title: Stabilizing two IgG1 monoclonal antibodies by surfactants: Balance between aggregation prevention and structure perturbation.
abstract: Surfactants are widely used as stabilizers in the biopharmaceutical formulations to minimize protein aggregation. Under a fixed stress condition, the protecting and destabilizing effects of surfactants are hypothesized to be highly dependent on the species and concentrations of surfactants and mAb. Therefore, we here studied the aggregation-prevention and structure-perturbation effects of eight commonly used surfactants (Tw20, Tw80, Brij35, Chaps, TrX-100, SDS, Pluronic F68 and F127) on two IgG1 solution formulations under agitation, using analytical methodologies including visual inspection, OD350measurement, HPLC-SEC, circular dicroism, fluorescence spectroscopy and differential scanning calorimetry. We found that: (1) With concentrations range from 0.02 to 2mg/mL, nonionic surfactants were found to offer efficient aggregation-prevention effect, which is superior than the ionic surfactants; and higher surfactant concentration prevented mAb aggregation better especially under prolonged stability test under stress conditions. (2) The surfactant induced structure-perturbation emerged when even higher surfactant concentration (≥2mg/mL) was used, and such effect was surfactant-property dependent; and (3) the two IgG1 demonstrated different aggregation mechanisms and surfactant dependency, especially at high mAb concentrations. In conclusion, surfactants usage in mAb formulations, including the types and concentrations, should strike an optimal balance between the desirable aggregation-prevention and the detrimental structure-perturbation effects, while the consideration of mAb aggregation mechanism and concentration is also required for surfactant assessment.
authors.affiliation: School of Pharmaceutical Sciences and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
authors.forename: Shujing
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Tian
authors.affiliation: China R&D and Scientific Affair, Shanghai Discovery Center, Janssen Research & Development, Johnson & Johnson, Shanghai 200030, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: China R&D and Scientific Affair, Shanghai Discovery Center, Janssen Research & Development, Johnson & Johnson, Shanghai 200030, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.affiliation: Janssen Research & Development, Johnson & Johnson, Malvern, PA 19355, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Dai
authors.affiliation: School of Pharmaceutical Sciences and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China. Electronic address: qianfeng@biomed.tsinghua.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D004339:Drug Compounding; D005079:Excipients; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D007202:Indicators and Reagents; D019999:Pharmaceutical Solutions; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D005079:Excipients; D007074:Immunoglobulin G; D007202:Indicators and Reagents; D019999:Pharmaceutical Solutions; D013501:Surface-Active Agents
keywords: Aggregation prevention; Agitation; Monoclonal antibody; Structure perturbation; Surfactants; mAb formulation