Downstream processing refers to the recovery and purification of biosynthetic products, such as recombinant proteins or vaccines, from natural sources like animal and plant cells, tissues and fermentation broths. It involves a series of physical, chemical and biochemical methods to separate and purify the product of interest from other contaminants and impurities present in fermentation or cell culture harvest.
Methods Used in Downstream Processing
A variety key techniques are employed at various stages of downstream processing to achieve the desired level of purification. Some of the commonly used methods are:
Clarification and Cell Removal
The first step of Downstream Processing involves removal of cells and insoluble matter from the fermentation broth. This is done through techniques like centrifugation, hollow fiber filtration and depth filtration. Clarification helps remove unwanted whole cells, cell debris and insoluble aggregates from the solution.
Chromatography
Chromatographic techniques like Ion-Exchange Chromatography (IEX), Affinity Chromatography, Hydrophobic Interaction Chromatography (HIC) and Size-Exclusion Chromatography (SEC) are utilized to separate the target product from contaminants based on differences in their binding affinities and molecular properties. IEX separates molecules based on charge while Affinity Chromatography exploits the specific binding of target protein to immobilized ligands.
Virus Removal Filtration
Filters with pore sizes smaller than virus particles are used at this stage to remove viral contaminants. Types of virus removal filters include Planova filters and ultrafiltration/diafiltration membranes. Certain viral clearance validation steps are also performed to check effectiveness of virus removal.
Diafiltration and Concentration
Diafiltration is carried out to replace the buffers used in earlier purification steps with the final buffer needed for storage and transportation. Concentration techniques like ultrafiltration help increase the product concentration to the required levels.
Formulation and Filling
The purified protein is then formulated with suitable stabilizers, bulking agents and buffers specific to its intended use and long term stability. Final filling of the formulation is done aseptically into vials, syringes or other containers.
Quality Control Testing
Comprehensive quality control release testing of physico-chemical properties, identity, purity, potency and safety is done to ensure consistency and compliance of final drug substance with predefined quality specifications.
Advantages of Downstream Processing
Some key advantages of downstream processing in biopharmaceutical industry are:
- Yields highly purified target product suitable for clinical use and commercialization
- Maintains product quality, batch to batch consistency and reduces immunogenicity risks
- Allows separation of product from contaminants and host cell proteins which can have adverse effects
- Helps meet stringent regulatory requirements on purity, stability and safety
- Enables scale up of processes for large scale commercial manufacturing
- Improves process economics by achieving high product recoveries
Downstream processing is a vital and highly specialized part of overall bioprocessing that determines purity, yield, and stability of therapeutic proteins and vaccines. Continuous advancements in chromatography resins, filtration techniques and development of novel purification methods have significantly enhanced capabilities for manufacture of high quality biopharmaceutical products.
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About Author-
Alice Mutum is a seasoned senior content editor at Coherent Market Insights, leveraging extensive expertise gained from her previous role as a content writer. With seven years in content development, Alice masterfully employs SEO best practices and cutting-edge digital marketing strategies to craft high-ranking, impactful content. As an editor, she meticulously ensures flawless grammar and punctuation, precise data accuracy, and perfect alignment with audience needs in every research report. Alice's dedication to excellence and her strategic approach to content make her an invaluable asset in the world of market insights.
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