HLA Chip Product for FDA 510K Approval

描述（由申请人提供）：我们在此描述了第二阶段竞争性更新赠款申请，该申请将支持ASHI（美国组织相容性和免疫学学会）的三年计划。 免疫学）和FDA 510 K审查，我们在过去两年中开发的“HLA芯片”，具有第二阶段SBIR支持。在本竞争延续的第三年年底，可交付的产品将是一个产品平台，该平台已被批准用于DNA水平的极高通量、基于微阵列的HLA分型，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和足够高的处理量交付，相同的临床批准的HLA芯片将随时准备支持HLA筛查医学更广泛的未来作用：用于癌症风险筛查，疫苗反应筛查和微生物敏感性筛查等应用，用于新生儿，军事和平民成人。因此，在更高的抽象层次上，我们认为通过HLA-Chip的HLA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中所预见的。为了协助完成这一关键而复杂的临床审批流程，我们获得了以下人员的合作支持：FDA审批流程专家Tony Lam博士，他在基于微阵列的IVD方面具有特殊专长;新西兰血液服务HLA分型实验室ASHI主任Paul Dunn博士，以及ASHI认证委员会前主席、ASHI前任主席Kamala Balakrishnan博士。 公共卫生相关性：第二阶段竞争性更新的具体重点是获得ASHI认证（作为服务提供）和FDA 510 K批准的HLA-Chip，以支持广义的HLA分型。在目前的医学和公共卫生实践中，这种广义HLA分型的具体的、临床验证的应用是实体器官和骨髓移植，因此，开始，我们寻求的ASHI和FDA批准将允许HLA芯片用于这两种特定的情况。 然而，目前对疫苗风险反应的理解，正如我们在马约的合作者所倡导的那样，（波兰博士）和其他人建议，我们将提交给ASHI和FDA审查的HLA芯片的基因内容（A、B、C、DRB 1、DQA、DQ B、DPA和DQ B）将非常相似，如果不与支持疫苗接种医学所需的HLA芯片相同，一旦HLA分型被证实是疫苗接种医学实践的关键组成部分。我们认为，在获得ASHI和FDA批准用于器官、骨髓和干细胞移植的HLA芯片后，将大大促进用于疫苗治疗的HLA芯片的必要后续批准。在我们与FDA的初步讨论中，HLA芯片的移植和疫苗接种应用之间的等效性已经得到了很好的验证。

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.