Advances in the development of recombined human serum albumin

The emergence of blood products originated in the 1940s and is only about seventy years old.
University E. Professor J. Cohn and his team developed a process called cryoethanol that purified human serum albumin from human blood, and the first blood product was born.
human serum albumin is the most abundant protein in human plasma, accounting for 50% to 60% of the total plasma protein, concentration of 38 to 48g/L, is the most important protein in human plasma, maintain the body nutrition and osmosis pressure, in the body has important physiological functions.
liver is about 12g of albumin per day.
HSA belongs to a single-stranded sugar-free protein consisting of 585 amino acids with a molecular weight of 66.5 kD and an isoelectric point between 4.7 and 4.9.
table 1. Human serum albumin has an important physiological effect in the body Human serum albumin is called the "golden life-saving medicine" in the blood.
human serum albumin is extracted from the blood of healthy people and can be injected directly into the patient's body, which is mainly used clinically for the following adaptations: (1) blood loss trauma, shock caused by burns; (2) maintenance treatment for patients with advanced cancer; (3) elevated cranial pressure caused by cerebral edema and injury; (4) ) edema or aspirin caused by cancer, cirrhosis and kidney disease; (5) prevention and treatment of hypoproteinemia; (6) neonatal hypermericemia; (7) auxiliary treatment of cardiopulmonary schizophrenia, burns or hemodialysis, adult respiratory distress syndrome, is a special drug for clinical first aid.
In the field of biomedicine, human serum albumin can not only be used directly by intravenously as a drug, but also as an excellent drug carrier, prolonging the half-life of the drug, achieving long-term drug stability, can also be used as a stabilizer of biological agents such as vaccines, or as a media for cells such as CHO.
serum albumin market competition pattern Because human serum albumin comes from blood products, and in china's blood resources are relatively scarce, so the price of human serum albumin is also relatively expensive.
statistics, the market size of Chinese serum albumin industry in 2018 was 23.844 billion yuan, an increase of 9.1% year-on-year.
the total number of domestic serum albumin batch issuances in 2019 (in 10g/branch size) was 47.3108 million units, an increase of 0.6% YoY, of which the number of domestic serum albumin batches issued was 19.2297 million units (-0.9%), and the imported human blood white eggs were 28.0811 million units (-0.3%).
2019, the proportion of imported human serum albumin reached 59.35 percent.
January-October 2020, a total of 48.84 million human haemoglobins were issued (in 10g/branch size), an increase of 18% year-on-year.
, the total number of domestic human haemoglobin batch issuance was 18.1 million units (YoY plus 4%), accounting for 37%, and the total number of domestic haemoglobin batch issuance was 30.73 million units (YoY plus 28%), accounting for 63%.
Figure 1. Data on the issuance of human serum albumin batches in China (10,000 units) ( 10,000 units) , from January to October 2020, among importing enterprises, Jetblyn (CSL), Grifols, Baxter, Oakett Octa-pharma has the main import market share at 11.37, 660, 656 and 5.66 million units, respectively, with year-on-year growth rates of plus 6%, plus 51%, plus 12% and plus 100%, respectively.
January-October 2020, a total of 14 domestic enterprises were approved for human haemoglobin.
, Tiantan Bio, Taibang Bio, Shanghai Lais and Hualan Bio occupied the main domestic wholesale market share, with batch issuance volume of 400, 300, 252 and 2.1 million units, respectively, with yoY growth rates of 5%, -13%, 18% and 9%, respectively, with market share of 22%, 17%, 14% and 12%.
table 2. China's main enterprises human serum albumin batch issuance data (10,000 units) the international situation of recombination of human serum albumin China's human serum albumin market has been in short supply, subject to raw plasma supply, foreign large enterprises swept the impact of domestic blood products enterprises competition is extremely fierce.
china is a large country with a large population and a strong demand for human serum albumin.
At present, the clinical application of human serum protein mainly from blood extraction, however, there may be chronic hepatitis B, AIDS and other infectious diseases factors in human blood, and even after purification process is difficult to ensure that the virus will not be brought into the product;
fact, the international attempt to produce recombined human serum albumin through genetic engineering since 1981 has not been a breakthrough for more than 30 years.
