MAb

Decision-Support Tools for Monoclonal Antibody and Cell Therapy Bioprocessing: Current Landscape and Development Opportunities

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Industrial-scale manufacturers in a number of fields — from automobiles to biotherapeutics — have long relied on powerful computational and mathematical tools to aid in the scale-up, optimization, quality control, and monitoring of product development (1–5). Typical process pathways are highly multifactorial, with numerous branch points, feedback steps, instrumental attributes, and target parameters. Moreover, margins for error are minimal for most industrial processes, requiring high standards of precision from industrial and operational pathways (6). For those reasons, the complexity of…

December 16, 2015

Comprehensive Hands-On Training for Biopharmaceutical Manufacturing: BTEC’s Program to Deliver Training to FDA Investigators

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Training and continuing education play a vital role in carrying out the US Food and Drug Administration’s mission to protect and promote the public health — not only for consumers, health professionals, and industry, but also for the agency’s own personnel. Since 2008, the Golden LEAF Biomanufacturing Training and Education Center (BTEC) at North Carolina State University has filled a niche in the agency’s internal training program and provided a series of courses to more than 100 FDA investigators. The…

September 23, 2015

Uniting Small-Molecule and Biologic Drug Perspectives: Analytical Characterization and Regulatory Considerations for Antibody–Drug Conjugates

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Cosponsored by CASSS (an international separation science society) and the US Food and Drug Administration (FDA), the January 2010 CMC Strategy Forum explored antibody–drug conjugates (ADCs), which are monoclonal antibodies (MAbs) coupled to cytotoxic agents. The ADC platform of products is being used more and more for clinical evaluation in oncology. More than a dozen companies are developing several types, including products conjugated with calicheamicin, auristatins, and maytansinoids. Such products use the specificity of a MAb to deliver a cytotoxic…

September 23, 2015

Compatibility Assessment of a Model Monoclonal Antibody Formulation in Glass and Blow–Fill–Seal Plastic Vials

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PREPRINT October 2015 issue Blow–fill–seal (BFS) technology has been recognized by the industry as an advanced aseptic solution (1–3). Catalent Pharma Solutions has been commercially supplying sterile BFS products to the pharmaceutical industry for decades, primarily in the respiratory and topical ophthalmic markets. Such product formulations range from simple solutions to emulsions with drug substances from classical small molecules to large complex proteins such as biologics. The company also has optimized BFS processes and its Advasept plastic container system for…

July 13, 2015

Anion-Exchange Chromatographic Clarification: Bringing Simplification, Robustness, and Savings to MAb Purification

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Monoclonal antibodies (MAbs) are the most prominent and successful therapeutic proteins in the pharmaceutical industry. More than 35 MAbs have been approved to treat a range of conditions, and hundreds more are in development (1, 2). Once, the upstream cell culture process was considered the bottleneck to producing high antibody doses required for treatment, but recent advances in cell culture technology have boosted antibody titers to the range of 5–10 g/L (3). That increase in productivity has shifted focus onto…

June 16, 2015

An Industrial Platform Solution for Antibody Fragment Purification

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Compared with traditional approaches such as chemotherapy and radiotherapy, monoclonal antibodies (MAbs) have become the most successful cancer treatments in the past 20 years (1). With great clinical success in many therapeutic areas, MAbs now account for >40% of the entire biotechnology drug market, and sales are projected to be >US$160 billion over the next few years in the United States alone (2). More than 35 MAbs have been approved for clinical use, and hundreds more are filling industry development…

June 16, 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

The Importance of the Concentration-Temperature-Viscosity Relationship for the Development of Biologics

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JIM DELILLO (WWW.FREEIMAGES.COM) Patient preference and a competitive landscape in the parenteral market have fueled the need for convenient delivery systems and a desire for less‑frequent dosing injections. Monoclonal antibodies (MAbs) often have high dose requirements, so they must be formulated at very high concentrations (1). At low concentrations, an antibody solution’s viscosity increases moderately as a function of protein concentration. But at high concentrations (>100 mg/ mL, depending on the molecule), viscosity increases exponentially (2, 3). Thus, a specification…

March 10, 2015

Characterization of Postcapture Impurity Removal Across an Adsorptive Depth Filter

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In the manufacture of monoclonal antibodies (MAbs), the first purification step following harvest clarification is normally protein A affinity chromatography because of its high selectivity for IgG and high process yield (1, 2). At this stage, a MAb is eluted from a protein A ligand at low pH and then held or adjusted to a low pH (pH ≤ 3.8) for a given amount of time before pH adjustment, usually ≥30 minutes, in a virus inactivation (VI) step targeted at…

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