Near patient molecular diagnostics test for infections

患者附近感染分子诊断测试

基本信息

批准号：
9540791
负责人：
Vincent Jen-Jr Gau
金额：
$ 100万
依托单位：
GENEFLUIDICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-15 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9540791
关键词：
Acute Affect Agreement Antibiotic Resistance Antibiotic Therapy Antibiotics Antimicrobial Resistance Antimicrobial susceptibility Area Automation Bacteria Bacterial Infections Biological Assay Blood Blood specimen Categories Centers for Disease Control and Prevention (U.S.)Certification Classification Clinical Clinical Protocols Clinical Research Clinical Sensitivity Code Culture Media Data Detection Development Devices Diagnosis Diagnostic Feasibility Studies Genetic Genotype Geographic Locations Geology Goals Gold Grant Growth Guidelines Health system Healthcare Hospitals Hour Incentives Infection Infection Control International Intervention Marketing Medical center Methods Michigan Molecular Molecular Analysis Molecular Diagnostic Testing National Institute of Allergy and Infectious Disease Nosocomial Infections Outcome Patients Pattern Performance Phase Phenotype Powder dose form Predisposition Preparation Protocols documentation Readiness Reagent Refrigeration Regulation Reporting Reproducibility Research Project Grants Resistance Resistance profile Resistance to infection Ribosomal RNA Risk Safety Sampling Sensitivity and Specificity Site Small Business Innovation Research Grant Specimen Swab System Technology Testing Time Universities Urinalysis Urinary tract infection Urine Whole Blood antimicrobial base clinical research site commercialization cost cost effective evidence base improved microorganism multi-drug resistant pathogen pathogen point of care programs prospective research and development research clinical testing

项目摘要

ABSTRACT Currently, there are no FDA cleared molecular-based tests for urinary tract infection (UTI) pathogen identification and antimicrobial susceptibility testing to replace the 'gold standard' of dipstick urinalysis and urine culturing. All pathogen identification tests still rely on clinical isolates from urine cultures, largely unchanged from Koch's postulates developed in the 19th century as general guidelines to identify pathogens. What has changed over time, however, is the dramatic and progressive emergence of antibiotic resistance among these pathogens. Data from the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) indicate that 70% of the pathogens isolated from hospital-acquired infections (HAIs) now are resistant to at least 2 major classes of antibiotics. Recent developments in molecular diagnostic testing for multidrug resistant (MDR) pathogens can provide a sensitive, specific, and real-time solution to support active surveillance-driven infection control interventions, but these PCR-based tests can only be performed on simple specimen matrices such as swabs or positive blood culture media (1:10 blood-to-broth ratio). No molecular-based method is cleared by the FDA to test directly on urine or whole blood samples. The goal of this Commercialization Readiness Pilot (CRP) Grant is to accelerate the commercialization effort of the program outcome from our NIAID SBIR R44AI088756 project titled “An Integrated Diagnostic System for Rapid Antimicrobial Susceptibility Testing (AST)”. We propose technical assistance on regulatory strategy development and cost-effective manufacturing, as well as later stage research and development activities on independent replication of key studies in compliance with FDA requirements and ISO 13485 standards. The goal of our NIAID Advanced Technology SBIR project is to develop and validate RAST (rapid antimicrobial susceptibility testing), an integrated and compact diagnostic system that enables clinicians direct point-of-care (POC) with an evidence-based selection of antibiotics for treatment of acute bacterial infections. Our first compact automated system is capable of rapid pathogen identification (ID) and AST directly from patient's samples with evidenced-based information to start patient-specific antimicrobial treatment. It is expected to obtain a CE Mark after the coming ISO 13485 surveillance certification audit in February 2016. However, the FDA clearance is hindered by: (1) no molecular-based predicate test cleared by the FDA for urinary tract infections (UTI), (2) the low cost of conventional dipstick urinalysis tests, and (3) the lack of fresh urine specimens through a multi- site clinical feasibility study. We will overcome these hurdles through the following aims: TECHNICAL ASSISTANCE Aim 1: Obtain a risk-based classification of the Class II device through a de novo request with external regulatory assistance from NSF International (an international certification organization) in 18 months Aim 2: Reduce the cost of goods sold of <$3 for cartridge and <$5k for system with external manufacturing development assistance LATE STAGE RESEARCH AND DEVELOPMENT ACTIVITIES Aim 3: Conduct a multi-center clinical performance study and demonstrate >95% clinical sensitivity/specificity and >95% susceptibility categorical agreement In this study, we focus on validating the rapid UTI diagnostic device according to federal regulations 21 CFR 866.2660 (microorganism differentiation and identification device), 21 CFR 866.1640 (antimicrobial susceptibility test powder), and 21 CFR 866.1645 (fully automated, short-term incubation cycle antimicrobial susceptibility testing system). The FDA product codes for such systems are “JSS” and “LON.” The regulatory strategy will be finalized in Aim 1 (Regulatory) for preparation of the clinical protocol and multicenter clinical performance study in Aim 3 (Clinical study) that will utilize the cost-effective system and consumables optimized in Aim 2 (Manufacturing).

