Complex drug products are medicinal products for which the active substance consists of molecules of different structures that cannot be isolated and fully quantitated, or characterized by physicochemical analytical means, such as peptides, complex mixtures, or biological source products. The composition, quality, and in vivo performance of complex drug products are highly dependent on the manufacturing processes of the active ingredients, as well as the formulations. However, both characterizing pharmaceutical equivalence and assessing bioequivalence of two drug complex products (i. e., the reference product and its generic version)are challenging. In general, the evaluation requires a stepwise approach including a full chemistry, manufacturing, and control (CMC)package, non-clinical studies, and sometimes the results of a comparative clinical trial. Therapeutic equivalence clinical study in patients is not necessary when the total data (quality comparison, non-clinical data and human PK study)demonstrate similarity.%复杂药物的活性物质由多种不能通过物理化学分析方法分离和完全定量、表征其结构的复杂分子组成,例如多肽、复杂的混合物、大分子聚合物以及生物制品.复杂药物的活性物质组成、质量和体内性能高度取决于活性成分的生产过程以及配方.然而,复杂药物仿制药的药学等效性和生物等效性评价对研发和监管提出了新的科学挑战.总体来说,建议采用逐步递进方法进行等效性评价,包括完整的化学、制造和控制(CMC)数据、非临床研究结果,有时候包括比较性临床试验结果.如果总体数据(质量比较、非临床数据和人PK研究)证明了相似性,在患者中进行治疗等效性临床研究是没有必要的.
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