Upcoming Technologies to Facilitate More Efficient Biologics Manufacturing - Choosing the right tools to enhance the process. - BioPharm International


Upcoming Technologies to Facilitate More Efficient Biologics Manufacturing
Choosing the right tools to enhance the process.

BioPharm International
Volume 22, Issue 2


Figure 1
The Kleenpak tangential flow filtration microfiltration (MF) capsule from Pall Life Sciences (East Hills, NY) uses an Ultipleat pleated filter cartridge and Kleenpak Nova capsule with their operation based on TFF principles. The capsule is configured similarly to hollow fibers or cassette formats with feed, retentate, and permeate ports. As Figure 1 shows, the pleated construction is used inside the capsule to create multiple parallel flow channels while increasing the effective membrane area in a reduced footprint. It is simple to install and requires limited preconditioning before exposure to process fluid.

Figure 2
This technology has been tested with representative industrial strains such as Chinese hamster ovary (CHO) cells, bacteria such as E. coli, and yeast. Feed volumes of 50–100 L have been processed per single full-scale capsule (0.5 m2), depending on cell type and characteristics. The capsules can be manifolded together in series or in parallel to accommodate larger process requirements. For example, a six capsule assembly can process up to 1,000 L. Stable performance has been observed for monoclonal antibody (MAb) clarification from CHO cell feed with starting cell counts up to 1x107 cells/mL and step yields of greater than 98% have been obtained. For clarification of hybridoma cells expressing monoclonal antibodies, filtrate flux rates of 70 L/m2/h (LMH) to a volumetric throughput (VT) of 180 L/m2 have been obtained with a protein transmission of 100%. Protein expression for these cells was approximately 0.1 mg/mL.

Figure 3
A comparison of the Kleenpak TFF technology and two different types of cassettes for concentrating E. coli with all three devices incorporating membranes rated at 0.2 m (nominal) is presented in Figure 2. All three devices were operated at a crossflow flux rate (CFF) of 1.5 L/min/ft2. A five-fold volumetric concentration followed by a three-fold diafiltration buffer exchange was performed. The data shows that all three devices can be operated at a flux rate of 30 LMH throughout both concentration and diafiltration stages. Although the start and finish transmembrane pressure (TMP) values are different for the Kleenpak TFF filter compared to the cassette formats, the TMP gradient is similar for all three technologies and suggests stable operation. The flux and throughput performance of all three technologies was similar during these trials. Figure 3 presents a comparison of a Kleenpak TFF MF capsule with a Pall Microza hollow fiber module for clarification of IgG from a CHO cell culture with a cell density of approximately 2x106/mL. Each format was operated at a pumping capacity or crossflow flux rate (CFF) of 20 L/min/m2. It is seen that the Kleenpak TFF outperforms the hollow fiber module by processing more than three times the filtrate volume for a similar terminal TMP.

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