抽象的目前，尚无 FDA 批准的用于尿路感染 (UTI) 病原体识别和诊断的分子测试。抗菌培养物敏感性测试取代试纸尿液分析和尿液所有病原体分析的“金标准”。鉴定测试仍然依赖于尿液培养物的临床分离物，与科赫提出的假设基本没有变化 19 世纪作为识别病原体的一般准则，然而，随着时间的推移，发生了巨大的变化。这些病原体中逐渐出现的抗生素耐药性来自疾病控制中心和预防 (CDC) 国家医疗安全网络 (NHSN) 表明，70% 的病原体是从医院获得性感染 (HAI) 现在对至少 2 类主要抗生素具有耐药性。多重耐药 (MDR) 病原体的分子诊断检测可以提供灵敏、特异和实时的诊断结果解决方案来支持主动监测驱动的感染控制干预措施，但这些基于 PCR 的测试只能在简单的样本基质上进行，例如拭子或阳性血液培养基（血液与肉汤的比例为 1:10）否。基于分子的方法已获得 FDA 批准，可直接对尿液或全血样本进行检测。该商业化准备试点（CRP）拨款的目标是加速该项目的商业化工作我们的 NIAID SBIR R44AI088756 项目的项目成果，题为“快速集成诊断系统” 抗菌药物敏感性测试 (AST)”。我们提出有关监管策略制定和实施的技术援助。具有成本效益的制造，以及后期独立复制关键技术的研发活动符合 FDA 要求和 ISO 13485 标准的研究我们 NIAID 先进技术的目标。 SBIR 项目旨在开发和验证 RAST（快速抗菌药物敏感性测试），这是一种集成且紧凑的方法诊断系统，可实现直接护理点 (POC)，并基于证据选择抗生素我们的第一个紧凑型自动化系统能够快速识别病原体 (ID)。直接从患者样本中提取 AST，并提供基于证据的信息，以开始针对患者的抗菌治疗。预计将于 2016 年 2 月即将进行 ISO 13485 监督认证审核后获得 CE 标志。但是， FDA 批准受到以下因素的阻碍：(1) FDA 没有批准针对尿路感染的基于分子的谓词测试（UTI），（2）传统试纸尿液分析测试的成本低，以及（3）缺乏通过多种方法获得的新鲜尿液样本现场临床可行性研究。我们将通过以下目标克服这些障碍：技术援助目标 1：通过向外部提出从头请求，获得 II 类器械基于风险的分类 18 个月内获得 NSF International（国际认证组织）的监管援助目标 2：将墨盒的销售成本降低至 < 3 美元，将外部制造的系统的销售成本降低至 < 5,000 美元发展援助后期研究和开发活动目标 3：进行多中心临床表现研究并证明 >95% 的临床表现敏感性/特异性和 >95% 敏感性绝对一致在本研究中，我们重点根据联邦法规 21 CFR 866.2660 验证快速 UTI 诊断设备（微生物分化和鉴定装置）、21 CFR 866.1640（抗菌药敏试验粉末）、和 21 CFR 866.1645（全自动、短期培养周期抗菌药敏感性测试系统）。此类系统的产品代码为“JSS”和“LON”。监管策略将在目标 1（监管）中最终确定：准备目标 3（临床研究）中的临床方案和多中心临床表现研究，其中将利用在目标 2（制造）中优化的经济高效的系统和消耗品。