In the process of biological drug production, cell culture will be done, in cell culture, often encounter the trouble of foam, easy to lead to liquid flood running material, have to reduce the canning coefficient, reduce or stop ventilation stirring, so that fermentation efficiency and production capacity are more affected. The addition of a small amount of defoamer can effectively eliminate foam and inhibit the generation of foam, thereby increasing production capacity.
The addition of defoamers has introduced new substances to the subsequent production process, in view of the increasingly strict supervision of the national biopharmaceutical process, especially the raw materials and excipients and process control processes, it is necessary for enterprises to conduct in-depth research on the residue detection of defoamers. The application of defoamers in the field of biopharmaceuticals is mainly based on polyether defoamers and silicone defoamers.
Polyether defoamers are characterized by low toxicity, can be used for microbial fermentation, and can withstand high temperatures, high alkaline and high acidity. Silicone defoamers are characterized by: strong defoaming performance, not resistant to high temperature and acid, mainly including dimethicone, symethyl silicone oil, polyether silicone oil and so on. Micro source detection In order to objectively express the role of defoamers used in biological fermentation broth, we did a comparative test as shown in the figure below, the left is a test tube with a drop of defoamer added, and the right is a test tube without defoamer added, which can be seen more obviously, and the defoamer has a relatively strong defoaming ability.
Figure 1: Comparison of defoamers before and after use
At this stage, most of the defoamers used by domestic biopharmaceutical enterprises are imported from abroad, for the types of defoamers, defoamer components, system composition does not have a complete concept, the entry inspection of materials does not have a sound quality management system document, while defoaming as an important link in the biological fermentation process, inevitably the introduction of new substances, in order to control, it is necessary to conduct in-depth research on defoamers, micro-source detection using instrument resource advantages, rich industry experience, developed a set of biological fermentation liquid in the defoamer residue detection and analysis methods, and passed the verification work.
Figure 2: Typical pattern of blank solution
Figure 3: Typical atlas of the control solution
The sample injection volume of the test product under this method is 10uL, and the quantitative limit of defoamer (bubble enemy) can reach 20ug/mg, which can meet the requirements of the degree of separation, and the defoamer residue in the biological fermentation broth can be effectively detected.
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