New insights into the performance characteristics of the Planova‐series hollow‐fiber parvovirus filters using confocal and electron microscopy

The capacity to remove viruses by Planova filters produced by Asahi Kasei, primarily by small virus‐retentive filters, were compiled from data in peer‐reviewed publications and, partly, publicly available data from presentations at conferences (Planova workshops). Data from more than 100 publications and presentations at conferences covering Planova filters were assessed. The data were grouped according to the different virus filters regarding mean pore sizes and viruses of different sizes for plasma and cell culture derived products. Planova 15N and 20N filters removed parvoviruses below the limit of detection of viruses in the filtrate in approx. 50% of all studies and mean LRFs (log reduction factors) for viruses detected in the filtrate were above 4, demonstrating effective parvovirus reduction. Parvovirus removal capacity increased for Planova BioEX filters as well as for 2 Planova 20N in series. Large viruses as retroviruses (e.g., HIV and MuLV), herpesviruses, flaviviruses and togaviruses were removed effectively by Planova 15N, 20N and BioEX filters and also by Planova 35N filters. Flow interruption, transmembrane pressure, volume and protein concentration per filter area had had no substantial impact on virus removal capacity at manufacturing specification. In conclusion, the incorporation of Planova filters in manufacturing processes of biologicals remove, depending on the filter pore size, small and large viruses from the feed stream reliably. This virus reduction step with an orthogonal mechanism integrated in the manufacturing processes of biologicals, based primarily on size exclusion of viruses, improves the virus safety of these biopharmaceutical products considerably.

Section: Resultsmentioning

confidence: 99%

Integration of Planova filters in manufacturing processes of biologicals improve the virus safety effectively: A review of publicly available data

Gröner

2023

“…This finding is consistent with those of previous publications. 16,23,25,27 However, aggregate retention was not seen near the outer surface of the membrane unlike the nanoparticles in the publication of Nazem-Bokaee et al 24 In this kind of gradient structure, aggregates are captured based on size in different layers dispersed throughout the membrane rather than all in one specific capture layer. Moreover, each layer likely functions as a prefilter, capturing and removing aggregates in size order from larger to smaller moving from the inner to the outer surface, thereby protecting the pores located toward the outer surface from fouling by large aggregates.…”

Section: Visualization Of Aggregate Retentionmentioning

confidence: 97%

“…There are abundant filtration studies using different‐sized particles such as fluorescent or gold nanoparticles. For example, different‐sized nanoparticles were used to reveal the pore size distribution of filters 21–23 and another study demonstrated that nanoparticle capture by a filter was affected by transmembrane pressure 24 . Furthermore, the impacts of IgG fouling on nanoparticle capture were investigated using nanoparticles 25,26 or fluorescently labeled virus 27 .…”

Section: Introductionmentioning

confidence: 99%

“…For example, different-sized nanoparticles were used to reveal the pore size distribution of filters [21][22][23] and another study demonstrated that nanoparticle capture by a filter was affected by transmembrane pressure. 24 Furthermore, the impacts of IgG fouling on nanoparticle capture were investigated using nanoparticles 25,26 or fluorescently labeled virus. 27 The present study established a method for evaluating fouling caused by different-sized aggregates.…”

mentioning

confidence: 99%

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Size‐based analysis of virus removal filter fouling using fractionated protein aggregates

Tsukamoto,

Hamamoto,

Oguri

et al. 2023

Fouling by protein aggregates reduces virus removal filter performance. In the present study, we investigated the effects of different‐sized protein aggregates on fouling and aggregate retention in order to better understand the fouling mechanisms. Human immunoglobulin G was denatured by heating to produce aggregates of various sizes and then fractionated by size exclusion chromatography into different‐sized aggregates with a narrow size distribution. The fractionated aggregates were filtered on Planova 20N, a virus removal filter known for its stable filtration capability. Analysis of flux behavior demonstrated different flux decrease patterns for different‐sized aggregates. Observation of aggregate retention by staining revealed that larger aggregates were captured closer to the inner surface of the membrane while smaller aggregates penetrated farther into the membrane. These findings demonstrate that Planova 20N has a gradient structure with decreasing pore size from the inner to the outer surface of the membrane. This structure minimizes fouling and enables stable filtration by protecting the smaller pores located closer to the outer surface from clogging by large aggregates. Applying the predominant clogging models to the present filtrations revealed that clogging behavior transitioned from complete blocking to cake filtration as filtration progressed. In this combination model, after a certain number of pores are blocked by complete blocking, newly arrived aggregates begin to accumulate on previously captured aggregates, generating cake between capture layers within the membrane. Application of the approaches described here will facilitate elucidation of membrane fouling and virus removal mechanisms.

“…To design a robust and high-throughput virus filtration step, optimization of the feed solution conditions and/or selection of an appropriate virus-retentive filter are required. [15][16][17][18] For Planova 20N and Planova BioEX which are representative virus retentive filters of Asahi Kasei Medical, data have been reported regarding the relationship between their virus retention capability and feed solution conditions 11,16,[19][20][21][22][23][24][25] ; however, reports focused on the relationship between their filterability and feed solution conditions remain limited. No reports evaluated their filterability using mAbs under various buffer conditions, although some reports presented data regarding polyclonal IgG.…”

Section: Introductionmentioning

confidence: 99%

Effect of pH, NaCl concentration, and mAb concentration of feed solution on the filterability of Planova™ 20N and Planova™ BioEX

Hashikawa‐Muto,

Yokoyama,

Hamamoto

et al. 2023

Virus filtration is one of the most important steps in ensuring viral safety during the purification of monoclonal antibodies (mAbs) and other biotherapeutics derived from mammalian cell cultures. Regarding the various virus retentive filters, including Planova filters, a great deal of data has been reported on the virus retention capability and its mechanism. Along with the virus retention capability, filterability is a key performance indicator for designing a robust and high‐throughput virus filtration step. In order to obtain higher filterability, optimization of the feed solution conditions, and filter selection is essential; however, limited data are available regarding the filtration characteristics of Planova filters. Furthermore, for Planova 20N and Planova BioEX, the virus retention characteristics were reported to differ due to their respective membrane materials and layer structures. Whether these filters differ in their filtration characteristics is an interesting question, but no comparative evaluations have been reported. In this study, the filterability of the two filters was investigated and compared using 15 feed mAb solutions of a single mAb selected by design of experiments with different combinations of pH, NaCl concentration, and mAb concentration. The filterability of Planova 20N was affected not only by the feed solution viscosity, but also by the mAb aggregate content of the feed mAb solution and mAb‐membrane electrostatic interactions. In contrast, the filterability of Planova BioEX decreased under some buffer conditions. These findings and the established design spaces of these filters provide valuable insights into the process optimization of virus filtration.