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Purpose Cleanrooms are highly controlled enclosed rooms where air quality is monitored and ensured to have less contamination according to standard cleanliness level. Air filters are used to optimize indoor air quality and remove air pollutants. Filter media and filtering system are decided as per requirement. Depth filter media are mostly used in cleanroom filtrations. This paper aims to present a comprehensive review of the evolution of cleanroom filter media. It evaluates the advantages and disadvantages of air filter media. It is also studied which air filters have additional properties such as anti-microbial properties, anti-odour properties and chemical absorbent. Development and innovation of air filters and filtration techniques are necessary to improve the performance via the synergistic effect and it can be a possible avenue of future research. Design/methodology/approach This paper aims to drive the future of air filter research and development in achieving high-performance filtration with high filtration efficiency, low operational cost and high durability. Air pollutants are classified into three types: suspended particles, volatile organic pollutants and microorganisms. Technologies involved in purification are filtration, water washing purification, electrostatic precipitation and anion technology. They purify the air by running it through a filter medium that traps dust, hair, pet fur and debris. As air passes through the filter media, they function as a sieve, capturing particles. The fibres in the filter medium provide a winding path for airflow. There are different types of air filters such as the high-efficiency particulate air filter, fibreglass air filter and ultra-low particulate air filter. Findings Emerging filtration technologies and filters such as nanofibres, filters with polytetrafluoroethylene membrane are likely to become prevalent over the coming years globally. The introduction of indoor air filtration with thermal comfort can be a possible avenue of future research along with expanding indoor environment monitoring and improving air quality predictions. New air filters and filtration technologies having better performance with low cost and high durability must be developed which can restrict multiple types of pollutants at the same time. Originality/value The systematic literature review approach used in this paper highlights the emerging trends and issues in cleanroom filtration in a structured and thematic manner, enabling future work to progress as it will continue to develop and evolve.

Two samples of multi-layered depth filter media and single layers were prepared for this study. Filtration performance of these samples was evaluated using lab scale test unit with KCl as test aerosol. Filter media samples were composed of three layers, two of them of meltblown fiber layers and one of thermal-bonded microfiber layer. A commercial filter media was used as reference sample to compare the filtration performance. Quality factors were calculated in addition to evaluate the overall filtration performance of the new composite filter media. The results indicate a satisfactory filtration efficiency of the media M2U, over 90% for the studied particle size range. Compared to reference media, new media M2U shows better performance, especially for the particle size greater than 50 nm. Charged (M2U) and uncharged (M2U-2) composite media were tested and results compared with theory calculations. Due to upstream layer of high packing density, the loading tests reveal a tendency of clogging for media M2U. Both media, M1U and M2U, exhibit better filtration performance compared to the reference media RefM and could be applied for collection of nanoparticles in HVAC system by replacing the high grade efficiency filters.

This work introduces novel scenarios for the breakthrough curve modeling of an adsorption column/depth filtration hybrid system. Four well-known theoretical breakthrough models including Thomas, Adams–Bohart, Yoon–Nelson, and BDST were employed to describe the normalized concentration profiles. In the first approach, the theoretical models were combined for better estimation of the breakthrough curves and the Thomas/Yoon–Nelson and Thomas/BDST combinations were obtained as the best extensions. In the second approach, an adsorption-transport model was developed for the depth filter to obtain the transient concentration gradient across the filter medium thickness. The model was then combined with the theoretical breakthrough models to predict the adsorption column breakthrough curves. Results revealed that a decrease in the feed flowrate and filter pore size could intensify the concentration polarization on the filter surface. Both model extensions could successfully approximate the breakthrough curves of the hybrid system with more than 99% agreement with the experimental data, while the prediction accuracy of the original breakthrough models seldom exceeds 93%.

Bioprocess intensification can be achieved through high cell density perfusion cell culture with continuous protein capture integration. Protein passage and cell retention are commonly accomplished using tangential flow filtration systems consisting of microporous membranes. Significant challenges, including low efficiency and decaying product sieving over time, are commonly observed in these cell retention devices. Here, we demonstrate that a macroporous membrane overcomes the product sieving challenges when comparing to several other membrane chemistries and pore sizes within the microporous range. This way, variable chromatography column loading is avoided. The macroporous membrane yielded a 13,000 L/m2 volumetric throughput. The membrane's cut-off size results in an increased permeate turbidity due to particles passage, such as cell debris, through pores ranging from 1 to 4 µm. In addition, successful chromatography column plugging mitigation was achieved by employing depth filtration before the chromatographic step. Depth filtration volumetric throughputs were between 600 and 1,000 L/m2 . Combing a macroporous cell retention device with a depth filter not only provided an alternative to address the challenge of undesired long protein residence times in the bioreactor due to product sieving decay, but also exhibited a throughput increase, making the integration of multicolumn capture chromatography with a perfusion cell culture a more robust process.

Textile industry production processes generate one of the most highly polluted wastewaters in the world. Unfortunately, the field is also challenged by the availability of relatively cheap and highly effective technologies for wastewater purification. The application of natural zeolite as a depth filter offers an alternative and potential approach for textile wastewater treatment. The performance of a depth filter treatment system can be deeply affected by the column depth and the characteristics of the wastewater to be treated. Regrettably, the information on the potential of these filter materials for the purification of textile wastewater is still scarce. Therefore, this study investigated the potential applicability of natural zeolite in terms of column depth for the treatment of textile wastewater. From the analysis results, it was observed that the filtration efficiencies were relatively low (6.1 to 13.7%) for some parameters such as total dissolved solids, electrical conductivity, chemical oxygen demand, and sodium chloride when the wastewater samples were subjected to the 0.5 m column depth. Relatively high efficiency of 82 and 93.8% was observed from color and total suspended solids, respectively, when the wastewater samples were subjected to the 0.5 m column depth. Generally, the 0.75 m column depth achieved removal efficiencies ranging from 52.3% to 97.5%, whereas the 1 m column depth achieved removal efficiencies ranging from 86.9% to 99.4%. The highest removal efficiency was achieved with a combination of total suspended solids and 1 m column depth (99.4%). In summary, the treatment approach was observed to be highly effective for the removal of total suspended solids, with a 93.8% removal efficiency when the wastewater was subjected to the 0.5 m column depth, 97.5% for 0.75 m column depth, and 99.4% for 1 m column depth. Moreover, up to 218.233 mg of color per g of the filter material was captured. The results derived in this study provide useful information towards the potential applicability of natural zeolite in the textile wastewater treatment field.

