During a September 2022 webinar, Kyle Deluca (a senior scientist in engineering at Merck) highlighted bottlenecks in his group’s workflow for characterizing production of a pneumonia vaccine. In that process, purified components undergo chemical modification in a synthesis reactor, followed by buffer exchange, size-based separation, additional chemical modification, and final purification. Because the modification steps were time and labor intensive, Merck automated them. With support from Mettler Toledo, Deluca and Felix Milman (a specialist in engineering at Merck) described how…
Product Characterization
Investigation of HCP Enrichment During CGMP Scale-Up
On paper, scaling a bioprocess from a 10-L to a 100-L to a 2,000-L bioreactor may seem like a straightforward math problem that could be solved by software. In practice, however, the exercise relies on a complex set of biological, chemical, and engineering assumptions; on maintenance of healthy cell cultures; and on management of equipment and analytics while adjusting to each increase in scale (1). Process development and quality control groups need to monitor how scale-up might affect critical quality…
High-Selectivity HPLC mRNA Analytics: Quantification and Characterization
Robust and precise chromatographic analytical methods are key for the efficient development of the mRNA production process. Three different analytical methods, which utilize three different column chemistries, are embedded in a ready-to-use PATfix™ HPLC analytical platform to support mRNA process development and product quantification and characterization. Fill out the form below to download the full report from BIA Separations, now a Sartorius Company.
Transforming the Biopharmaceutical Development Roadmap
Biopharmaceutical analytical methods have improved significantly since the early 1990s. Techniques and fundamental mechanisms largely have remained the same, but modern analytical tools are delivering better insights into drug-product characteristics thanks to improved reagent quality, method intensification, and automation. Harmonized regulations and the revolutionized role of contract development and manufacturing organizations (CDMOs) also continue to support bioprocess transformations. Improved Analytics and Standardized Single-Use Equipment Today’s analytical methods provide high resolutions and deliver reliable results quickly. For example, sodium dodecyl sulfate–polyacrylamide…
eBook: Potency Bioassays — Development, Trending, Transfer, and Automation
Bioassay development is a complex process that must be undertaken with great rigor and attention to detail. Potency testing experts use a range of methods including cell-based and binding assays. Consistency and reliability of results over time are paramount. Well-developed and -characterized methods are the end result of much phase-appropriate development work that goes on in parallel with bioprocess and biotherapeutic product development. This eBook begins with BPI senior technical editor Cheryl Scott’s report from the Biopharmaceutical Emerging Best Practices…
AAV Downstream Process and Product Characterization: Integrating Advanced Purification and Analytical Tools into the Workflow
The optimization of the downstream process for Adeno-associated virus (AAV) production with consistent quality depends on the ability to characterize critical quality attributes affecting potency, purity and safety of the final product. As the gene therapy field continues to push products through the clinical pipeline, an increasing need for efficient purification and analytical tools has become evident. In addition, the regulatory space has expanded in parallel to the use of AAV, driving the demand for simple and efficient assays to…
Analysis of Trace-Level, High-Risk HCPs: Proteomics Advances for Preventing Degradation of Polysorbates in Biotherapeutic Formulations
Polysorbate-80 (PS-80) and polysorbate-20 (PS-20) are used widely in formulation of biotherapeutic products for preventing surface adsorption and as stabilizers against protein aggregation (1). Degradation of polysorbates can cause turbidity and potential formation of subvisible particles mainly consisting of poorly soluble hydrophobic free fatty acids (1). Polysorbate degradation is an industry-wide challenge both in biotherapeutics processing and formulation development. The risk of such degradation increases with higher cell densities and greater expression titers in bioprocessing, as well as with higher…
Ask the Expert: Critical Steps in Potency Assay Development
Biologics undergo extensive characterization to demonstrate their safety, purity, and efficacy. Jennifer Lawson (product manager for cell line, media, and testing solutions at Sartorius) highlighted the role of potency assays in that process. Because they reflect the complexity of biological systems, scientists must develop robust assays that will provide sufficient data for good-practice (GxP) applications. Lawson pointed out milestones in the bioassay life cycle and explored ways to help ensure method suitability. Lawson’s Presentation Development Criteria: Potency assay development requires…
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…