Downstream

Continuous Capture Chromatography, A simple, Robust Approach to Move From Batch to Continuous Capture

Increasing demands for the production of biopharmaceuticals, such as monoclonal antibodies (mAbs), vaccines and recombinant proteins, require new, innovative purification approaches with higher efficiency and productivity while maintaining or reducing costs. One of these approaches is continuous capture chromatography. Continuous capture chromatography, also known as CaptureSMB was developed by ChromaCon AG. CaptureSMB is a 2-column periodic counter current chromatography (2-PCC) process where the first column is fully loaded and breaks through to the second column. The first column is eluted…

Quantum ReNu SU Technology® Validation Guide and Performance Testing Summary

As the use of disposable systems within biopharmaceutical manufacturing has moved from niche preclinical applications to large scale commercial processes. This has led to the requirement for novel technologies that improve processing throughput and allow manufacturers to increase their output. To this end, WMFTG has developed a new pumping technology to enable end-users to meet their downstream processing needs for unit operations such as chromatography and tangential flow filtration (TFF). Quantum allows end-users to use novel peristaltic technology for their…

Achieving Continuous Downstream Bioprocessing Through Multi-Column Chromatography (MCC)

In recent years, improving downstream manufacturing has become an emerging challenge to the biopharmaceutical industry. Initially, the bottleneck in biopharmaceutical manufacturing existed in the output of bioreactors. Due to advances in cell line development and upstream process (i.e., perfusion), the output of bioreactors has increased at a much faster pace than downstream processing capacity. Therapeutic biologics, including monoclonal antibodies (mAbs), represent the fastest growing segment of the pharmaceutical market. By 2019, the biological market is expected to exceed 20% of…

Optimizing Unit Operations In Biopharmaceutical Manufacturing

There are many critical material-handling challenges regarding flow rates, pressure levels and the prevention of shear in the chromatography, virus filtration and TFF processes that are used in the manufacture of biopharmaceuticals. In order for these unique operations to be implemented successfully while handling fluids that can be sensitive, delicate and expensive, the operator must be aware of their specific operating characteristics and choose a pumping technology that can meet the strict demands for successful operation. While lobe and peristaltic…

Pegasus™ Prime: Robust Retention after Pressure Interruptions (Stop and Start)

Virus filtration is a vital part of the viral clearance strategy in bioprocesses. In filtration, size exclusion mechanisms are orthogonal to other inactivation or removal techniques and target the physical dimensions of the virus to achieve a high degree of virus reduction. Any flow or pressure interruption during filtration has been shown to increase the risk of virus passage. This application note reviews the PegasusTM Prime virus removal filters and demonstrates robust, high viral clearance in the presence of prolonged…

MiniTEM speeds up ‘time-to-insight’: automated purity analysis of two different Adenovirus samples

MiniTEM™ is a low-voltage transmission electron microscope system designed for nanoparticle characterization. The high-quality images it acquires reveal particle morphologies that can be transformed into accurate metrics. A metric for sample purity based on the ratio of the total area of debris to that of intact Adenovirus particles is presented in this study. The automated analysis that MiniTEM offers encompasses a far larger number of particles compared with studies performed manually using conventional electron microscopy, resulting in accurate and statistically…

An Example of Evaluation of protein A Multicolumn Processes for the Capture of Large-Volume, High Concentration Bioreactors, Based on BioSC® Predict Optimization Software

The present paper provides some recent data regarding the optimization of BioSC® processes using three commercially available protein A resins, based on the BioSC® Predict software. A rapid description of the first steps to develop a multi-column process guided by simulation is provided to avoid generating unrealistic conclusions. Other approaches could however be applied depending on the objectives targeted. Examples of multicolumn systems based on three commercially available protein A resins are also provided, for the purification of a 15,000-L…

Fast monoclonal antibody titer determination with the TSKgel® Protein A-5PW column

The antibody therapeutics market is enjoying high growth rates, the major areas of therapeutic application being cancer and immune/inflammation-related disorders. Six of the top ten best-selling global drug brands are monoclonal antibody-based. This market is predicated to show continued growth for many years to come, with more monoclonal antibodies (mAbs) designed and produced for treatments of specific diseases. Early in mAb development there are many harvested cell supernatant samples which contain mAbs that are secreted by cell cultures. These samples…

TOYOPEARL NH2-750F: Flow-through Removal of Endotoxin

Endotoxins are remnants of bacterial cell walls that may contaminate drug products and cause an immunogenic response. They are often referred to as “pyrogens” due to their fever-inducing effects. Endotoxins may be found in drug products either due to contamination from host cells used to produce a drug product in a bacterial expression system or due to adventitious bacterial contamination in non-microbial products. Thus, endotoxin clearance is a requirement of downstream processing of biologics, especially those derived from microbial expression…

A comparative study of MiniTEM™ versus DLS Zetasizer Nano and NTA NanoSight NS300 performance when analyzing < 50 nm particles

Characterization and analysis of subvisible particles of biological origin can be challenging or give insufficient information. In this study Adeno associated virus (AAV) particles contaminated by host cell proteasomes are analysed with direct versus indirect methods performed in a standard laboratory setting to reveal the difference in performance and quality of the information obtained. The focus is on the ability to detect the AAV particles of interest and distinguish them from the contaminating proteasomes. The compact, tabletop MiniTEM system enables…