Commercialization Readiness Pilot (CRP) program support for: Direct-from-specimen identification of pathogens common in endocarditis

商业化准备试点 (CRP) 计划支持： 直接从样本鉴定心内膜炎常见病原体

• 批准号: 10758417
• 负责人: Alon Singer
• 金额: $ 100万
• 依托单位: HELIXBIND, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-20 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10758417
• 关键词: Acceleration; Address; Affect; Antibiotic Resistance; Antimicrobial Resistance; Automation; Autopsy; Award; Bacteria; Biological; Biological Assay; Biopsy; Blinded; Blood; Blood Circulation; Breakthrough device; Cardiac; Cardiology; Caring; Clinic; Clinical; Clinical Microbiology; Clinical Research; Clinical assessments; Communicable Diseases; Coxiella burnetii; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Early identification; Economic Burden; Endocarditis; Engineering; Ensure; Evaluation; Exhibits; Feedback; Freeze Drying; Grant; Heart; Hospitalization; Hospitals; Hour; Impairment; Infection; Infective endocarditis; Intervention; Leadership; Lesion; Life; Manuals; Marketing; Medical center; Methods; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Nature; Organism; Patient Care; Patient-Focused Outcomes; Patients; Performance; Phase; Quality of life; Readiness; Reagent; Resistance; Resistance development; Resolution; Risk; Sampling; Sensitivity and Specificity; Sepsis; Septicemia; Site; Small Business Innovation Research Grant; Specific qualifier value; Specificity; Specimen; Surface; Symptoms; Technology; Temperature; Testing; Time; Tissues; University Hospitals; Whole Blood; analytical method; antimicrobial; assay development; commercialization; commercialization readiness; design; diagnostic strategy; evidence base; experience; fungus; improved; improved outcome; instrument; interest; manufacture; manufacturing process; manufacturing scale-up; member; microbial; microorganism; mortality; novel; novel diagnostics; pathogen; pathogenic bacteria; pathogenic fungus; prevent; programs; standard of care; success; validation studies; verification and validation; Acceleration; Address; Affect; Antibiotic Resistance; Antimicrobial Resistance; Automation; Autopsy; Award; Bacteria; Biological; Biological Assay; Biopsy; Blinded; Blood; Blood Circulation; Breakthrough device; Cardiac; Cardiology; Caring; Clinic; Clinical; Clinical Microbiology; Clinical Research; Clinical assessments; Communicable Diseases; Coxiella burnetii; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Early identification; Economic Burden; Endocarditis; Engineering; Ensure; Evaluation; Exhibits; Feedback; Freeze Drying; Grant; Heart; Hospitalization; Hospitals; Hour; Impairment; Infection; Infective endocarditis; Intervention; Leadership; Lesion; Life; Manuals; Marketing; Medical center; Methods; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Nature; Organism; Patient Care; Patient-Focused Outcomes; Patients; Performance; Phase; Quality of life; Readiness; Reagent; Resistance; Resistance development; Resolution; Risk; Sampling; Sensitivity and Specificity; Sepsis; Septicemia; Site; Small Business Innovation Research Grant; Specific qualifier value; Specificity; Specimen; Surface; Symptoms; Technology; Temperature; Testing; Time; Tissues; University Hospitals; Whole Blood; analytical method; antimicrobial; assay development; commercialization; commercialization readiness; design; diagnostic strategy; evidence base; experience; fungus; improved; improved outcome; instrument; interest; manufacture; manufacturing process; manufacturing scale-up; member; microbial; microorganism; mortality; novel; novel diagnostics; pathogen; pathogenic bacteria; pathogenic fungus; prevent; programs; standard of care; success; validation studies; verification and validation

