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Updated: Jan 13, 2026
Laboratory Scale Production and Purification of a Therapeutic Antibody
Published on: January 24, 2017
Process optimization to remove immunoglobulin A, immunoglobulin M and prekallikrein activator for intravenous
Wen-Rong Xia1,2, Yi Zhong2, Yang-Li Lu2
1College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.
Background And Objectives:
The demand for intravenous immunoglobulin (IVIG) is increasing, but supply is limited. Some residual protein contaminants such as prekallikrein activator (PKA) and immunoglobulin A (IgA) can cause severe adverse effects, necessitating a more efficient purification process with high recovery and fewer impurities.
Materials And Methods:
We used IVIG intermediate from caprylic acid precipitation as the starting material. Diatomite adsorption and two-step anion exchange chromatography (AEX) were employed to remove PKA, Factor XII, prekallikrein and kallikrein. Three resins for the second-step flow-through mode AEX were evaluated, and the loading conditions were optimized by Design of Experiments (DoE) and high-throughput screening experiments to better remove IgA and immunoglobulin M (IgM). Pilot-scale experiments validated the feasibility of the optimized process.
Results:
Diatomite adsorption (300 g/kg, 1 h) and two-step AEX could remove PKA, Factor XII, prekallikrein and kallikrein to below the limit of detection. The best AEX resin and optimal loading condition (pH 6.0 with 3.0 mS/cm conductivity) to remove IgA and IgM were obtained. As a result, IgA and IgM could be reduced to 3.83 and 10.70 μg/mL, respectively, with the immunoglobulin G (IgG) recovery over 86.9%. The 800-L pilot-scale results demonstrated successful process scale-up, achieving robust IgG recovery and effective impurity removal for IVIG production.
Conclusion:
The combination of diatomite absorption and optimized two-step AEX resulted in IVIG preparation with enhanced purity and high recovery.
