Now you know what upstream processing is, what happens once you’ve expanded the cell culture and product formation? Is that it? The short answer is NO! You can’t just give the cell broth to someone! The cell broth produced after upstream processing contains cells, product impurities (improperly folded product, product that has been modified in some way), media components, cell debris, etc. This stuff is potentially dangerous to the end user, and is also likely to cause the product to degrade quicker, leading to crappy storage.
In order to create a pure, consistent, safe and defined product, we must isolate it from the rest of the cell broth. This is called downstream processing. Downstream processing consists of various unit-operations in which the product is isolated and purified, producing a bulk drug substance (where the majority of the mass is the product). Fill/finishing (where more impurities are removed and excipients are added to improve long-term stability / change the state of the product to allow storage and transport) then produces the drug product from the bulk drug substance.
*In most cases, for FDA / regulatory body approval, the product needs to be at 95% purity, and majority of impurities must be less than 1 part per million in the final drug product.
Downstream processing unit operations can be split into 4 categories based on their purpose:
- Recovery: Initial isolation of the product from other components of the cell broth. Unit operation examples: centrifugation, filtration.
- Isolation: Further isolation of the product from cell broth components. Unit operation examples: precipitation, capture chromatography, liquid-liquid extraction.
- Purification: Removal of impurities/ other remaining non-product components. Unit operation examples: Crystallisation, Polishing chromatography.
- Fill/Finish: Removal of remaining impurities + preparing drug product for storage and transport. Examples: Ultrafiltration, nanofiltration, freeze-drying.
After downstream processing and fill/finish, the product can now be used!
If you have any questions, please leave a comment below and I will get back to you ASAP
Bioprocessing Explained 