Regulatory Frameworks for AI-Enabled Medical Device Software in China: Comparative Analysis and Review of Implications for Global Manufacturer.

The China State Council released the new generation artificial intelligence (AI) development plan, outlining China's ambitious aspiration to assume global leadership in AI by the year 2030. This initiative underscores the extensive applicability of AI across diverse domains, including manufacturing, law, and medicine. With China establishing itself as a major producer and consumer of medical devices, there has been a notable increase in software registrations. This study aims to study the proliferation of health care-related software development within China. This work presents an overview of the Chinese regulatory framework for medical device software. The analysis covers both software as a medical device and software in a medical device. A comparative approach is employed to examine the regulations governing medical devices with AI and machine learning in China, the United States, and Europe. The study highlights the significant proliferation of health care-related software development within China, which has led to an increased demand for comprehensive regulatory guidance, particularly for international manufacturers. The comparative analysis reveals distinct regulatory frameworks and requirements across the three regions. This paper provides a useful outline of the current state of regulations for medical software in China and identifies the regulatory challenges posed by the rapid advancements in AI and machine learning technologies. Understanding these challenges is crucial for international manufacturers and stakeholders aiming to navigate the complex regulatory landscape.

Medical Device Software: From Requirements to Certification.

The role of software in healthcare is getting more and more pervasive. Nevertheless, manufacturers sometimes forget that these software are medical devices and must be certified according to the EU Medical Device Regulation 2017/745. In this work we propose a pipeline for developing a Medical Device Software (MDS) compliant with the regulations and certifiable. The pipeline includes the phase of requirements elicitation, risk assessment and analysis of effectiveness as key elements. The preparation of the technical file should be carried out in parallel with the MDS development. In the overall, it can be stated that the certification process starts with the conceptualization of the MDS and proceeds all along its design and implementation.

[Research on the Classification Management of Digital Therapeutics Software].

According to the current domestic laws and regulations of the medical devices classification management, combined with the characteristics of digital therapeutics products and the existing status of classification management of medical software products in China, and drawing on international classification management experience, this study discusses and analyzes the attribute definition and classification of digital therapeutics software products, with a view to provide reference for the classification management of digital therapeutics software products.

Research on the Classification Management of Digital Therapeutics Software / 中国医疗器械杂志

According to the current domestic laws and regulations of the medical devices classification management, combined with the characteristics of digital therapeutics products and the existing status of classification management of medical software products in China, and drawing on international classification management experience, this study discusses and analyzes the attribute definition and classification of digital therapeutics software products, with a view to provide reference for the classification management of digital therapeutics software products.

Key Aspects to Teach Medical Device Software Certification.

Certification of Medical Device Software (MDS) according to the EU Medical Device Regulation 2017/745 requires demonstrating safety and effectiveness. Thus, the syllabus of a course on MDS development must provide tools for addressing these issues. To assure safety, risk analysis has to be performed using a four-step procedure. Effectiveness could be demonstrated by literature systematic review combined with meta-analysis, to compare the MDS performances with those of similar tools.

Recommendations for IVDR compliant in-house software development in clinical practice: a how-to paper with three use cases.

OBJECTIVES: The In Vitro Diagnostics Regulation (IVDR) will be effective in May 2022 by which in-house developed tests need to apply to the general safety and performance requirements defined in Annex I of the IVDR ruling. Yet, article 16 from Annex I about software can be hard to interpret and implement, particularly as laboratories are unfamiliar with quality standards for software development. METHODS: In this paper we provide recommendations on organizational structure, standards to use, and documentation, for IVDR compliant in-house software development. RESULTS: A practical insight is offered into novel standard operating procedures using three examples: an Excel file with a formula to calculate the pharmacokinetics of tacrolimus and to calculate the new dose, a rule for automated diagnosis of acute kidney injury and a bioinformatics pipeline for DNA variant calling. CONCLUSIONS: We recommend multidisciplinary development teams supported by higher management, use of ISO-15189 in synergy with IEC-62304, and concise documentation that includes intended purpose, classification, requirement management, risk management, verification and validation, configuration management and references to clinical or performance evidence.

How precise is PreSize Neurovascular? Accuracy evaluation of flow diverter deployed-length prediction.

