been taken to investigate them. MethodsA systematic literature search was performed across five academic databases including Medline, Cochrane Library, Web of Science, Compendex, and Scopus from January 2013 to September 2023. This was done in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Overall, 31 articles were deemed appropriate for inclusion in the scoping review. ResultsThe literature has converged towards three overarching categories of factors underpinning AI acceptability including: user factors involving trust, system understanding, AI literacy, and technology receptiveness; system usage factors entailing value proposition, self-efficacy, burden, and workflow integration; and socio-organisational-cultural factors encompassing social influence, organisational readiness, ethicality, and perceived threat to professional identity. Yet, numerous studies have overlooked a meaningful subset of these factors that are integral to the use of medical AI systems such as the impact on clinical workflow practices, trust based on perceived risk and safety, and compatibility with the norms of medical professions. This is attributable to reliance on theoretical frameworks or ad-hoc approaches which do not explicitly account for healthcare-specific factors, the novelties of AI as software as a medical device (SaMD), and the nuances of human-AI interaction from the perspective of medical professionals rather than lay consumer or business end users. ConclusionThis is the first scoping review to survey the health informatics literature around the key factors influencing the acceptability of AI as a digital healthcare intervention in medical imaging contexts. The factors identified in this review suggest that existing theoretical frameworks used to study AI acceptability need to be modified to better capture the nuances of AI deployment in healthcare contexts where the user is a healthcare professional influenced by expert knowledge and disciplinary norms. Increasing AI acceptability among medical professionals will critically require designing human-centred AI systems which go beyond high algorithmic performance to consider accessibility to users with varying degrees of AI literacy, clinical workflow practices, the institutional and deployment context, and the cultural, ethical, and safety norms of healthcare professions. As investment into AI for healthcare increases, it would be valuable to conduct a systematic review and meta-analysis of the causal contribution of these factors to achieving high levels of AI acceptability among medical professionals.

Human Factors Impact on the Development of Software as a Medical Device (SaMD): A Case Study Using the System Usability Scale (SUS)

We are in a stage of transition as artificial intelligence (AI) is increasingly being used in healthcare across the world. Transitions offer opportunities compounded with difficulties. It is universally accepted that regulations and the law can never keep up with the exponential growth of technology. This paper discusses liability issues when AI is deployed in healthcare. Ever-changing, futuristic, user friendly, uncomplicated regulatory requirements promoting compliance and adherence are needed. Regulators have to understand that software itself could be a software as a medical device (SaMD). Benefits of AI could be delayed if slow, expensive clinical trials are mandated. Regulations should distinguish between diagnostic errors, malfunction of technology, or errors due to initial use of inaccurate/inappropriate data as training data sets. The sharing of responsibility and accountability when implementation of an AI-based recommendation causes clinical problems is not clear. Legislation is necessary to allow apportionment of damages consequent to malfunction of an AI-enabled system. Product liability is ascribed to defective equipment and medical devices. However, Watson, the AI-enabled supercomputer, is treated as a consulting physician and not categorised as a product. In India, algorithms cannot be patented. There are no specific laws enacted to deal with AI in healthcare. DISHA or the Digital Information Security in Healthcare Act when implemented in India would hopefully cover some issues. Ultimately, the law is interpreted contextually and perceptions could be different among patients, clinicians and the legal system. This communication is to create the necessary awareness among all stakeholders.

