Development of a web-based platform implementing novel Predictor of Skin Sensitization for Medical Devices (PreSS/MD)

开发基于网络的平台，实施新型医疗器械皮肤过敏预测器 (PreSS/MD)

• 批准号: 10079701
• 负责人: YVES RIBEILL
• 金额: $ 16.79万
• 依托单位: PREDICTIVE, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10079701
• 关键词: Acute; Address; Advanced Development; Allergic Contact Dermatitis; Animal Testing; Animals; Bayesian Method; Bayesian Modeling; Biological Assay; Cavia; Chemical Structure; Chemicals; Computer Models; Computer software; Consumption; Contact Dermatitis; Data; Data Set; Databases; Detection; Development; Devices; Economics; Evaluation; Feedback; Generations; Human; Immune response; Instruction; Interagency Coordinating Committee on the Validation of Alternative Methods; International; Knowledge; Lead; Medical; Medical Care Costs; Medical Device; Methods; Modeling; Modernization; Mus; Occupational; Online Systems; Pathway interactions; Phase; Poison; Prevalence; Prostheses and Implants; Public Health; Publishing; Pythons; Quantitative Structure-Activity Relationship; Reaction; Reporting; Resources; Safety; Skin; Small Business Innovation Research Grant; Structure; Test Result; Testing; Time; Toxic effect; Toxin; United States Food and Drug Administration; Validation; Workers' Compensation; Workplace; adverse outcome; chemical release; cost; experience; in silico; in vitro Assay; in vivo; innovation; knowledge graph; lymph nodes; machine learning algorithm; model development; novel; novel strategies; occupational hazard; operation; phase 1 study; response; skin patch; software as a service; success; systemic toxicity; tool; web portal; web server

PROJECT SUMMARY Medical devices have been documented to contain toxic chemicals that can leach and cause acute contact dermatitis (ACD) after repeated exposure or prolonged contact of the skin to these toxins. ACD is credited for 10-15% of all occupational illnesses and is also the second highest reported occupational hazard. Given its prevalence, ACD is also a great public health burden with combined yearly costs of up to $1 billion, which spans including medical costs, worker’s compensation and lost working time due to workplace absence. To this end, the U.S. Food and Drug Administration has mandated that all medical devices must be evaluated for possible skin sensitization using in vivo animal assays, which includes the Guinea pig maximization test (GPMT). Although GPMT tests provide valuable data on the skin sensitization effects of potential toxins, these assays are time-consuming and expensive. Moreover, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) recently published a Strategic Roadmap, calling for the development of alternative approaches to reduce animal testing of chemical and medical agents. Thus, there is a stated need to modernize safety evaluation of medical devices to reduce animal testing and shorten the regulatory review time, which would ultimately bring safer devices to the market faster. To address this unmet need, the key objectives of our FDA Phase I SBIR project are to (i) produce rigorously validated computational models for the GPMT assay integrating data obtained in human, mouse, and in vitro assays; and (ii) integrate these models into a software product termed PreSS/MD (Predictor of Skin Sensitization for Medical Devices). Our specific aims for this study include: 1) collecting, curating, and integrating the largest publicly available dataset for GMPT; 2) creating and validating novel computational models for GMPT data; 3) developing the PreSS/MD web server to allow users to make predictions of skin sensitization potential in medical devices. We will also develop a model for mixtures, including compounds tested jointly in different concentrations, using an approach that we developed previously. Finally, we will implement novel approaches to help users of our PreSS/MD platform interpret the developed models in terms of key chemical features responsible for skin sensitization. In addition, we will employ biomedical knowledge graphs to elucidate Adverse Outcome Pathways (AOPs) for skin sensitizers. Successful execution of this Phase I project will yield in the development of PreSS/MD as a centralized resource to evaluate the skin sensitization potential for medical devices. We expect this software-as-a-service web server platform will be of great value for companies and sponsors seeking regulatory approval of medical devices.

项目摘要 已经记录了医疗设备，以含有可能行走并引起急性接触的有毒化学物质 皮肤反复接触或与这些毒素接触长时间接触后，皮肤炎（ACD）。 ACD被认为 在所有遭受疾病的疾病中，有10-15％也是据报道的第二高危害。鉴于它 患病率，ACD也是一种巨大的公共卫生烧伤，年度总成本高达10亿美元 包括医疗费用，工人的赔偿和由于工作场所缺席而损失的工作时间。为此， 美国食品药品监督管理局已要求对所有医疗设备进行评估 使用体内动物测定的皮肤敏感性，其中包括豚鼠最大化测试（GPMT）。 尽管GPMT测试提供了有关潜在毒素皮肤敏感性影响的有价值的数据，但这些测定是 耗时且昂贵。此外，机构间协调委员会验证 替代方法（ICCVAM）最近发布了战略路线图，呼吁开发 减少化学和医疗剂的动物测试的替代方法。那有一个陈述 现代化对医疗设备的安全评估以减少动物测试并缩短监管审查时间， 最终将把安全的设备更快地带入市场。为了满足这个未满足的需求，关键目标 我们的FDA I阶段SBIR项目是（i）生成了严格验证的计算模型 GPMT分析集成在人，小鼠和体外测定中获得的数据； （ii）整合了这些 模型中的软件产品称为Press/MD（医疗设备的皮肤致敏的预测指标）。 我们对这项研究的具体目的包括：1）收集，策划和整合最大的公开可用 GMPT的数据集； 2）为GMPT数据创建和验证新颖的计算模型； 3）开发 按下/MD Web服务器，允许用户预测医疗设备中皮肤敏感性的潜力。我们 还将开发一个用于混合物的模型，包括以不同浓度共同测试的化合物，使用 我们以前开发的方法。最后，我们将实施新颖的方法来帮助我们的用户 按/MD平台根据负责皮肤的关键化学特征来解释开发的模型 致敏。此外，我们将采用生物医学知识图来阐明不良结果途径 （AOPS）用于皮肤传感器。该阶段项目的成功执行将在开发中产生 按/MD作为集中资源，以评估医疗设备的皮肤敏感性。我们期望 这个软件即服务网络服务器平台对于寻求公司和赞助商的价值将具有巨大的价值 医疗设备的监管批准。