Downstream

Taking Advantage of High Capacity Protein A: An Economic Comparison of the Resin Cost Per Gram of Antibody Produced

With pressures mounting to reduce production costs at many companies, and protein A being the most expensive resin used in mAb purification, the use of a high capacity protein A resin can significantly impact the overall cost of doing business. This report details how using a high capacity protein A resin will reduce production costs, on a per-gram produced basis, for companies that implement its use in their chromatography platform.

Robust, Load Independent Viral Clearance in Monoclonal Antibody Purification

Anion exchange chromatography is an important flow-through polishing step for viral clearance of monoclonal antibodies. Resin based materials are most commonly used for this but the large size of virus particles limits diffusion and binding capacity. It is therefore necessary to use large volumes of resin and oversized column hardware. Column chromatography as a unit operation also means high operational costs, including validation, cleaning and storage. This is a particular issue for clinical manufacturing, where a column is used for…

Increased Monoclonal Antibody Resolution with TSKgel® UP-SW3000 Columns

The antibody therapeutics market is enjoying high growth rates, the major areas of therapeutic application being cancer and immune/inflammation-related disorders including arthritis and multiple sclerosis. In 2013, six of the top ten best-selling global drug brands were monoclonal antibodies (mAbs) and more than 400 mAbs were in clinical trials. The characterization of these complex biomolecules is a major challenge in process monitoring and quality control. The main product characteristics to be monitored are aggregate and fragment content, glycosylation pattern and…

Characterization of Subvisible Particles in Vaccine Development

Vaccine manufacturers want meaningful information that can be linked to process knowledge to increase product quality and eliminate patient safety issues. New requirements from the United States Pharmacopeial Convention (USP) and the U.S. Food and Drug Administration (FDA) put pressure for root cause analysis to understand impact on changes during process and product development. The new demands involve not only size and distribution but deeper characterization that involves morphology and composition studies as part of particle characterization. Nanoparticles like virus,…

Safety Considerations for Gas Filtration in High-Temperature and Oxygen Enrichment Applications

Gas filtration using sterilization-grade filters is a key part of the production, manufacturing and packaging process of biopharmaceuticals and other products. While it may seem a simple step, there are major safety considerations that have to be taken in to account to protect staff, equipment and facilities from hazard, particularly when working in high temperature and oxygen enrichment applications. This paper examines the safety issues involved, looks at material design considerations and introduces a ready-made solution for safe, effective, robust…

Monoclonal Antibody Production: Viral Clearance and Host Cell Protein Reduction Using a High Capacity Single-Use Strong Anion Exchange Device

Strong anion exchange (Q) chromatography is an industry standard for polishing purification steps of mAb production. It is a proven technology which removes viruses, and host cell proteins from process feed streams in flow through mode. NatriFlo HD-Q devices adsorbers feature a hydrogel membrane which combines high dynamic binding capacity and salt tolerance to deliver best-inclass performance. This makes it possible to rapidly process large sample volumes using a small disposable device. This article examines the ability of NatriFlo HD-Q…

Monitoring Protein Unfolding and Refolding

Proteins exist in a highly ordered, folded state. This highly ordered structure of a protein is integral to the efficacy and safety of a protein-based biotherapeutic. Protein unfolding and refolding are an indicator of protein stability. As a protein begins to unfold, the hydrodynamic radii of the protein species change. Denaturation of proteins may range from slight and reversible conformational changes to a drastic loss of solubility, leading to irreversible aggregation. Monitoring the stability of the different protein conformations is…

Changing Column Packing from an Art into a Science

Chromatography is often the most critical step in biopharmaceutical downstream processing because of its role as the engine for separating impurities from target biologics. The most demanding operation in production scale chromatography is typically packing the column in a way that ensures first time success and a validation result which meets the batch record standards. Traditionally column packing has been the responsibility of a few specialist operators and has been regarded almost as an art by most observers. When the…

Monoclonal Antibody Production: Viral Clearance and Host Cell Protein Reduction Using a High Capacity Single-Use Strong Anion Exchange Device

Strong anion exchange (Q) chromatography is an industry standard for polishing purification steps of mAb production. It is a proven technology which removes viruses, and host cell proteins from process feed streams in flow through mode. NatriFlo HD-Q devices adsorbers feature a hydrogel membrane which combines high dynamic binding capacity and salt tolerance to deliver best-inclass performance. This makes it possible to rapidly process large sample volumes using a small disposable device. This article examines the ability of NatriFlo HD-Q…

The Effect of Membrane Selection and Operating Parameters on Sterile Filtration of Hyaluronic Acid

Hyaluronic acid (HA)-based solutions are traditionally difficult to filter, due to their high viscosity. Many users have found sterile filtration of hyaluronic acid solutions very challenging to implement, from both an economical, as well as a practical standpoint. This White Paper evaluates commercially-available sterilizing-grade products for filtration of HA and explains how sterilizing-grade filters can offer a highly efficient, economical solution even under the worst-case bacterial challenge conditions. It outlines how the combination of various properties of HA-based solutions and…