Analytical

Mitigate Risk with Effector Function Characterization for Antibody Therapeutics

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The complexities of biomanufacturing combined with heterogeneity introduced by cellular expression systems present significant challenges to assessing the quality of biologics such as monoclonal antibodies (MAbs). Information related to the critical quality attributes (CQAs) of MAb drug candidates is unknown during early phase drug development. It must be established empirically by physical, structural, and functional analyses as early as possible to accelerate development and mitigate risk through greater understanding of product characteristics. High-resolution analytical techniques are required to answer questions…

December 4, 2019

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

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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,…

October 30, 2019

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

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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…

October 28, 2019

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

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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…

October 21, 2019

Smart Sensors and Data Management Solutions for Modern Facilities

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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…

October 21, 2019

CMC Development Platforms and Outsourcing to Reduce Timelines

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Forty Seven is a company developing novel therapies based on anti-CD47 and other immuno-oncologies. CD47 is called the “don’t eat me” signal that cancer cells give out to escape elimination by the body’s immune system. Qinghai Zhao, vice president of technical development and manufacturing, is one of the scientists working on the company’s magrolimab (5F9) monoclonal antibody that is designed to block the binding of the CD47 signal to the cell receptor SIRP-α while boosting the “eat me” signal that…

October 21, 2019

Introduction: Reporting from the Frontiers of Cell Line Engineering at BPI Europe and BPI West

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Every biomanufacturing process begins with transfection of recombinant genes into pools of cells — followed by a succession of screenings from which will emerge (ideally) a single progenitor cell of the new production cell line. Cast aside will be those cells that do not uptake the correct genetic material, those incapable of thriving in bioprocess conditions, those that fail to produce recombinant protein at relevant levels, and those without demonstrated clonality and relative genetic stability. Over the past several years,…

September 26, 2019

Time Is of the Essence: Optimizing Cell Line Development

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Cell line development is a critical upstream step for the manufacture of monoclonal antibodies (MAbs). Cells must be engineered to produce a biologic of interest, and the right clone must be selected to deliver material for preclinical and clinical studies. A high-producing cell line is then needed to support clinical studies and, ultimately, commercialization of the therapeutic. Please fill out the form below to read more. Corresponding authors are Aurore Poles, Global Technical and Compliance Expert, and Guillaume Plane, Global…

September 21, 2019

Biosimilarity Assessments: The Totality of Evidence Framework

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Biosimilars are evaluated through comparisons with their reference products using abbreviated pathways that have evolved significantly over the past few years. Scientists and regulators now accept that some quality attributes can vary from batch to batch over a product’s lifecycle, even for reference products. Moreover, reference and similar biotechnology products can show differences in noncritical quality attributes but still demonstrate comparable efficacy and safety (1). Here we describe a similarity assessment approach that is also applicable to comparability of lifecycle…

September 21, 2019

Embedded Particles in Single-Use Bags: Risk to Bag Integrity and Drug Product Purity, or Only a Cosmetic Defect?

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When using single-use systems (SUS) to process biopharmaceuticals, preventing drug product contamination from extractables and leachables (E&Ls) and embedded particulate matter (gel particles) in the polymer films used to make bioprocess bags is critical. Using a pressure burst test to assess film integrity, Sartorius Stedim Biotech’s Klaus Wormuth and colleagues compared Flexboy and Flexsafe samples with gel-particle-free materials to assess their potential for contamination. The results showed that only large (2–4 mm2) gel particles affected the burst test results, concluding…

September 21, 2019