Driving Advancements in Biopharmaceutical Manufacturing

Continuous Processes Reduce Equipment Size and Cost

Single-use tubing and bags can be used instead of costly stainless-steel for all common biopharmaceutical manufacturing scales.

Jan 06 2021

How does a PAK BioSolutions purification suite revolutionize the manufacture of pharmaceuticals? With a correctly-designed continuous purification process, a PAK Bio system can reduce capital equipment costs by as much as 50 percent compared to batch.  But how do we get there?

Continuous purification processes can be designed to reduce piping or tubing diameters over 4-fold while the batch volume and run duration are maintained (see our article on productivity). For a continuous process, all steps are run simultaneously for the duration of the batch. As a result, each process step can be completed over days or weeks rather than hours.  To process the same batch volume over a longer duration, the process flow rate is reduced. For example, if the step is run for four days instead of twenty-four hours, the flow rate can be four times lower. With lower flow rates a smaller pump and smaller piping diameters are needed. Notably, the flow rates are reduced to an extent that relatively inexpensive flexible tubing can be used instead of costly stainless-steel piping for all common biopharmaceutical manufacturing scales.

Equipment cost savings also come from 10 to 1,000-fold reduction in intermediate hold vessel volumes compared to conventional manufacturing. Since all steps of a continuous process are performed simultaneously, the entirety of the batch volume does not need to be held in a tank from the completion of one step to the start of the next. For the continuous process, a small vented vessel is placed in the flow path between steps connected in series primarily to provide a pressure break. The minimum vessel volume is only limited by the automation’s ability to maintain the vessel within a range that does not cause it to overflow or drain. With this consideration, a break vessel that has a ten-minute residence time has been shown to be sufficient for all steps with one exception. Bind and elute chromatography steps, which have periodic elutions and varying concentrations across the peak, require a vessel that can hold approximately five elution volumes and is well mixed.  This ensures that consistent material, with no notable spike in concentration, is supplied to the downstream process step.  In one scenario, a 200ml break vessel and 5L elution vessel were used for a batch that purified 1Kg mAb in four days (50L of cell culture per day) – 500-fold and 20-fold lower vessel volumes, respectively, than conventional manufacturing.

Equipment savings are most easily realized when a new facility is to be built or an existing one requires a significant upgrade; however, existing facilities can achieve measurable benefits in production outputs and consumable cost savings. Furthermore, they can serve as a demonstration of the benefits of continuous processing for future facilities that will eventually be built.

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