Depth filtration-based harvesting is widely used in mAb manufacturing to remove cell and process-related impurities. However, it has not been studied on control of product-related impurities, which are very critical for product quality. In this article, we studied the interactions of depth filter with high and low molecular weight species (HMWs and LMWs) for their direct removal from cell culture. The process parameters (filter, loading, temperature, and flux) were evaluated for adsorption of HMWs and LMWs by depth filters. The adsorption is significantly dependent on filter media and loading capacity and is mainly on the basis of hydrophobic interaction during harvesting. The HMW and LMW species were characterized as HMW1, HMW2, LMW1, and LMW2. The increasing binding from LMW2 to LMW1, HMW1, and HMW2 is correlated with their increasing hydrophobicity score. Adsorption using enriched HMW sample demonstrated similar total protein binding capacity (36-40 g/m2 ) between depth filters D0HC and X0HC. However, X0HC has stronger HMW binding than D0HC (71% vs 43% of bound protein), indicating more hydrophobic interaction in X0HC. HMW2 DBC on X0HC reached 12 g/m2 , similar to protein binding on hydrophobic interaction membrane adsorbers. Further study showed LMW can induce HMW formation. This study provides a critical understanding of HMW and LMW interaction with depth filters. The strategy of HMW and LMW control by depth filtration-based harvesting was implemented successfully in mAb manufacturing.

The purpose of this study was to investigate the effect of alcoholic strength by volume (ASV) and storage conditions on turbidity in plum brandies. Different types of filter sheet were also tested for their effects on turbidity, as well as on the chemical composition and organoleptic characteristics of the distillates. The raw materials used were two plum distillates with initial ASVs of 76.77% v/v and 81.92% v/v. The distillates were diluted to alcohol contents of 37.5%, 40% and 50% v/v and stored under various conditions for 64 days. Filtration was performed using two depth filter sheets, with nominal retention rates of 0.40–0.48 μm and 0.80 μm, or with an activated carbon-based filter sheet. The lowest turbidity was observed in samples stored at ambient temperature with an ASV of 50% v/v. Reducing the alcohol content and storage temperature caused turbidity to increase. Samples prepared from distillate with an initial alcohol content of 76.77% v/v were characterized by significantly higher turbidity than those produced from spirit with an initial ASV of 81.92% v/v. Lowering the storage temperature resulted in a larger decrease in the concentration of volatile compounds after filtration. Use of an activated carbon filter sheet caused the greatest decrease in the majority of volatiles. Use of a filter sheet with a nominal retention rate of 0.80 μm led to the greatest improvement in the organoleptics of the tested plum distillates.

We report a comprehensive study on depth filter functionality by using a slurry, colloidal silica, used for chemical mechanical polishing process in semiconductor manufacturing. We show that the depth filters with nominal pore size ranging from 0.1 $\mu \text{m}$ to 0.5 $\mu \text{m}$ selectively reduces the concentration of ‘large’ particles up to 80%, and maintains other critical properties of slurry including solid content ratio, mean diameter of particles, pH, zeta potential, and conductivity. Furthermore, we find the particle size-dependent filter efficiency, and the stable and allowable pressure drop across the filters. The depth filtration efficiently reduces the large particle concentration in slurry, and thus could be useful for suppressing the associated manufacturing defects such as micro-scratches and pits on the polished wafers.

Depth filtration is a commonly-used bioprocessing unit operation for harvest clarification that reduces the levels of process- and product-related impurities such as cell debris, host-cell proteins, nucleic acids and protein aggregates. Since depth filters comprise multiple components, different functionalities may contribute to such retention, making the mechanisms by which different impurities are removed difficult to decouple. Here we probe the mechanisms by which double-stranded DNA (dsDNA) is retained on depth filter media by visualizing the distribution of fluorescently-labeled retained DNA on spent depth filter discs using confocal fluorescence microscopy. The extent of DNA displacement into the depth filter was found to increase with decreasing DNA length with increasing operational parameters such as wash volume and buffer ionic strength. Finally, using 5ethynyl-2'-deoxyuridine (EdU) to label DNA in dividing CHO cells, we showed that Chinese hamster ovary (CHO) cellular DNA in the lysate supernatant migrates deeper into the depth filter than the lysate re-suspended pellet, elucidating the role of the size of the DNA in its form as an impurity. Apart from aiding DNA purification and removal, our experimental approaches and findings can be leveraged in studying the transport and retention of nucleic acids and other impurities on depth filters at a small scale.

Changing drivetrain architectures and designs such as highly integrated e-Axles and hybrid transmissions require different filtration solutions. Not only the requirements towards oil cleanliness and differential pressure of the lubrication and cooling circuit become more challenging, but also the dielectric and electric oil properties and the insulating function, for instance, come more and more into focus. To protect all system components starting from the oil pump MANN+HUMMEL developed a new generation of filters using their depth filter media MULTIGRADE eM-CO. The new concept increases the degrees of freedom for the development of the lubrication circuit significantly. Offering an ultra-compact and flexible installation space, lowest differential pressure or highest filtration efficiencies for system reliability. The new MANN+HUMMEL filter media portfolio MULTIGRADE eM-CO offers filter media with excellent properties and a gradient structure that provides a high dust holding capacity at a low differential pressure. Customized numerical development tools are supporting the media development by analyzing and optimizing the structure and the filtration performance. To multiply these advantages and to add further benefits for the customers a new generation of pleated suction-side filters has been developed. With up to 60% higher filter area the new concept uses the given installation space to the maximum. A 3D structured drainage grid keeps the media performance at a maximum level over the whole filter life. The latest computational fluid dynamics (CFD) analysis tools are used to optimize the differential pressure of the housing even in challenging installation spaces. Special oil drying units are applied to minimize water induced increase of conductivity. This allows the dielectric properties of the oils to be kept constant and even water sensitive oils can be used for the applications. With this knowledge and expertise, MANN+HUMMEL developed a sensor-supported oil management system with intelligent cooling function and integrated oil drying for highest oil quality over the entire life of the system.

