In Vitro Diagnosis (IVD) refers to extract blood, body fluids, tissues and other samples from the human body, and use in vitro testing reagents and instruments to test and calibrate the samples, which are divided into three major categories according to the methodology: biochemical diagnosis, immunological diagnosis and molecular diagnosis.
The IVD market volume is very large, among which chemiluminescence technology in immunodiagnostics is the most advanced technology in the sub-sector due to its advantages of high sensitivity, wide linear range, accurate quantitative detection, stable results, small error and easy operation, occupying more than 70% of the share of immunodiagnostics, and the annual market growth rate is over 30%.
However, the domestic chemiluminescence diagnostic market, Roche, Abbott, Danaher and Siemens, the four giants occupy more than 70% of the share, the other brands only account for a small share, most are still on the road of research and development. During chemiluminescent diagnostic reagents development process, how to improve the sensitivity and increase the kinetic range? How to avoid false positives, false negatives or other non-specific interference? How to improve stability and reduce inter-batch variation? The answer is to start strict control from upstream raw materials and select high-quality and stable diagnostic reagent raw materials.
As the most abundant protein in plasma, albumin is the transport carrier of hormones, lipids and free fatty acids, and widely used as an important raw material in diagnostic reagents because it can reversibly bind many substances. Its effects are as follows.
1. As a stabilizer
Albumin is a macromolecular stabilizing protein that binds antibodies, antigens or enzymes to make these sensitive components more stable under proteolytic and denaturing conditions.
2. As a Sealing Agent
Albumin can be used as a blocking agent against non-specific solid-phase interference in immune reactions and is used to seal non-specific binding sites in immune reactions.
3. As a carrier protein
Ligands bound by albumin include fatty acids, cationic and neutral detergents, acetylcholine, ascorbic acid, penicillin, thyroxine, digitalis, hormones, metal ions, bilirubin, sugars, etc.
4. As a plasma matrix
Albumin is used in conjunction with PBS to simulate human plasma in certain index tests, to prepare standard control solutions, and to determine standard curves
5. As a buffer/co-mixer
Albumin can be used as a good buffer component or as a co-mixing reagent to release bound components into the reaction mixture and can adsorb impurities from the medium.
Albumin includes human serum albumin (HSA) and bovine serum albumin (BSA), of which human serum albumin is divided into natural plasma derived human serum albumin (pHSA) and recombinant human serum albumin (rHSA). Are all these albumins good raw materials for diagnostic reagents? Of course not!
Natural plasma derived human serum albumin (pHSA) is extracted from human plasma by low-temperature ethanol protein separation and treated with virus inactivation. In addition to albumin, there are many kinds of fatty acids, lipids, hormones and growth factors, and there are large inter-batch differences between different batches of pHSA from different manufacturers, which can interfere with the detection of certain indicators and bring batch volatility to the finished diagnostic reagents. Another important point is that pHSA, as a clinical shortage drug, is not easy to buy in large quantity and is often out of stock.
Bovine serum albumin (BSA), also known as the fifth component, is usually an accessory product after the slaughter of beef and is also obtained by ethanol precipitation. The quality of BSA varies from manufacturer to manufacturer, from batch to batch from the same manufacturer. Usually, the purity of BSA (SDS-PAGE) is less than 95%, the color of BSA lyophilized powder is yellowish, the odor is heavy, and the content of hormones and heavy metals is high, which may cause greater interference when used in diagnostic reagents, and the great batch-to-batch difference will certainly cause the quality fluctuation of finished diagnostic reagents.
The plant-derived recombinant human serum albumin (OsrHSA) expressed through rice endosperm cell-specific efficient expression platform OryzHiExp, used in in vitro diagnostic reagents, has the following advantages.
1. Higher purity
OsrHSA purity is more than 99% (SDS-PAGE), non-animal source, less impurities, which used in diagnostic reagents can avoid non-specific interference.
2. Better stability
OsrHSA has the same raw material source and large capacity in a single batch, so it can be used for diagnostic reagents to reduce batch volatility.
3. More stable supply
OsrHSA has achieved mass production with annual capacity of i metric-ton or more, which can supply in large quantity and stably, and diagnostic reagent manufacturers have no risk of stock out.
4. Better protection effect
OsrHSA has better protection effect on sensitive substances such as enzymes and antibodies/antigens than BSA, which in turn enhances the stability of diagnostic reagents.
Wuhan Healthgen Biotechnology Co., Ltd (hereinafter referred to as "Healthgen Biotech") is committed to the researc h and development of a series of protein products using the "rice endosperm specific expression platform",. It has established a complete industrialized system of plant biopharmaceuticals in China, and initially formed an internationally renowned biopharmaceutical enterprise focusing on biopharmaceuticals research and product development of plant systems.
The plant-derived recombinant human serum albumin (OsrHSA) independently developed by Healthgen Biotech was approved by the National Food and Drug Administration (CFDA) (Now National medical Products Administration, NMPA) to enter clinical research on April 28, 2017, and again approved by the U.S. Food and Drug Administration (FDA) to enter clinical research on August 10, 2019. Plant-derived recombinant human serum albumin is the first class I innovative drug based on rice endosperm cell bioreactor production in China and even internationally, and has finished the clinical trials phase I in U.S. and is currently undergoing clinical trials phase II.
In addition, there are a series of recombinant growth factors and recombinant proteins, such as recombinant human basic fibroblast growth factor (OsrhbFGF), recombinant human epidermal growth factor (rhEGF), recombinant human insulin-like growth factor (rhIGF-1 LR3), recombinant human vascular endothelial growth factor (OsrhVEGF), recombinant human keratinocyte growth factor (OsrhKGF), recombinant human lactoferrin (OsrhLF), recombinant human serum albumin (defatted) OsrHSA (Fatty acid free). The production system has been certificated by ISO certification and is complianced with GMP production.