Product Characterization

eBook: Product Variants in Bioprocesses

Product variants are contaminants because they bear properties that are different from those of desired biological products with respect to activity, efficacy, and safety. Thus, such variants can compromise product quality and consistency. In this eBook, Yuval Shimoni explores different types of variants — including primary-sequence variants, undesirable posttranslational modifications, aggregates, and degraded proteins — and explains how their presence can diminish the performance and quality of drug substances and products. He also discusses how product variants form at different…

Analytical Methods for Cell Therapies: Method Development and Validation Challenges

Advanced-therapy medicinal product (ATMP) characterization and analysis play important roles in providing chemistry, manufacturing, and controls (CMC) information for regulatory applications as well as in supporting product-release and stability studies. Each type of advanced therapy presents different analytical development challenges, so each requires specific characterization, potency, purity and identity assays. Variability in cells and among patients, multiple and complex mechanisms of action (MoAs), a general lack of readily available reference materials, and complicated analytical methods and instruments underlie the major…

Expanding the Flow Cytometry Toolkit with Next-Generation Polymer Dyes

Since the emergence of SARS-CoV-2, scientists have discovered more about the role of our immune systems and cytokine-associated processes responsible for systemic immune reactions that are typical in patients with COVID-19 (1). Flow cytometry is used to understand those processes at a single-cell level. It is the standard method used in immunology to characterize multiple phenotypic and functional parameters of single cells, including cytokine analysis. Despite advances in flow cytometry instrumentation, reagents, and analytical software, several challenges remain. Conjugated antibodies…

SARS-CoV-2 Hyper-Immunoglobulin: Purification and Characterization from Human Convalescent Plasma

The novel severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) emerged as a major pandemic coronavirus disease in 2019 (COVID-19) and since then has killed many people and paralyzed the global economy (1, 2). With specific antiviral therapeutic agents or antibodies yet to be approved, other antivirals and novel vaccine strategies have been essential to containing the virus and disease transmission. Passive antibody therapy can be used to limit the scope of epidemics by providing patients with antibodies that recognize…

Improving Cell Manufacturing Outcomes Using In-Line Biomarker Monitoring

Cell-based advanced therapies are changing modern medicine dramatically. Immunotherapies such as chimeric antigen receptor (CAR) T-cell therapies are treating different forms of cancer. Gene therapies are reversing the course of inherited diseases, and tissue-engineered medical products are restoring, maintaining, and replacing damaged organs (1–4). The development of new advanced therapies is booming. As of January 2020, the US Food and Drug Administration (FDA) has reported more than 900 investigational new drug (IND) applications for cell and gene therapy products. However,…

Ask the Expert: New and Improved Analytical Methods for Traditional and Unique Modalities

On 10 December 2020, BPI presented an “Ask the Expert” webinar with Jason Sterling, PhD (principal scientist and project director in analytical and formulation resources), and John Rockwell (group leader) of Catalent Pharma Solutions. Biophysical characterization is critical to understanding the makeup and behaviors of biologic therapies and vaccines both early in development and throughout scale-up for manufacturing. As biologics become more complex in structure and as scientists improve their understanding of the effects of structure on stability, efficacy, and…

Advanced Analytics to Accelerate Development of Genetic Vaccines

Biopharmaceutical companies are racing to develop vaccines that mitigate the COVID-19 pandemic, taking a wide range of vaccine-development approaches that include traditional modalities and cutting-edge technologies based on DNA and RNA. Vaccine developers are leveraging robust manufacturing concepts and integrated processes to shorten timelines. Advanced analytics also are playing a critical role in ensuring the safety and efficacy of those emerging vaccines. A New Wave of Vaccines Vaccines based on attenuated viruses entail development timelines ranging from four years to…

Ultracentrifugation for Recombinant Adenoassociated Virus Therapies

Quantitation of different capsid species in viral-vector gene-delivery drugs, including recombinant adenoassociated virus (AAV) therapies, is essential for proper assessment of critical quality attributes before regulatory approval and during commercial production. If rAAV full-capsid percentages are maximized, and variants such as empty or partially-filled capsids are reduced as much as possible, then potency is increased for improved dosing and tolerance outcomes. Traditionally, characterization of AAV purity with respect to empty, full, and other variants has been performed by techniques such…

Development of Patient-Focused Commercial Specifications: Understanding Clinical Relevance and Criticality of Quality Attributes

The CASSS chemistry, manufacturing, and controls (CMC) Strategy Forum on 23 January 2019 in Washington, DC, was entitled, “The Development of Patient-Focused Commercial Specifications Through Understanding of Clinical Relevance and Criticality of Quality Attributes.” This forum covered the definition, identification, control, and management of patient-focused attributes throughout the life cycle (from discovery through approval) of biological products, including vaccines. Participants investigated how to differentiate through the product development life cycle which attributes are “clinically meaningful” from those applied for manufacturing…

Ask the Expert: An Innovative System for Advanced, High-Throughput Aggregate Analysis

Distinguishing aggregated active pharmaceutical ingredients (APIs) from other particle types is critical to evaluating a protein product’s stability, but standard characterization tools struggle to discriminate proteins from nonproteins with similar sizes, shapes, and morphologies. In a 25 June 2020 “Ask the Expert” webcast, Bernardo Cordovez (founder and chief scientific officer of Halo Labs) introduced his company’s Aura subvisible-particle analyzer. He explained how the device combines an innovative microscopy technique with sophisticated imaging software to characterize subvisible particles more quickly and…