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

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


BioPharm International
Volume 22, Issue 2


Figure 6
Figure 5B shows the effect of concentration of ammonium sulphate in 50 mM potassium phosphate buffer pH 7.0 on the static protein binding capacity of the phenyl membrane compared to the base cellulose membrane (without phenyl functional groups). Data shown on binding of human polyclonal antibody to the membrane indicates negligible nonspecific interaction from the cellulose base matrix. Scalability of the hydrophobic membrane adsorbers is further shown in Figure 6. The study involved loading of human polyclonal IgG in 0.9 M (NH4)2SO4, 50 mM potassium phosphate, pH 7.0 on Sartobind phenyl membrane adsorber at 10 mL/min (Nano, 120 cm2/3 mL) and 500 mL/min (5-inch capsule, 5,000 cm2/125 mL), respectively. The amount of polyclonal IgG was normalized to membrane area. The normalized breakthrough curves of Sartobind phenyl Nano and 5" capsules in Figure 6 represent a successful 42-fold scale up.


Table 2
To summarize, the newly designed membrane structure in combination with appropriate hydrophobic surface functionalization provides a new scalable and disposable tool for the large-scale purification and separation of biomolecules as well as for polishing applications in the biopharmaceutical industry. The unique membrane-based technology addresses the requirements for high throughput production while reducing process time and complexity (no packing and packing testing) and adding flexibility.

SOLUTIONS FOR HIGH PARVOVIRUS RETENTION


Figure 7
Parvovirus filters are commonly used as means of effective removal of viruses from biological products by manufacturers as required by applicable industry regulations.10,11 The Viresolve Pro Solution from Millipore (Billerica, MA) is based on a dual layer polyethersulfone (PES) membrane and is designed to simultaneously deliver high parvovirus retention, capacity, and flux. It is also supported by an extensive safety assurance package. The formats are fully disposable, shipped gamma irradiated, and are caustic stable. The binary gas test (BGT) has been developed as a manufacturing release test and provides an increased sensitivity over air-water diffusion in its ability to detect small defects that could negatively impact virus retention. The expectation is that high capacity, flux, and fast set-up, combined with easy integrity testing, would translate into productivity gains from process development to full-scale production, thus reducing the cost of ownership for the virus filtration unit operation.


Table 3




Table 2 shows the results of a mice minute virus (MMV) retention study where grab samples were collected from two MAb solutions at various flow decay points. These samples were collected to determine if virus passage would occur through the Viresolve Pro Micro device as the membrane became increasingly fouled. Challenging the membrane at high flow decay tests the robustness. All feed and filtrate samples were assayed using validated TCID50 procedures and large volume assays were performed for filtrate samples with a total volume of 4 mL assayed for each sample. The log reduction value (LRV) was determined as the log10 of the ratio of input virus load and the output virus load as shown in the calculation below:

in which v1 and t1 are input volume (mL) and virus titer (TCID50/mL) respectively and v2 and t2 are output volume and virus titer (TCID50/mL) respectively.


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