BPI White Papers

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…

Best Practices For Successful Filter Integrity Testing Using The Water Intrusion Test (WIT) Method

Hydrophobic filter cartridges which utilize sterilizing-grade polyvinylidene fluoride or polytetrafluoroethylene membranes are widely used in the pharmaceutical industry to sterilize compressed air or gases for product contact, as well as acting as sterile tank vents. However, hydrophobic membranes can also make filter integrity testing in situ difficult, as the membrane must be fully wetted prior to testing by the widely accepted integrity test methods of Bubble Point and Forward Flow. The Water Intrusion Test (WIT) is widely accepted within the…

Secondary Packaging: Creating Value with Product Lifecycle Management

with Daniela Guttmann and Susanne Hall Increasing regulatory requirements combined with the market pressure to develop patient-friendly drug delivery systems make product lifecycle management (PLM) a decisive field for today’s pharmaceutical and biotechnology companies. Their strategic service providers also are affected by those conditions. For example, as an internationally operating contract development and manufacturing organization (CDMO), Vetter reports an increasing number of life-cycle management projects with its customers in the past years. Learn more in this white paper from Vetter.…

The Path to Genderless Connectors: How Genderless Connectors Lead to More Flexibility, Faster Changeovers and Reduced Costs

Genderless sterile connectors — with their ability to interconnect with each other without male/female limitations — can enhance the flexibility of single-use systems in a wide range of bioprocessing applications. Genderless connectors reduce system complexity, which in turn lowers requirements for inventory management, simplifies operator training and reduces misconnections in the manufacturing suite. In fact, it’s possible this new connector design will drive industry change similar to the transition from stainless, reusable systems to single-use. How can something as small…

New Device for Biomass Monitoring in Shake Flask Culture

We developed a novel system for online biomass measurement in shake flasks based on near 360° scattered light detection. The optosensoric components were combined with the established PreSens SFR Shake Flask Reader technology, so biomass, pO2 and pH can be monitored non-invasively through the flask bottom. First application of the prototype SFR vario on Escherichia coli K12 and Kluyveromyces marxianus culture resulted in highly reproducible online biomass data, with relative errors matching those of standard offline OD measurements.

CaPure-HA™: Purification of MAb Fragments

Making use of chromatography resins with better selectivity, resolution and capacity is one approach to solving the problem not only of aggregate removal, but also that of MAb fragment and other digest products, in a column chromatography purification step. The data presented here demonstrate the capabilities of CaPure-HA to separate Fab and Fc fragments from undigested MAb in a papain digest of an IgG1 monoclonal antibody.

Cadence™ Single-Pass TFF Coupled with Chromatography Steps Enables Continuous Bioprocessing While Reducing Processing Times and Volumes

Continuous bioprocessing initiatives have accelerated in recent years. The transition from batch to continuous bioprocessing offers numerous advantages, including process time savings and lower capital costs due to smaller equipment, tanks, and tubing sizes. Additionally, hold tanks may no longer be needed between unit operations, which can be especially valuable for facilities with limited manufacturing floor space. Furthermore, reduced system hold-up volumes improve product recoveries and also contribute to the smaller system footprint of continuous bioprocessing systems. One unit of…