Manufacturing

Boosting Yield and Preserving Quality: Increasing Production of Induced Pluripotent Stem Cells for Cell Therapy and Regenerative Medicine Applications

Induced pluripotent stem cells (iPSCs) are promising starting materials for several clinical and industrial applications in cell therapy production, drug discovery, and in vitro screening. But as I learned from Maxime Feyeux (cofounder and chief science officer of TreeFrog Therapeutics in Bordeaux, France), such cells are a relatively new option in the toolbox of cell therapy developers. Advanced-therapy products can require controlled proliferation and differentiation of millions or even billions of iPSCs depending on the clinical indication, he pointed out,…

Scaling AAV Production: Easing the Transition from Laboratory Scales to Commercial Manufacturing

Adenoassociated virus (AAV) has emerged as the leading vector for gene therapy delivery. Compared with options such as lentivirus and adenovirus, AAV exhibits a strong safety profile because it has low pathogenicity and requires a helper virus to replicate. AAV is also capable of long-term gene expression, and it can infect both dividing and nondividing cells (1–5). Developers of advanced therapies have found such advantages to be quite attractive. As of January 2021, two gene therapy products have gained US…

Mind the Gap: Managing Relationships Between Upstream and Downstream Intensification

Process intensification (PI) describes an integrated framework of strategies to maximize the output of a unit operation, a process, or an entire facility. By implementing PI strategies, biomanufacturers can accomplish their productivity goals by increasing production speeds and titers, reducing facility footprints, and cutting costs. Overall, such changes improve production efficiency and flexibility. Collectively, the biotherapeutic industry has made multiple advancements in intensifying upstream processing. PI strategies include using high-density cell banks, implementing seed-train intensification (n – 1 perfusion), and…

eBook: Gene Therapies —
Developers Slowly Emerge from a Pandemic

This eBook gauges shifting expectations for the gene therapy industry amid the COVID-related uncertainties and clinical setbacks of the past couple years. BioProcess Insider founding editor Dan Stanton reports on the January 2022 Phacilitate Advanced Therapies Week event, specifically a standing presentation on the 10 most important industry drivers from the past year. Since 2017, advancements in gene therapies have featured prominently in these presentations. In 2021, gene therapies again made the list, but this time for more troubling reasons,…

Antibody-Derivative Biotherapeutics: Fragments and Fusions Define the Future

Monoclonal antibodies (MAbs) remain the dominant biopharmaceutical product class, but as biotechnologies have advanced in recent decades, developers have found ways to exploit their “magic-bullet” capabilities while putting aside their limitations. That has led to a new generation of antibody-related therapeutics created by cutting and pasting molecular domains. Researchers are mixing and matching functional moieties of antibodies and other molecules to create custom-designed proteins with powerful efficacy and tunable targeting. A simple search at Taylor & Francis Online (https://www.tandfonline.com), the…

Development and Manufacture of Therapeutic Bispecific Antibodies

To meet the ongoing need for new and improved drugs, the biopharmaceutical community strives to create molecules with new functions. Bispecific antibodies (bsAbs), which can simultaneously home in on two different targets, illustrate the scientific ingenuity needed for this task. The basic proof of concept for these complex molecules was established in 1960 (1), and their application to the redirection of effector cells was reported in the mid-1980s (2–4), but producing them has proved to be challenging. Many technical advances,…

Lymphocyte Activation Gene 3 in Immunooncology: A Soluble Protein Alternative

Early in 2021 at the American Society of Clinical Oncology’s (ASCO’s) annual meeting, attendees witnessed the first validation of a novel checkpoint target: lymphocyte activation gene 3 (LAG-3). Bristol Myers Squibb’s (BMS’s) recent success in a phase 3 study of the relatlimab anti-LAG-3 monoclonal antibody (MAb) proved that the combination of LAG-3 and programmed cell death protein 1 (PD-1) is more effective than the standard of care in first-line metastatic melanoma (1). For about seven years, that standard has been…

eBook: Antibody–Drug Conjugates —
A New Generation of Approaches Is Changing the Game

Combining large proteins with linkers and cytotoxins, antibody–drug conjugates (ADCs) may be the most complex drug molecules in development today. Despite early promise and product approvals, a number of technical concerns arose during product and process development. Characterizing and ensuring consistency in the number of small molecules that attach to the antibody — as well as ensuring their proper attachment and biophysics — all present significant challenges to ADC developers. Solving early problems associated with product quality has introduced a…

Tris, a Critical Raw Material: Improving the Quality and Consistency of Supply

ANGUS Life Sciences is the world’s largest supplier of tromethamine buffers and the only manufacturer of the tris molecule based in the Western hemisphere. The company sells directly to biopharmaceutical customers and contract manufacturing organizations as well as to reprocessors who repackage the chemical or process it into different grades and derivatives. After recent expansions in both the United States and Germany, the company now boasts dual-source manufacturing capabilities for its highest-purity tris products and is confident about its ability…

Realization of Quality By Design and Beyond: The Intelligent Cell Processing System

Cells are used as raw materials, intermediates, and final products in biopharmaceutical and cell therapy manufacturing. Because living cells are always in a dynamic state, their characteristics must be kept within specified ranges throughout bioprocessing to preserve their utility. Cell population expansion without changing the original cell properties is key for obtaining the required number of cells at the next step. However, limited process data are collected during the expansion phase — information that could be used to understand and…