Japan's Mitsubishi Tianbian Pharmaceutical Co., Ltd. recombined human serum albumin Medway as an injection in 2008, but in March 2009, the Ministry of Health, Labour and Industry issued an order to Mitsubishi Corporation to stop manufacturing operations after test data were found to be suspected of tampering.
NOVISIN Biopharmaceuticals, a recombinant human serum albumin, was used as a medicinal accessories protection agent in Merck, USA, as a triumal vaccine, and has been widely used as a media and human stem cell culture grade product, and applied for import registration as a pharmaceutical accessories in China in 2014.
. VENTRIA BIOSCIENCE in the United States uses gene recombination to transform rice genes to express recombinant human serum albumin in rice endosperm cells and to achieve reagent sales.
domestic related enterprises that recombine human serum albumin are below to make a simple combing of the related enterprises and clinical progress of human serum albumin in domestic recombination.
01 North China Pharmaceuticals in 2011 by North China Pharmaceutical research and development of "pharmaceutical accessories grade gene recombinant human serum albumin" obtained the Hebei Food and Drug Administration "drug production license", marking the domestic gap to fill the gap in the recombinant human serum albumin technology has matured, with industrialization capacity, North China Pharmaceutical has become the third after the United Kingdom, Japan, two enterprises to achieve recombinant human serum albumin industrialization enterprises.
has completed the first phase of the recombinant human serum albumin project with a production capacity of 6 tons, and the accessories use gene recombinant human serum albumin is conducting Phase III. phase III. clinical trials in combination with the vaccine.
recombined human serum albumin for the purpose of recombination is currently sold in kg class, has not yet formed a scale of sales.
02 Wuhan Yuyuan Wuhan Yuyuan uses gene recombination to transform the genes of rice to achieve the expression of recombined human serum albumin in rice endosperm cells, and to build a production line with an annual output of 1 ton.
August 10, 2019, Wuhan Yanyuan Bio obtained FDA approval for clinical study using the biopharmaceous drug "Plant-source recombinant human serum albumin injection" developed by the rice endosperm cell expression platform.
present, plant-source recombinant human serum albumin injection in the United States completed phase I clinical study, the results show that plant-source recombinant human serum albumin has very good safety and tolerance.
has been granted 41 patents worldwide for inventions related to technology platforms and recombination of human serum albumin.
project has also received major projects from the Ministry of Science and Technology, the National Development and Reform Commission, Hubei Province, Wuhan City and other important science and technology projects.
03 Haizheng Pharmaceuticals received approval for a clinical trial of recombinant human serum albumin in 2017 and terminated the project in 2019 due to technical difficulties.
04 Tonghua Amrett Biopharmaceutical Company Tonghua Amrett Biopharmaceutical Company was established by Tonghua Dongbao Group and Shanghai Amrett Biopharmaceutical Technology Co., Ltd. a joint venture of 760 million yuan to restructure the human serum albumin project as the country's major new drug creation "three The "Double Ten Project" project, which is supported by Jilin Province, was officially completed in April 2018 as the first phase of the automated biopharmaceutical plant linked by 100,000 liters of fermentation, purification and preparation, and the phase I clinical trial was officially launched in June last year at Jilin University First Hospital.
80 healthy subjects in the 7 dose groups who were given a single dose and multiple dosages have all been admitted to the group, in good condition, without serious adverse reactions, and with good drug safety.
is currently in Tonghua City Center Hospital officially launched phase .b Phase I clinical trials.
This year, enterprises will plan to build a research and development and manufacturing in one of the recombination of human serum albumin industrial park, covers an area of 1000 acres, all up to the post-partum can produce recombined human serum albumin 100 tons, will meet 15% of the market demand.
From the beginning of research to the present, recombinant human serum albumin has gone through nearly 40 years of history, but there is still no clinical level of product market, which is mainly due to recombinant human serum albumin production problems, cost problems, scale problems, purity problems, impurities (endotoxin) detection and removal problems and other factors.
the future, with the development of modern DNA recombinant technology, large-scale culture and purification technology, recombinant human serum albumin will replace human serum albumin and become a new heavy-weight biological drug.
References to the Dynamic Report of the Securities Industry of banking in China ( 2 ) Wang Zongtai, Maninging. Recombinant Human Albumin Industry Application Research Progress. China Contemporary Medicine, 2017, 24 (19): 7-10 .