Biotechnologies use resources from living organisms and genetic modification (cell lines, DNA, clones, etc.) to discover and manufacture macromolecules (proteins, antibodies, bispecifics, etc.) which could lead to new innovative treatments in many diseases (oncology, neurology, immuno-inflammation, etc.).
Biomedecines have a complex structure and are bigger molecules compared to a chemical drug substance which is small in size and has a simple molecular structure.
To allow reproducible and reliable therapeutic results for patients, it is essential to perfectly master the manufacturing process development of sterile macromolecules, in accordance with the required quality criteria.
Let’s have a closer look at how a biomedecine is manufactured
1: cell culture – also referred to as upstream process
Cells that manufacture the therapeutic molecule or protein stored at low temperatures are cultured in vials to multiply in the presence of nutrient culture environment.
As and when the number of cells increases, they are transferred into bigger and bigger bioreactors. This process is known as the Scale-up. During this step, the cells produce antibodies, the active ingredient of the future medicine.
The cells are harvested from the bioreactors and separated from the culture medium by a filtration stage or centrifugation.
The filtrate (from filtration) or supernatant (from centrifugation) is then isolated in order to purify the product. The product of interest, the protein, is mixed with numerous impurities (cell debris, constituents of the culture medium, etc.), so a series of purification steps are then carried out.
Step 3: purification – also referred to as downstream process
Purification is a complex and critical process to remove all impurities and contaminants by adjusting the concentration of the active substance in a formulation buffer allowing stabilization.
The BDS (Bulk Drug Substance) obtained will be packaged in pouches or bottles, then refrigerated or frozen, while awaiting the final step, aseptic filling (fill and finish).
Step 4: Fill& Finish
The product is transferred into suitable containers (syringes, vials) under sterile conditions. At that time, the finished product is in a form administered to man and will have to pass many tests of quality before it can be marketed.
The analytical/quality control laboratory analyses samples taken at each stage of the manufacturing process to make sure the quality of the product released follows the criteria defined by the specifications established during the development phase.