基于高通量方法对高浓度单克隆抗体A的稳定性预测

Evaluation of the Exploitability of High Monoclonal Antibodies based on Polyethylene Glycol Precipitation

通过高通量方法研究单抗分子的溶解特性、热稳定性、胶体稳定性等稳定性相关特性,建立稳定性预测方法,快速评估单抗分子的可开发性特性。采用聚乙二醇(Polyethylene glycol,PEG)沉淀法这种高通量的方法同时结合扩散相互作用系数(Diffusion interaction parameter,kD)、Kirkwood-Buff integrals(G_(22))以及不同处方条件下的等温稳定性来预测单抗的溶解度、胶体稳定性和热稳定性等特性。本研究通过高通量方法确定的kD、G_(22)、C_(mid)等指标组合,确定了预测单抗在高浓度条件下稳定性的初步方法。预测的较优处方条件(20 mmol/L Histidine-HCl,200 mmol/L ArgCl,pH 6.0)可以保证单抗产品在高浓度条件下的溶解度以及胶体稳定性,这也得到了加速稳定性的证实。此研究通过采用多种高通量预测指标组合,为准确高效地开展制剂处方尤其是高浓度制剂处方开发提供了一定的依据。

The solubility,thermal stability,colloidal stability and other stability related properties of monoclonal antibodies were studied by high throughput method,and a stability prediction method was established to rapidly evaluate the developability of mono-clonal antibodies.By utilizing combinations of high throughput methods including Polyethylene glycol(PEG)precipitation method,Diffusion Interaction Parameter(kD)and Kirkwood-Buff integrals(G_(22))analysis by DLS,the solubility,colloidal stability and thermal stability of monoclonal antibodies were predicted and then confirmed by the preliminary stability study.In this study,a preliminary method for predicting the stability of monoclonal antibodies at high concentrations was established by combining kD,G_(22),C_(mid)and other indicators determined by high-throughput methods.The predicted optimal formulation conditions(20 mmol/L Histidine-HCl,200 mmol/L ArgCl,pH6.0)ensured the solubility and colloidal stability of the monoclonal antibody product at high concentrations,which was also confirmed by the accelerated stability study.This study provides a basis for predicting the preliminary stability of mAbs by using a variety of high-throughput predictor combinations,which would help efficient formulation especially high-concentra-tion formulation development.