OBJECTIVE: The use of flow-diverting stents has been increasingly important in intracranial aneurysm treatment. However, accurate sizing and landing zone prediction remain challenging. Inaccurate sizing can lead to suboptimal deployment, device waste, and complications. This study presents stent deployment length predictions offered in medical software (PreSize Neurovascular) that provides physicians with real-time planning support, allowing them to preoperatively "test" different devices in the patient's anatomy in a safe virtual environment. This study reports the software evaluation methodology and accuracy results when applied to real-world data from a wide range of cases and sources as a necessary step in demonstrating its reliability, prior to impact assessment in prospective clinical practice. METHODS: Imaging data from 138 consecutive stent cases using the Pipeline embolization device were collected from 5 interventional radiology centers in the United Kingdom and retrospectively analyzed. Prediction accuracy was calculated as the degree of agreement between stent deployed length measured intraoperatively and simulated in the software. RESULTS: The software predicted the deployed stent length with a mean accuracy of 95.61% (95% confidence interval [CI] 94.87%-96.35%), the highest reported accuracy in clinical stent simulations to date. By discounting 4 outlier cases, in which events such as interactions with coils and severe push/pull maneuvers impacted deployed length to an extent the software was not able to simulate or predict, the mean accuracy further increases to 96.13% (95% CI 95.58%-96.69%). A wide discrepancy was observed between labeled and measured deployed stent length, in some cases by more than double, with no demonstrable correlation between device dimensions and deployment elongation. These findings illustrate the complexity of stent behavior and need for simulation-assisted sizing for optimal surgical planning. CONCLUSIONS: The software predicts the deployed stent length with excellent accuracy and could provide physicians with real-time accurate device selection support.

The EU medical device regulation: Implications for artificial intelligence-based medical device software in medical physics.

Medical device manufacturers are increasingly applying artificial intelligence (AI) to innovate their products and to improve patient outcomes. Health institutions are also developing their own algorithms, to address specific needs for which no commercial product exists. Although AI-based algorithms offer good prospects for improving patient outcomes, their wide adoption in clinical practice is still limited. The most significant barriers to the trust required for wider implementation are safety and clinical performance assurance . Qualified medical physicist experts (MPEs) play a key role in safety and performance assessment of such tools, before and during integration in clinical practice. As AI methods drive clinical decision-making, their quality should be assured and tested. Occasionally, an MPE may be also involved in the in-house development of such an AI algorithm. It is therefore important for MPEs to be well informed about the current regulatory framework for Medical Devices. The new European Medical Device Regulation (EU MDR), with date of application set for 26 of May 2021, imposes stringent requirements that need to be met before such tools can be applied in clinical practice. The objective of this paper is to give MPEs perspective on how the EU MDR affects the development of AI-based medical device software. We present our perspective regarding how to implement a regulatory roadmap, from early-stage consideration through design and development, regulatory submission, and post-market surveillance. We have further included an explanation of how to set up a compliant quality management system to ensure reliable and consistent product quality, safety, and performance .

Medical Device Apps: An Introduction to Regulatory Affairs for Developers.

The Poly Implant Prothèse (PIP) scandal in France prompted a revision of the regulations regarding the marketing of medical devices. The new Medical Device Regulation (MDR [EU]) 2017/745 was developed and entered into force on May 25, 2017. After a transition period of 3 years, the regulations must be implemented in all EU and European Economic Area member states. The implementation of this regulation bears many changes for medical device development and marketing, including medical device software and mobile apps. Medical device development and marketing is a complex process by which manufacturers must keep many regulatory requirements and obligations in mind. The objective of this paper is to provide an introduction and overview of regulatory affairs for manufacturers that are new to the field of medical device software and apps with a specific focus on the new MDR, accompanying harmonized standards, and guidance documents from the European Commission. This work provides a concise overview of the qualification and classification of medical device software and apps, conformity assessment routes, technical documentation, clinical evaluation, the involvement of notified bodies, and the unique device identifier. Compared to the previous Medical Device Directive (MDD) 93/42/EEC, the MDR provides greater detail about the requirements for software qualification and classification. In particular, rule 11 sets specific rules for the classification of medical device software and will be described in this paper. In comparison to the previous MDD, the MDR is more stringent, especially regarding the classification of health apps and software. The implementation of the MDR in May 2020 and its interpretation by the authorities will demonstrate how app and software manufacturers as well as patients will be affected by the regulation.