For solid–liquid separation, filter meshes are still used across large areas today, as they offer a cost-effective alternative, for example, compared to membranes. However, particle interaction leads to a continuous blocking of the pores, which lowers the flow rate of the mesh and reduces its lifetime. This can be remedied by filter aids. In precoat filtration, these provide an already fully formed filter cake on the fabric, which acts as a surface and depth filter. This prevents interaction of the particles to be separated with the mesh and thus increases the service life of the mesh. In this work, the influence of a precoat layer with different fibre lengths of cellulose on the filtration behavior is investigated. A satin with a pore size of 11 µm is used as the filter medium. The effects of the precoat layer on the filter media resistance, the filter cake resistance, the turbidity impact, and the regenerability of the fabrics are investigated. This study shows an overview of the suitability of various cellulose fibres based on different aspects as filter aids for particles in ultrafine filtration.

The increased cell density and product titer in biomanufacturing have led to greater use of depth filtration as part of the initial clarification of cell culture fluid, either as a stand-alone unit operation or after centrifugation. Several recent studies have shown that depth filters can also reduce the concentration of smaller impurities like host cell proteins (HCP) and DNA, decreasing the burden on subsequent chromatographic operations. The objective of this study was to evaluate the HCP removal properties of the Pall PDH4 depth filter media, a model depth filter containing diatomaceous earth, cellulose fibers, and a binder. Experiments were performed with both cell culture fluid (CCF) and a series of model proteins with defined pI, molecular weight, and hydrophobicity chosen to match the range of typical HCP. The location of adsorbed (fluorescently labeled) proteins within the depth filters was determined using confocal scanning laser microscopy. Protein binding was greater for proteins that were positively charged and more hydrophobic, consistent with adsorption to the negatively charged diatomaceous earth. The lowest degree of binding was seen with proteins near their pI, which were poorly removed by this filter. These results provide new mechanistic insights into the factors governing the filter capacity and performance characteristics of depth filters containing diatomaceous earth that are widely used in the clarification of CCF.

Beta-glucans are polysaccharides of D-glucose monomers linked by (1-3) beta-glycosidic bonds, are found to have a potential immunogenicity risk in biotherapeutic products, and are labeled as process contaminants. A common source of beta-glucans is from the cellulose found in traditional depth filter media. Typically, beta-glucan impurities that leach into the product from the primary clarification depth filters can be removed by the subsequent bind-and-elute affinity chromatography capture step. Beta-glucans can also be removed by a bind-and-elute cation exchange chromatography step, which is useful for removing beta-glucans introduced by a post-Protein A depth filtration step. However, the increasing prevalence of flowthrough polishing chromatography poses a challenge for beta-glucan removal due to the lack of any bind-and-elute chromatography steps after the post-Protein A depth filter. In this work, a depth filter flush strategy was developed to control beta-glucan leaching into the product pool. Different loading conditions for the depth filtration and subsequent chromatography steps were evaluated to determine the robustness of the optimized flush strategy. Carry through runs demonstrated greater than two-fold reduction in beta-glucan levels using the optimized wash as compared to standard filter flush conditions.

Technologies suitable for the harvest clarification of cell cultures have experienced significant advancements in recent years. These advancements are motivated in part by increased cell densities and impurity levels, widespread industry adoption of single-use technologies, evolving regulatory landscapes, and a resurgence of perfusion cell cultures for continuous processing. This chapter details the major recent developments in the field of harvest clarification and includes discussions of core methods as well as emerging technologies. Core solid/liquid separation technologies such as centrifugation and depth filtration remain as cornerstones for the clarification of batch and fed-batch processes while microfiltration processes are being adopted for perfusion processes. Legacy methods, such as centrifugation have also advanced to incorporate new bowl designs for high density cell cultures, and process modifications have been made to improve product quality. Scale-down models for replicating shear and separation efficiencies have been reported. Recent developments for depth filters include new encapsulated devices, multistage depth filtration, and all-synthetic depth media grades. Tangential flow filtration and alternating tangential flow microfiltration methods are being adopted for high cell density perfusion processes. Recent developments in the areas of cell culture pretreatment and flocculation technologies, particle size characterization, and indirect analytical methods will also be discussed.

Depth type composite filters are porous materials heavily loaded with adsorbents and can remove contaminants from liquids by combining mechanical entrapment and adsorption. There is still a need for developing high performance filters by controlling the internal structure at micro and nano level. In this study, highly fibrillated nanocellulose (NC) with increased surface area was used as partial substitute for the fibre matrix to tailor the filter structure as well as the adsorption and filtration performance. Polyamide-amine-epichlorohydrin (PAE) was added both to adjust the charge of medium and provide wet strength. Filters were fabricated by embedding perlite particles into the cellulose fibre matrix by papermaking technique. The structure of composites was characterized for pore size distribution and surface morphology. Adsorption and filtration characteristics were quantified using two model dyes and silicon dioxide particles. Adsorption was found to be electrostatically controlled and dependent on the charge of the dye molecules and the filter medium. The addition of NC doubled the removal of a cationic dye by increasing the surface area and the available negative charges; it however decreased the removal of an anionic dye by 75%. PAE addition decreased the adsorption of the cationic methylene blue dye, while increasing the adsorption of the anionic metanil yellow dye. Rejection by filtration of 1 µm particles was over 90% for all filters. This study demonstrates that highly fibrillated NC fibres combined with a cationic wet strength polyelectrolyte can be used to tailor the filter structure and properties.

Optimization of a depth filter structure requires information about the filter's performance during its loading with particles. In this paper a macroscopic model of filtration process was proposed. It was based on the description of the loading process of three different gradient fibrous filters produced in the melt-blown technology process. Due to the contamination deposition on fibers, a new method of determination of the filter porosity transition, was suggested. It was based on growth of the deposit mass accumulated in individual filter layers, which was defined upon the scanning electron microscope images, the clearance of layer samples, and the overall increase of the filter mass. Local phenomena, i.e. the agglomerate structure, its spatial distribution and resuspension, were exposed through a two-stage character of the process. The empirical correlations obtained for deposition kinetics and pressure drop development are helpful in filter design. By knowing the desired contamination removal, fiber diameter and porosity can be verified mathematically, so that the filter will work the most efficiently. The proposed description of the structural loading of the multilayer filter is simple and reliable. Further research on biotic and abiotic particle transport mechanisms should be performed.

