Downstream Processing

Discover, Develop, Deliver

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Astrea Bioseparations is the only adsorbent supplier that can discover new affinity ligands designed to bind selectively to a molecule of interest or specific impurity, develop efficient purification adsorbents and downstream methods, and deliver industrial-scale adsorbents (up to 1,000-L batch sizes) as loose slurry or in good manufacturing practice (GMP)-ready columns. With over 30 years of experience in development of affinity products and design and manufacture of new custom adsorbents, Astrea Bioseparations is a world leader in its field. The…

June 10, 2020

Reduce Downstream Processing Costs for MAbs By Switching to a Two-Step Platform

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Downstream processing operations make up to 80% of the total costs for processing biotherapeutics. Given the current drive to reduce downstream costs, chromatographers and process engineers will need to streamline processes. Herein, we describe the benefits offered by using Tosoh’s two-step process for purifying monoclonal antibodies (MAbs) and compare that method with the standard industrial process. By combining high-performance protein A capture and a single polishing step on salt-tolerant anion-exchange resin, Tosoh’s approach can reduce downstream costs by 45% and…

June 10, 2020

Capture of CH1-Containing Bispecific Antibodies: Evaluating an Alternative to Protein A

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Bispecific antibodies (BsAbs) are designed to recognize and bind two different antigens, in many cases for the purpose of immune effector-cell activation to destroy cancer cells (1). Such BsAbs mediate cell killing by binding simultaneously to an antigen that is overexpressed on tumor cells and to the CD3 receptor, activating cytotoxic T lymphocytes (2). Using proprietary UniRat human heavy-chain technology combined with OmniFlic human fixed–light-chain antibody technology licensed from Ligand Pharmaceuticals, Teneobio has produced several bispecific antibodies, each targeting a…

May 24, 2020

Dynamic Binding Capacities of Protein A Resins for Antibody Capture: A Comparative Evaluation

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The dynamic binding capacity (DBC) of a chromatography resin represents the total amount of target protein that the resin will bind under actual flow conditions before significant breakthrough of unbound protein occurs. This is a useful parameter for predicting what the process performance of a resin will be in actual use. DBC affects the overall amount of resin that can be packed in a given column for a process — and the number of batches that can be processed cost-effectively…

May 24, 2020

A Challenge in Viral Clearance Determination: Estimation of Fifty-Percent Tissue Culture Infective Dose (TCID50) for Low Virus Concentrations

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Performing viral clearance studies is an important safety element of manufacturing all biopharmaceuticals expressed from mammalian cells (1). Typically, viral clearance is described as a log reduction value (LRV) and calculated as the log10 of the ratio of input to output virus load. Amounts of virus load are calculated from the volume and concentration of input and output fractions. Virus concentration is often calculated as 50% of tissue-culture infective dose (TCID50) using the Spearman–Kärber (SK) equation (2, 3). In this…

May 24, 2020

Setting a Cornerstone for Platform Purification of Exosomes

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Exosomes are a subject of rapidly growing therapeutic interest in the biopharmaceutical industry for two principal reasons. The first reason is that they are the primary communicators of instructions from source cells to target cells. Exosome surface features define their destination. They recognize complementary features on target cells, dock with them, and deliver their programmed instructions in the form of microRNA. The second reason is that exosomes are immunologically silent. As normal human cell products, and by contrast with gene…

April 13, 2020

Ask the Expert: Highly Sensitive Host-Cell Protein Analyses Using Novel Chromatography Technology

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Geert Van Raemdonck (global field support expert at PharmaFluidics) and Koen Sandra (scientific director of the Research Institution for Chromatography, RIC) teamed up for a 10 October 2019 “Ask the Expert” webinar to introduce micro Pillar Array Column (μPAC™) technology for liquid chromatography–mass spectrometry (LC–MS) for host-cell protein (HCP) detection. Van Raemdonck explained that μPAC technology approaches chromatography differently than does packed-bed technology. Microfluidic channels with arrays of free-standing pillars are etched lithographically into a silicon wafer. The resulting permeability…

February 6, 2020

Monoclonal Antibody Aggregate Polish and Viral Clearance Using Hydrophobic-Interaction Chromatography

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Hydrophobic Interaction chromatography (HIC) is a powerful polishing tool for the downstream purification and manufacture of biotherapeutics. HIC offers orthogonal selectivity for the clearance of difficult process and product-related impurities such as aggregates, host cell proteins and endogenous and adventitious viruses.  In this study, a family of POROS HIC resins with novel ethyl and benzyl chemistries was used to successfully polish two clinical stage monoclonal antibodies harboring very high levels of product aggregation (>10%). In addition to aggregate removal, viral…

December 16, 2019

Adenovirus Downstream Process Intensification: Implementation of a Membrane Adsorber

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Historically, companies developing vaccines have used attenuated pathogens, inactivated infectious agents, or antigenic constituents purified from pathogenic sources. In the past 20 years, technological advances such as recombination and viral vectors, have enabled development of vaccines against diseases with previously no available treatments (1). Viral vectors have become one of the most rapidly evolving and promising fields in vaccinology and regenerative medicine. In addition to preventing infectious disease, they have a broad range of potential applications, including treatment of hereditary…

October 28, 2019

Addressing Regulatory Requirements for Filter Integrity Testing

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Filter integrity is a fundamental element of sterility assurance during production of biopharmaceutical and vaccine products. Integrity test results are a key foundation for drug lot release, so any external element that could affect their reliability must be viewed as a critical issue. But when should a filter integrity test be performed? This article highlights the Sartocheck 5 Plus filter integrity tester as a means to address regulatory requirements. Please fill out the form below to read the full article…

October 28, 2019