药学英语药学英语 (29).ppt

《药学英语药学英语 (29).ppt》由会员分享，可在线阅读，更多相关《药学英语药学英语 (29).ppt（6页珍藏版）》请在淘文阁 - 分享文档赚钱的网站上搜索。

1、 Unit NineNonclinical Development of Biopharmaceuticals 生物药物Part three vAssay Types Used in Nonclinical Development of Biologics 生物制品非临床研究中使用的分析类型vWhen developing a PK assay strategy,the needs of the nonclinical and clinical development program have to be considered,such as sensitivity of the assay

2、based on nonclinical and estimated clinical dose,planed combination treatments,estimated target levels,pharmacokinetics pharmacodynamics(PK/PD)modeling approaches and so on.v当研究一种PK分析策略时，必须考虑非临床和临床研发项目的需要，例如基于非临床剂量和估算的临床剂量确定分析方法的敏感性、计划的联合治疗方案、估算的靶点浓度、PK/PD的建模方法等。vLooking beyond assay technologies,sa

3、mple-clean procedures routinely used for small molecules(e.g.solvent extraction and affinity chromatography)can usually not be used for biologics.vBiologics are mostly analyzed without extraction or only with a crude protein precipitation step.vTherefore,extensive tests of the matrix effect are requ

4、ired during method development.v除分析技术之外，对小分子药物常规使用的样品纯化操作(如，溶剂萃取和亲和色谱法)通常也不适用于生物制品。v生物制品几乎不使用萃取方法分析或仅通过个粗蛋白质沉淀步骤进行分析。v因此，在方法研究过程中需要对基质效应进行广泛试验。vLigand-binding assays(immunoassays)are still widely used for quantification of biologics.vInnovations in MS instrumentation with much higher widely used for

5、 mass accuracy have already been applied to smaller MW biologics but still remain unavailable for routine quantification of large proteins(20kDa)in biomatrices.v配体结合分析(免疫测定法)仍广泛应用于生物制品的定量分析。vMS仪器的革新使其具有更高的质量准确度并且已应用于低分子量生物制品，但仍然不能用于在生物基质中对大分子蛋白质(20kDa)进行常规定量分析。vImmunoassays require the use of a spec

6、ific antigen or antibody to capture and/or detect the analyte of interest.vEssential reagents such as poly-or monoclonal antibodies might be difficult to obtain in early stages of development.vFurthermore,assay development often encounters challenges stemming from interfering residuals in the sample

7、 matrix.v免疫检测需要使用特异性抗原或抗体来捕获和(或)检测目标分析物。v在研发早期很难获得诸如多克隆或单克隆抗体的重要试剂v而且样品基质中的干扰性残留使分析方法的研发遭遇重重挑战。vDynamic range and linearity,limited in comparison to MS methods,are additional issues that often need to be addressed.vImmunoassays are also generally less precise than methods such as MS.vHeterogeneity htrdniti 异质性 of biologics(e.g.mixtures of differently glycosylated species and various degradation products)can raise specificity problems.v与质谱法相比，有限的动力学范围和线性关系是另外一些需要解决的问题。v免疫检测的准确度要低于MS等方法。v生物制品的不均一性(如，不同糖基化物质和各种降解产物的混合物)会引起一些特异性问题。