Background Integrated continuous production technology is of great interest in biopharmaceutical industry. Efficient, flexible and cost effective methods for continuous cell removal have to be developed, before a fully continuous and integrated product train can be realized. The paper describes the development and testing of such an integrated continuous and disposable set-up for cell separation by flocculation combined with depth filtration. Results Screening of multiple flocculation agents, depth filters, and conditions demonstrated that the best performance was obtained with 0.0375% polydiallyldimethylammonium chloride (pDADMAC; a polycationic flocculation agent) in combination with Clarisolve® depth filters. Using this set-up, a 4-fold decrease of filtration area was achieved relative to standard filtration without flocculation, with yields of ≥97% and DNA depletion of up to 99%. Continuous operation was accomplished using a simple tubular reactor design with parallelization of the filtration. The reactor length was selected to allow a 13.2-min residence time, which was sufficient to complete flocculation in batch experiments. Continuous flocculation performance was monitored on-line using focused beam reflectance measurement. Filter switch cycles based on upstream pressure were controlled by in-line pressure sensors, and were stable from one filter to the next. Conclusion It was demonstrated that stable and efficient continuous flocculation associated with depth filtration can be easily accomplished using tubular reactors and parallelization. Continuous cell separation is essential for the development of fully continuous integrated process trains. This cost-efficient disposable design run in continuous mode significantly reduces facility foot print, process costs and enables great flexbility. © 2017 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Because there is no general design method for depth filters, especially for layered configurations, we here address this methodological gap. Using optimal control theory, paths of the filter coefficient, a measure for local filtration performance, are determined along the filter depth. An analytical optimal control solution is derived and used to validate the numerical algorithm. Two optimal control scenarios are solved numerically: In the first scenario, the goal of constant deposition along the filter depth is addressed. The second scenario aims at maximizing the time until some maximal pressure drop is reached. Furthermore, we present a computational strategy to derive discrete layers suitable for practical design from the continuous optimal control solutions. All optimized scenarios are compared to one-layered filter designs and significant improvements are found. As this work is based on strongly validated and widely used filtration models, the presented methods are expected to have broad applicability. This article is protected by copyright. All rights reserved.

Gaseous microemboli (GME) may originate from the extracorporeal circuit and enter the arterial circulation of the patient. GME are thought to contribute to cerebral deficit and to adverse outcome after cardiac surgery. The arterial filter is a specially designed component for removing both gaseous and solid microemboli. Integration of an arterial filter with an oxygenator is a contemporary concept, reducing both prime volume and foreign surface area. This study aims to determine the air-handling properties of four contemporary oxygenator devices with an integrated arterial filter. Two oxygenator devices, the Capiox FX25 and the Fusion, showed significant increased volume of GME reduction rates (95.03 ± 3.13% and 95.74 ± 2.69%, respectively) compared with both the Quadrox-IF (85.23 ± 5.84%) and the Inspire 6F M (84.41 ± 12.93%). Notably, both the Quadrox-IF and the Inspire 6F M as well as the Capiox FX 25 and the Fusion showed very similar characteristics in volume and number reduction rates and in detailed distribution properties. The Capiox FX25 and the Fusion devices showed significantly increased number and volume reduction rates compared with the Quadrox-IF and the Inspire 6F M devices. Despite the large differences in design of all four devices, our study results suggest that the oxygenator devices can be subdivided into two groups based on their fibre design, which results in screen filter (Quadrox-IF and Inspire 6F M) and depth filter (Capiox FX25 and Fusion) properties. Depth filter properties, as present in the Capiox FX25 and Fusion devices, reduced fractionation of air and may ameliorate GME removal.

Recent progress in mammalian cell culture process has resulted in significantly increased product titers, but also a substantial increase in process- and product-related impurities. Due to the diverse physicochemical properties of these impurities, there is constant need for new technologies that offer higher productivity and improved economics without sacrificing the process robustness required to meet final drug substance specifications. Here, we examined the use of new synthetic adsorptive hybrid filters (AHF) modified with the high binding capacity of quaternary amine (Emphaze™ AEX) and salt-tolerant biomimetic (Emphaze™ ST-AEX) ligands for clearance of process-related impurities like host cell protein (HCP), residual DNA, and virus. The potential to remove soluble aggregates was also examined. Our aim was to develop a mechanistic understanding of the interactions governing adsorptive removal of impurities during filtration by evaluating the effect of various filter types, feed streams, and process conditions on impurity removal. The ionic capacity of these filters was measured and correlated with their ability to remove impurities for multiple molecules. The ionic capacity of AHF significantly exceeded that of traditional adsorptive depth filters (ADF) by 40% for the Emphaze™ AEX and by 700% for the Emphaze™ ST-AEX, providing substantially higher reduction of soluble anionic impurities, including DNA, HCPs and model virus. Nevertheless, we determined that ADF with filter aid provided additional hydrophobic functionality that resulted in removal of higher molecular weight species than AHF. Implementing AHF demonstrated improved process-related impurity removal and viral clearance after Protein A chromatography and enabled a two-step purification process. The consequences of enhanced process performance are far reaching because it allows the downstream polishing train to be restructured and simplified, and chromatographic purity standards to be met with a reduced number of chromatographic steps.

The development of de-dusting hot gases is of increasing importance and growing interest, especially in advanced power generation systems and (petro-)chemical processes. High temperature de-dusting has advantages of exceeding dew points, enhancing energy recovery at higher temperatures, protecting the downstream heat recovery equipment from fouling or erosion, and potentially simplifying the overall process. Additional benefits are a reduced power consumption and the possibility to simultaneously capture gaseous pollutants (SO2, HCl) by the gas-solid reaction with injected alkali or by integrating catalysts to abate NOx, VOC (volatile organic compounds) and PCDD/F (polychlorinated dioxins and furans). Both porous ceramic and porous metal fiber filters have been proposed, with a growing preference for the rigid metal fibre filters. Either surface or depth filters are applied. The operation parameters of hot gas de-dusting by rigid fibre filters include the applied face velocity, the porosity of the filter fleece, its construction and the pulse jet cleaning performance. These parameters will be integrated into design equations to determine the operational pressure drop and filtration efficiency for a given gas flow rate, operating temperature, dust characteristics and pulse-jet cleaning mode. The broad range of potential applications of the filters prior to an energy recovery stage will be illustrated for petrochemical/chemical processes and for combustion and gasification. The expected durability and long-term successful operation necessitate a proper design of the filter media (porosity, pore size, thermal, mechanical and corrosion resistance). The appropriate fabrication materials will be evaluated, with stainless steel or high grade metal alloys recommended for use in the extreme conditions at high temperatures and pressures. Finally prospects and challenges are summarized.

