Preparation method of anti-human IFNAR1 monoclonal antibody concentrated solution

Abstract

The invention discloses a preparation method of an anti-human IFNAR1 monoclonal antibody concentrated solution, which comprises the following steps: first ultrafiltration concentration: concentrating a solution containing an anti-human interferon alpha receptor 1 (IFNAR1) monoclonal antibody until the protein concentration is 20-60mg / ml under the conditions that the flow rate is 120-300L / m<2>.h and the transmembrane differential pressure (TMP) is 0.6-1.5 bar, so as to obtain a concentrated sample; ultrafiltration replacement: replacing the concentrated sample with a replacement buffer solution, and obtaining an ultrafiltration replacement solution when the usage amount of the replacement buffer solution is 6-10 times of the weight of the concentrated sample; and second ultrafiltration concentration: uniformly mixing the ultrafiltration replacement solution and the alkaline amino acid mother liquor to enable the concentration of amino acid to be 100-150mM, and performing ultrafiltration concentration to obtain a concentrated solution with the protein concentration of 100-200mg / ml. According to the preparation method, the viscosity of the high-concentration antibody liquid medicine can be reduced, the stability can be improved, the method is simple and easy to implement, large-scale production can be carried out, the high purity of a sample can be guaranteed, and the high recovery rate can be obtained.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a method for preparing a concentrated solution of anti-human IFNAR1 monoclonal antibody. Background technique [0002] As a fast-growing market, the biologics market has numerous R&D pipelines and brings more innovative treatments to patients. For some diseases that are difficult to treat with traditional chemical drugs, biologics targeted drugs provide more choices. On the other hand, in order to reduce the cost of clinical use of biological agents and improve patient compliance, the dosage forms of biological agents have gradually changed from freeze-dried dosage forms to aqueous injection dosage forms, and from intravenous administration to subcutaneous injection dosage forms. Since the dosage of monoclonal antibody injection is usually in the range of 100mg to 600mg, and the volume of subcutaneous injection is generally limited to less than 2ml, in such cases, highly concentrated...

AI Technical Summary

Problems solved by technology

In some extreme cases, a gel-like substance may even form, which brings great challenges to the ultrafiltration membrane and the ultrafiltration equipment itself, such as the decrease in the tangential flow rate caused by the rapid increase in the pressure difference during the final concentration, and the concentration difference Polarization gets out of control until protein precipitation clogs the membrane, which inevitably leads to reduced recovery or process failure

On the other hand, even if the final high-concentration protein solution is obtained by improving the equipment or membrane type, it is difficult to put it into actual clinical application, because it needs to be sucked by disposable sterile syringe or prefilled needle for subcutaneous administration The final packaging form, and too high viscosity will reduce the sliding performance of the filled syringe, so that it cannot be manually pushed into the subcutaneous

Another difficulty in concentrating high-concentration monoclonal antibody solutions by ultrafiltration is that protein samples tend to aggregate to form soluble aggregates when highly concentrated, and further aggregate to form protein precipitates

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