In recent years there has been a lot of interest to test for similarity between biological drug products, commonly known as biologics. Biologics are large and complex molecule drugs that are produced by living cells and hence these are sensitive to the environmental changes. In addition, biologics usually induce antibodies which raise the safety and efficacy issues. The manufacturing process is also much more complicated and often costlier than the small-molecule generic drugs. Because of these complexities and inherent variability of the biologics, the testing paradigm of the traditional generic drugs cannot be directly used to test for biosimilarity. Taking into account some of these concerns we propose a functional distance based methodology that takes into consideration the entire time course of the study and is based on a class of flexible semiparametric models. The empirical results show that the proposed approach is more sensitive than the classical equivalence tests approach which are usually based on arbitrarily chosen time point. Bootstrap based methodologies are also presented for statistical inference.

近年来，测试生物药品（通常称为生物制剂）之间的相似性引起了很多兴趣。生物制剂是由活细胞产生的大而复杂的分子药物，因此对环境变化敏感。另外，生物制剂通常诱导产生安全性和功效问题的抗体。制造过程也比小分子仿制药要复杂得多，而且往往要贵一些。由于生物制剂的这些复杂性和固有的可变性，传统仿制药的测试范例无法直接用于测试生物相似性。考虑到其中一些问题，我们提出了一种基于功能距离的方法，该方法考虑了整个研究过程，并基于一类灵活的半参数模型。实证结果表明，所提出的方法比通常基于任意选择的时间点的经典等效测试方法更为敏感。还介绍了基于Bootstrap的方法，以进行统计推断。