In these days, patients and doctors in operation room are surrounded by many medical devices as resulting from recent advancement of medical technology. However, these cutting-edge medical devices are working independently and not collaborating with each other, even though the collaborations between these devices such as navigation systems and medical imaging devices are becoming very important for accomplishing complex surgical tasks (such as a tumor removal procedure while checking the tumor location in neurosurgery). On the other hand, several surgical robots have been commercialized, and are becoming common. However, these surgical robots are not open for collaborations with external medical devices in these days. A cutting-edge "intelligent surgical robot" will be possible in collaborating with surgical robots, various kinds of sensors, navigation system and so on. On the other hand, most of the academic software developments for surgical robots are "home-made" in their research institutions and not open to the public. Therefore, open source control software for surgical robots can be beneficial in this field. From these perspectives, we developed Open Core Control software for surgical robots to overcome these challenges. In general, control softwares have hardware dependencies based on actuators, sensors and various kinds of internal devices. Therefore, these control softwares cannot be used on different types of robots without modifications. However, the structure of the Open Core Control software can be reused for various types of robots by abstracting hardware dependent parts. In addition, network connectivity is crucial for collaboration between advanced medical devices. The OpenIGTLink is adopted in Interface class which plays a role to communicate with external medical devices. At the same time, it is essential to maintain the stable operation within the asynchronous data transactions through network. In the Open Core Control software, several techniques for this purpose were introduced. Virtual fixture is well known technique as a "force guide" for supporting operators to perform precise manipulation by using a master-slave robot. The virtual fixture for precise and safety surgery was implemented on the system to demonstrate an idea of high-level collaboration between a surgical robot and a navigation system. The extension of virtual fixture is not a part of the Open Core Control system, however, the function such as virtual fixture cannot be realized without a tight collaboration between cutting-edge medical devices. By using the virtual fixture, operators can pre-define an accessible area on the navigation system, and the area information can be transferred to the robot. In this manner, the surgical console generates the reflection force when the operator tries to get out from the pre-defined accessible area during surgery. The Open Core Control software was implemented on a surgical master-slave robot and stable operation was observed in a motion test. The tip of the surgical robot was displayed on a navigation system by connecting the surgical robot with a 3D position sensor through the OpenIGTLink. The accessible area was pre-defined before the operation, and the virtual fixture was displayed as a "force guide" on the surgical console. In addition, the system showed stable performance in a duration test with network disturbance. In this paper, a design of the Open Core Control software for surgical robots and the implementation of virtual fixture were described. The Open Core Control software was implemented on a surgical robot system and showed stable performance in high-level collaboration works. The Open Core Control software is developed to be a widely used platform of surgical robots. Safety issues are essential for control software of these complex medical devices. It is important to follow the global specifications such as a FDA requirement "General Principles of Software Validation" or IEC62304. For following these regulations, it is important to develop a self-test environment. Therefore, a test environment is now under development to test various interference in operation room such as a noise of electric knife by considering safety and test environment regulations such as ISO13849 and IEC60508. The Open Core Control software is currently being developed software in open-source manner and available on the Internet. A communization of software interface is becoming a major trend in this field. Based on this perspective, the Open Core Control software can be expected to bring contributions in this field.

Annex G of ISO 10993-11:2017 lists 24 substances that are allegedly material-mediated pyrogens (MMPs) in medical devices and recommends using the rabbit pyrogen test (RPT) for MMP evaluation. We aimed to establish whether medical devices contain MMPs; determine if MMPs are pyrogens or uncouplers of oxidative phosphorylation (UOPs); complete a survey of RPT failures; and develop a UOP screening list. A literature search was conducted to identify MMPs associated with medical devices. Concurrently, data mining was conducted to search for MMPs in medical device extractables databases and collect RPT data from industry and contract research labs. The literature search produced the conclusions: (1) Annex G’s endogenous biological compounds are pyrogenic; (2) Annex G’s drugs and UOP substances are not pyrogenic but thermogenic; (3) numerous other UOPs were identified; and (4) nearly all UOPs are poorly soluble in saline (the RPT’s injection solvent). The data mining found two Annex G MMPs in medical device extracts that were not pyrogenic and confirmed that the RPT failure rate was low, with investigated failures caused by endotoxin or test incompatibilities, not by Annex G MMPs. Since no pyrogenic Annex G MMPs or saline soluble UOPs were found in medical device extracts, the RPT is unnecessary. If UOPs are detected during chemical characterization studies, an ISO 10993-17:2023 toxicological risk assessment can be used to determine their hazard potential. Residual biological contamination can be evaluated with the human monocyte activation test, which detects all biological pyrogens. The term “MMP” is inaccurate and obsolete. Plain language summary Pyrogens cause fevers in mammals. Medical devices contaminated with bacterial components or chemicals generate a material-mediated pyrogenic (MMP) response. The rabbit pyrogen test (RPT) is used to detect MMPs even though its accuracy is questionable. An international standard lists 24 chemicals that are alleged to be medical device MMPs. To evaluate this belief, a search of the scientific literature was conducted to identify MMPs associated with medical devices along with a data mining effort that searched for MMPs found by chemistry laboratories that test medical devices. Failure rates for the RPT were also studied. Only two of the 24 chemicals were found in medical devices, and they were not pyrogens, plus the RPT failures were not due to MMPs. It was concluded that MMPs do not exist and therefore the RPT could be replaced with a human blood cell test that detects all types of biological pyrogens.