Depth filtration is widely used for clarification of liquid feeds, including the purification of biopharmaceuticals. The performance characteristics of these depth filters can be strongly influenced by the local flow and pressure distribution within the filter capsule, but there is currently little information on these phenomena in commercial depth filter modules. This work used a combination of computational fluid dynamics (CFD), residence time distribution (RTD) measurements, and dye binding experiments to obtain detailed information on the pressure and flow distribution within a small-scale Supracap™ depth filtration capsule, containing two layers of depth filter media with different pore size, that is of high interest in bioprocessing. The results confirmed the presence of four distinct flow paths through the capsule, with less than 40% of the flow passing completely through both layers of the depth filter media and nearly 11% bypassing the large pore size prefilter layer. Model calculations were in good agreement with the measured RTD and images of dye binding, providing further confirmation of the flow phenomena. These studies provide important insights into the performance characteristics of these depth filters, while providing a framework that can be applied to analyze the pressure and flow distribution in other membrane and depth filtration modules.

Background: The indication for arterial line filtration (ALF) is to inhibit embolisation during cardiopulmonary bypass. Filtration methods have developed from depth filters to screen filters and from a stand-alone component to an integral part of the oxygenator. For many years, ALF has been a standard adopted by a majority of cardiac centres worldwide. The following review aims to summarize the available evidence in support for ALF and report on its current practice in Europe. Method: The principles and application of ALF in Europe was investigated using a survey conducted in 2014. The scientific evidence for ALF was examined by performing a systematic literature search in six different databases, using the following search terms: “Cardiopulmonary bypass AND filters AND arterial”. The primary endpoint was protection against cerebral injury verified by the degree of cerebral embolisation or cognitive tests. The secondary endpoint was improvement of the clinical outcome verified elsewise. Only randomised clinical trials were considered. Results: The response rate was 31% (n=112). The great majority (88.5%) of respondents were using ALF, following more than 10 years of experience. Integrated arterial filtration was used by 55%. Of respondents not using ALF, fifty-four percent considered starting using integrated arterial filtration. The systematic literature database search returned 180 unique publications where 82 were specifically addressing ALF in cardiopulmonary bypass. Only four out of the 82 identified publications fulfilled our inclusion criteria. Of these, three were more than 20 years old and based on the use of bubble oxygenation. Conclusion: ALF is a standard implemented in a majority of cardiopulmonary bypass procedures in Europe. The level of scientific evidence available in support of current arterial line filtration methods in cardiopulmonary bypass is, however, poor. Large, well-designed, randomised trials are warranted.

Ultra scale‐down (USD) methods operating at the millilitre scale were used to characterise full‐scale processing of E. coli fermentation broths autolysed to different extents for release of a domain antibody. The focus was on the primary clarification stages involving continuous centrifugation followed by depth filtration. The performance of this sequence was predicted by USD studies to decrease significantly with increased extents of cell lysis. The use of polyethyleneimine reagent was studied to treat the lysed cell broth by precipitation of soluble contaminants such as DNA and flocculation of cell debris material. The USD studies were used to predict the impact of this treatment on the performance and here it was found that the fermentation could be run to maximum productivity using an acceptable clarification process (e.g., a centrifugation stage operating at 0.11 L/m2 equivalent gravity settling area per hour followed by a resultant required depth filter area of 0.07 m2/L supernatant). A range of USD predictions was verified at the pilot scale for centrifugation followed by depth filtration. © 2016 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 32:382–392, 2016

Depth filtration is employed in the production of many biological products. Although high throughput process development is available for most purification operations, options for high throughput depth filtration are limited. In this report, we describe the development and qualification of an ultra scale-down (USD) device for high throughput depth filtration. The system enables the parallel evaluation of eight single- or multi-layer depth filters approximately 0.2 cm2 in cross-sectional area, greater than two logs smaller than the smallest commercially available devices. To assess precision, scalability, modularity, and media heterogeneity in USD depth filtration, several types of adsorbent media were qualified in the USD device, with filtration performance compared to lab-scale devices (cross-sectional area: 23–25 cm2). The performance was further investigated with several high throughput clarity measurements, including particle characterization of filtrate fractions. Historically, depth filtration development has been limited by the amount of material required to run lab-scale filters. The described high throughput technology enables the screening of filter media early in development, optimization of operating parameters, and coupling of upstream operations to filtration performance. These high throughput capabilities will create efficiencies for development and manufacturing that were unattainable previously and create an important tool for screening novel biological entities.

The requirements for gas purification systems are getting increasingly stricter. This is due to the development of new technologies, increasing environmental pollution, and greater emphasis placed on the protection of human health and the environment. Fibrous filters are among the most widely used tools for removing particles from fluids. This paper explains the very complex process of the non-steady state aerosol particle filtration in fibrous filters using such a technologically advanced solution as an X-ray computed tomography for this purpose. Since online monitoring of the process inside the filter structure or marking particles flowing into the filter in any way, which would facilitate distinguishing between fresh and replaced particles, might be difficult to deploy, a simulation of the process was chosen instead. The experiment was divided into four stages. At the first stage, the advantages of the melt-blown technique were adopted to produce two non-woven fabric types of a given structure – one made of micro-sized fibers, and the other made of submicro- and nano-sized fibers. At the subsequent stage, the provided separating materials were loaded with solid silica particles in identical conditions, and then a stream of clean air at various flow velocities was blown through them. This experiment was designed to examine the behavior of the deposits in the filter during filtration, observe whether they travel inside the filter structure, remain in place or entirely leave the filter. At the last stage of the process, a macroscopic analysis of the filter structure and silica particles deposited inside it was carried out using an X-ray microtomography system. Based on the acquired tomography images, profiles of changes in local porosity of the filters along their depth were made. It was found that deposited particles re-entrain from the fibers during filtration process but they do not leave the filter, only move to its deeper parts.

Depth type composite filters are used to remove contaminants from liquids by combining mechanical entrapment and adsorption. Commonly, depth filters can adsorb either anionic or cationic charged contaminants, but not both, as well as filter micron-sized particles. Therefore, there is still a need to improve the existing depth filter performance. In this study, we developed a two-layer filters with enhanced functionality by spray coating an anionically charged cellulose nanofibre (CNF) layer onto a cationically charged depth filter layer. The depth filter layer was prepared via papermaking technique of vacuum filtration from wood pulp fibres, perlite adsorbent and cationic polyamide-amine epichlorohydrin (PAE) wet strength resin. The CNF coat weight ranged from 4 to 30 g per square metre (gsm). The two layer filters were proven to have triple functionality, capable of adsorbing anionic molecules in the cationic depth filter layer, while the anionic CNF layer could adsorb cationic molecules and was also a microfiltration membrane. A gradual increase in CNF coat weight improved filtration performance but decreased the filter flux. The optimum performance was found at an 8 gsm CNF coat weight, where the membrane layer rejected 80% of 5000 kDa molecular weight polyethylene glycol, at a flux of 133 Litres per square meter per hour (LMH) under 1.5 bar pressure, while still achieving a good breakthrough curve when absorbing cationic methylene blue dye.

