Technical and Economic Benefits of Membrane Chromatography During Polishing Steps - An analysis of flow rate, load density, viral clearance, footprint, and cost. - BioPharm International

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Technical and Economic Benefits of Membrane Chromatography During Polishing Steps
An analysis of flow rate, load density, viral clearance, footprint, and cost.


BioPharm International
Volume 23, Issue 8

DISPOSABLE FT-AEX MEMBRANE CHROMATOGRAPHY FOR POLISHING

AEX resins typically are used as a polishing step in a FT mode for contaminant removal. Because the AEX resins remove only trace level of impurities, in principle, a small column should be significant to meet the impurity clearance requirements. However, the columns usually are over-sized at the manufacturing scale to meet process throughput requirements. AEX membrane chromatography provides an attractive alternative because of its convective mode of mass transport, which allows operation at a significantly higher linear flow-rate or smaller residence time than columns. The convective mode of mass transport coupled with the need for trace levels of impurity clearance enables the use of a membrane chromatography adsorber that is significantly smaller in size than a conventional column, which reduces buffer requirements.

Zhou and his collaborators at Amgen have extensively studied the membrane chromatography technology using Sartobind membrane capsules.13,14 The authors estimated water and buffer consumption comparing a stainless steel column to disposable membrane chromatography during polishing steps for contaminant removal and virus clearance in MAb purification processes. The authors observed a 95% buffer savings with the FT membrane chromatography as compared to traditional column chromatography, regardless of the production scale.15 The buffer and water consumption did not include buffers for column packing and validation incurred with resin reuse. At the 2,000-L scale, a 35-L column was necessary to accommodate the throughput, whereas a 0.18-L membrane volume was sufficient to clear contaminants and pathogens and achieve the required product purity. The smaller membrane chromatography device provides product of the same quality while reducing floor space requirements, hardware equipment, processing time, and labor use.

EVALUATION METHODOLOGY


Figure 1. BioSolve model used to estimate total CoG and CoG breakdown by cost categories. Data provided by Biopharm Services.
Figure 1 shows BioSolve (Biopharm Services, Ltd.), the Excel-based model that was used in this study. Models are useful tools to define process performance and gain insight into process fit in the confines of an existing plant. Of course, they only provide an approximation—a model of the real situation limited by the information available for input. The use of the model provides an estimation of CoG and CoG breakdown by cost categories. In the model, the CoG takes into consideration the fixed overheads of the facility and the variable operations costs of the process. The fixed overheads include capital charges, taxes, and insurance, whereas the variable costs include materials, consumables, labor, and waste management.12,16


Figure 2. Framework of the BioSolve model. The model comprises the user interface, process definition, productivity, cost calculations, and output.
Figure 2 depicts the framework of BioSolve, which comprises the user interface, process definition, productivity levels, cost calculations, and outputs. The interface provides a list of predefined key input parameters (e.g., process scale, expression level, solution preparation basis, single-user options) that enable the user to perform quick what-if analyses for different scenarios. The process information is defined in the cost model, which consists of the sequence of unit operations, mass and volume balances, equipment sizing, process operating conditions, and resource allocation. The model computes the facility throughput, equipment list, materials and consumables usage, and labor requirements. The model outputs include plant productivity, bill of materials and consumables, capital expenditure, and CoG.


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