April 2016

From the Editor

Included with this issue is our first of two supplements this year focused on cell therapies. It has been fascinating to watch this journey toward maturation of advanced therapeutics. Some early assumptions that commonalities with protein production would resolve manufacturing problems are being tempered now that we know more about the unique demands of cell and gene therapy development. Still, the future looks brighter for these new modalities. As Invetech’s Richard Grant (global VP, cell therapy) noted in his plenary…

Spotlight

Preventing Vaccine Shortages Few people worry about vaccine supply until a shortage occurs. New research from Duke University’s Fuqua School of Business focuses on market tensions that can keep vaccine manufacturers out of the business and price points needed to entice them in. “The government doesn’t want to overpay,” says professor David Ridley, “but there’s a tension between responsible use of government funds and giving manufacturers sufficient incentives to get into vaccine manufacturing — and stay in.” Together with colleagues…

Bioprocessing Standards for Single-Use Components Are Moving Forward

With the escalating use of single-use technology in bioprocessing, suppliers have had to rapidly develop disposable components such as fittings, tubing, pumps, sensors, and flexible containers for bioprocessing. Single-use technology is growing so fast that the organizations tasked with guiding its growth are having difficulty keeping up. Contributing to this problem are factors such as company needs, regulatory requirements, market pressures, and costs. That growth has posed considerable concerns for the bioprocessing industry about the presence of organic and inorganic…

Achieving Competitive Advantage in the Biopharmaceutical Industry

Drug development is a complex process that is associated with high drug-candidate attrition rates, long development times, and high costs (1, 2). Drug development costs have increased over the past two decades, with current average development cost of about US$2.6 billion, of which $1.4 billion is the direct cost (1, 2). On average, drug development takes at least 10 years to market authorization (2). Biopharmaceutical companies often follow a strategy of developing drugs for multiple clinical indications and biological targets…

CMC Strategy Forum Special Focus Series: Part 2 Product-Related Impurities, An Overview

Introduction by Cheryl Scott The CMC Strategy Forums focus on relevant chemistry, manufacturing, and controls (CMC) issues throughout the life cycle of a therapeutic and thereby foster collaborative technical and regulatory interaction. Forum chairs share information with regulatory agencies to help them merge good scientific and regulatory practices. Outcomes of forum meetings are published in BioProcess International and on the CASSS website. This process is meant to help ensure that biopharmaceutical products manufactured with advancing technologies in a regulated environment…

Fucosylation of a Therapeutic Antibody: Effects on Antibody-Dependent, Cell-Mediated Cytotoxicity (ADCC) Potency and Efficacy

Product quality attributes are critical for the functionality and manufacturability of therapeutic antibodies. They can be significantly influenced by a number of production process parameters, such as cell culture media. The composition of growth and feed media can influence antibody glycosylation, including the concentration of ammonia, glutamine, glucose, and metal ions (1, 2). Thus, it is critical during media development and optimization to monitor and consider a culture medium’s impact on glycosylation. For therapeutic antibodies whose mechanism of action includes…

Rapid Formulation Development for Monoclonal Antibodies

Monoclonal antibodies (MAbs) are at the focal point of biologics development. Many of the best-selling drugs are therapeutic MAbs or related proteins (1–2). The combined world-wide sales from MAbs will be nearly US$125 billion by 2020 (3). About 50 MAb products treating a range of diseases have been approved in the United States or Europe. With the large number of MAbs progressing through discovery, biomanufacturers need to accelerate process development and move projects rapidly into clinical manufacturing (4–5). Formulation development,…

Prepacked Chromatography Columns: Evaluation for Use in Pilot and Large-Scale Bioprocessing

Time to market, resource requirements, cost, and flexibility are key considerations in designing purification processes suitable for manufacturing biopharmaceutical products. Over the past decade, many advances have been achieved in disposable processing systems that have allowed for increased processing at a lower cost. That is in part attributable to reductions in necessary resources, changeover costs, and cleaning-validation requirements. Large-scale, prepacked chromatography columns have recently become available for clinical and commercial manufacturing, and they represent a growing trend in the industry.…

Benefits of Using Tetradetector SEC to Characterize Membrane Proteins

About 60% of all drug targets are membrane proteins. So understanding their structure and function as well as their interactions with drug candidates is critical to discovery and development of new therapeutic agents. Solubilization of these proteins is an essential precursor to in vitro studies of receptor function, structure, and activity. Purification and crystallization are important aspects. However, solubilization is complicated by the hydrophobic nature of a protein’s membrane-spanning part. Surfactant micelles and other stabilizing systems thus are used to…

Virus-Filtration Process Development Optimization: The Key to a More Efficient and Cost-Effective Step

Size-exclusion–based parvovirus filtration is an important step toward drug product safety in biopharmaceutical production. However, once a virus filter is in place, and the required virus safety is ensured, less attention typically is paid to its optimization within the process. That might seem odd given that virus filtration can be one of the more expensive downstream processing steps ($/g protein processed). Most likely, the lack of attention can be attributed to aggressive timelines, limited process development resources, and the virus…