2014

Business Model Considerations for Development of Cell Therapies

The cell therapy industry continues to make progress, as measured by increasing numbers of clinical trials and patients treated (1). Although discussions of the differences between “off-the-shelf” (allogeneic) and “patient-specific” (autologous and matched allogeneic) therapies continue, we are confident that both will find success. The best way to approach development for a cell therapy product is to consider these three fundamental drivers that guide development: Speed to market (Which pathway will allow for fastest access to the commercial market?) Operational…

Establishing Single-Use Assemblies on Filling Equipment

Biotest is a worldwide-operating company specializing in innovative hematology and immunology products with the holistic approach of a global pharmaceutical and biotherapeutics group. The company’s products are used to treat life-threatening diseases such as coagulation disorders (hemophilia), severe infections, and disorders of the immune system. The most important starting material for Biotest’s pharmaceutical products is human blood plasma, which is processed into medicinal products at a production facility in Dreieich, Germany. The company has explored using single-use assemblies as part…

FDA Inspection Trends for Cellular Therapies

According to the late Norman Cousins, “Wisdom consists of the anticipation of consequences.” When it comes to regulatory inspections, those consequences can be severe. However, the consequences of a problem anticipated can be prevented — given effective action to remediate the issue. In two previous articles (1, 2), I discussed the whys and hows of using the US Food and Drug Administration's (FDA's) notices of deficiency, FDA warning letters, and other information about inspection results to create an effective system…

High–Cell-Density Clarification By Single-Use Diatomaceous Earth Filtration

Single-use concepts are widespread in all unit operations of the biopharmaceutical industry. Although single-use technology is rapidly advancing and considered to be highly advantageous in many regards (1,2,3), in some cases it cannot (yet) compete with classical manufacturing systems. Processes with a demanding character (e.g., high cell densities, high titers, high turbidities, increased particle/contaminant loads) especially can bring disposables to their limit of technical feasibility, especially in product harvesting (4,5,6). Here we focus on that step, which is defined as…

The Heat of the Moment

Calorimetry (from the Latin calor for heat and the Greek metry for measuring) measures thermodynamics in chemistry. If energy enters or leaves a system, its temperature changes, and most chemical reactions involve changes in energy. Exothermic processes generate heat; endothermic processes consume it. So calorimeters measure the heat of chemical reactions or physical changes to a system. Since calorimetry's advent in the late 18th century, a number of different techniques have been developed. Early techniques were based on simple measurement…

Comparing Multiuse and Single-Use Bioreactors for Virus Production

In the past decade, single-use bioreactors gained significant importance in manufacturing processes of monoclonal antibodies (MAbs) and recombinant proteins. The success of such technologies comes from their numerous advantages over multiuse equipment (1). Overall, disposables offer an answer to some key challenges in the biopharmaceutical industry: time to market, validation complexity, process security, production efficiency, and cost of goods. Because the same challenges apply to vaccine production, single-use bioreactors also have the potential to optimize manufacturing processes and offer further…

Comparing SDS-PAGE and CE-SDS for Antibody Purity Analysis

Antibody-purity analysis is critical to successful development of monoclonal antibody (MAb) biopharmaceuticals. Their manufacture involves processes of protein purification, formulation, and stability evaluation. All those processes need highly accurate and reproducible analytical results to support decisions made by product developers and manufacturers. A common technology for antibody-purity analysis is sodium-dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). In this technique, a polypeptide chain binds SDS proportionally to its relative molecular mass. The detergent nature of SDS denatures proteins by disrupting their noncovalent…

Understanding Particulates in Single-Use Bags

The biopharmaceutical industry is facing many challenges. Global economic changes, increasing healthcare costs, expiring patents, and increasingly personalized medicine all affect the way manufacturers approach bioprocessing steps and the equipment and systems used to make biological drug products (1). Demands for smaller batch sizes, greater process flexibility, reduced manufacturing costs, and increased speed to clinic have driven the acceptance of single-use systems (SUSs) in this industry (Figure 1). SUS suppliers have rapidly developed components such as fittings, tubing, pumps, sensors,…

Accelerating Purification Process Development of an Early Phase MAb with High-Throughput Automation

Purification process development of monoclonal antibodies (MAbs) has traditionally relied on a strategic trial-and-error approach using small-scale preparative chromatography for determining the operational parameters that would be optimal for clinical manufacturing. Doing so is demanding of both time and resources, and it thus restricts the number of early phase therapeutic drug molecules that can be evaluated in a company's development pipeline toward clinical trials. With high-throughput (HT) technologies incorporated at key points in development and laboratory operations, an operating space…

Efforts Toward the Harmonization of Single-Use Standards

During the 2013 BioProcess Conference and Exhibition, in Boston, MA, BPI held a town hall on single-use standardizations and best practices. The purpose was to update attendees on the current status of standardization and harmonization of single-use systems from the perspectives of a number of user groups and discuss the approach of each organization to such efforts. James D. Vogel, founder and director of The BioProcess Institute, moderated a panel of representatives from the Parenteral Drug Association (PDA), the International…