Simplifying Clarification and Achieving Process Intensification with a Novel Chromatographic Technology
Process intensification is the concept of making dramatic improvements to production efficiency. This definition can have broad implications. Process intensification can be approached from different pathways such as process advancements that result in increased productivity using existing equipment, lower energy and material consumption, integration of multiple process steps into a single unit operation, and replacement of current technologies with breakthrough solutions that are faster and more compact. A common thread across these strategies is the need for innovative approaches that drive substantial leaps in progress, rather than incremental improvements. The key idea of process intensification is doing more with less: producing biotherapeutics faster and more efficiently with fewer resources [4].
With increasing product titers and higher cell densities, process bottlenecks have shifted towards downstream clarification and purification operations. Multi-layer or synthetic depth filters with more retention capacity for clarification and chromatography resins with higher binding capacities have been commercialized to try to keep up with the increased impurity loads and target protein concentrations. At a certain point, process improvements with existing technologies hit a limit, and further advancements are marginal or incremental at best. Current strategies in process intensification are often focused on one of two approaches: deploying current technologies such as chromatography steps in different ways, for example by operating in continuous mode, or by adopting completely novel technologies [4]. Advanced material science and newly commercialized solutions can offer the tools needed to overcome the reported challenges and unlock the potential for improvements in productivity.
3M™ Harvest RC Chromatographic Clarifier: A Game-Changer in Process Intensification
3M™ Harvest RC Chromatographic Clarifier has been designed as an innovative solution for process intensification in clarification operations. This tool not only simplifies operations and reduces its operational footprint, but also improves purity early in the process, leading to greater efficiency.
A key feature of 3M™ Harvest RC Chromatographic Clarifier is its high porosity, with a fibrous media that offers 70% porosity compared to 30% of depth filters. This higher void volume allows for more efficient capture of cells and cell debris. Additionally, its open structure and charge-based separation can handle a wide range of particle sizes, simultaneously removing large whole cells and small soluble impurities. Traditional methods such as centrifugation and mechanical filtration, which rely on density and size, often require multiple stages that each treat a subset of particles within a certain size range. 3M™ Harvest RC Chromatographic Clarifier replaces this multi-stage clarification process with a single, efficient step.
Fewer Capsules, Greater Efficiency
In a comparative performance study with five CHO (Chinese Hamster Ovary) cultures, loading capacities of the new technology ranged from 50-140 L/m², where depth filters showed 35-75 L/m² for the combined area of the first and second stage. The average improvement in throughput was 62% [1].
Higher loading capacity equates to a decrease in the number of capsules required to process a given bioreactor volume, as well as fewer capsule holder hardware systems. Synthetic media, which has lower pre-use flush requirements than traditional depth filters, contributes significantly to reducing the water or buffer demand of the facility.
Streamlining Chromatographic Clarification with a Simplified Process
Chromatographic clarification techniques are instrumental in removing soluble impurities such as DNA or chromatin before they reach downstream columns. 3MTM Harvest RC Chromatographic Clarifier is particularly effective, reducing DNA levels to less than 500 ppb, improving the performance of the protein A capture step and alleviating the load of impurity levels on downstream processing steps.
A comparative study of 3M™ Harvest RC Chromatographic Clarifier demonstrated lower clarified cell culture fluid turbidity values than depth filtration, and lower DNA and HCP (Host Cell Proteins) concentrations, especially after the protein A column [2]. An additional study showed reduced levels of HCP impurities at each chromatography step in the process, and > 90% decrease in HCP concentration in the final drug substance when chromatographic clarification was utilized, compared to non-chromatographic alternatives [3].
Reducing the number of stages generally results in a higher target protein recovery, as every additional step causes some product loss. Due to its purely charge-based separation and effective media utilization, 3MTM Harvest RC Chromatographic Clarifier is expected to deliver a recovery of over 95%. Published case studies demonstrated recovery increases from 91% to 98% [2] and from 91% to 99% [3] if a two-stage depth filtration system is replaced by the single stage chromatographic solution. Reduced product losses result in increased drug substance output per batch, and ultimately, higher productivity with more doses produced in the same facility.
There is no doubt that chromatographic clarification delivers on the promise of process intensification. The benefits are clear – it effortlessly merges multiple steps into a single unit operation and decreases operational footprint. Its efficacy is further illustrated by its ability to improve purity, while significantly boosting productivity.
Download the brochure to learn more about 3M’s clarification and purification portfolio for mAb/recombinant protein solutions. Do not miss the opportunity to optimize your clarification operations. One step can transform your recombinant protein manufacturing process — from adopting 3M’s next gen, single-stage products, to upgrading your process for greater scalability, efficiencies and faster speed to market.
