The invention discloses an efficient purification process of a
bispecific antibody and a special
chromatography system thereof. The efficient purification process of the
bispecific antibody comprises the following steps: pretreatment: performing 0.22 mu m
microfiltration on a
cell culture supernatant to remove
cell debris, and performing deep
filtration to reduce
turbidity to be less than or equal to 1NTU so as to reduce subsequent
chromatography medium
pollution; carrying out improved
Protein A
affinity chromatography, namely carrying out
affinity chromatography by adopting an
agarose medium modified by a recombinant
Protein A ligand, taking 20mM
Tris-HCl as a loading
buffer solution, and taking the pH value of the loading
buffer solution as 7.4, taking 100mM
citric acid as an
elution buffer solution, and taking the pH value of the
elution buffer solution as 3.2-3.5; performing
mixed mode chromatography: adopting a composite mode medium containing a
benzamidine functional group, taking 50mM
sodium phosphate as a buffer solution, adjusting the pH value to 6.0-6.5, adjusting the NaCl concentration to 0.1-0.3 M, and specifically removing a double-
antibody polymer and a mismatched isomer by utilizing a
hydrophobic effect and an
ion exchange synergistic effect; and performing nanoscale
filtration and terminal treatment: removing viruses by adopting a
virus filtration membrane with the aperture of 30nm, and performing 0.22 mu m
sterile filtration to obtain a final product. According to the process, the purification efficiency, the yield and the product purity are remarkably improved, and the process is suitable for efficient purification of the
bispecific antibody.