Medical device software: defining key terms.

INTRODUCTION: one of the areas of significant growth in medical devices has been the role of software - as an integral component of a medical device, as a standalone device and more recently as applications on mobile devices. The risk related to a malfunction of the standalone software used within healthcare is in itself not a criterion for its qualification or not as a medical device. It is therefore, necessary to clarify some criteria for the qualification of stand-alone software as medical devices Materials and methods: Ukrainian, European Union, United States of America legislation, Guidelines developed by European Commission and Food and Drug Administration's, recommendations represented by international voluntary group and scientific works. This article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. CONCLUSION: the legal regulation of software which is used for medical purpose in Ukraine limited to one definition. In European Union and United States of America were developed and applying special guidelines that help developers, manufactures and end users to difference software on types standing on medical purpose criteria. Software becomes more and more incorporated into medical devices. Developers and manufacturers may not have initially appreciated potential risks to patients and users such situation could have dangerous results for patients or users. It is necessary to develop and adopt the legislation that will intend to define the criteria for the qualification of medical device software and the application of the classification criteria to such software, provide some illustrative examples and step by step recommendations to qualify software as medical device.

Comparative analysis of FDA software submission guidance / 中国医学装备

Objective: The FDA regulation requirements for medical device software are relatively mature and systematic, and the research on the FDA regulation thinking of medical device software helps to promote the regulation work of the medical device software in our country. Methods:Based on the comparison of the 1998 edition and 2005 edition FDA software submission guidance, the trend of the FDA regulation requirements for medical device software was analyzed, and then its regulation thinking was discussed according to other current effective software-related guidance. Results:FDA integrally improves the submission requirements for all medical device software, especially for the minor Level of Concern software, and simplifies the requirements for design specification, verification and validation, but strengthens the requirements for traceability analysis and revision history. Conclusion: The regulation work of the medical device software in our country needs to fully consider the particularity of the medical device software, strengthen the audit of software quality management system, implement the software traceability analysis, and determine the regulation requirements for software change.

The integration of the risk management process with the lifecycle of medical device software.

OBJECTIVES: The application of software in the Medical Device (MD) domain has become central to the improvement of diagnoses and treatments. The new European regulations that specifically address software as an important component of MD, require complex procedures to make software compliant with safety requirements, introducing thereby new challenges in the qualification and classification of MD software as well as in the performance of risk management activities. Under this perspective, the aim of this paper is to propose an integrated framework that combines the activities to be carried out by the manufacturer to develop safe software within the development lifecycle based on the regulatory requirements reported in US and European regulations as well as in the relevant standards and guidelines. METHODS: A comparative analysis was carried out to identify the main issues related to the application of the current new regulations. In addition, standards and guidelines recently released to harmonise procedures for the validation of MD software have been used to define the risk management activities to be carried out by the manufacturer during the software development process. RESULTS: This paper highlights the main issues related to the qualification and classification of MD software, providing an analysis of the different regulations applied in Europe and the US. A model that integrates the risk management process within the software development lifecycle has been proposed too. It is based on regulatory requirements and considers software risk analysis as a central input to be managed by the manufacturer already at the initial stages of the software design, in order to prevent MD failures. CONCLUSIONS: Relevant changes in the process of MD development have been introduced with the recognition of software being an important component of MDs as stated in regulations and standards. This implies the performance of highly iterative processes that have to integrate the risk management in the framework of software development. It also makes it necessary to involve both medical and software engineering competences to safeguard patient and user safety.

Exploration on Application of CMMI for Development Process of Medical Device Software / 医疗卫生装备

Objective To correctly apply the Capability Maturity Model Integration(CMMI) model to the development process of medical device software,thus optimizing and improving the development process and enhancing the software process capability.Methods The matching between CMMI and IEC62304 was analyzed.The compatibility on application was investigated by taking risk management(the core process) as an example.Results The interface between CMMI and IEC62304 was discovered as well as their optimized process in risk management.Conclusion The process of medical device software development not only can be improved by CMMI model,but also should be.