The future of protein particle characterization and understanding its potential to diminish the immunogenicity of biopharmaceuticals: A shared perspective
The future of protein particle characterization and understanding its potential to diminish the immunogenicity of biopharmaceuticals: A shared perspective
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DOI：
10.1002/jps.23247
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发表时间：
2012-10-01
影响因子：
3.8
通讯作者：
Ragheb, Jack A.
中科院分区：
文献类型：
--
作者：
Bee, Jared S.;Goletz, Theresa J.;Ragheb, Jack A.
生物制药是一类重要的、不断增长的药物。患者对生物药物的免疫原性反应有时会导致安全性和有效性降低。虽然已知多种因素影响免疫原性，但我们对复杂的潜在机制的理解仍然不完善。特别是，蛋白质聚集体（颗粒）对免疫原性的潜在影响目前还不清楚。本评论讨论了颗粒评估的新兴技术，颗粒与产品安全性和有效性之间的联系，以及当前的监管指南和观点。我们认为，在未来可能允许特定的颗粒属性与相对免疫原性风险，包括来自临床和上市后监测的数据的价值的方法。最后，我们确定了一些关键的剩余问题，这些问题一旦得到回答，可能会指导未来降低生物药物免疫原性的策略。(C)2012 Wiley Periodicals，Inc.和American Pharmacologist Association J Pharm Sci 101：35803585，2012
Biopharmaceuticals represent an important and growing class of medicines. Immunogenic responses to biopharmaceuticals in patients can sometimes result in reduced safety and efficacy. Although multiple factors are known to influence immunogenicity, our understanding of the complex underlying mechanisms remains imperfect. In particular, the potential impact of protein aggregates (particulates) on immunogenicity is currently not well understood. This commentary discusses emerging technologies for particle assessment, what is known about the link between particulates and product safety and efficacy, and current regulatory guidances and perspectives. We consider approaches that in the future may permit specific particle attributes to be correlated with relative immunogenic risk, including the value of data derived from clinical and postmarketing surveillance. Finally, we identify some key remaining questions, which, when answered, may guide future strategies for decreasing the immunogenicity of biopharmaceuticals. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:35803585, 2012