Analytical

eBook: Bioassays for Biopharmaceuticals: Finding Best Practices in a Quality Systems World

Bioassays are complex and challenging experiments to run reliably with accurate and dependable results. Consistent performance requires a controlled environment and qualified reagents; skilled analysts who understand cell physiology, regulatory requirements, and the latest techniques; and assay protocols that are intelligently developed, characterized, and validated. Here, BPI’s senior technical editor discusses bioassay best practices with representatives of the Biopharmaceutical Emerging Best Practices Association (BEBPA) organization. Topics span quality by design, assay validation, cell banking, potency testing and host-cell protein monitoring,…

Comparative Study of Single-Use and Reusable Fermentors: Production of Recombinant Proteins Through Bacterial Fermentation

Single-use bioreactors have become widely accepted and well established for cell culture applications in the biopharmaceutical industry for over a decade (1). Abbott Diagnostics has moved into this technology already for commercial production of some biologic molecules. However, single-use systems (SUSs) are rarely available for microbial applications, mostly because of the technical challenge in designing cost-effective SUSs that can meet high oxygen transfer needs and remove excessive heat generated during fermentation. Thus, an important part of our biologics manufacturing —…

Viral Nanofilter Integrity: Using Variable-Pathlength UV-Vis Spectroscopy for the Gold Nanoparticle Test

Viral filtration (VF) using nanofilters removes endogenous and/or adventitious viruses from biologic drug-substance manufacturing processes (1). The gold particle test (GPT) is performed as part of postuse integrity testing — to complement postuse leakage testing — for cellulose filters such as Planova 20N filters from Asahi Kasei Corporation. First, a proprietary gold-colloid solution matched to the filter type (e.g., 20N) is filtered through the test article. That filter’s pore-size distribution can be assessed using spectrophotometric absorbance readings of the integrity-test…

Adenovirus Downstream Process Intensification: Implementation of a Membrane Adsorber

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…

The Critical Role of Media in Intensified Upstream Processes

As the need for novel therapeutics increases, so does pressure on the biopharmaceutical industry to improve productivity, accelerate development, increase, and reduce costs — all while ensuring drug product quality. Upstream intensification strategies such as perfusion culture can address those challenges and achieve higher protein titers that can translate into higher throughput, improved flexibility, and compressed timelines. Successful implementation of perfusion culture or the transition to perfusion from fed-batch culture requires a different and strategic approach to media selection, not…

Flow Monitoring in Continuous Processing and Single-Use Systems

Flow sensors placed at critical points in both upstream and downstream processes fulfill the regulatory goals of the process analytical technology (PAT) framework. PAT has been defined as a mechanism for design, analysis, and control of biotechnical and pharmaceutical manufacturing processes through measurement of critical process parameters (CPP). Constant flow monitoring can support its overall targets fundamentally to reduce production cycling time prevent rejection of batches enable real-time release increase automation and control improve energy and material use facilitate continuous…

Special Report: Current Analytical Approaches to Biophysical Characterization in a Regulatory Environment

Structural integrity of protein-based therapeutics is one of the major challenges in the biopharmaceutical industry. Multiple factors such as product stability, efficacy, and shelf life could be affected following minor changes in manufacturing process. Multiple biophysical methods employing spectroscopic and calorimetric tools can be used to analyse Higher Order Structure (HOS). Moreover, with an increasing demand for generating as much structural information as possible for regulatory submissions, a requirement for these analyses in a GMP environment is also important. This…

Technology Highlights from the 2019 BioProcess International Conference

This year’s BioProcess International Conference and Exhibition, held 9–12 September 2019, hosted nearly 200 exhibitors showcasing technical innovations for the biopharmaceutical industry. This year’s conference sessions also included daily technical workshops detailing supplier solutions and technologies. Below are some notable technologies featured that demonstrate the industry’s dedication to finding new ways to help manufacturers shorten time to market. Most systems offer the benefits of single use, integration, process control, economies of scale, automation, and closed-system processing. Upstream Production The exhibit…

Smart Sensors and Data Management Solutions for Modern Facilities

Bioprocess manufacturers continue to seek technologies for increasing productivity and shortening timelines from discovery to commercialization. Innovations such as high-throughput systems, automated platforms, and the latest clarification systems all have made processes efficient and robust. And with the increasing adoption of quality by design (QbD) principles, including the use of process analytical technologies (PAT), biomanufacturers are mitigating the risks of errors in their operations better than ever before. A critical part of mitigating risk is gathering meaningful process data and…

Rapid Implementation of Novel Affinity Purification: Manufacture of Commercial-Scale Next-Generation Antibody Therapies

The rapid and cost-effective production of conventional monoclonal antibodies (MAbs) for clinical trials and commercial supply has contributed toward their wide adoption. Production processes have become more efficient because common purification processes are being used across structurally similar MAbs during key steps of process development and manufacturing. Such successful platform approaches can remove unwanted impurities and are stable across processing conditions, irrespective of the MAb being purified. In addition, they are readily available at the required volume to support large-scale…