In underground mining operation, air is contaminated with fine dusts that can be removed by filtration effectively. Filter cleaning is envisioned to prolong filter media lifetime and to ensure uninterrupted operation requiring little maintenance. For cake filtration, reverse airflow or pulse flow, or filter shaking are widely used. But for depth bed filtration which is needed to meet more stringent emission requirement, continuous filter cleaning is generally not practical. The concept of continuous liquid rinsing of depth filter media is proposed and preliminary studies are performed. These laboratory studies on single vertical fibers include hydrodynamic tests of water along various filter fibers as well as cleaning with different sample dusts. All tested fibers have hydrophobic properties that result in the formation of clamshell droplets with moderate particle removal success. Small, plate-like particles are particularly difficult to remove. Comparative tests with oil that forms a homogeneous film provide excellent particle removal.

Depth filtration is widely used in downstream bioprocessing to remove particulate contaminants via depth straining and is therefore applied to harvest clarification and other processing steps. However, depth filtration also removes proteins via adsorption, which can contribute variously to impurity clearance and to reduction in product yield. The adsorption may occur on the different components of the depth filter, that is, filter aid, binder, and cellulose filter. We measured adsorption of several model proteins and therapeutic proteins onto filter aids, cellulose, and commercial depth filters at pH 5-8 and ionic strengths

Rapid depth filtration is the dominant pre-treatment technology in seawater desalination industry today. Optimizing the pre-treatment filter’s energy performance provides economies of scale in the total energy usage of desalination facilities on a broader sense. However, this objective remains difficult to achieve by far. In this study, we develop a numerical algorithm, termed as Dynamical Rapid Filtration Model (DRFM), to simulate the effective clogging dynamics occurring inside a depth filter which depends on a multitude of controlled and non-controlled operating parameters. DRFM quantifies the filtration kinetics with a modified Yao’s model to represent the particle removal mechanisms occurring within the simulated filter. A unique length scale is also introduced to account for the particle size effect on the filter’s energy loss rate incurred, i.e. its energy performance, during its effective filtration stage. Concurrently, we performed an experimental study with a lab-scale depth filter to develop a model equation for measuring its total contaminant mass removal rate ( R c ) due to effective clogging conditions. For a predicted R c transient profile, good agreement is obtained between the experimental results and predicted values from DRFM. We then extensively discuss on a novel DRFM hybrid model to optimize the filter’s energy performance which subsequently affects the filter’s optimized backwashing timing for achieving economies of scale. The simulation results from the hybrid model demonstrates on how various filter configurations can result in lower energy cost to effectively pre-treat each unit volume of intake seawater as compared to the current industrial average of 0.39 kWh / m 3 . Finally, we include a cost analysis to demonstrate on how the obtained economies of scale alleviates a portion of the total energy cost for each unit volume of desalinated water.

High titer (>10 g/L) monoclonal antibody (mAb) cell culture processes are typically achieved by maintaining high viable cell densities over longer culture durations. A corresponding increase in the solids and sub-micron cellular debris particle levels are also observed. This higher burden of solids (≥15%) and sub-micron particles typically exceeds the capabilities of a continuous centrifuge to effectively remove the solids without a substantial loss of product and/or the capacity of the harvest filtration train (depth filter followed by membrane filter) used to clarify the centrate. We discuss here the use of a novel and simple two-polymer flocculation method used to harvest mAb from high cell mass cell culture processes. The addition of the polycationic polymer, poly diallyldimethylammonium chloride (PDADMAC) to the cell culture broth flocculates negatively-charged cells and cellular debris via an ionic interaction mechanism. Incorporation of a non-ionic polymer such as polyethylene glycol (PEG) into the PDADMAC flocculation results in larger flocculated particles with faster settling rate compared to PDADMAC-only flocculation. PDADMAC also flocculates the negatively-charged sub-micron particles to produce a feed stream with a significantly higher harvest filter train throughput compared to a typical centrifuged harvest feed stream. Cell culture process variability such as lactate production, cellular debris and cellular densities were investigated to determine the effect on flocculation. Since PDADMAC is cytotoxic, purification process clearance and toxicity assessment were performed.

Traditional clarification of mammalian cell culture typically combines multiple separation technologies to remove cells in a primary step, and colloids in a secondary step. Recent advances in mammalian expression systems have not only led to cell cultures with very high density and increased protein titers, but also to feed streams with a high proportion of solids and colloids that reduce the efficiency of the separation step. Issues with scale-up, flexibility and installation limit the attractiveness of centrifugation, whereas clarification solely by depth filtration can be costly due to high filter areas required. Therefore, an efficient manufacture process must be developed to overcome these restrictions. In this study we present a complete separation solution that combines cell harvest pretreatment with a polycationic flocculating agent (polydiallyldimethylammonium chloride or pDADMAC), followed by depth filtration using depth filters that were specifically developed for filtration of flocculated or precipitated feed streams. Multiple antibody feed streams treated with pDADMAC and subsequently filtered using pretreatment adapted depth filters resulted in improved removal of cells and colloids, increased clarification throughput, efficient reduction of DNA and high process yield. The residual level of pDADMAC in the filtrates was assessed by surface plasmon resonance spectroscopy. Overall, this next generation clarification solution presented herein led to a robust, high yield, economical separation process with enhanced impurity removal that can be readily incorporated into current clarification platforms.

