Digging Deep into the Process of Downstream Processing

Downstream processing is concerned with the abstraction of anticipated products from the upstream biomass. It is the purification of biosynthetic products from their crude preparation like tissue solutions or fermentation broth. In the whole process, the products desired are purified and separated via the process of fermentation or enzyme reactions. The anticipated products are sensitive to temperatures and, have numerous items to distinct, in aqueous medium they are watered down, might have properties alike impurities.

Browse detailed report on Global Downstream Processing Industry Growth and Demand Forecast Report 2030

Downstream Processing means recovery of favourite products from its crude extract. For example, recovery of antibiotics from fermented broth to form to a pill form.


Downstream processing includes the purification of a precise molecule like a protein or nucleic acid from the wet biomass. The key aim is to disinfect the active pharmaceutical ingredient to make it in the form of a tablet.

Downstream Methods

Downstream processing embraces wide variety of methods of fractionation and purification.
• Filtration
• Chromatography
• Distillation
• Centrifugation and precipitation

Principles of Downstream Processing

Most significant principle of downstream processing is that one size certainly does not fit all. A blend of 2 or 3 purification techniques needs to be employed for fruitful parting of wanted product. The simplest and inexpensive separations should be carried out early in the procedure. Where exclusive and complex separations are essential, these should be run toward the end of procedure.

Downstream Process Steps

Harvesting, Cell Disruption & Clarification

The first step of downstream processing is cell harvesting and cell disruption after that clarification to eliminate insoluble and particulate matter. The first step is to harvest the cells by separating the cellular biomass from the fermentation broth. Usually attained by Centrifugation with separators or tangential flow percolation on microporous membranes.

Cell lysis

Cell lysis is attained by mechanical disturbance under pressure, releasing the desired product into the lysate. This is trailed by additional round of tangential flow filtration with the use of a better microporous membrane for eliminating the subcellular wreckage. Next step depends on whether the product is solvable or accrues as inclusion bodies.


If the product is soluble, it ends up in the illuminated permeate and can be sent to next step for product capture. If the product accrues a body incision, incessant Centrifugation can distinct the dense inclusion bodies from other particles. Other solubilizing step is needed which involves the use of strong, denaturing buffers, before protein refolding and recovery by chromatography.


The preliminary point for product capture is a fresh filtrate containing desired product and numerous different contaminants. Capturing is generally done by first chromatography designed as rough cut for eliminating many impurities. Capture or polish model approach is used where the capturing achieves most purification in one module and significantly decreases the feed volume by concurrently concentrating on the product in the flow-through.

Purification And Polishing

Purification is the removal of all contaminants and the presentation of the desired product in a homogeneous form. It involves a series of chromatography and filtration actions, polishing being the final stage of purification. It is the most challenging because of involving separating the anticipated product from impurities.

Formulation, Fill and Finish

The operation occurring subsequently to protein purification like freeing of the purified protein, melting of the bulk, formulation, sterile separation, filling, freeze dying and review are called Formulation and fill-finish operations.

Because of the increasing success of biopharmaceuticals, the demand for downstream processes is on the rise, and the total value will reach to $51 billion in 2030.