Scale‐up of Microfiltration Processes

Abstract

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Supporting Information available onlineA flow rate and resistance-based approach for upscaling of microfiltration processes from lab scale to process scale is presented, in correlation with biopharmaceutical processes. Basic element is the modeling of filtration curves using a resistance-in-series model based on the Darcy equation. The influences of the filtration setup and the fouling layer are described as additional resistances that change in course of filtration. The necessary parameters, such as setup resistances and filtration areas, are determined by water flow rate measurements. The model is validated by filtration of a particulate test solution. The presented approach can be used for constant flow and constant pressure driven filtration processes.

Scale‐up issues during sterile filtration of glycoconjugate vaccines

“…Second, the effective permeability of the membrane in the Opticap® XL2 (evaluated using buffer flow measurements) was five times smaller than that in the Amicon filtration cell due to the additional pressure losses associated with the inlet / outlet ports as well as flow within the pleats. This large difference in permeability is surprising given that a number of previous studies have reported similar permeabilities for disk and pleated filters of the same membrane material, 15 although this behavior is very similar to results reported by Haindl et al 10 and Rajniak et al 11 Third, there is significant variability in glycoconjugate fouling within the Opticap® XL2 (as seen in the confocal images), reflecting the variation in flow and pressure within the pleated cartridge. The first two factors can be accounted for by evaluating the resistance of the fouling deposit, which shows a similar variation with increasing volumetric throughput in both the small‐ and large‐scale filters (Figure 5), with the non‐uniform flow primarily effecting the initial increase in resistance at the start of the filtration.…”

“…The effective membrane permeability (L p ) was evaluated directly from the slope of the flux vs TMP data (with the intercept fixed at the origin), giving values of 500 L/m 2 /h/psi for the 0.22 μm Durapore ® membrane in the small-scale Amicon device compared to only 100 L/m 2 /h/psi for the large-scale pleated cartridge. A similar (7-fold) difference in permeability was reported by Haindl et al10 for the water permeability between a 47 mm disk and size 4 capsule, both employing Sartopore ® 2 polyethersulfone membranes. Rajniak et al11 also reported a significant (3-fold) difference in initial flux J o between small and pilot scale modules, with J o determined by fitting the filtration data to the standard blocking model.…”

“…A wide range of scale‐up factors ( S F ) have been reported in the literature: due to differences in flow geometries, extra‐membrane flow resistances, and fouling phenomena 9 . A recent study by Haindl et al 10 found values from S F = 0.75 to 2.5 in their review of the literature, although calculations performed based on water flow rates gave a scale‐up factor of 7.17 between a 47 mm disk and a Size 4 pleated capsule due to the additional resistance to flow in the large‐scale module. Rajniak et al 11 showed that the initial pressure‐normalized flux in pilot scale modules was smaller than that at bench scale due to differences in the pressure drop across fittings and within the module itself.…”

Development of an Experimental Dead-End Microfiltration Layout and Process Repeatability Analysis

“…The goal of the filter selection and validation is to ensure that the filter will operate without failure for the whole product batch [15]. The focus of this paper is on a small-scale laboratory experimental set, which was developed for laboratory testing since it is cheaper, faster, more controllable, and easier to change the process parameters [16,17]. It is beneficial to perform laboratory tests to select the proper filter and estimate its lifespan before actual filter implementation and process validation.…”

Microfiltration of micelles from fermentation of "Streptomyces tsukubaensis" for the production of tacrolimus

“…According to the Food and Drug Administration (FDA), filtration steps are important in the proper removal of specific microorganisms and contaminants and, therefore, have an essential impact on the smooth running of the entire biopharmaceutical process, on product yield and quality. Biopharmaceutical formulations are quite expensive, which is why the filter must be sized to avoid dead volume (HAINDL et al, 2020). Filtration is found in various industrial processes, for example, those present in water treatment, drug processing, and in the food industry.…”