Human growth hormone is a single-chain polypeptide produced commercially from recombinant animal cells as well as recombinant microorganisms. Its increased applications have requested development of highly efficient production systems using particularly animal cells. Depth filter perfusion system (DFPS) has been developed and successfully used for production of recombinant proteins such as antibodies from recombinant Chinese hamster ovary (rCHO) cells. In this study, rCHO cells expressing recombinant human growth hormone (rhGH) were successfully cultivated in the DFPS for 2,200 h. Parameters affecting the performance of the DFPS for rhGH production were investgated. The depth filter with 40 µm pores was selected for stable operation. The shifts of culture temperature and pH were tested at 37 and 33℃, and 7.2 and 7.0, respectively. In the begining of the culture, more than 80% of the seeded cells were immobilized in 200 min by medium/cell circulation. When the culture temperature was lowered from 37 to 33℃, about 50% increase of the volumetric productivity (VP) at a perfusion rate of 2.0/day was achieved, and the VP reached 168 mg/L/d at perfusion rate of 3.0/day, showing the benefit of cultures in low temperature. In contrast, when pH was shifted from 7.2 to 7.0, maintaining rhGH concentration at about 60 mg/L and decreased perfusion rate from 2.0 to 1.0/day, the VP dropped to 50%. As the DFPS showed stable and efficient production of rhGH for long-term periods from this study, it can be an attractive choice for production of rhGH from recombinant animal cells.

A depth filter is widely used in biopharmaceutical manufacturing process. In this study, we found that buffer exchange to reduce conductivity dramatically improved the removal of impurities in depth filtration. The host cell protein clearance was comparable to that of protein A affinity chromatography, which is generally used as a first capture step in monoclonal antibody purification. In addition, a combination of different depth filters showed enhanced purification. Additional flow-through purification is possible without any sample preparation, and a biopharmaceutical-quality purity level (

Cell harvesting is the separation or retention of cells and cellular debris from the supernatant containing the target molecule Selection of harvest method strongly depends on the type of cells, mode of bioreactor operation, process scale, and characteristics of the product and cell culture fluid. Most traditional harvesting methods use some form of filtration, centrifugation, or a combination of both for cell separation and/or retention. Filtration methods include normal flow depth filtration and tangential flow microfiltration. The ability to scale down predictably the selected harvest method helps to ensure successful production and is critical for conducting small-scale characterization studies for confirming parameter targets and ranges. In this chapter we describe centrifugation and depth filtration harvesting methods, share strategies for harvest optimization, present recent developments in centrifugation scale-down models, and review alternative harvesting technologies.

There are essentially two main types of filters from a layout design point of view. There are those that are essentially ancillary fittings, such as line strainers, and those which are unit operations in their own right. Nowadays, filtration tends toward continuous operation, though batch and semibatch operation is still very important in the pharmaceutical, food, and water sectors. The most important technological advance in filtration in recent years has been the increased availability of consistent and economical membrane filters. As these tend to come in standardized packages of a fixed size, membrane plant layouts tend to be highly modularized.

The effect of increasing the hydrophobicity of poly(propylene) (PP) fibers, the most frequently used synthetic filter materials, on depth filtration performance was investigated. Reduced graphene oxide (RGO) was employed to fabricate highly hydrophobic surfaces by a dip-coating method. The anchoring of RGO on the surface of the PP fibers was confirmed by the appearance of signals corresponding to RGO in Raman and X-ray photoelectron spectra. In addition, scanning electron microscopy images revealed the presence of wrinkled and folded RGO sheets on the PP fibers. The water contact angle increased from 108° to 125° after the first RGO coating, and it was saturated at about 135°. Using kaolin as model hydrophilic particles, the depth filters with RGO-coated PP fibers showed a superior performance in terms of water flux and trans-filter pressure in comparison with those with the pristine and hydrophilic PP fibers prepared by coating functionalized GO. More importantly, particle detachment was enhanced by the hydrophobic coating during backwashing. This can be ascribed to the weakened attractive force between the RGO-coated fiber surfaces and kaolin particles due to the increase of hydrophobicity. This approach provides an effective means of enhancing the performance of synthetic fiber-based depth filters.

This work investigates the performance and optimization of a hybrid process consisting of a fixed-bed adsorption (FBA) column and a dead-end filtration (DEF) cell for the removal of methylene blue (MB) from water. Granular activated carbon and cellulose acetate depth filter sheets were used as adsorbent and filter medium, respectively. Effects of four operation parameters (initial concentration, feed flowrate, bed length, and filter type) on the MB removal rate (RR) were investigated using breakthrough data analysis and response surface methodology. This RR (mass of MB removed per second) captures the removal capacity and separation rate, simultaneously. The maximum RR was found theoretically equal to 3.875 s−1 at the optimized conditions of initial concentration =39.86 mg/L, flowrate = 1.15 L/min, bed length =29.95 cm, and filter type = OS100, and validated with the experimental data with 99% agreement. The performance of the hybrid process operating at the optimal operation conditions was found to be superior to those of the individual FBA column and DEF cell. After 100 s from the process commencement, the RR obtained with the hybrid process was about 64% higher than that obtained with the FBA column and 30% higher than that obtained with the DEF cell.

Depth filter media are usually composed of multiple layers to attain optimal values of main filtration parameters such as pressure drop and particle collection efficiency (PCE). Understanding the performance of the single layers that make up the filter media can contribute to attaining these optimum values. For the purpose of this study, we have developed two samples of depth filter media, 2LM and 3LM, composed of two and three layers, respectively. Samples of the media and single layers have been prepared in flat sheet form. Filtration performance of these samples has been evaluated using a lab-scale flat sheet filter media test unit with KCl as the test aerosol. Results from these tests have been compared with those from an automated filter tester (AFT) with NaCl as the test aerosol. These media have been characterized based on filter media properties and data from the filtration performance tests and the effect of layers on filtration performance has been observed. Pressure drop data from the tests wit...

Increasingly high cell density, high product titer cell cultures containing mammalian cells are being used for the production of recombinant proteins. These high productivity cultures are placing a larger burden on traditional downstream clarification and purification operations due to higher product and impurity levels. Controlled flocculation and precipitation of mammalian cell culture suspensions by acidification or using polymeric flocculants have been employed to enhance clarification throughput and downstream filtration operations. While flocculation is quite effective in agglomerating cell debris and process related impurities such as (host cell) proteins and DNA, the resulting suspension is generally not easily separable solely using conventional depth filtration techniques. As a result, centrifugation is often used for clarification of cells and cell debris before filtration, which can limit process configurations and flexibility due to the investment and fixed nature of a centrifuge. To address this challenge, novel depth filter designs were designed which results in improved primary and secondary direct depth filtration of flocculated high cell density mammalian cell cultures systems feeds, thereby providing single-use clarification solution. A framework is presented here for optimizing the particle size distribution of the mammalian cell culture systems with the pore size distribution of the gradient depth filter using various pre-treatment conditions resulting in increased depth filter media utilization and improved clarification capacity. Feed conditions were optimized either by acidification or by polymer flocculation which resulted in the increased average feed particle-size and improvements in throughput with improved depth filters for several mammalian systems.

