Cost Reduction and Resource Efficiency Through Single Stage Chromatographic Clarification
As described in the first Chapter of this eBook, monoclonal antibody therapeutics are being used more than ever, benefiting an ever-growing patient population. However, the cost of these biologic treatments remains significant for patients and healthcare systems alike. To improve access to these life-saving therapies, there is a pressing need to reduce their costs. One promising approach to achieve this is through process intensification, a comprehensive strategy aimed at enhancing production efficiency.
A key strategy in achieving this endeavor involves optimizing product yield. One effective way to boost the overall process recovery is by minimizing the number of process steps, as each step will inevitably cause some degree of product loss. Single stage chromatographic clarification with 3M™ Harvest RC Chromatographic Clarifier can replace a multi-stage clarification train, and typically shows a high unit operation recovery of > 95%, as shown by the data in the previous section. Consequentially, it is common to see an increase in recovery of the clarification operation by around 10%. A decrease in product loss translates to higher output of the drug substance per batch. That means the annual capacity of the facility can be increased and more doses may be produced. As a result, the cost of goods sold (COGS) per gram of product produced can be significantly lowered, making these essential therapies more affordable, paving the way for wider accessibility.
Case Study: Cost of Single Stage vs. Multistage Clarification
A published study showed a 16% reduction in COGS ($/g mAb) for the single stage chromatographic clarification compared to a two-stage state-of-the-art alternative [2]. Cost reductions were attributed to decreased operational complexity, higher loading capacity, increased recovery, lower utility demands, among others. Out of the 16% reported cost savings, 10% was attributed to the increase in product yield. This highlights the paramount role played by the improvement in product yield as the primary driver behind the observed cost efficiencies.
An additional study reported a 25% relative increase in cumulative yield at the end of the downstream process (DSP) for the novel single stage clarification approach, compared to a three-stage alternative [3]. An economic analysis showed a reduction in cost of the clarification process by 17-30%, depending on the bioreactor volume (in the range of 200 to 2000 L). An economic modeling case study performed by 3M for a hypothetical, and representative single-use facility showed a smaller yet significant reduction in COGS of 11% compared to a two-stage depth filtration system.
Sustainability Benefits
In addition to cost benefits, process intensification may also have favorable effects on certain sustainability aspects.
The fully synthetic media of 3M™ Harvest RC Chromatographic Clarifier has a reduced pre-conditioning flush need of only 25 L/m² compared to the 50-100 L/m² typically required by traditional depth filters with natural raw material components. By adopting this single stage approach, the number of capsules and total surface area may be reduced, further reducing flush volumes. One case study presented a water for injection (WFI) flush volume reduction of 76.8%, achieved by a combination of 52% reduction in total surface area and reduced volume applied per m² [1]. Given that purification of process water to purified water (PW) or WFI is energy intensive, a lower water demand can benefit the energy consumption of utility operations.
Furthermore, large surface area requirements for depth filter and membrane clarification may result in significant numbers of capsules applied per batch. The clarification operation can account for >50% of the total solid consumable waste of a single-use process. If process intensification can increase throughputs or reduce the number of stages, a reduction in the weight of consumables used can be expected.
Using Process Modeling to Understand Resource Use Efficiency
Process modeling of a hypothetical case study for a single-use facility was performed using the commercial Biosolve Process™ software package (version 9.0) from Biopharm Services Limited to show some of those effects. A scenario using 3 holders with 21 depth filter capsules was compared to using 2 holders and 14 capsules of 3M™ Harvest RC Chromatographic Clarifier. Such a reduction in the number of capsules would lower the total weight of these capsules by a third and decrease the total consumable waste of the entire process by 20%.
Finally, it is important to acknowledge that the gains in recovery and productivity can also benefit specific key performance indicators. A higher product output per batch can reduce the process mass intensity (PMI), a widely recognized indicator of process resource efficiency. The modeling results showed a decreased PMI due to a combination of lower water demand, a reduction in consumable use, and an increase in product output. These developments collectively contribute to greater process efficiency and resource optimization.
Do you want to learn more about reducing processing costs and environmental footprint with single stage clarification?
Watch this webinar from our 3M School of Purification Educational Series: Modelling of Bioprocesses to Understand Costs and Sustainability.
The 3M School of Purification is a program designed by a team of 3M technical experts, with the purpose of educating the industry on a range of important biopharmaceutical separation and purification topics. The program offers a variety of content and tools, available in a range of formats, to help you learn more about biopharmaceutical separation and purification.
