Downstream Processing

Using 3D Imaging To Understand Sterilizing-Grade Filtration of Liposomes

Sterilizing-grade filtration is an essential operation for biomanufacturing. It ensures that drug substances are free from microorganisms at the end of a downstream process. The COVID-19 pandemic has highlighted the need for high-quality therapies to be manufactured efficiently at scale, with particular focus on the need for multiple vaccines to be developed, produced, and distributed globally (1). Some vaccines have used lipid nanoparticle encapsulation technology, which also has potential for use in gene therapy development in the near future. Lipid…

Opportunities in the Field of Host Cell Proteins: Part 2: Ensuring Patient Safety

Process-related impurities such as host cell proteins (HCPs) can raise concerns about biological product efficacy, quality, safety depending on their properties and levels. In the first part of this series, we surveyed relevant regulatory frameworks and detailed potential effects of HCPs on biologic efficacy. Here in part 2, we review available literature on HCPs and patient safety, including information about HCP-related immune responses and adverse clinical events. HCP Effects on Patient Safety At least five HCP-induced factors can influence a…

Overcoming the Productivity Bottleneck in MAb Capture

It is no secret that progress toward intensifying monoclonal antibody (MAb) production processes has focused on upstream steps. Although the industry welcomed increased production, that also created bottlenecks in downstream processing, including during capture chromatography steps. Technologies that are intended to alleviate such bottlenecks must meet four important criteria to increase productivity and profitability. They must • improve productivity of the MAb capture process, such as by purifying more MAbs, using less media, and/or reducing timelines. • perform as well…

Two-Step Monoclonal Antibody Purification Using a Multicolumn Continuous Chromatography Platform

Biomanufacturers typically have relied on multistep processes for optimal removal of impurities such as host-cell proteins (HCPs), DNA, adventitious viruses, and aggregates. However, additional purification steps increase downstream expenses significantly, including costs of supplementary resin, hardware, and buffers. The substantial footprint required at a processing site and additional time needed to perform a complete multistep purification process also increase production costs and complicate process execution. Thus, it is imperative to design and test effective purification procedures for high-quality biotherapeutics, but…

eBook: Chromatography — Addressing Pain Points To Mitigate Downstream Bottlenecks

Compared with significant advances in upstream production of recombinant proteins, downstream purification processes have undergone far less development over the past twenty or thirty years. Technologies are emerging for continuous-mode and/or multicolumn chromatography (MCC) operations, but commercial-scale biomanufacturing operations still rely on chromatography equipment and processes that closely resemble those used at the advent of monoclonal antibody (MAb) manufacturing. Thus, chromatography operations generally have not kept pace with upstream gains, resulting in manufacturing bottlenecks at purification stages. Compounding that concern…

Development of a Stand-Alone Monitoring Application for Purification Processes in Biomanufacturing

The ability to monitor unit operations in biomanufacturing is essential because it enables early fault detection and effective root-cause analysis. Below, we present a case study on the development of a stand-alone, data-driven, process-monitoring application for a biomanufacturing purification process. We review the application’s functionality and highlight its utility using a few examples from commercial manufacturing of a therapeutic protein. Lessons learned from the development of that application also are presented. The progress and performance of a purification process have…

Mechanistic Modeling for a Hydrophobic-Interaction Chromatography Process: Use in Vaccine Antigen Purification

Bioprocess models and simulations are the basis for digital twins, which are virtual representations of physical processes and enabling methods of biopharma 4.0. Early adopters in the industry have shown potential application of this approach in nearly all stages of a product development life cycle. Experts in academia and the biopharmaceutical industry have studied mechanistic modeling as the main method of chromatography modeling. Mechanistic models are mathematical descriptions of physiochemical phenomena. They are based on first principles and thus can…

Comprehensive Virus Clearance Evaluation Using Microscale Membrane Adsorbers

Membrane adsorbers can be a simple and effective choice for anion-exchange (AEX) purification of biopharmaceuticals. However, as Sherri Dolan (global technology consultant for virus clearance at Sartorius) explained during a May 2022 presentation, biomanufacturers generally do not leverage their membranes’ full loading capacities. Doing so could improve process economics and decrease costs for several downstream applications. Dolan’s Presentation Membrane adsorbers are ideal for flow-through AEX applications (e.g., secondary purification and polishing) because they can be used at high flow rates…

Next-Generation Software Solutions for Analytical Chromatography Processes

High-performance liquid chromatography (HPLC) has become a leading analytical method for biopharmaceutical process development and optimization, particularly for therapies that leverage plasmid DNA (pDNA), messenger RNA (mRNA), and viral vectors. In July 2022, Blaž Goričar (manager of process analytics development at BIA Separations, a Sartorius company) demonstrated the features of his company’s PATfix software for HPLC data processing and analytics. He described how the program can simplify method execution and enhance evaluation of resulting data. Goričar’s Presentation PATfix software is…

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.