Biologics Manufacturing Processing Steps
By Mike Barlow, Paul Van Buskirk
Typical biologics manufacturing involves culturing cells in bioreactors (upstream processing) to produce the target protein, followed by harvesting to separate cells from the product-containing broth. The product is then purified through downstream processing methods like filtration and chromatography. Finally, it's formulated with stabilizers, filled into sterile containers, and undergoes quality testing before release.
How Biologics Are Made: A Look at the Manufacturing Process
Biologics—therapies made from living cells—require a carefully controlled manufacturing process to ensure safety, quality, and effectiveness. Below is a streamlined overview of the major steps involved:
Upstream Manufacturing: Growing Cells for Protein Production
Biologics manufacturing starts by growing genetically engineered cells in a series of bioreactors:
- Vial Thaw: Frozen cell banks are thawed to start a new production run.
- Shake Flask Expansion: Cells are transferred to shake flasks with nutrient-rich media to begin multiplying.
- Expansion Train (N-2, N-1 Stages): Cells are scaled up through
progressively larger bioreactors, optimizing growth conditions. - Production Stage (N Stage): The main bioreactor, where cells reach peak density and produce the target protein.
- Harvest: The culture is clarified to separate cells from the protein-rich broth. Viral inactivation typically occurs here as a safety measure before moving to downstream steps.
Downstream Manufacturing: Purifying the Protein
After harvest, the focus shifts to purifying and formulating the therapeutic protein:
- Chromatography: Proteins are purified through techniques like affinity, ion exchange, and size exclusion chromatography. Multiple steps are often combined in a chromatography train to remove impurities and achieve required purity levels.
- Viral Filtration: Specialized filters remove potential viral contaminants.
- Tangential Flow Filtration (TFF): Concentrates the protein and exchanges buffers to prepare for formulation.
- Bulk Drug Substance (BDS) Fill: The purified protein is filled into containers for storage and transport.
- Final Fill: The drug substance is filled into its final form—vials, syringes, or cartridges—ready for patient use after passing final safety and quality checks.
Tags
#Biologics