Fouling of reverse osmosis (RO) water filtration membranes is a common problem throughout the industry. Most membrane fouling has an organic component that is typically derived from planktonic transparent exopolymer particles (TEP). Polysaccharides are a major constituent of TEP that are produced both abiotically from organic colloid precursors and by a variety of organisms in marine and freshwaters. The microgel character of TEP makes them difficult to remove through conventional filtration other than by ultra filtration and RO membranes. However, removal of TEP by these membranes is also problematic. When the membrane surface is initially fouled with TEP, the TEP layer then acts as an attachment substrate for organism, colloids and other submicron particulates, further contributing to membrane clogging. We report on an innovative electroadsorptive, depth filter media that is shown to be effective in significantly reducing TEP from fresh water, sea water, and wastewater. This technology has sign...

Considering the common use of sheet filtration for clarification of fruit brandies, the aim of this study was to evaluate the influence of its application on the stability and composition of volatile compounds of apricot brandy after cold stabilisation. Cold stabilisation treatment involved holding of the brandy at -1°C during 24 hours. Five depth filter sheets with the nominal retention rate of 0.3 μm, 0.5-0.7 μm, 0.7-1.0 μm, 1.0-2.0 μm and 2.5-4.0 μm, were tested in the study. It was shown that all assessed filter sheets were efficient in removing chill haze by significantly reducing the content of fatty acid esters (primarily ethyl palmitate and ethyl laurate). Other volatile and aromatic compounds were not significantly influenced by the applied treatments. However, the filter sheets with higher nominal retention rate (> 0.7 μm), had a smaller impact on the sensory characteristics of the apricot brandy. The re-exposure to lower temperatures did not lead to chill haze formation in any sample obtained after sheet filtration. [Projekat Ministarstva nauke Republike Srbije, br. TR-31002]

A string-wound filter cartridge/candle is characterized by its shape and the method of manufacturing it. The term candle indicates its shape (ie, cylindrical) while string-wound points to the method of manufacturing it. Normally, the raw material used is a coarse yarn laid spirally on a perforated core produced with the intent of trapping suspended particles. The raw material of yarn can be chosen according to the environment in which it will be placed. String-wound filter cartridges come under the umbrella of depth filters. As the name indicates, this type depends on its thickness to trap the particles, rather than the contaminant entering inside the filter matrix to get arrested. The thickness of media therefore plays an important role in its performance. As media thickness changes, pressure drop is found to be affected, as is particle-trapping efficiency.

A remotely controlled autonomous method for long-term high-frequency sampling of environmental waters in remote locations is described. The method which preserves sample integrity of dissolved trace metals and major ions for month-long periods employs a gravitational filtration system (GFS) that separates dissolved and particulate phases as samples are collected. The key elements of GFS are (1) a modified "air-outlet" filter holder to maximize filtration rate and thus minimize filtration artifacts; and (2) the direct delivery of filtrate to dedicated bottle sets for specific analytes. Depth and screen filter types were evaluated with depth filters showing best performance. GFS performance is validated using ground, stream, and estuary waters. Over 30 days of storage, samples with GFS treatment had average recoveries of 95 ± 19% and 105 ± 7% of Fe and Mn, respectively; without GFS treatment, average recoveries were only 16% and 18%. Dissolved major cations K, Mg, and Na were stable independent of collection methodology, whereas Ca in some groundwater samples decreased up to 42% without GFS due to CaCO(3) precipitation. In-field performance of GFS equipped autosamplers is demonstrated using ground and streamwater samples collected at the Angelo Coast Range Reserve, California from October 3 to November 4 2011.

Gamunex®-C is a highly purified liquid 10% IgG preparation manufactured by a process that includes caprylate precipitation and incubation, and chromatography steps. In the original process, caprylate precipitation was followed by cloth filtration to remove impurities. The highly porous cloth filter has since been replaced with a tight depth filter. The impact of this process modification on pathogen reduction and product is presented. Virus and prion reduction was determined under set-point conditions using scaled-down models of the manufacturing process, and at or outside operating limits to determine robustness. Product protein compositions before and after the process modification were compared directly using manufacturing data. Filtration through a tight depth filter substantially increased nonenveloped virus reduction, and virus reduction was maintained even when a compromised depth filter was used. In addition, prion reduction was improved by about three logs. The product IgG content, purity, and IgG subclass distribution remained comparable to the original cloth filtration process. The replacement of cloth filtration with depth filtration increased the pathogen safety margin of the manufacturing process without impacting the product composition.

This paper introduces the fiber filter device by adjusting the charge and discharge water to adjust the fiber density - filter accuracy, interception capacity, filtration resistance and other parameters. In the industrial, commercial market prospects, environmental, economic and social benefit is remarkable.

The removal efficiency of a nanoalumina depth filter (Disruptor™) was tested using raw seawater from the North Sea in a laboratory scale filtration unit and reverse osmosis (RO) test unit. Permeate flux was measured against time using untreated and pre-filtered seawater. Untreated seawater exhibited a rapid permeate flux decline. Seawater pre-filtered through the DisruptorTM showed showed high flux that declined only slightly after 120 min of operation due to increasing of osmotic pressure and formation of scaling on the membrane surface. The surface morphologies of clean and fouled RO membranes were examined using scanning electron microscope (SEM). The surface of the membrane fouled by untreated seawater was completely covered by a fouling layer, while the membrane surfaces exposed to Disruptor™ pre-filtered seawater were clean and only scaling was detected. The functional groups on clean and fouled RO membrane samples were investigated by attenuated total reflection — Fourier transform infrared spectro...

Protein A chromatography has become widely established for the preparative purification of mAbs (monoclonal antibodies). Low pH elution from Protein A columns followed by neutralization can often lead to precipitation of impurities in the product stream, leading to a visually turbid solution. Pretreatment of the cell culture harvest stream with an increased surface area of the depth filter was found to reduce the magnitude of this problem through exploitation of the adsorptive properties of harvest depth filters. However, this was not a complete solution. Clarification of this turbid product stream prior to the polishing chromatographic steps in the downstream process posed significant filtration challenges. Development of a staged filtration process with the use of low plugging glass fibre depth filters as the first stage prior to membrane filtration through an absolute pore size membrane is described. Finally, a cost calculation is used to drive the selection of the final filter train for this application. The results presented here are expected to have wide applicability in mAb downstream processing as well as for other turbid solutions encountered in the downstream processing of other biomolecules.