Downstream Bioprocessing

Downstream processing refers to the part of the process where the cell mass from the upstream process is processed to meet purity and quality requirements. Downstream processing is usually divided into three main sections: cell disruption, purification, and polishing.
Steps of downstream processing are:
Step 1

#1: Separation of Biomass

Separating the biomass (also called cell mass) from the cell culture media can be carried out by centrifugation, ultra-centrifugation or coarse filtration. If the product is biomass, then it is recovered for processing and the spent cell culture medium is discarded. If the product is extra cellular the biomass will...

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Centrifugation Filtration Discard Waste Biomass
Step 2

#2: Cell Disruption

If the desired product is intra cellular the cell biomass can be disrupted so that the product is released. Cell disruption cab be achieved through either mechanical (bead milling, homogenization, cavitation and agitation), or non-mechanical methods (osmotic shock, pH and temperature extremes, sonication, desiccation, solvents, enzymes etc.) The resulting solid-liquid...

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Mechanical Disruption Bead Milling Non-Mechanical Osmotic Shock pH/Temp Extremes Sonication Suspension Centrifugation/Filtration
Step 3

#3: Concentration of Broth

The spent medium is concentrated if the product is extracellular, or present in very low concentrations, typically by tangential flow filtration....

Tangential Flow Filtration Concentrated Spent Medium Concentrate Product
Step 4

#4: Purification of the target product

According to the physico-chemical nature of the product molecule several methods for recovery of product from the clarified cell culture broth can be used, a combination of multiple steps using tangential flow filtration, various chromatography methodologies and buffer exchange steps are needed being the most common....

Tangential Flow Filtration Chromatography Buffer Exchange Purified Product
Step 5

#5: Polishing

Is the removal of minute levels of impurities in the final phase of biopharmaceutical manufacturing. These impurities can include high molecular weight impurities, host cell proteins, DNA, viruses, and endotoxins if the production platform is based on bacteria, such as E. coli....

Polishing Filter Impurities: Proteins DNA Endotoxins Viruses Purified Product
Applications of Downstreams:

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