Alternative Strategies for Toxicity Testing of Species-Specific Biopharmaceuticals
Alternative Strategies for Toxicity Testing of Species-Specific Biopharmaceuticals
复制标题
DOI：
10.1177/1091581809337262
复制
发表时间：
2009-05-01
影响因子：
2.2
通讯作者：
Horvath, Christopher
中科院分区：
文献类型：
--
作者：
Bussiere, Jeanine L.;Martin, Pauline;Horvath, Christopher
尽管毒理学研究应始终在生物学相关种属中进行，但许多生物药物的特异性可能会对相关种属的鉴别提出挑战。在某些情况下，即当临床产品仅在人类或黑猩猩中具有活性时，或者如果临床候选药物在其他种属中具有活性，但免疫原性限制了进行全面安全性评估的能力，则必须考虑评价生物药物安全性的替代方法。替代方法，包括疾病的动物模型，转基因小鼠，或使用替代分子，可能会提高物种特异性生物药物的临床前安全性评估的预测价值，但必须考虑与这些模型相关的许多警告。由于本文中讨论的许多注意事项，只有当临床候选药物无法在至少一个相关物种中进行测试以识别潜在危害时，才应使用替代方法来评价安全性。
Although toxicology studies should always be conducted in pharmacologically relevant species, the specificity of many biopharmaceuticals can present challenges in identification of a relevant species. In certain cases, that is, when the clinical product is active only in humans or chimpanzees, or if the clinical candidate is active in other species but immunogenicity limits the ability to conduct a thorough safety assessment, alternative approaches to evaluating the safety of a biopharmaceutical must be considered. Alternative approaches, including animal models of disease, genetically modified mice, or use of surrogate molecules, may improve the predictive value of preclinical safety assessments of species-specific biopharmaceuticals, although many caveats associated with these models must be considered. Because of the many caveats that are discussed in this article, alternative approaches should only be used to evaluate safety when the clinical candidate cannot be readily tested in at least one relevant species to identify potential hazards.