Author Archives: Steven M. Chamow

Therapeutic IgG-Like Bispecific Antibodies: Modular Versatility and Manufacturing Challenges, Part 1

Antibody-based immunotherapy has advanced significantly since 1986, when the US Food and Drug Administration (FDA) approved the first mouse monoclonal antibody (MAb) for clinical use: Orthoclone OKT-3 (muromonab-CD3). In the intervening years, researchers have applied the tools of genetic engineering to clone immunoglobulin G (IgG) genes into a number of expression vectors. In the 1990s, the bioprocess industry was able to produce fully human antibodies in cultured cells. As of June 2017, the FDA and the European Medicines Agency (EMA)…

Buffers in Biologics Manufacturing

Biotechnology has enabled commercialization of protein-based drugs including insulin, growth factors, blood factors, and antibodies. Production and purification of such biologic products require different buffers for pH control and stabilization of reactions in different steps during biomanufacture. These processes include cell culture production (the “upstream” phase), purification (the “downstream” phase), and a final phase in which excipients are introduced to the drug substance to create a drug product (“formulation and storage”). In upstream processes, buffers are primarily used for their…

Immunoglobulin Fc-Fusion Proteins Part 2: Therapeutic Uses and Clinical Development

The potential therapeutic value of many proteins — including enzymes, receptors, cytokines, blood factors and peptides — can be realized by fusing them to the Fc region of human immunoglobulin G. Of the 46 monoclonal antibody (MAb) and MAb-derivative products approved by the FDA to date as human therapeutics, 10 are Fc-fusion proteins (Table 2). Among approved products, several structural variations are represented (Figure 4). In BPI’s October 2014 issue, Part 1 of this review examined the structure and manufacturing…

Immunoglobulin Fc-Fusion Proteins Part 1: Their Design and Manufacture

Over the past three decades, 45 monoclonal antibody (MAbs) and MAb-derivative products have been approved for therapeutic use in the United States (Table 1). One class of antibody derivatives is growing in importance: Fc-fusion proteins. Many biologically active proteins, including receptor ECDs (see “Abbreviations” box), cytokines, enzymes, and bioactive peptides have very short serum half lives because rapid renal clearance limits their exposure in target tissue (and, consequently, their pharmacological effect). The primary reason for fusing a biologically active protein…