Downstream Processing

Worst-Case Conditions for Viral Clearance

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As described in ICH Q5A on virus safety of biotechnological products (1) and the European guideline on virus safety of biotechnological products, EMEA 398498 (2), viral clearance studies are mandated as part of the viral safety evaluation of products derived from human or other mammalian cell lines. When acceptable ranges of process parameters are known, both guidelines recommend that scale-down models be evaluated under worst-case conditions for viral clearance. The BioPhorum Development Group’s viral clearance workstream performed a benchmarking survey…

December 12, 2022

Hollow-Fiber Nanofiltration for Robust Viral Clearance of Non-MAb Biologics

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Monoclonal antibody (MAb) and other therapeutic biologics produced by mammalian cells have the potential to introduce endogenous retroviruses and can be infected with adventitious viruses through raw materials or other parts of the biomanufacturing process (1–3). Based on regulatory guidelines, products derived from mammalian cells must contain less than one virus particle per million doses, which requires purification processes to demonstrate virus removal capabilities of about 12–18 log10 clearance of endogenous retroviruses and 6 log10 clearance for adventitious viruses (4).…

December 12, 2022

Purity by Design

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After launching Nereus LentiHERO, a game changing fit-for-purpose solution for lentiviral vector purification in 2022, Astrea Bioseparations present this end of year report with a selection of interviews, application notes, and articles. Identifying the gaps in lentiviral purification, they discuss how to increase processing efficiency, purity, and recovery of LVV particles. They also look towards the future to bring a radical change in bioprocessing for cell and gene therapies. The Nereus LentiHERO spin column is the first product in a…

December 8, 2022

Opportunities in the Field of Host Cell Proteins Part 3: Case Studies in Impurity Detection and Identification

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Rigorous physicochemical and bioanalytical methods must be performed on biological products to ensure that they contain minimal levels of host cell proteins (HCPs) and other process-related impurities. In the first and second parts of our article, we surveyed literature about HCPs of concern, the mechanisms behind their immunogenicity, and ultimately, their consequences for patient safety. Herein, we highlight published case studies to explore difficulties with detecting, identifying, and quantifying such impurities. These examples demonstrate that much remains to be learned…

December 6, 2022

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

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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,…

December 6, 2022

A Novel Membrane Technology for Robust, Scalable Antibody Capture

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Biopharmaceutical manufacturers usually apply resin-based affinity- chromatography media for monoclonal-antibody (MAb) capture. Such materials are costly, and their biophysical limitations can create operational difficulties. In an October 2022 webinar, Volkmar Thom (director of membrane chromatography R&D at Sartorius) spoke about his company’s development of a “convecdiff” affinity membrane. He described how the technology can help users to intensify capture processes, reducing downstream manufacturing costs. The Presentation Protein A resins contain porous beads of 50–100 μm in diameter. MAbs must diffuse…

December 6, 2022

eBook: Chromatography Column Packing — Best Practices and Considerations from Laboratory to Manufacturing Scale

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Column chromatography is a powerful separation tool for biopharmaceutical research and industry, with applications ranging from laboratory bench-scale purification to process development and commercial-scale manufacturing of biotherapeutics. Ensuring the highest quality of separations depends on many factors, including the technique used for packing the chromatography column. Well-packed columns provide for the best chromatographic separations. Successful column packing ensures proper mobile-phase distribution and resin contact. Scaling up to large columns can introduce many challenges. Manufacturers of chromatography media provide best-practice advice…

December 5, 2022

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

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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…

October 20, 2022

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

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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…

October 20, 2022

Overcoming the Productivity Bottleneck in MAb Capture

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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…

October 20, 2022