Analytical

Toward Industry Standardization of Extractables Testing for Single-Use Systems: A Collective BPSA Perspective

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Here we present a consensus position of the membership of the Bio-Process Systems Alliance (BPSA), the trade organization for the single-use industry based in Washington, DC. BPSA’s membership includes 48 corporate and institutional entities, among them component suppliers, systems integrators, end users, and independent testing laboratories. Consensus within this membership is reached through an official ballot of representative voting members, as provided for in the organization’s by-laws. The position outlined below was approved by such an internal consensus-balloting process. Building…

March 10, 2015

Extractables Profiles: A Comprehensive Approach Produces Long-Term Results

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Biopharmaceutical manufacturers spend years developing and testing new drug and biologic products to ensure their efficacy, safety, and usability for patients. Such knowledge is extremely valuable, but those same principles often get overlooked in selection of packaging and delivery systems. Decisions on packaging and delivery often are made almost as an afterthought. However, issues related to components such as extractables and leachables can affect patient safety and product quality. In addition, a lack of extractables and leachables data in filings…

March 10, 2015

Culturing a Duck ES-Derived Cell Line in Single-Use Bioreactors: A Rapid, Efficient, and Cost-Effective Vaccine Manufacturing System Based on Suspension Culture

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Cell substrates managed in controlled culture environments have become, over the past few decades, the subject of intensive technological developments for the biomanufacturing of viral vaccines. The driving force of such work is an expanding demand for safety, high production capacities, cost savings, and flexibility. Egg, tissue, and primary-cell–based manufacturing methods of limited capacity are now considered to be outdated technologies. In the influenza vaccine field, for example, time delays in vaccine delivery (especially during pandemic responses) have increased concerns…

March 10, 2015

Improved Fluorescent Labeling Efficiency of N-Linked, High-Mannose Oligosaccharides: Using 8-Aminopyrene-1,3,6-Trisulfonic Acid (APTS) for Analysis of Glycoproteins

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Glycosylation of proteins, including monoclonal antibodies (MAbs), is recognized as important for the efficacy, immunogenicity, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) of biotherapeutics (1–6). So research and development of protein candidates is increasingly focused on the effects of glycosylation and how its pathway is affected in the Golgi system of cells involved in biosynthetic processes (7). Such attention on glycosylation has helped advance analytical technologies such as high-pH anion-exchange chromatography (HPAEC) (8); normal-phase chromatography (NP- HPLC), hydrophilic-interaction chromatography…

March 10, 2015

A Multidisciplinary Approach to Manufacturing Biotherapeutics

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Optimizing antibody manufacturing processes has gone beyond the first-order goal of achieving elevated protein titers and now also focuses on understanding biologic and manufacturing process variables that define cellular machinery and protein quality. A holistic approach to biotherapeutic manufacturing incorporates several applied disciplines such as biology, engineering, process control, signal processing, and modeling to reduce the “black-box†model of cell- based protein production into an operational design space. This is in line with the US Food and Drug Administration’s quality…

March 10, 2015

30 Years of Upstream Productivity Improvements

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We recently completed an analysis of the past 30 years of industry progress in commercial-scale expression titers and bioprocessing yields. These basic measures of biopharmaceutical manufacturing efficiency also benchmark the technological progress made in bioprocessing over recent decades. Titer and yield improvements generally indicate related bioprocessing cost savings, something most commercial-scale manufacturers work to improve. This focus on efficiency and productivity has led to constant bioprocessing improvements even for long-approved and -marketed products. Our findings indicate that although upstream titers…

February 6, 2015

Affinity Capture of F(ab’)2 Fragments: Using Twin-Column Countercurrent Chromatography

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Antibody fragments are potent active drug substances (1–4). Because they lack glycosylation, they can be produced using different biological expression systems, including yeast and microbial systems as well as mammalian cells. These molecules are interesting as biopharmaceuticals because they are smaller than full-size antibodies and therefore may penetrate better into different tissues. Antibody fragments are cleared faster in biological systems because they lack the Fc antibody structural region (4). However, fragments may be conjugated to increase their size for improved…

February 6, 2015

Simulating Seal Life with Finite-Element Analysis

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Finite-element modeling is an attractive alternative to physical testing for predicting seal life, particularly when aging poses major concerns and seal replacement is expensive. For years, seal manufacturers and users alike have searched for a reliable method for predicting how long seals will last in service. Past methods for evaluating an elastomer’s potential as a static or dynamic seal use American Society for Testing and Materials (ASTM) or other standard immersion tests. These tests involve submerging a material in a…

February 6, 2015

Evaluating Adsorptive Filtration As a Unit Operation for Virus Removal

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To date, the majority of recombinant monoclonal antibodies (MAbs) have been produced by mammalian cells. During such production processes, the potential risk of entrained viruses must be critically considered (1). Contamination can arise from animal cell lines or from adventitious viruses introduced during manufacturing. To ensure the viral safety of biotechnology products, companies can take four complementary approaches (2, 3): Using animal-component–free raw materials wherever possible Virus testing of master cell banks Virus testing of unprocessed harvest Performing downscale virus…

February 6, 2015

Protein A Intermediate Wash Strategies

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Protein A affinity chromatography offers efficient monoclonal antibody (MAb) purification and is used extensively in large-scale MAb production. As is the case with most chromatography media, protein A resins often have some degree of nonspecific binding, which causes host-cell proteins (HCPs) to coelute with a MAb. To reduce nonspecific binding interactions, an intermediate wash step can be performed before product elution. Doing so can improve product purity, extend column lifetime, and potentially eliminate a subsequent polishing step. For large- scale…

February 6, 2015