BACKGROUND:Materiovigilance is a method for tracking, documenting, and analyzing the causal factors of adverse outcomes or complications associated with the use of medical devices. In addition, it recommends that the Indian regulatory authority takes necessary steps with the aim of enhancing patient safety. The present study was taken up as there are hardly any studies available in the public domain on adverse events due to radiotherapy.OBJECTIVE:The objective of the study is to analyze the pattern of adverse events due to medical devices used in the department of radiation oncology.METHODS:It was a cross-sectional study carried out from June to September, 2022. The patients who were treated with the medical devices in radiation oncology at Victoria Hospital affiliated with Bangalore Medical College and Research Institute, Bengaluru, were included. The medical device used on the patients causes adverse events. The data were collected from the patient's health records available in the department of radiotherapy.RESULTS:Total 40 adverse events collected as per inclusion and exclusion criteria were analyzed. All the adverse events associated with medical devices were filled in the medical device adverse event reporting form and submitted to materiovigilance program, which also included the causality assessment. All the adverse events were caused due to external beam radiotherapy/teletherapy device. Dermatitis was the most common adverse event found in the reported cases (n = 20, 50%).CONCLUSION:Materiovigilance program is in budding stage. It was observed that the adverse events in patients were due to medical devices used in radiation oncology. Medical devices with skin-sparing effect (radiation is converged onto tumor) should be promoted and more research and engineering are required in designing of advanced medical devices for the treatment of cancer across the globe.

Introduction: Enzymatic detergents are widely used in the cleaning of the reprocessing of medical devices (MD), such as endoscopes, surgical instruments and dental-hospitalmaterials. Objective: To identify researches that approach the effectiveness of these detergents in the removal of dirt present in MD, aiming to answer questions regarding their effective action. Method: The integrative review method, which allows the analysis of scientific research in a broad and systematic way, was used, favoring the characterization and dissemination of the knowledge produced. We used the following electronic databases: Scientific Electronic Library Online (SciELO), National Library of Medicine (PubMed), Scopus and Web of Science. Articles published from 2002 to 2017 were included, using the following descriptors: enzymatic and detergents and cleaning. Results: After the analytical reading of the 148 articles found, 113 were excluded (repetition [48] was the main cause of exclusion) and 35 were selected. Conclusions: It was verified the diversity of MD used. It was also verified that depending on their complexity, MD influence on the final results of the analysis. Most of the experimental research specifically on the action of enzymatic detergents (71% – 20/28) emphasize their effectiveness in the removal of microbial and/or biofilm and other soils. Therefore, they are indicated for the reprocessing of MD, such as laparoscope, laryngoscope, endoscope and endodontic instruments. Endodontic instruments have an advantage over other MD, since they do not have internal surfaces that cannot be reached.

Regulatory science can be defined as the science aimed at the optimal introduction into society of new products of science, such as discovered substances and new scientific tools and technologies as well as knowledge and information. In addition to engineering researches that create novel medical devices, scientific methods for evaluating efficacy, safety and quality of medical devices are necessary to enable rational and scientific evaluation of the device in device approval process. Engineers and medical doctors involving research and development of novel medical devices are required to have basic knowledge on medical device safety standard, medical device regulation, and relevant methodologies. In Japan, several graduate schools in Japan have started educational programs on regulatory sciences in collaboration of Pharmaceuticals and Medical Devices Agency (PMDA), Japan. In 2012, program for researches for development of evaluation guidelines for novel medical device products started where personnel exchanges between academic researches institutes and PMDA. Example of these programs will be introduced in the presentation and its impact on improvement of medical device research and development process will be discussed.

