Cell Line Development Archives - BioProcess InternationalBioProcess International

Building the Next Generation of Cell-Line–Development Platforms

by Lisa Blaschke, Catherine Krikelis, Joel Watkinson and Katy McLaughlin

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

by Brian Gazaille and Cheryl Scott

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

by Jason Condon

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

by Cheryl Scott, with Niall Barron

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

by Bernardo Cordovez and Steven Le

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

by Regine Brokamp

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

by BPI Contributor

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…

Shortening Clinical Development Timelines Using Novel Technology for Generating Stable, High-Producing Cell Pools and Cell Lines

by BPI Contributor

Greg Bleck, vice president of research and development, Catalent. Bleck described Catalent’s work in creating the GPEx Lightning cell-line development platform, which combines three key technologies to accelerate work to produce high-expressing cell lines. The platform combines a GPEx retrovector for gene insertion with a glutamine synthetase (GS) knockout cell line and a recombinase- or transposase-like system that “flips” genes into place. Catalent scientists insert the genes for dedicator-of-cytokinesis (DOCK) proteins — which are involved in intracellular signaling — at…

Advances in Cell-Line Development, Banking, and Authentication

by James Fantuzzo, Catherine Fox, Shalmica Jackson, Patrick Laverty, Toni Pipes, Brian Shapiro and Fang Tian

Living cells are foundational technologies in the biopharmaceutical industry. They serve as hosts for production of therapeutic proteins, models by which to test clinical candidate efficacy and potency, tools for developing and validating bioanalytical methods, and even as medicines. To enrich our understanding of the past 20 years of bioprocessing, BPI distributed questions to supplier companies, including those that have spurred on innovation in the manufacture of critical starting materials. Below, representatives from ATCC reflect on advances in developing, banking,…

Introduction: Cell-Line Engineering and Development at BPI West

by Cheryl Scott

Critical to the manufacturing of biotherapeutics is development of robust and stable cell lines that express high-quality products in large quantities. Chinese hamster ovary (CHO) cells are the “workhorse” expression host for manufacturing glycoprotein-based therapeutics — from antibodies to enzymes and hormones and beyond — making them the subject of most industry discussion regarding both cell-line development (CLD) and engineering. Most methods, technologies, and strategies apply regardless of the type of protein to be expressed or the type of cells…