Downstream Processing

Tangential-Flow Filtration Process Control and Data Acquisition System for Process Development

PendoTECH tangential-flow filtration (TFF) process control systems have been widely adopted in the filtration community. The system’s features enable its implementation in multiple unit operations and biopharmaceutical processing applications, including ultrafiltration–diafiltration (UF–DF) of proteins, viruses, and compounds such as oligonucleotides and antibody–drug conjugates (ADCs). The control system can be used to develop process parameters for UF–DF processes that have different membrane formats (e.g., flat-sheet cassette and hollow fiber). TFF laboratory setups often are manual or semiautomated processes that use pumps,…

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…

Optimizing and Intensifying ADC Aggregate Removal: A DoE Approach to Membrane Chromatography and Rapid Cycling

Antibody–drug conjugates (ADCs) represent a growing therapeutic segment of the oncology field. Five such treatments received market approval from the US Food and Drug Administration (FDA) between 2008 and 2018, whereas three were approved in 2019 and two each were approved in 2020 and 2021 (1). This disruptive technology combines highly potent small-molecule payloads with monoclonal antibodies (MAbs) to improve their specificity as cancer treatment. The antibodies deliver those toxic compounds directly to cancer cells but not to healthy cells,…

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…

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…

Removing Aggregates and Fragments of Recombinant IgG1: Evaluating a Process Change to Implement Appropriate Chromatographic Media

High–molecular-weight (HMW) and low–molecular-weight (LMW) product variants are critical quality attributes (CQAs) for monoclonal antibodies (MAbs) because they can cause severe immunogenic responses in human recipients. Aggregation is a common problem that can compromise the quality, efficacy, and safety of therapeutic proteins. It can occur at different stages in a biomanufacturing process: during cell-culture–based production, downstream process purification, drug-substance formulation, and storage of bulk drug substances or formulated drug products. Hence, the removal and control of MAb aggregates and fragments…

Chromatography in mRNA Production Workflow

Rapid response to global pandemics requires the manufacture of billions of vaccine doses within months. This short timeline must allow for design and testing of active ingredients, development of production and purification processes, clinical evaluations, regulatory filings, and manufacturing. Existing purification methods often have been adopted from laboratory-scale techniques to allow rapid implementation, and those have provided adequate product quality. But future mRNA development will require optimized production and purification processes. Chromatography has been a workhorse of biomanufacturing for decades,…

Purity By Design

Astrea Bioseparations has a well-established modular program to support customer projects from small to large scales with ligands, adsorbents, and chromatography columns that design purity into each process. Demand for increased productivity in biopharmaceutical manufacturing has placed new pressure on downstream purification operations. For recombinant proteins and monoclonal antibodies (MAbs), such pressure stems from significant gains in upstream productivity, particularly from high titers produced using increasingly efficient cell-culture systems. For viral vectors used in gene and gene-modified cell therapies and…

Rethinking Chromatography

Dynamic trends in the biotherapeutic industry are shifting manufacturers towards new modalities and intensified production strategies. This development is supported by ongoing scientific and technical advances in both upstream and downstream processing steps. Downstream processing of new modalities requires chromatography technologies that can handle large, fragile molecules (such as mRNA and viral particles). To maximize speed and productivity, platforms supporting continuous processing will become essential. In this feature, Sartorius discusses current and future concerns for process chromatography operations. They then…