Objective: Medical device development, from the product's conception to release to market, is very complex and relies significantly on the application of exact processes. This paper aims to provide an analysis and summary of current research in the field of medical device development methodologies, discuss its phases, and evaluate the associated legislative and risk aspects.Methods: The literature search was conducted to detect peer-reviewed studies in Scopus, Web of Science, and Science Direct, on content published between 2007 and November 2019. Based on exclusion and inclusion criteria, 13 papers were included in the first session and 11 were included in the second session. Thus, a total of 24 papers were analyzed. Most of the publications originated in the United States (7 out of 24).Results: The medical device development process comprises one to seven stages. Six studies also contain a model of the medical device development process for all stages or for just some of the stages. These studies specifically describe the concept stage during which all uncertainties, such as the clinical need definition, customer requirements/needs, finances, reimbursement strategy, team selection, and legal aspects, must be considered.Conclusion: The crucial factor in healthcare safety is the stability of factors over a long production time. Good manufacturing practices cannot be tested on individual batches of products; they must be inherently built into the manufacturing process. The key issues that must be addressed in the future are the consistency in the classification of devices throughout the EU and globally, and the transparency of approval processes.

BackgroundThe integration of connected medical devices (MDs) into health care brings benefits but also introduces new, often challenging-to-assess risks related to cybersecurity, which have the potential to harm patients. Current regulations in the European Union and the United States mandate the consideration of these risks in the benefit-risk analysis (BRA) required for MD approval. This important step in the approval process weighs all the defined benefits of a device with its anticipated risks to ensure that the product provides a positive argument for use. However, there is limited guidance on how cybersecurity risks should be systematically evaluated and incorporated into the BRA.ObjectiveThis scoping review aimed to identify current legal frameworks, guidelines, and standards in the United States, Canada, South Korea, Singapore, Australia, the United Kingdom, and the European Union on how cybersecurity risks should be considered in the BRA of MDs.MethodsThis scoping review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) framework. A systematic literature search of 10 databases was conducted in two phases on July 3, 2024 and September 30, 2024, including the guidance databases of the Food and Drug Administration, the Medical Device Coordination Group, and other International Medical Device Regulators Forum members; the International Medical Device Regulators Forum database; PubMed; and Scopus. Search terms included “cybersecurity,” “security,” “benefit/risk,” “benefit-risk,” and “risk-benefit.” Additional references were identified via citation searching and expert interviews. Inclusion criteria were met if a document was a guideline or standard in force that provided guidance on the BRA or cybersecurity risks of MDs. Documents were excluded when they were not relevant to MDs, they were limited to a subclass of devices, they were about in vitro diagnostic MDs or investigational devices, and the content of the source was insufficient to undertake a scientific analysis. Data were extracted and analyzed using MAXQDA 2022, and the findings were narratively summarized and visualized in figures and tables.ResultsThe search identified 150 documents, with 34 (22.7%) meeting the inclusion criteria. These 34 documents included 4 (12%) regulations, 5 (15%) standards, 6 (18%) technical reports, and 19 (56%) guidance documents. While cybersecurity risks were acknowledged in most documents, detailed methods for their integration into the BRA were lacking. Some standards and guidelines provided examples of how to consider cybersecurity risks in the BRA, but a comprehensive and standardized approach was lacking.ConclusionsThis review highlights a substantial gap between the recognition of cybersecurity risks in MDs and the guidance on their incorporation into the BRA. Standardized frameworks are needed to provide clear methods for evaluating cybersecurity risks and their impact on the safety and security of MDs.

Stimulated by regulations and standards as well as commercial imperatives, medical device manufacturers are striving to make medical devices safer by decreasing the potential for harmful use errors. Accordingly, manufacturers are observing and interviewing intended users about their interactions with devices en route to developing user interface requirements; applying human factors engineering (HFE) principles when designing user interfaces; and conducting formative and summative usability tests to improve and validate their devices’ interactive quality. This has represented significant work for manufacturers, particularly the majority who started with little HFE knowledge and experience. Today, the “awakening” to HFE in medical device development is essentially over—an established manufacturer who is just now discovering HFE has been out of touch. After all, the U.S. Food and Drug Administration (FDA) and AAMI conducted their first joint conference on HFE in 1995 when they previewed HFE expectations related to recent changes in quality system regulation (QSR). So, it has been 17 years since HFE entered the medical industry’s zeitgeist. HFE specialists working in the medical industry used to focus on making devices more usable (i.e., user friendly). Since the QSR change, use safety has become the primary focus, resulting in user interfaces that are less vulnerable to harmful use errors. It is rather obvious how HFE affects the safety of some medical devices. In the design of a surgical instrument, for example, HFE’s aim would be to reduce the chance of cutting anything other than the intended target. This goal could be accomplished by including a blade guard and a mechanical interlock that requires more than one deliberate action to enable cutting.