生物类似药研究中相似性的主成分分析评价（英文）

发布时间：2019-04-26 16:07

【摘要】：为了评价仿制生物制品(follow-on biologics)的生物类似性,美国食品药品监督管理局(FDA)在2012年2月颁布了3个指导原则草案。在有关"科学考量"(scientific consideration)的指导原则草案中,FDA要求产品的相似性必须在安全性、纯度和有效性等各特征区中具有"证据链完备性"(totality-of-the-evidence)。然而,即使在同一特征区内,也会有各种因素对生物类似性的确证产生不同程度影响。为在生物类似药物的特征区内提供类似性的证据,本研究采用了包括主成分分析(PCA)在内的不同加权分析法进行了类似性的试验分析和比较。并在2×2交叉设计基础上进行了广泛的模拟研究,以对所提出的方法在有限样本条件下的评价性能进行研究。由于在特征区域内也存在不同变量间的相关性,权重主成分分析(PCAweight)评价的把握度最高。该方法可进一步拓展应用于生物类似药物各种特征区域间的生物类似性的"证据链完备性"评价。
[Abstract]:In order to evaluate the biosimilarity of bionic biological products (follow-on biologics), the (FDA) issued three draft guidelines in February 2012. In the draft guiding principles for "Scientific considerations" (scientific consideration), FDA requires that the similarity of products must be "totality-of-the-evidence" in each characteristic region, such as safety, purity and effectiveness. However, even in the same characteristic region, there are various factors which have different influence on the confirmation of biological similarity. In order to provide evidence of similarity in the characteristic region of biological analogues, different weighted analysis methods including principal component analysis (PCA) were used for experimental analysis and comparison of similarity. On the basis of 2 脳 2 cross design, a wide range of simulation studies are carried out in order to study the evaluation performance of the proposed method under the condition of limited samples. Because of the correlation between different variables in the characteristic region, the control degree of weight principal component analysis (PCAweight) is the highest. This method can be further applied to the "evidence chain completeness" evaluation of biological similarity among different characteristic regions of biological analogues.
【作者单位】： Department
【分类号】：R917

【共引文献】