Culture Development

Cell Culture Media: An Active Pharmaceutical Ingredient or Ancillary Material?

Cell-based therapies are used to treat diseases that require the replacement of diseased, dysfunctional, and injured cells (1). To produce these therapies, a wide range of reagents and materials such as antibodies, growth factors, and enzymes are used in their manufacturing processes. Such necessary materials are administered through a cell culture medium. Active pharmaceutical ingredients (APIs) are the main ingredients that make products therapeutic. Ancillary materials (AMs) and raw materials (RMs) are essential components used during production but are not…

Enhanced Galactosylation of Monoclonal Antibodies: Using Medium Supplements and Precursors of UDP-Galactose, Part 1

The biopharmaceutical industry needs better understanding of how monoclonal antibody (MAb) glycosylation is influenced by components in cultivation media — and it needs methods to exert some control over the structure of MAb glycans. That structure can affect MAb function. Thus, a high-throughput (HTP) assay is needed for characterizing MAb glycosylation so that developers can observe the effects of cultivation conditions on MAb glycosylation rapidly, with a goal of producing MAbs that have a desired glycan structure. The method also…

Special Report: Effect of Insulin on Cell Growth and Virus Production

Recombinant insulin is a key component in serum-free growth media for mammalian cells. It is used for the manufacturing of monoclonal antibodies, virus vaccines, gene therapy products and many other biological drug products approved by regulatory bodies worldwide, including FDA and EMA. Canada’s National Research Council (NRC) helps companies develop and commercialize new health technologies. Recently it partnered with Novo Nordisk Pharmatech to determine the effect of Insulin on cell growth and virus production. The results are detailed in this…

Platform Solutions for Cell Therapy Manufacturing

Advances in cell therapy have resulted in significant progress toward treating some widespread and difficult diseases, many of which represent unmet medical needs. For example, phase 3 clinical trials are already under way for therapies based on mesenchymal stem cells (MSCs), including therapies for graft-versus-host disease, acute myocardial ischemia, and chronic obstructive pulmonary disease (COPD) (1–3). Successful cell therapy treatments for such afflictions will be not only significant medical breakthroughs, but also in very high demand. However, their commercialization is…

Setting Raw-Material Specifications Using Prediction Models: Determination of a Specification Limit for a Raw-Material Impurity in mPEG-Aldehyde

Impurities related to raw materials used for bioproduction can be inadvertently introduced into a manufacturing process, causing potential failure to meet in-process controls or release specifications. Unexpected impurities also can reduce yield and affect the quality, safety, and effectiveness of a final product (1). Raw-material impurities can originate from starting components or reagents used in manufacture. They can be generated in situ during synthesis or as degradation products. Impurities also can result from improper handling, packaging, and storage. Identification and…

Providing Lipids Boosts Protein Productivity: Testing a Feed Supplement with Multiple Cell Clones and Media Formulations

As the biologics (and now biosimilar) markets continue to grow, pressure increases on biomanufacturers to reduce cost of goods sold (CoGS). One way they can reduce cost is by increasing protein productivity in terms of protein titer per volume of culture. Media optimization is a key strategy for increasing protein productivity. In the past few decades, average titers across the industry have increased greatly — from <0.5 g/L in the 1980s to >3 g/L today, and it is not uncommon…

Orbital Shaking and Acoustic-Resonance Mixing: Comparing Culture Characteristics

Production of recombinant proteins usually happens in suspension cultures, with oxygen limitation playing a major role. Oxygen and nutrition feeds are of great significance to aerobic suspension cultures. Oxygen is often the controlling factor in orbital shaken systems because oxygen transfer occurs only through diffusion, which is limited by gas-exchange surface and mixing characteristics. Here, we compare growth characteristics of microbial cultures in a standard shaken incubator with those of cultures in a RAMbio fermentation system, paying particular attention to…

Process- and Product-Relate Impurities: Part 1 – Process-Related Impurities An Overview

Introduction by Cheryl Scott The CMC Strategy Forums focus on relevant chemistry, manufacturing, and controls (CMC) issues throughout the life cycle of a therapeutic and thereby foster collaborative technical and regulatory interaction. Forum chairs share information with regulatory agencies to help them merge good scientific and regulatory practices. Outcomes of forum meetings are published in BioProcess International and on the CASSS website (www.casss.org). This process is meant to help ensure that biopharmaceutical products manufactured with advancing technologies in a regulated…

Ask the Expert: Cell Culture Media Supplementation

with Dr. James Brooks (BD Biosciences) Improvements in cell culture media and supplementation have enabled significant advancements in bioproduction titers. But optimization to meet the specific needs of individual production cell lines is key to achieving desired production and protein quality, especially for biosimilars. Not only is it desirable to achieve cost-effective levels of production, but quality characteristics also are essential — and for biosimilars must closely resemble those of the originator molecules. Fully chemically defined (CD) media formulations are…

Bioreactor Design for Adherent Cell Culture — The Bolt-On Bioreactor Project, Part 3: Containment, Sterility

The Bolt-on Bioreactor (BoB) project is an independent initiative aimed at developing and commercializing a bioreactor for the automated and efficient culture of adherent cells, especially for application in the production of therapeutic cells and other biopharmaceuticals (1). After conducting thorough research on available culture systems for adherent cells, the BoB team believes that a successful alternative to existing devices must answer four major challenges. Addressed in the first article of this series (2), the first challenge has to do…