Expert Opin Drug Discov. 2012 Jun;7(6):457-61. doi: 10.1517/17460441.2012.679615. Epub 2012 Apr 4.
Biomarker data are essential in the discovery and development of new drugs. However, pathways needed to make sure that biomarker data are accepted by regulatory agencies may be considered an unnecessary burden on the critical path for drug development. There is the need to consider early in discovery and development that these pathways for biomarker acceptance or qualification not only are necessary, but may also enhance the success of novel therapies through regulatory review and clinical use. There also needs to be a focus on the challenge in the application of biomarkers as these approach regulatory evaluation. Regulatory guidance is needed on how a patient population may be defined by the molecular phenotype classification associated with specific mutations in patient genomes. Enzyme replacement therapies have been implicitly approved in the past assuming a molecular phenotype of a defective enzyme, but these and other precedents have not yet been translated into regulatory guidance. A second regulatory pathway for biomarkers is a biomarker qualification process. Biomarker data may be submitted, in the context of a specific NDA, but the biomarker qualification process has added a path through which efficacy and safety biomarkers useful in product development across multiple companies may be qualified through pre-competitive collaboration between these companies.
生物标志物数据对于新药的发现和开发至关重要。然而，为了确保生物标志物数据被监管机构接受而需要走的途径，可能被认为是药物开发关键路径上不必要的负担。在发现和开发的早期就需要考虑到，这些接受或确证生物标志物的途径不仅是必要的，而且还可以通过监管审查和临床应用提高新疗法的成功率。在应用生物标志物时也需要关注挑战，因为这些方法需要进行监管评估。需要有监管指导，说明如何根据与患者基因组中特定突变相关的分子表型分类来定义患者群体。过去，酶替代疗法在假设存在缺陷酶的分子表型的情况下被默示批准，但这些和其他先例尚未转化为监管指导。生物标志物的另一个监管途径是生物标志物确证过程。可以在特定的 NDA 背景下提交生物标志物数据，但生物标志物确证过程增加了一条途径，通过该途径，多个公司在产品开发中有用的疗效和安全性生物标志物可以通过这些公司之间的竞争前合作来确证。
