Development of mathematical modelling tools for comparison of biosimilars

随后进入制药（也称为非专利或仿制药）生产可以为患者和医疗保健系统节省大量资金。要进入市场，后续进入的药物必须被证明与原始专利版本一样有效。对于大多数传统的小分子药物，等效性的证明相对简单，因为原始药物的分子复制品可以通过化学合成容易地产生。相比之下，证明新型生物药物（如治疗性抗体）的等效性是不可能的，因为这些药物是由不同的生物来源（如活细胞）生产的，这导致其结构（因此化学）在生产过程中存在相当大的差异，甚至在生产批次之间。因此，生物仿制药不能仅根据结构和化学特征与原始专利生物制剂进行比较;因此，通常被称为生物仿制药而不是仿制药。美国制药公司Apobiologix（ApoPharma USA，Inc的分部; Apotex集团公司的成员）正在探索新的方法，以验证其新的后续进入生物类似物与临床批准的乳腺癌生物制剂曲妥珠单抗（以赫赛汀上市）的相似性。他们正在研究曲妥珠单抗及其生物仿制药的细胞反应特征，以确定药物作用的相似性和差异。作为表征的一部分，拟议的研究涉及开发计算建模框架，以解释来自实验的数据，比较这些药物对乳腺癌细胞生化反应网络的影响。这些建模分析的见解有望缩短Apobiologix的曲妥珠单抗生物仿制药进入市场的开发时间，为乳腺癌患者和医疗保健系统带来更早而不是更晚的成本节约。

Subsequent entry pharmaceutical (also known as off-patent or generic) drug manufacturing can providesignificant savings to patients and healthcare systems. To enter the market, a subsequent entry pharmaceuticaldrug must be demonstrated to be as therapeutically effective as the original patented version. Demonstrationsof equivalence are relatively straightforward for most traditional small-molecule drugs, as molecular replicas ofthe original can be readily generated by chemical synthesis. In contrast, demonstration of equivalence of thenew class of biologic drugs (such as therapeutic antibodies) is not possible because these drugs are producedfrom diverse biological sources (such as living cells) which results in considerable variability in their structure(and hence chemistry) during manufacturing, even between production batches. As a consequence, subsequententry biologics cannot be compared to the original patented biologic solely on the basis of structural andchemical features; and are therefore, often referred to as biosimilars rather than generics. The Canadianpharmaceutical company Apobiologix (Division of ApoPharma USA, Inc; a member of the Apotex Group ofCompanies) is exploring new approaches for verifying the similarity of its new subsequent entry biosimilar toa an the clinically approved breast-cancer biologic known as trastuzamab (marketed as Herceptin). They areseeking to characterize cellular responses of trastuzumab and their biosimilar to identify similarities anddifferences in drug action. As part of that characterization, the proposed research involves development of acomputational modelling framework to interpret data from experiments comparingthe effects of these drugs onbiochemical response networks in breast cancer cells. Insights from these modeling analyses are expected toreduce the time for development efforts of Apobiologix's trastuzamab biosimilar to reach the market, bringingcost-savings to breast cancer patients and healthcare systems earlier rather than later.