Every process industry that produces utile products, be it chemical, biochemical or purely biotech based, will have a systematic process layout which gives an overall idea about the step by step procedure involved in its large scale industrial production. Generally, the bioreactor or fermenter is considered as the basis for dividing the unit operations prior to it as upstream and following it as downstream. In simple terms, the product extraction and purification steps carried out subsequent to product formation are called downstream processing. It is the most important part that decides the quality of the desired product obtained from the initial raw materials.
The same pattern applies to large-scale production of biological products too, which are nowadays extensively used for varied applications like medical diagnostics, research and development, biotransformation and also in food, pharmaceutical and cosmetic industries. In some cases, bio-products are used as crude extracts, which seldom need any purification. However, biological or biotechnology products that are used in pharmaceutical industry demand for high grades of purity and quality to meet their standards. Here is where downstream processing becomes a crucial step in the overall process. Most of the biopharmaceuticals produced are mainly proteins, which are being used in industry since almost half a century back. Blood plasma fractionation, which is purified by precipitation technique and chromatographic separation, and anti-venom antibodies and other anti-toxins are some of the examples. At present, recombinant DNA technology is used to produce a majority of the biotech products and these are purified mainly by chromatography and membrane filtration.
The different steps and unit processes used in downstream processing of biotech products highly depends on the nature of the product, the level of purification required and whether the product is intracellular or extracellular. Non-proteinaceous biomolecules like plasmids, complex polysaccharides and viruses are developed today. But, because of certain special properties of proteins like tolerance, high potency and long half-life, proteins will continue to lead in the bio-product demand. Biopharmaceutical products like antibodies, antibody fragments, and enzymes like insulin, growth factors, cytokines and erythropoietin are major products obtained from micro-organisms, animal or plant cells, etc.
In case a biological cell is not included in the production, the fermentation broth can be directly concentrated and then purified to get the final form of product. Whereas products obtained from cells can either be secreted by the cell to the surrounding medium, or formed inside the cell. The very first step in downstream processing is solid-liquid separation, in which the cells are separated from the fermentation broth. This can be done by filtration, centrifugation, sedimentation, flocculation or gravity settling. Each of these processes has unique principle by which it works to separate the solid content from liquid broth. If the desired product is extra-cellular, we can proceed to product concentration. Here, any unwanted component which has notably different property from that of the product is removed. Water is usually the main impurity. Product concentration is carried out using the unit operations like solvent extraction, ultrafiltration, adsorption and precipitation. Once the product is isolated and concentrated, next is purification, which is the most costly procedure of all. In this, unwanted components which closely resemble the product in its physical and chemical properties are removed. Highly sensitive and sophisticated equipment is essential for product purification and hence it is considered to make up a significant fraction of downstream processing expenditure. Different types of chromatography, crystallization and fractional precipitation are the highly popular and preferred methods.
When the product is intra-cellular, one more step is added after cell separation. This is cell disruption, to release the product contained within. Cells are broken by mechanical, physical or chemical methods. Applying thermal shock or adding chemicals that break the cell wall are used. One of the popular methods is ultra-sonication, in which high frequency waves are used to break the cell. After releasing the product, we can proceed with product concentration and purification, as discussed above. The last part is product polishing in which the purified product is packed into a form which is stable, easily portable and convenient to use. Crystallization, lyophilisation or spray drying can be done for this purpose. Product sterilization and removal of trace contaminants are then performed to ensure the safety of the product.
When dealing with biological or biotech products, quality is more important than quantity. And the quality of the product is decided by the purity. This requirement has led to the increased focus on the significance of downstream processing in biotech industry.
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