The Development of a PCR-based Commercial Diagnostic Assay for Avian Influenza A

描述（由申请人提供）：我们的总体目标是开发、生产并在适当的政府监管机构注册标准化诊断试剂，用于基于实时pcr检测甲型禽流感病毒病原体（H5N1），以及所有甲型流感病原体（人类和动物）。这项工作将与疾病控制中心的科学家合作进行。诊断试验将包括(1)由疾病控制中心设计的TaqMan PCR引物和探针，这些引物和探针现在提供给公共卫生实验室用于监测、诊断和研究目的；(2)阳性和阴性对照。Celera Diagnostics根据FDA的质量体系法规开发这些试剂，将包括试剂的优化、工艺开发、在现行良好生产规范（cGMP）条件下扩大试剂生产、临床前测试和分析的验证、提交FDA批准的510k申请以及商业化。Celera Diagnostics在开发和商业化用于检测病毒病原体的敏感和特异性PCR检测方面具有丰富的经验。研制出强大、稳定的人造试剂，并向公共卫生实验室和世界卫生组织提供这些试剂，将有助于广泛分发和采用监测和诊断甲型禽流感病原体H5N1的标准化方法。检测甲型H5N1亚型禽流感的标准化试剂的可用性将使检测能够在更多地点进行，最重要的是，实验室之间的结果将具有可比性。此外，广泛获得对H5N1型禽流感敏感和特异的检测方法有助于进一步开展有关这种病原体的传播和毒力的基础研究，并可作为疫苗生产的工具。在人类中早期发现H5N1禽流感，可以通过抗病毒治疗药物、疫苗接种或隔离进行干预，以防止或延缓感染的国际传播。H5N1型禽流感是一种高致病性流感，由于禽类死亡率高，目前对受影响国家造成严重的经济影响。迄今为止，人类感染病例很少，但死亡率为50%。该病毒对基因重组和突变非常敏感，因此可以迅速传播给人类。

DESCRIPTION (provided by applicant): Our overall goal is to develop, produce and register with the appropriate government regulatory agencies standardized diagnostic reagents for the real-time PCR-based detection of the Avian Influenza A viral pathogen (H5N1), as well as for all Influenza A pathogens (human and animal). This work will be performed in collaboration with scientists at the Centers for Disease Control. The diagnostic assay will be comprised of (1) the TaqMan PCR primers and probes designed by the Centers for Disease Control that are now supplied to public health laboratories for surveillance, diagnosis and research purposes, and (2) positive and negative controls. Development of these reagents by Celera Diagnostics under the FDA's Quality System Regulations will involve optimization of the reagents, process development, scale-up of reagent production under current Good Manufacturing Practice (cGMP) conditions, pre-clinical testing and validation of the assay, submission of a de novo 510k application for FDA clearance, and commercialization. Celera Diagnostics has experience in the development and commercialization of sensitive and specific PCR assays for the detection of viral pathogens. The development of robust, stable, manufactured reagents and their availability to public health laboratories and the World Health Organization will allow for widespread distribution and adoption of a standardized approach to surveillance and diagnosis of the Avian Influenza A pathogen H5N1. The availability of standardized reagents for the detection of Avian Influenza A subtype H5N1 will enable testing to be performed in more locations, and most importantly, results will be comparable between laboratories. In addition, the widespread availability of a sensitive and specific test for avian influenza H5N1 could help further basic research into the transmission and virulence of this pathogen, as well as being a tool for vaccine production. Early detection of avian influenza H5N1 in humans could allow for intervention with antiviral therapeutic drugs, vaccination or quarantines to prevent or delay international spread of the infection. Avian influenza H5N1 is a highly pathogenic form of influenza that currently has a severe economic impact upon affected countries due to a high avian fatality rate. To-date there have been few cases of human infections, however they had a 50% fatality rate. The virus is highly susceptible to genetic reassortment and mutation, and thus could rapidly become readily transmissible to humans.