2022 Archives - Page 2 of 19 - BioProcess InternationalBioProcess International

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

by Williams Olughu, Christos Stamatis, Suzanne S. Farid and David Gruber

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…

Allogeneic Cell Therapy Manufacturing: Preparing for Tomorrow’s Success

by Elena Matsa

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…

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

by Mahesh Khot

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,…

Streamlining Vaccine Process Characterization Using an Automated Reactor System

by Kyle Deluca and Felix Milman

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…

Accelerating Early Upstream Screening Activities for Viral Vector Therapies

by Andres Castillo and Shanya Jiang

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…

A Novel Membrane Technology for Robust, Scalable Antibody Capture

by Volkmar Thom

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…

Managing Patient Data in the Supply Chain

by Matthew Lakelin

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…

Harnessing the Untapped Power of the Human Commensal Virome

by Tuyen Ong

Viruses are ubiquitous members of every ecosystem, including the human body (1). A common misconception is that all viruses are harmful. In fact, their relationships to human hosts can be pathogenetic, symbiotic, or commensal. In the latter case, a virus benefits from but neither harms nor helps its host (2). Commensal viruses are as abundant as human cells, and their coexistence has persisted for millennia, permitting our immune systems to recognize them as part of us. Among the most abundant…

Optimize Your Early Preclinical Process for Gene Therapy Success

by Katie Roberts

Early decisions can impact the success of a novel gene therapy, so how can therapeutics companies make sure to set off on the right track? In this article, drug developers will learn some things that they should consider at the start of their therapeutic journey. We explore the impact of early technical decisions, including the importance of seeking high-yielding plasmids and a well-validated cell line. We cover logistical considerations, such as plasmid supply chain challenges and how to avoid them.…

Addressing Unwanted Immunogenicity in Gene Therapies

by Carsten Brunn and Kei Kishimoto

Immunogenicity is the ability of a substance, such as a foreign and/or potentially dangerous protein, to provoke an antigen-specific immune response. However, some immune responses can be detrimental, such as in autoimmune diseases and unwanted reactions to biological therapeutics. The latter case can compromise biopharmaceutical safety and efficacy, and preexisting immunity against biologic components can preclude patients from receiving life-changing treatments, perhaps most notably in gene therapy (1). Gene therapies are designed to target the root cause of a genetic…