Tuesday, December 6, 2022 Daily Archives

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

Cell-Free Synthesis of Highly Potent Recombinant Neurotoxins: A Process Economic Feasibility Study

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Since its inception four decades ago, cell-free synthesis (CFS) has been used to produce biomolecules such as RNA, DNA, peptides, and proteins (1). However, most of these applications have been in early stage research and small-scale proof-of-concept studies, with rare examples of large-scale production. The slow industrial uptake of CFS has been attributed to low productivity, which suggests an uneconomical path to large-scale manufacture. Typically, a CFS platform includes a genetic template (encoding the product of interest), chemical additives (nucleotides…

December 6, 2022

Allogeneic Cell Therapy Manufacturing: Preparing for Tomorrow’s Success

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Cell therapies are promising new drug products that treat or cure diseases that, until the past decade, had no other treatment options. Several autologous cell therapies have been approved, and their efficacy has been proven, especially in immunooncology. However, autologous therapies can present some difficulties for both developers and patients (e.g., short timelines, point-of-care drug administration). Allogeneic cell therapies are not associated with those challenges. For example, patient access to an autologous treatment can take months, time that patients with…

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

Streamlining Vaccine Process Characterization Using an Automated Reactor System

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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…

December 6, 2022

Accelerating Early Upstream Screening Activities for Viral Vector Therapies

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Biopharmaceuticals delivered by viral vectors (VVs) face distinctive obstacles during early upstream development. In October 2022, Andres Castillo (a portfolio manager at Sartorius) noted that drug makers set short development timelines to hasten therapies into the clinical evaluation. Doing so limits time for analyzing complex biointeractions, and studies for culture-media and VV screening are time- and resource-intensive. Castillo and Shanya Jiang (also a portfolio manager at Sartorius) explored how integrated technologies facilitate robust cell-line and VV screening. The Presentation Reflecting…

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

Managing Patient Data in the Supply Chain

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The personalization of autologous advanced therapy medicinal products (ATMPs) makes patients an intrinsic part of the supply chain. It begins with collection and registration of starting materials, which necessitates tracking and recording chain-of-identity (CoI) and chain-of-custody (CoC) information for every dose. This situation could expand the challenges of patient data management throughout the whole supply chain, increasing data privacy risks to both patients and suppliers. ATMP manufacturers must therefore protect data privacy not only as clinical trials start, but also…

December 6, 2022

Addressing Challenges in Analyzing Heterogeneous AAV Populations

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Adenoassociated virus (AAV) vectors are made from nonenveloped virus capsids that contain single-stranded DNA. As a leading delivery system for gene therapy, AAVs are in development to treat a number of genetic diseases (1). As the industry has advanced, the number of clinical trials involving such vectors has risen dramatically (2), increasing the need for effective manufacturing and quality control (QC) methods. During biomanufacturing, expressed AAV capsids can incorporate both target and host-cell DNA in a heterogeneous population. Viral capsids…

December 6, 2022

Cell and gene sector still facing capacity crunch, say experts

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Cell and gene therapy firms still face a “capacity crunch” – a lack of manufacturing space, technology, or raw materials that delay projects – according to experts, who say disruption caused by COVID-19 and the surge in R&D as the pandemic ebbs have made the situation worse. In 2017, the New York Times suggested a lack global capacity for the production of viral vectors was slowing the development of cell and gene therapies. The thrust of the article was that…

December 6, 2022