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

项目总结 感染性心内膜炎(IE)是细菌或真菌附着在心内膜表面形成微小病变时发生的。 这种侵袭性疾病的特点是死亡率超过25%，与 住院，而且往往损害幸存者的生活质量。早期微生物诊断和 抗菌干预对改善患者预后和减少住院时间至关重要。然而， 目前公认的诊断方法仍然依赖于初级血培养，这种方法表现出较长的时间和可变的 周转时间，并可能提供假阴性结果。因此，非常需要新的诊断方法 不需要区域性的方法，并提供更快、更准确的结果。 为了解决这一未得到满足的需求，HelixBind开发了RAPID/IE，这是一种完全自动化的样本到答案测试， 在~3小时内直接从血液中鉴定和鉴定这些感染，而不需要培养。实施日期 快速(抗性和病原体鉴定)平台，适合放置在整个 医院，RAPID/IE结合了广泛的测试菜单，包括细菌和真菌病原体，以及 抗菌素耐药性的标志物。至关重要的是，该测试不会因之前的抗菌治疗而受到影响 提供物种级别的细节，具有单个CFU/ml的灵敏度，从而能够选择适当的抗菌剂。 RAPID/IE的商业化将及时识别和表征侵入性药物和 从而能够通过有针对性的抗微生物治疗进行干预。这有望改善患者的病情 结果和减少不必要的抗菌剂的使用，减缓了抗菌素耐药性的上升。 HelixBind已经达到并超过了第二阶段SBIR中定义的所有具体目标。这包括菜单 扩大范围以涵盖抗生素耐药性以及与IE相关的病原体，这些病原体无法通过 临床培养，由台式仪器操作的一次性一次性仪器的自动化验，以及 临床标本的检测。临床诊断的敏感性和特异性分别为92.7%和98.8%。 分别进行了分析。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共享症状的病原体的覆盖范围。一次性的和 仪器已过渡到制造阶段，并进行了广泛的分析测试，以确保 检测符合与法规和市场要求相关的规范。 在此CRP计划中，HelixBind将在第二阶段取得成功的基础上，为监管审批和 市场投放。这包括(1)根据FDA的反馈，开发分析方法，要求 成功完成分析和临床验证研究；以及(2)可扩展制造的开发 确保试剂盒的12个月、室温稳定性的某些试剂组的工艺，以及(3) 完成现场分析评估和盲法临床评估研究。在完成此操作后 随着该项目的实施，我们将很好地启动正式的分析和临床研究，以帮助FDA清除快速/IE。

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.