by Downstream bioprocessing refers to the recovery and purification of biosynthetic products or biotherapeutics such as vaccines, recombinant proteins, monoclonal antibodies etc from the culture medium in which living cells have grown or fermented. It involves a series of unit operations such as centrifugation, filtration, chromatography etc to separate, purify and concentrate the product of interest from other contaminating substances like host cell proteins, DNA, and media components. The purified product is then formulated to meet specifications for quality, stability and activity before being sent for filling into vials, cartridges or other final containers.
Advantages Of Single Use Systems
Traditionally, downstream processes employed stainless steel equipment which required cleaning and sterilization between each manufacturing cycle. This was a time consuming process adding to production timelines. Single use or disposable systems address this issue by utilizing plastic bags, tubing, filters and connectors designed for single batch use. They eliminate the need for cleaning and sterilization between batches. This provides significant advantages:
– Reduced time to manufacture – Without clean-in-place and sterilize-in-place cycles, single use systems allow switching between products much faster. This accelerates clinical and commercial manufacturing.
– Flexible operations – Single use skids and modular assemblies are easy to assemble and reconfigure. This provides flexibility to run multiple smaller batches or quickly switch manufacturing campaigns.
– Reduced costs – At small and intermediate scales, single use systems are economically viable and reduce capital expenditure on large stainless steel equipment which need higher utilization to be profitable.
– Limited cross-contamination – Eliminates risks of carryover of process residues and product between cycles which is a possibility with stainless steel equipment. This is especially important when producing different products in the same facility.
– Simplified facilities – Without the need for large process equipment, single use systems require smaller footprints for operation and support areas like CIP facilities. This lowers facility construction and maintenance costs.
Centrifugation And Depth Filtration
Two key unit operations in downstream processing are centrifugation and filtration used for clarification and intermediate concentration/purification of biomolecules. In centrifugation, impurities are separated from the target product based on density/size differences under the influence of centrifugal forces generated in the equipment. Traditionally, centrifuges were large stainless steel designs. Single use counterparts available now include disposable centrifugation tubes/bowls and centrifuge separators utilizing centrifugal or tangential flow designs in plastic cassettes.
Depth filtration using membrane filters is another workhorse operation to remove cells and fine particulate matter. It relies on a size based sieving mechanism wherein impurities larger than pore size of membrane are trapped at the surface while target product passes through. Single Use Downstream Bioprocessing containing hollow fiber or stacked sheet membrane filters are now commonly used. They provide sealed, pre-sterilized systems integrated with tubing manifolds eliminating process hold times.
Chromatography
Chromatography techniques are the workhorses of downstream purification employing principles of selective adsorption to separate product from impurities. Main types used are ion exchange, hydrophobic interaction, affinity and size exclusion chromatography. Traditional columns were stainless steel pressure vessels containing resins while single use versions now available include plastic chromatography columns, cartridges and pre-packed minicolumns optimized for bind-and-elute or fluidized bed chromatography.
Single use loaded with chromatography resins enable fast, modular processing within compact footprints. Skid mounted pre-packed columns connected with single use tubing, connectors, vent filters and sensors form self-contained disposable chromatography systems supplementing or replacing traditional equipment. Besides capital and operational benefits, they help accelerate clinical and commercial manufacturing through rapid process development and scale up while maintaining product quality.
Filtration And Viral Clearance
Nanofiltration and viral retentive ultrafiltration are important steps to remove viruses, remove and concentrate product while exchanging buffers before finishing filtrations and filling. Hollow fiber cassettes containing various ultrafiltration/diafiltration membrane types optimized for throughput and retention capacities have become popular single use options.
Their planar design allows high surface area in compact footprints. Integrated sensors monitor process parameters like pressure, flow and conductivity. Together with single use tubing and connectors, they form closed self-contained viral retentive filtration skids eliminating hold times for cleaning validations. Despite lower longevity, their low cost, rapid deployment and reduced facility requirements make them economically viable at smaller commercial scales.
Formulation, Filling And Storage
Final single use filtration using sterilizing grade membrane filters further clarifies product before aseptic filling lines. Disposable bags, tubing manifolds, fittings and filters have enabled closed transfer of purified drug product to the filling isolators. Likewise, storage containers like pre-filled syringes, vials or bags minimize risk of contamination compared to traditional stainless steel tanks requiring cleaning. Single use containment together with disposable filling lines, accessories and stoppers enable sterile processing while eliminating cleanup validations. Overall, such integrated single use processing trains have boosted biomanufacturing flexibility, speed, and responsiveness.
The single use downstream bioprocessing using disposable plastic bags, tubing, filters and pre-assembled modular systems has significantly benefited the development and production of biologics by reducing timelines, capital costs, production volumes and changing regulatory expectations. By incorporating advanced sensor technology, single use systems promise further opportunities to optimize processes with real-time data acquisition and process analytical techniques. They have emerged as the technology of choice especially for clinical and smaller commercial manufacturing by speeding product availability.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
About Author - Money Singh
Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemicals and materials, defense and aerospace, consumer goods, etc. LinkedIn Profile
