Abstract
This paper describes a method of predicting constant flow filtration capacities using constant pressure datasets collected during the purification of several monoclonal antibodies through depth filtration. The method required characterisation of the fouling mechanism occurring in constant pressure filtration processes by evaluating the best fit of each of the classic and combined theoretical fouling models. The optimised coefficients of the various models were correlated with the corresponding capacities achieved during constant flow operation at the specific pressures performed during constant pressure operation for each centrate. Of the classic and combined fouling models investigated, the Cake-Adsorption fouling model was found to best describe the fouling mechanisms observed for each centrate at the various different pressures investigated. A linear regression model was generated with these coefficients and was shown to predict accurately the capacities at constant flow operation at each pressure. This model was subsequently validated using an additional centrate and accurately predicted the constant flow capacities at three different pressures (0.69, 1.03 and 1.38bar). The model used the optimised Cake-Adsorption model coefficients that best described the flux decline during constant pressure operation. The proposed method of predicting depth filtration performance proved to be faster than the traditional approach whilst requiring significantly less material, making it particularly attractive for early process development activities.
Highlights
The market for therapeutic monoclonal antibodies has seen unprecedented growth in recent years and this expansion is predicted to continue over the decade [1]
In order to highlight the advantages of constant pressure operation compared to constant flow operation the depth filter performance was evaluated in both modes of operation using a wide range of processed materials
Whilst depth filter sizing at constant pressure is not common practice, this mode of operation has the advantage of processing samples more quickly than when operating at constant flow mode
Summary
The market for therapeutic monoclonal antibodies (mAb) has seen unprecedented growth in recent years and this expansion is predicted to continue over the decade [1]. Bolton et al [9] investigated the transition between these two modes of operation on dead-end microfiltration through characterisation of a bovine serum albumin foulant on a membrane filter They found that the parameter coefficients of various theoretical models used to fit the flux decline during constant pressure operation could be used within the constant flow model to predict the observed pressure increase. Additional experiments were performed to validate further the model and demonstrate its ability to predict accurately capacity at constant flow using data performed at constant pressure while using significantly less material This method may be highly beneficial at an early stage in the development of new molecules or proteins where material and time resources for process studies are often in short supply
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