Modeling of Filtration Processes—Microfiltration and Depth Filtration for Harvest of a Therapeutic Protein Expressed in Pichia pastoris at Constant Pressure

Abstract

Filtration steps are ubiquitous in biotech processes due to the simplicity of operation, ease of scalability and the myriad of operations that they can be used for. Microfiltration, depth filtration, ultrafiltration and diafiltration are some of the most commonly used biotech unit operations. For clean feed streams, when fouling is minimal, scaling of these unit operations is performed linearly based on the filter area per unit volume of feed stream. However, for cases when considerable fouling occurs, such as the case of harvesting a therapeutic product expressed in Pichia pastoris, linear scaling may not be possible and current industrial practices involve use of 20-30% excess filter area over and above the calculated filter area to account for the uncertainty in scaling. In view of the fact that filters used for harvest are likely to have a very limited lifetime, this oversizing of the filters can add considerable cost of goods for the manufacturer. Modeling offers a way out of this conundrum. In this paper, we examine feasibility of using the various proposed models for filtration of a therapeutic product expressed in Pichia pastoris at constant pressure. It is observed that none of the individual models yield a satisfactory fit of the data, thus indicating that more than one fouling mechanism is at work. Filters with smaller pores were found to undergo fouling via complete pore blocking followed by cake filtration. On the other hand, filters with larger pores were found to undergo fouling via intermediate pore blocking followed by cake filtration. The proposed approach can be used for more accurate sizing of microfilters and depth filters.

Membrane Fouling for Produced Water Treatment: A Review Study From a Process Control Perspective

“…The models described in Table 4 do provide a common framework that is extensively deployed within membrane filtration [33,55,[124][125][126][127][128][129]. The models were originally intended for dead-end filtration and did not consider flux recovery methods.…”

Fouling mechanism and screening of backwash parameters: Seawater ultrafiltration case

“…These models were originally developed for frontal filtration at constant pressure [6][7][8][9]. However, it has been demonstrated that, under specific conditions, Hermia models could be applied in tangential filtration [10][11][12][13][14][15][16][17][18][19][20][21]. Hong et al [22] showed during tangential filtration of colloidal suspensions that the filtration process before the "pseudo stationary state" is similar to the frontal filtration.…”

Investigations of the mechanism of the fouling in microgranular adsorptive filtration

“…The intermediate blocking model is used when particles smaller than the pore size enter the pores and get either adsorbed or deposited onto the pore walls. And when particles get accumulated inside the membrane on the pore walls and the resulting constrictions of pores reduce the membrane's permeability the standard blocking model can be used [FIELD 2010;SAMPATH et al 2014]. These mechanisms have been used individually as well as in combination to explain experimental various observations [HALE, DANIELS 1961;HO, ZYDNEY 2000;SAMPATH et al 2014].…”