Looking at the development of biopharmaceutical separation and purification technology from CISILE 2014
Instrument Information Network News In recent years, the development center of the global pharmaceutical market has gradually shifted from small molecule chemical drugs to large molecule biopharmaceuticals. It is expected that by 2020, global biopharmaceutical sales will reach 140 billion US dollars, and the proportion of global biopharmaceutical sales will exceed one-third. Major multinational pharmaceutical companies have continued to expand their investment in biopharmaceuticals. For example, in 2013, Roche announced that it planned to invest 800 million Swiss francs in the production of global biopharmaceuticals. In 2014, Samsung announced that it would enter the biopharmaceutical market with an investment of at least US$2 billion.
One of the important technologies affecting the development of biopharmaceuticals today is separation and purification technology. Kong Shuangquan from Beijing Science Sun Pharmaceutical Co., LTD. Co., Ltd. analyzed the characteristics of existing separation and purification technologies used in the biopharmaceutical industry and the development of emerging purification technologies at the CISILE 2014 "Drug Purification and Detection Technology Special Forum". From a mechanism perspective, the current separation and purification technologies in the biopharmaceutical industry mainly fall into five categories: separation and purification technologies based on solubility differences, separation and purification technologies based on differences in molecular size, separation and purification technologies based on differences in selective adsorption, separation technologies based on different charges, and separation technologies based on differences in affinity to ligands. Taking separation and purification technologies based on solubility differences as an example, they mainly include salt solution and salting out method, organic solvent precipitation method, isoelectric point method, aqueous two-phase extraction method and reverse micelle extraction method. Each method has its own obvious characteristics or suitable objects for separation.
It is learned from the report that there are four commonly used membranes in current membrane separation technology: microfiltration membranes for the separation of bacteria and viruses; ultrafiltration membranes for the separation of proteins and peptides; nanofiltration membranes for the separation of antibiotics, synthetic drugs, nucleotides, and inorganic salts; and reverse osmosis membranes for the analysis of inorganic salts. From the perspective of purification strategies, the separation and purification of biopharmaceuticals is mainly divided into four stages: sample preparation (crushing, filtration and centrifugation), crude extraction (separating, concentrating and stabilizing samples), intermediate purification (removing most impurities) and fine purification (high purity). Currently, the more mature biological separation and purification technologies such as IEX and HIC have different characteristics.
Factors affecting the industrialization of separation and purification mainly come from equipment and separation media. Currently, the equipment used in the purification industry of biopharmaceutical companies mainly includes GE AKTA Pure protein chromatography purification system, high-resolution analysis and preparation platform-BioLogic DuoFlow medium and high-pressure chromatography system, and Beijing Innovation Tongheng third-generation industrial production HPLC system; separation media mainly include BIO-RAD Company's high-pressure resistant chromatography media suitable for industrialization-UNOsphere SUPrA affinity media and UNOsphere Q Anion exchange media, preparation of chromatography media using perfusion chromatography technology - POROS colloid is a filler for perfusion chromatography technology and PALL company's HEA and PPA HyperCelTM mixed mode fillers. Based on the pursuit of high throughput and high resolution in biopharmaceutical purification, separation and purification technologies have also been rapidly developed. There are three main types: first, expanded bed adsorption technology, which combines the three steps of clarification, concentration and product capture, and has been well developed in the separation and purification process of genetic engineering products; second, radial membrane layer Due to the large cross-sectional area of the flow direction, this technology has the characteristics of fast purification speed, large processing capacity, and the ability to increase the sample loading simply by changing the column length, which is conducive to scale-up production; third, displacement chromatography technology, compared with traditional elution chromatography technology, its obvious advantages are high sample loading, high yield, high resolution, easy operation, etc.
At present, the equipment for biopurification technology is mainly based on GE's AKTA system. It is understood that this product has a global market share of about 90% in biopharmaceutical companies, and the share of China's biopharmaceutical market is nearly 100%. Relevant news shows that domestic research institutions and instrument manufacturing companies have begun the research and development of biological purification equipment products and have entered the late stage of research and development. Today, with the rapid development of biopharmaceuticals, biological purification equipment will also develop rapidly. (Written by Yang Gaixia)