为了更好地开发新型诊断方法来检测和诊断遗传疾病，美国食品药品监督管理局（FDA）于2018年12月4日正式认可了首个包含基因和遗传变异数据的公共数据库。

这个获得FDA认可的数据库是临床基因组资源中心（Clinical Genome Resource，ClinGen）名下的ClinGen人类基因数据库（ClinGen Expert Curated Human Genetic Data），由美国国立卫生研究院（NIH）资助。

该数据库现已被视为有效科学证据的来源，而这类科学证据可以为上市前申请的临床有效性提供支持。这意味着基因检测开发人员（包括下一代测序（NGS）开发人员）将能够确保数据的可靠性，他们可以使用该数据库来帮助其进行FDA上市许可申请，而不必自己生成相同数据。 

“例如，一项用于检测遗传性心肌病相关变异体的基因检测发起人可以利用ClinGen基因库中的心肌病遗传变异信息，作为证明其检测的临床有效性的部分提交材料，”FDA解释说。

在认可ClinGen的过程中，FDA对遗传性疾病中的变异类型和诱导生殖细胞（生殖系变异）发生基因变异的过程进行了审查。其中，如果基因发生变异，就很有可能发生遗传疾病或病症。基因检测可以利用种系变异信息来检测心肌病、听力丧失、先天性代谢缺陷和其他遗传性疾病。

FDA还表示，未来ClinGen可以持续增加或修改遗传变异信息，只要这些变异信息在认可范围内。FDA通过采用2018年4月最终指南中详述的流程对该数据库予以了认可。

“该机构所制定的这类政策旨在鼓励数据共享，并概述一种方法，阐明测试开发人员如何利用来自FDA认可的公共数据库的临床证据来支持其在基因检测方面的临床声明，并帮助其确保检测的‘临床有效性’。就基因检测而言，指的是基因变异与特定疾病之间的关联。” 该机构解释道。

FDA Formally Recognizes First Public Genetic Database

As a way to better the development of novel diagnostics to detect and diagnose genetic diseases, the US Food and Drug Administration (FDA) on Tuesday for the first time formally recognized a public database with gene and genetic variant data.

The recognized database is the Clinical Genome Resource (ClinGen) consortium’s ClinGen Expert Curated Human Genetic Data, which is funded by the National Institutes of Health (NIH).

The database is now recognized as a source of valid scientific evidence that can be used to support clinical validity in premarket submissions. This means that genetic test developers, including developers of next-generation sequencing tests, will be assured of the reliability of the data, and they can use it in support of their applications for marketing authorizations with the agency, rather than generating the same data on their own. 

“For example, the sponsor of a test that detects variants involved in hereditary cardiomyopathy could point to the cardiomyopathy genetic variant information available in ClinGen as part of a submission to support clinical validity of their test,” FDA explained.

In its recognition of ClinGen, FDA reviewed “variant classifications and the processes that support them for gene changes in reproductive cells (germline variant) in hereditary disease where there is a high likelihood that the disease or condition will materialize if the gene is altered. Genetic tests may use germline variant information to detect for cardiomyopathy, hearing loss, inborn errors of metabolism and other hereditary conditions.”

FDA also said that its recognition anticipates that ClinGen may add new or modify genetic variant information on an ongoing basis, provided they are within the scope of recognition. FDA recognized the database using a process detailed in final guidance from April.

“The agency’s policies seek to encourage data sharing and outline an approach clarifying how test developers may rely on clinical evidence provided in FDA-recognized public databases to support clinical claims for their tests and help provide assurance that the test is ‘clinically valid,’ which, in the case of genetic tests, is the relationship between a gene variation and a specific disease,” the agency explained.

内容来自：RAPS

整理翻译：奥咨达