Mark Schofield, director, R&D, and Nick Marchand, senior manager, Cytiva, share how modern filtration innovations are driving intensified bioprocessing, boosting efficiency, and supporting sustainability across emerging modalities.
Cytiva
Filtration is woven into every bioprocess - from small-scale lab workflows to quality critical steps in GMP manufacturing. It protects patients by removing harmful contaminants, and it keeps processes efficient by separating what is needed from what is not. Its longstanding reputation for reliability and simplicity - fluid in, fluid out - belies its strategic importance.
Nearly every major shift in bioprocessing - rising titers, single use technology, new modalities, continuous operations, and growing sustainability expectations - has required filtration to evolve. As organisations intensify and modernise manufacturing, filtration is no longer a background utility. It is an essential enabler of agility, productivity, and quality.
Filtration and the move toward intensified operations
Process intensification (PI) is about achieving more with less: higher productivity, smaller footprints, faster changeovers, and lower environmental impact. In filtration, intensification often means using smaller devices with higher capacity and flexible flow rates to accommodate faster processing or alternatively continuous processing with long durations. Modern filters routinely deliver five to tenfold performance gains over previous generations, directly accelerating upstream and downstream operations.
The industry’s move toward single use technology has amplified this effect. Single use systems eliminate non value added elements - cleaning, steaming, and validation - while shortening turnaround time and enabling flexible, closed operations. Filtration plays a central role in this shift. While membranes have long been single use, the evolution from stainless steel housings to fully integrated capsule based assemblies made single use truly plug and play.
Automation has pushed this transformation further. Operations once performed manually - filter flushing, integrity testing, and changeovers - are now built into automated skids or turnkey systems. This reduces operator variability, improves compliance, and supports leaner, more efficient processes. Pre-Use Post-Sterilisation Integrity Testing (PUPSIT) is critical for mitigating risk in aseptic processing, ensuring that sterilising-grade filters are not damaged during handling or sterilisation before product contact. It acts as a key safety check, mandated by EU GMP Annex 1, to confirm filter integrity, prevent contamination, and ensure final drug safety.
Keeping pace with modern upstream and downstream demands
Upstream productivity has increased dramatically, with today’s cell cultures producing up to ten times the titers achieved in early monoclonal antibody (mAb) processes. While this drives efficiency, it also increases solids, debris, and host cell contaminants—placing higher demands on clarification. Depth filtration technologies have evolved to handle these denser feeds, and single use formats are now the preferred choice for easy scaling and integration.
Perfusion and intensified seed train strategies push filtration even further. Hollow fibre tangential flow filtration (TFF) filters enable continuous cell retention at high densities, supporting long duration perfusion runs and productivities that would otherwise require much larger reactors. Gas and vent filters have also advanced to maintain sterility and airflow in high density environments.
Downstream, single pass TFF (SPTFF) represents a step change. Traditional TFF recirculates product, adding shear and extending processing time. SPTFF operates inline without recirculation or hold tanks, reducing shear and increasing yields. This isn’t just a continuous process technology; it can increase process efficiency in batch operations too. Inline concentration, such as precapture concentration, can helps synchronise upstream productivity with downstream facility capacity.
Higher concentration formulations introduce new challenges. More than one third of approved mAbs exceed 100 g/L, and many products target 150–200 g/L. These viscous feeds can overwhelm traditional sterilising grade filters, resulting in large filter trains, long process times, and product loss. Next generation asymmetric membranes, such as Supor Prime filters, deliver three to fivefold higher throughput, enabling smaller systems and protecting yield when every gram matters.
New challenges in virus safety, including virus breakthrough resulting from low pressure or depressurisation (stop and start) and complexities of intensified or fully continuous processes, are now better understood. Modern virus filters, such as the Pegasus Prime filters, are designed to maintain retention at low pressure and even after interruptions, supporting both batch and extended continuous processes without added risk.
Sustainability as an operational imperative
Sustainability has moved from aspiration to operational requirement. Many innovations that support intensification also advance environmental performance.
Higher capacity filters allow for smaller systems, reduced plastic use, lower packaging needs, and lighter shipments—direct benefits for Scope 3 emissions. Intensified operations reduce buffer consumption, energy use, and process time, supporting Scope 1 and Scope 2 objectives. These improvements reinforce the trend toward smaller, more flexible facilities with lower resource demands.
The industry is also responding to increased scrutiny of per and polyfluoroalkyl substances (PFAS). Hydrophilic PES membranes used in many liquid filters are PFAS free, while hydrophobic PVDF and PTFE membranes used in gas filtration do contain PFAS due to performance requirements. Regulatory pressure is encouraging innovation, but well structured risk assessments may continue to support PVDF in essential applications where performance, controlled manufacturing, and safe disposal minimise exposure risk.
Filtration materials and designs will continue to evolve as regulations develop—just as they have across every major shift in bioprocessing.
Beyond mAbs: filtration for emerging modalities
Filtration innovation must now keep pace with gene therapies, mRNA platforms, and cell based therapeutics—modalities that challenge traditional separation boundaries.
Lentiviral vectors (LVVs), ~ 0.12 µm in size, approach the lower limit of bacterial contaminants. This size proximity can cause meaningful yield loss during sterile filtration. In contrast, smaller adeno associated viruses (AAVs) transmit more readily through 0.2 µm filters.
Virus safety strategies for these modalities also look different. AAV is close in size to the model viruses used to validate 20 nm virus filters, making those filters unsuitable for AAV processes. Instead, 50 nm virus filters can remove larger adventitious viruses—such as retroviral particles—while still enabling high AAV recovery. To maintain virus safety there has been a focus on virus removal via chromatography steps and pre-filtration of culture media and process buffers to maximise risk reduction while ensuring that cell culture performance is not impacted.
A strong contamination control strategy pairs these filtration choices with upstream safeguards: 20 nm filtration of media containing animal origin materials, closed single use processing, and alignment with standards such as ICH Q5A(R2). As regulations for new modalities mature, early collaboration between therapy developers and filtration experts will be essential.
Filtration also protects critical quality attributes. Liposomal formulations can deform under certain membrane structures, increasing the risk of bacterial penetration. Lipid nanoparticles (LNPs) can shift in size distribution if filtration is not properly optimised. Early, data driven filter selection helps prevent late stage validation challenges.
Expertise: the differentiator for future ready processes
Filtration is easy to overlook—until it becomes the bottleneck. As processes intensify and diversify, filtration’s influence on yield, robustness, and compliance grows. The right filtration strategy unlocks performance across the workflow; the wrong one can create unnecessary constraints.
Access to expert guidance accelerates development, prevents downstream complications, and helps teams make informed decisions that balance performance, cost, and sustainability. When filtration is considered early, and integrated into broader process design, it becomes a strategic asset.
In a landscape defined by new modalities, rising productivity, and sustainability goals, filtration remains foundational and increasingly forward looking. As organisations build the next generation of bioprocesses, filtration innovation - and the expertise behind it - can be a powerful catalyst for long term success.