PROJECT SUMMARY Infective Endocarditis (IE) occurs when bacteria or fungi adhere to the endocardial surface forming small lesions. This invasive disease is characterized by a mortality rate exceeding 25%, is associated with extended hospitalization, and often impairs the quality of life for those who survive. Early microbial diagnosis and antimicrobial intervention are crucial to improved patient outcomes and reduced hospitalization time. However, currently accepted diagnostic approaches still rely on primary blood culture, which exhibits long and variable turnaround times and can provide false-negative results. There is therefore a significant need for new diagnostic approaches that do not require culture and provide faster, more accurate results. To address this unmet need, HelixBind developed RaPID/IE, a fully automated sample-to-answer test which identifies and characterizes these infections directly from blood in ~3 hours, without cultures. Implemented on the RaPID (Resistance and Pathogen IDentification) platform and appropriate for placement throughout the hospital, RaPID/IE incorporates a broad test menu including both bacterial and fungal pathogens, as well as a marker of antimicrobial resistance. Crucially, the test is not compromised by prior antimicrobial treatment and provides species level detail with single CFUs/ml sensitivity, enabling selection of appropriate antimicrobials. Commercialization of RaPID/IE will provide timely identification and characterization of the invasive agent and thus enable intervention with targeted antimicrobial treatment. This is expected to result in improved patient outcomes and a reduction in the use of unnecessary antimicrobials, slowing the rise of antimicrobial resistance. HelixBind has met and exceeded all the Specific Aims defined in the Phase II SBIR. This included menu expansion to cover antibiotic resistance as well as pathogens associated with IE which cannot be recovered by clinical cultures, automation of the assay onto single-use disposables operated by a benchtop instrument, and testing of clinical specimens. Clinical results demonstrate a sensitivity and specificity of 92.7% and 98.8%, respectively. In addition, based on feedback from potential customers, the test menu was expanded further to include coverage of pathogens associated with conditions sharing symptoms with IE. The disposable and instrument were transitioned to manufacturing and extensive analytical testing was performed to ensure the assay meets specifications associated with regulatory and market requirements. In this CRP program, HelixBind will build on our success in Phase II to prepare for regulatory clearance and market launch. This includes (1) development of analytical methods, based on FDA feedback, required to successfully complete analytical and clinical validation studies; and (2) development of scalable manufacturing processes for certain reagent sets to ensure 12-month, room temperature stability, of tests cassettes, and (3) completion of an on-site analytical evaluation and blinded, clinical assessment study. Upon completion of this project, we will be well placed to initiate formal analytical and clinical studies for FDA clearance of RaPID/IE.

项目摘要 当细菌或真菌粘附在形成小病变的心内膜表面时，会发生感染性心内膜炎（IE）。 这种侵入性疾病的特征是死亡率超过25％，与延长有关 住院，通常会损害生存者的生活质量。早期微生物诊断和 抗菌干预对于改善患者预后和减少住院时间至关重要。然而， 目前接受的诊断方法仍然依赖原发性血液培养 周转时间，可以提供虚假的结果。因此，新诊断非常需要 不需要文化并提供更快，更准确的结果的方法。 为了满足这种未满足的需求，HelixBind开发了Rapid/IE，即一种全自动的样本到答案测试， 识别并表征了这些感染，直接在〜3小时内直接从血液中，而无需培养。实施 快速（电阻和病原体识别）平台，适合整个整个 Hospital，Rapid/IE包含一个广泛的测试菜单，包括细菌和真菌病原体以及 抗菌抗性的标记。至关重要的是，该测试不会因先前的抗菌治疗和 提供单个CFU/ML敏感性的物种水平细节，从而可以选择适当的抗菌剂。 快速/IE的商业化将及时提供侵入剂的识别和表征， 因此，可以对靶向抗菌治疗进行干预。这预计会改善患者 结果和减少不必要的抗菌药物的使用，从而减慢了抗菌耐药性的升高。 HelixBind已经满足并超过了II期SBIR中定义的所有特定目的。其中包括菜单 扩展以覆盖抗生素耐药性以及与IE相关的病原体，无法通过 临床培养物，测定自动化在台式仪器操作的一次性一次性用品上，以及 临床标本的测试。临床结果表明，敏感性和特异性为92.7％和98.8％， 分别。此外，根据潜在客户的反馈，测试菜单进一步扩展到 包括与IE共享症状相关的病原体的覆盖范围。一次性和 仪器过渡到制造业，并进行了广泛的分析测试，以确保 测定符合与监管和市场要求相关的规格。 在此CRP计划中，HelixBind将基于我们在第二阶段的成功以准备监管清除和 市场发布。这包括（1）基于FDA反馈所需的分析方法的开发 成功完成分析和临床验证研究； （2）开发可扩展制造 某些试剂集的过程，以确保盒式盒子的12个月，室温稳定性和（3） 完成现场分析评估和盲目的临床评估研究。完成此任务后 项目，我们将很适合启动正式的分析和临床研究，以清除快速/IE。