I still vividly remember my first project involving industrial centrifuges. We were developing a scale-down model for the centrifugation of mammalian cell feed streams, a task that demanded precision and patience. We painstakingly measured every angle and calculated separation efficiencies and tried to replicate the dynamics of large-scale systems in miniature. It was a deep dive into the mechanics of clarification, and I was fascinated by how much could be achieved with the right design.
Later, when we moved to pilot-scale trials, I was amazed by the speed and efficiency of clarification. While watching the feed stream clarify so rapidly felt like witnessing industrial elegance, I also recall how long it took us to clean the centrifuge after each trial.
That early experience stayed with me and shaped my perspective. It planted the seed for a deep curiosity about how we could make centrifugation more effective and practical, especially in the context of modern intensified bioprocessing.
A new chapter in bioprocessing innovation
Every therapeutic protein, such as an antibody, undergoes a series of vital steps before it reaches a patient. The story begins in a bioreactor, in which living cells act as miniature factories, producing the protein during the 'upstream' process. Once the protein is produced, the 'downstream' process begins with separating the cells from the harvest liquid by using depth filtration, a process similar to straining pulp from juice. The resulting protein-rich liquid is then enriched through purification using pre-packed chromatography columns or membrane cartridges, which remove host-cell residue and other impurities. Finally, the purified therapeutic protein is concentrated and formulated with stabilizers and excipients to ensure safety and potency in its final dosage form.
All these manufacturing processes are established and well harmonized across platforms. However, as is often the case in science, progress in one area demands evolution in another.
The challenge of intensification
At Lonza, we have recently successfully implemented an innovative intensified bioreactor production process that relies on a high concentration of ‘factory’ cells. This strategy has led to significant process improvements, including shorter production times and increased product titer that in turn reduces the cost. However, advancements in upstream processes, such as increased cell density, can also introduce additional impurities, making downstream clarification and purification more complex and challenging.
Traditionally, clinical production facilities rely on disposable depth filters arranged in a two-stage configuration to efficiently remove cells and host cell–related impurities. The first filtration stage removes intact cells, while the subsequent stage eliminates host cell derived impurities originating from the host cells. Intensified fed batch processes strain these filters. Since the filtration capacity drops, the process requires a larger filter area and causes a facility fit issue due to increased footprint. In addition, elevated levels of soluble impurities impose additional challenges in the subsequent purification steps. Water consumption increases due to the need to rinse large filter surface, driving up operational costs.
Faced with these limitations and empowered by our excitement, my team knew a smarter, more scalable solution was needed.
A breakthrough in primary separation
Motivated by these challenges, and perhaps partly fuelled by my own memories of those time-sapping centrifuge cleaning sessions, my team and I set out to find a better way. We identified a game-changing solution: single-use, continuous discharge centrifuge technology.
To counteract the impact of increased cell density, we replaced the first stage depth filter with single-use continuous discharge centrifuge technology. This technology can continuously separate cells from product-containing media, leading to enhanced overall volumetric recovery and reduced water consumption. The centrifuge’s bowl and feed zone are designed to minimize cell lysis, which can occur during the initial stage of depth filtration and can negatively impact product quality. In addition, this technology can simplify the scale-up and technology transfer activities of the primary separation stage at commercial manufacturing sites.
Looking to the future, the centrifuge will be able to process feed streams with cell densities far higher than those of the current intensified process. This ensures that the cell removal step can withstand further intensification of the production process.
For the second stage depth filters, we selected materials based on the impurity clearance efficiency, and filter capacity. These choices were aligned with the post-centrifugation filters used at the commercial stage, where stainless steel centrifuges are implemented.
Sustainability at the Core
We’re proud to be the team to implement continuous discharge, single-use centrifuge technology for the primary separation stage in intensified bioprocesses at Lonza. By seamlessly integrating this system, we’ve achieved faster throughput, gentler handling of cells, and dramatically reduced cleaning and changeover times without compromising on product quality.
Beyond performance, this solution supports our sustainability goals. By reducing water consumption and minimizing disposable filter usage, we’re lowering our environmental footprint, an increasingly important consideration in modern bioproduction.
This innovation streamlines our workflows and empowers Lonza to respond more flexibly to clinical demands, while upholding the highest GMP standards. It’s a true testament to Lonza´s commitment to advancing biomanufacturing, and we are excited to see how this solution accelerates development timelines and brings lifesaving therapies to patients even sooner.