Error loading player: No playable sources found

3924349

Demonstration of integration of in-line low pH viral inactivation in a continuous process

Date
August 16, 2023
Explore related products in the following collection:

Virus inactivation (VI) by low pH is an important step in the overall viral reduction strategy during purification of monoclonal antibodies (mAbs). As manufacturers move from traditional batch-based production to continuous modes of operation, methods for performing in-line VI have been investigated. While much of the initial focus during development of in-line VI solutions has been around characterization of residence time distribution at low pH, significant questions remain on how to optimize integration of this step into an overall continuous process while robustly maintaining critical processing parameters and quality attributes within acceptable ranges.

In this study, we used a custom-built benchtop in-line VI system automated with NI™ LabVIEW software and CyboSoft feedback controllers for in-line titration with acid and base. Surge vessels were used on both the inlet and outlet of the system, and a 0.22 mm bioburden reducing filter was located after the inlet surge vessel. A coiled flow inverter was built to achieve a minimum residence time of >30 minutes at our process flowrates. The system was incorporated into a continuous mAb process consisting of 15L perfusion bioreactor, multi-column capture chromatography, in-line VI, flow-through polishing, and continuous concentration/diafiltration, which ran in fully connected mode at steady-state for three days. Important connectivity considerations were investigated to elucidate the impact on process performance of operational choices such as surge vessel volumes and mixing method, titrant molarities, filter sizing, and flowrate control strategy. Learnings, challenges, and next steps for automated in-line VI control will be discussed. This demonstration of fully connected in-line VI provides a valuable case study to inform future process, system, and control development needs.

Related Products

Thumbnail for Dual mode “Turn ON-OFF-ON” photoluminescence detection of ethylenediaminetetraacetic acid and lead using Moringa oleifera gum-derived carbon dots
Dual mode “Turn ON-OFF-ON” photoluminescence detection of ethylenediaminetetraacetic acid and lead using Moringa oleifera gum-derived carbon dots
Lead is one of the most prevalent toxic heavy metal ions, and its pollution poses a significant threat to the environment and human health…
Thumbnail for High cell density cryopreservation for upstream process intensification using LN2 vapor phase stored seed train intermediates
High cell density cryopreservation for upstream process intensification using LN2 vapor phase stored seed train intermediates
Standard seed train operations start by thawing of a single 1 ml vial with cell densities of 10 x 106 VC/ml. For reaching a sufficient absolute cell number for production bioreactor inoculation, several expansion steps, starting with shake flasks, need to be performed…
Thumbnail for Demonstration of an end-to-end integrated and continuous bench-scale mAb production process
Demonstration of an end-to-end integrated and continuous bench-scale mAb production process
Much of the biologics industry’s future lies with integrated and continuous manufacturing (CM). Continuous processes can offer higher throughputs, tighter process control, and reduced material usage, all in a smaller plant footprint…
Thumbnail for Dual drug encapsulation in solid lipid nanoparticles for treatment of chronic obstructive pulmonary disease
Dual drug encapsulation in solid lipid nanoparticles for treatment of chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a respiratory condition that makes breathing difficult by affecting the lungs. It typically develops over a prolonged period and is commonly caused by long-term exposure to harmful gases like cigarette smoke and air pollution…