HLA Chip Product for FDA 510K Approval

描述(由申请人提供)：我们在此描述一项第二阶段竞争性更新拨款申请，该申请将支持ASHI(美国组织相容性和免疫学协会)和FDA 510K审查的三年计划，用于我们在过去两年中开发的“人类白细胞抗原芯片”，第二阶段SBIR支持。在这一竞争延续的第三年结束时，可交付的产品平台将是一个已被批准在DNA水平上进行非常高吞吐量的基于微阵列的人类白细胞抗原配型的产品平台，以支持ASHI和FDA验证的器官和骨髓移植。然而，我们认为，该产品将以足够低的成本交付，并具有足够高的处理能力，相同的临床批准的人类白细胞抗原芯片将随时准备支持人类白细胞抗原筛查药物在未来发挥更广泛的作用：用于癌症风险筛查、疫苗反应筛查和微生物敏感性筛查，用于新生儿、军队和平民成年人。因此，在更高的抽象水平上，我们认为通过人类白细胞抗原芯片进行的人类白细胞抗原分型可以被视为所有复杂医学等位基因分型的通用原型：如基于基因的个性化医学、基于基因的体外诊断和基于基因的公共健康筛查所预见的那样。为了协助这一关键而复杂的临床审批流程，我们获得了FDA审批流程专家Tony Lam博士、ASHI新西兰血液服务中心HLA分型实验室主任Paul Dunn博士和ASHI认证委员会前主席、ASHI前总裁Kamala Balakrishnan博士的协力支持。 公共卫生相关性：这一第二阶段竞争性更新的具体焦点是同时获得ASHI认证(作为一项服务)和FDA对人类白细胞抗原芯片的510K批准，以支持通用的人类白细胞抗原分型。在目前的医学和公共卫生实践中，这种通用的人类白细胞抗原分型的特定的、临床验证的应用是固体器官和骨髓移植，因此，首先，我们寻求的ASHI和FDA的批准将允许在这两个特定的背景下使用人类白细胞抗原芯片。 然而，目前对疫苗风险反应的理解，正如我们在Mayo(Dr波兰)和其他人所倡导的那样，表明我们将提交ASHI和FDA审查的人类白细胞抗原芯片(A、B、C、DRB1、DQA、DQB、DPA和DQB)的基因内容将非常相似，如果不是完全相同的，将支持疫苗药物，一旦人类白细胞抗原分型被证实为疫苗药物实践的关键组成部分。我们认为，在获得ASHI和FDA对用于器官、骨髓和干细胞移植的HLA芯片的批准后，用于疫苗治疗的必要的后续批准将大大便利。在我们与FDA的初步讨论中，我们已经很好地验证了人类白细胞抗原芯片移植和疫苗应用之间的等价性。

DESCRIPTION (provided by applicant): We describe here a Phase II Competitive Renewal grant application, which will support a three year program of ASHI (American Society of Histocompatibility and Immunology) and FDA 510K review, for the "HLA-Chip" which we have developed over the past two years, with Phase II SBIR support. The deliverable at the end of year three of this Competitive Continuation will be a product platform that has been approved for very high throughput, microarray-based HLA typing, at the DNA level, in support of ASHI and FDA validated organ and marrow transplantation. However, we argue that the product will have been delivered at a cost that is low enough and with processing throughput that is high enough, that the same clinically approved HLA-Chip will stand ready to support a much broader future role for HLA screening medicine: for applications such as cancer risk screening, vaccine response screening, and microbial sensitivity screening, for neonates, for the military, and for civilian adults. Thus, at a somewhat higher level of abstraction, we argue that HLA-typing via the HLA- Chip can be viewed as a generalized prototype for all of complex medical allelotyping: as foreseen in gene- based personalized medicine, gene-based in vitro diagnostics, and gene-based public health screening. To assist in that critical and complex clinical approval process, we have obtained the collaborative support of Dr. Tony Lam, an expert in the FDA approval process, with special expertise in microarray-based IVDs; Dr. Paul Dunn, ASHI director for the New Zealand Blood Service HLA-typing laboratory, and Dr. Kamala Balakrishnan, former Chair of the ASHI Accreditation Committee, and past President of ASHI. PUBLIC HEALTH RELEVANCE: The specific focus of this Phase II Competing Renewal is to obtain both ASHI certification (as a service offering) and FDA 510K approval for the HLA-Chip, to support generalized HLA-typing. The specific, clinically validated applications for such generalized HLA-typing in the present practice of medicine and public health are solid organ and bone marrow transplantation and so, to begin with, the ASHI and FDA approvals that we seek will allow the HLA-Chip to be used in those two specific contexts. However, the current understanding of vaccine risk response, as championed by our collaborators at Mayo (Dr Poland) and others, suggests that the gene content of the HLA-Chip that we will submit for review by ASHI and by the FDA (A,B,C,DRB1,DQA,DQB,DPA &DQB) will be very similar, if not identical to the HLA-Chip that will be needed to support vaccination medicine, once HLA typing has been validated as a critical component of the practice of vaccination medicine. We argue that, having obtained ASHI and FDA approval for the HLA-Chip for organ, marrow and stem cell transplantation, the necessary follow-on approvals for the HLA- Chip for vaccine treatment, will be greatly facilitated. The idea of such equivalence between transplantation & vaccination applications for the HLA-Chip has been nicely validated in our preliminary discussions with the FDA.