Cell Line Development

Unlocking the Potential of CHO Cells: Advancing Bioproduction with Next-Generation Vector Design

Traditional cell line development to support bioprocessing often has relied on a “one-size-fits-all” vector, which can lead to suboptimal expression levels in Chinese hamster ovary (CHO) cell cultures. Scott Estes (head of cell line development at Asimov) and his team have brought a rational approach to how cells are engineered. The CHO Edge system integrates knowledge from experts in cell line engineering, synthetic biology, software design, machine learning, and omics-driven modeling of metabolism and gene expression. Estes’s Presentation Estes explained…

Engineering the Future: Cell-Line Development Discussions at BPI West

Big data, next-generation sequencing (NGS), automation, and powerful analytical technologies are helping biopharmaceutical companies achieve the parallel goals of cell-line development: precise integration of transgenes into production cells with documented monoclonality, shortening timelines and increasing productivity. Presentations in the most recent Biotech Week Boston (BWB) and the BPI Conference US West (BPI West) programs have demonstrated that there is no one way to accomplish those goals. Combining several of the approaches highlighted herein just might take biopharmaceutical production to new…

Benefits of a Customized Cell Line Development Program

Cell line development at Just-Evotec Biologics is focused on lowering the cost of manufacturing and creating highly productive cell lines for our clients and partners. To achieve this, we leverage our own in-house GS knockout CHO host cell line, which has been shown to support cell densities up to 80 M cell/mL and productivities upwards of 5 g/L/day in our perfusion bioreactor platform. Additionally, we have implemented advanced instruments and liquid handling automation to increase the throughput of processes that…

Building the Next Generation of Cell-Line–Development Platforms

Speed to market is a critical business driver in the biopharmaceutical industry. However, drug development success also requires building a robust process that maximizes efficiency while limiting the cost of goods. Achieving time and cost savings without compromising product quality is critical. Development of a productive and stable cell line is the foundation of an efficient and high-performing bioprocess. Cell-line development (CLD) represents some of the most resource-intensive steps within a process development pipeline. Bioprocess scientists must find a balance…

Introduction: Cell-Line Development Discussions at Biotech Week Boston

The genetic sequence of the Chinese hamster ovary (CHO) cell line first was published just over a decade ago (1, 2). As with the Human Genome Project, genomic knowledge of that and other biopharmaceutical production cell lines — both animal and microbial — has expanded greatly alongside dramatic increases in computing power (3–5). Meanwhile new and improved genetic engineering techniques have offered the potential for targeted rather than random integration of transgenes into production cells. And regulators began to emphasize…

Cell Lines Are the Foundation: A Methodical Approach to Derisking Outsourced Development and Improving Manufacturability of Novel Biologics

The most important choice for bringing a novel biologic into clinical development could be the cell line for expressing it. Somewhat determined by that, development of the initial manufacturing process comes in a close second. After an investigational new drug (IND) application, early clinical studies use materials made from the cell line and manufacturing process that were selected at the start of a clinical candidate’s life cycle. The objective for most sponsor companies is to get IND-enabling material produced in…

Targeting RNA: How Epitranscriptomics Can Improve Productivity

Cell-line development traditionally has focused on genetic engineering of chromosomal DNA in cellular nuclei. Combining technological advances such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) with ever-increasing genomic knowledge has enabled scientists to get impressive performance from microbial, plant, and animal cells. But few researchers have considered the potential for manipulating how genes are transcribed as an avenue for increasing productivity — until recently, that is. Niall Barron is a professor of biochemical engineering at Ireland’s National…

Rapid Identification of Stable Biologic Candidates During Cell Line Development

There’s no doubt that CHO cell lines are being pushed to their limits: Newer and more complex biologic modalities have low expression yield Dramatically higher concentration requirements of injectables Larger market demands with increasing awareness of new biologics based therapies. While advancements are being made, little has been done to characterize the physical stability of secreted antibodies from their inception during CHO cell line development. Scientists have been forced to stabilize biologics that were not designed with aggregation in mind…

Twenty Years of Innovation: Reflections on the Industry’s Past and Future

In honor of BPI’s 20th anniversary as a publication, the editors invited authors to reflect on the industry’s past, present, and future. Below, the chief operating officer of Selexis offers her perspectives along with responses to questions from the editorial team. Significant Scientific and Technological Innovations One of the most important innovations in bioprocessing has been the combination of next-generation sequencing with bioinformatics. The ability to sequence a host cell-line genome and transcriptome rapidly and cost-effectively and the development of…

How a Robust, Fully Integrated, and Highly Vetted Cell-Line Development Platform Accelerates IND Timelines

Sherry Gu, senior vice president of CMC management, WuXi Biologics. Since 2020, WuXi Biologics has supported process development and manufacturing for more than 30 biopharmaceuticals associated with COVID-19. Those include three authorized/marketed products and multiple advanced clinical candidates representing modalities such as monoclonal antibodies (MAbs) and vaccines. Gu explained how her company’s integrated platform for cell-line development (CLD) has enabled customers to advance their programs rapidly. The company’s custom protein-generation services support research and development (R&D) activities, culminating in developability…