There has been a rapid uptake of disposable technologies in the biopharmaceutical industry over the last decade, including disposable modules for chromatography. Disposable membrane chromatography has proven to be a powerful alternative to polishing columns, particularly for process-scale monoclonal antibody purification, because of advantages such as high throughput, faster processing time, reduced buffer consumption, and elimination of column packing and packing testing activities. Disposable technologies also allow facilities to run multiple products in a single plant without the risk of cross-contamination between batches. This article demonstrates through, a case study, the practical and economic benefits gained from replacing reusable column chromatography with disposable membrane chromatography. The study looks at the whole process and evaluates the production costs for the stainless steel option, in which all unit operations are performed using stainless steel equipment items, and the disposable option, in which column chromatography is replaced by disposable membrane chromatography and all other unit operations are based on stainless steel equipment items.
AEX chromatography is perhaps the most powerful tool to remove a variety of viruses, DNA, and endotoxins.8 In most cases, AEX chromatography is carried out using flow through (FT) mode, with the impurities binding to the chromatographic support and the product and the product of interest flowing through.
Replacing AEX column chromatography with AEX membrane chromatography has resulted in similar viral clearance at a much higher flow rate and load density compared with columns. Arunakumari, et al., recently reported >4 logs of minute mouse virus (MMV) and murine leukemia virus (MuLV) removal using Sartobind Q membrane adsorbers (Sartorius Stedim Biotech) in monoclonal antibody (MAb) processes at a load density of up to 20 kg MAb/L of membrane.9 The diffusion dependence and pressure limitation associated with column chromatography significantly limit throughput at large scales and lead to column oversizing in traditional polishing scale up. Because of the hydrodynamic benefits, membrane chromatography involves much smaller devices than columns with a similar output and no bottlenecks.1,2,10 Such disposable technology offers the added advantages of reducing buffer volume, processing time, and floor space requirement. Membrane chromatography is a disposable operation system; there is no need for column hardware, packing-related studies, resins life studies, carry-over studies, cleaning-in-place (CIP) and steaming-in-place (SIP) procedures, and validation. Membrane chromatography offers easy solutions to biomanufacturing, increases flexibility, and lowers capital requirements—all of which are benefits derived from disposable technology.
Whereas the disposable approach has been accepted for many years for operating certain unit operations in upstream and downstream processes such as cell harvest, filtration, and buffer and media storage, an increased trend toward disposable technologies only has been observed in the last five years in response to the needs of biopharmaceutical companies. In an effort to increase capacity without exposure to excessive investment risk, biopharmaceutical companies are considering disposable manufacturing.11 The economic benefits of single-use membrane chromatography for polishing as a single unit operation has been demonstrated.12 In this paper, we analyze the cost impact of replacing reusable chromatography technology with single-use membrane chromatography technology in the FT mode for the AEX polishing step, looking at the overall cost of goods (CoG) and the breakdown of the CoG into different categories (i.e., capital charges, materials, and consumables). The FT AEX polishing step was implemented as a unit operation in the whole process at a production scale of 2,000 L. The study evaluates the production costs for the whole process based on all stainless steel equipment and compares it to the process in which the Q column is replaced by the Q membrane capsule.