Bayer Schering Pharma AG, Müllerstrasse 170-178, 13353 Berlin, Germany +49 30 4681 7450 ; +49 30 4681 1527 ;
Expert Opin Drug Discov. 2008 Mar;3(3):289-97. doi: 10.1517/17460441.3.3.289.
To support the increasing number of biologics in drug discovery, preclinical development programs (PDPs) adopted for biologics are needed.
Differences in the physiochemical properties of biologics compared with small molecules require the adaptation of the standard PDP, incorporating tools specific for the characterization of biologics.
Preclinical development addressed in this review comprises preclinical and clinical bioanalytics, preclinical pharmacokinetics and nonclinical drug safety. Despite varying expectations for specific preclinical development of biologics across the industry, standard development plans are emerging for biologics, distinct to those well established for small molecules, driven by lessons learned from past experience and new regulatory guidance.
RESULTS/CONCLUSIONS: The PDP for biologics should be adapted to account for: target differences, lack of species crossreactivity and/or limited applicability of long-term studies as well as immunogenicity assessment. Special study designs may partially overcome these hurdles and should be scientifically justified.
为了支持药物发现中越来越多的生物制剂，需要采用用于生物制剂的临床前开发计划（PDP）。
与小分子相比，生物制剂的物理化学性质存在差异，这需要对标准 PDP 进行调整，纳入专门用于生物制剂特性描述的工具。
本文综述的临床前开发包括临床前和临床生物分析、临床前药代动力学和非临床药物安全性。尽管整个行业对生物制剂的具体临床前开发有不同的期望，但鉴于过去经验和新监管指导带来的教训，正在为生物制剂制定标准的开发计划，这些计划与为小分子制定的计划明显不同。
结果/结论：应调整生物制剂的 PDP，以考虑到：靶标差异、缺乏物种交叉反应性和/或长期研究的适用性有限以及免疫原性评估。特殊的研究设计可以部分克服这些障碍，并且应该有科学依据。
