Method for preparing high-concentration antibody preparation through ultrafiltration concentration

Abstract

The invention belongs to the technical field of high-concentration antibody preparation, and particularly relates to a method for preparing a high-concentration antibody preparation through ultrafiltration concentration. The method comprises the following steps: 1) keeping the feeding flow rate constant, adjusting the feeding pressure and the pressure of a reflux end so as to preliminarily concentrate antibody proteins to the concentration of 50-95 mg / mL under the condition of keeping TMP unchanged; and 2) concentrating the antibody proteins to a concentration of 180-250 mg / mL or a viscosity of 30 mPa.s or more under the condition of adjusting the feeding speed to keep the transmembrane pressure TMP unchanged. Sample ultrafiltration is carried out by adopting a sequence of primary concentration-washing filtration-reconcentration, and the concentration is firstly controlled to be less than or equal to 95 g / L, so that the stability of the sample in the ultrafiltration process can be greatly improved, the process time is shortened, and the process difficulty is reduced. In addition, the flow speed is kept constant in the first stage; in the second stage, the feeding flow rate is adjusted to keep TMP unchanged, and the solution is replaced with a target buffer solution, so that the generation of sample polymers is reduced, the concentration polarization phenomenon is relieved, andthe process time is shortened.

Description

technical field [0001] The technical field of high-concentration antibody preparation of the present invention particularly relates to a method for preparing high-concentration antibody preparations by ultrafiltration and concentration. Background technique [0002] With the development of biological antibody drug therapy, the need for subcutaneous high-concentration administration is becoming more and more urgent. Especially in the field of treatment of chronic diseases, such as tumor diseases, in order to improve the convenience of medication for patients and the treatment cooperation of outpatients, it is necessary to develop antibody preparations with smaller dosage volume and higher concentration. [0003] In the production process of antibody drugs, ultrafiltration / diafiltration (UF / DF) is usually the last step in the purification process. Ultrafiltration is a membrane filtration and liquid exchange technology based on the size of the prepared antibody molecule. Memb...

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Problems solved by technology

[0007] However, the concentration method disclosed in this patent has problems such as long concentration time and affecting the stability of the antibody concentration process. The specific reasons are as follows: ①The pressure control method is to control the feed pressure, which lacks flexibility and has a constant flow rate. Corresponding adjustments were not made according to the changes in antibody concentration during the concentration process; both resulted in prolongation of the concentration process time; ②The diafiltration was performed after initial concentration to a higher concentration (200g / L), which affected the stability of the sample during the ultrafiltration process, and Due to the high viscosity of the sample and the slow flow rate during diafiltration, the process difficulty is increased and the process time is prolonged

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