Since the mid-1970’s, when Kohler and Milstein first discovered the process by which myeloma cells and splenocytes could be fused to produce monoclonal antibodies (MAbs), a whole new world of important therapeutic, prophylactic and diagnostic products has opened up, bringing in huge benefits for patients and manufacturers. The total sales of therapeutic MAbs reached more than $13 billion in 2005. Sixteen of the 18 FDA-approved MAbs came to the market after 1997, and over 150 are currently in clinical development, suggesting their increasing medical importance and the remarkable, recent advancements in development technology…
BioProcessing Journal Posts
A number of antibody drugs are currently in clinical development and 22 antibodies (including five diagnostic antibodies) have received FDA market approval in the last decade. A number of different technologies are now being used successfully to isolate potent therapeutic antibodies with minimal immunogenicity and improved safety. These include chimerisation (mouse/human antibodies), humanisation (complementarity-determining region [CDR] grafting), transgenic mice, phage display, ribosome display, and other emerging technologies. The phage and ribosome display technologies used at Cambridge Antibody Technology (CAT) are based on the physical linkage of gene to gene product which enables the recovery and enrichment of genetic material encoding the selected antibody…
A program for control of biopharmaceutical raw materials is a critical quality system that helps assure patient safety and contributes to product quality. The systems for testing and acceptance must be scientifically based, and meet global regulatory requirements and standards. When a new raw material is sourced, it is important to quickly establish the quality profiles for the supplier and the raw material. Among the numerous challenges that confront a company attempting to establish an effective, compliant, raw materials program, this paper will address the following: • Challenges in sourcing and tracing raw materials that are suitable for use in human therapeutics • Challenges and obstacles in qualifying suppliers • Special challenges faced by a firm that has outsourced its manufacturing and/or quality control (QC) testing…
Polysorbate-80, or polysorbitan mono-oleate, a non-ionic surfactant commercially referred to as Tween-80, is commonly employed as an excipient in the biopharmaceutical industry due to its low toxicity as well as its ability to solubilize hydrophobic molecules. Thus, polysorbate-80 is employed as a stabilizer in order to control the formation of protein aggregates and larger particulates in biopharmaceutical drug substance and drug product formulations. Guidelines published by The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and the United States Pharmacopeia (USP) classify excipients such as polysorbate-80 as major components in biopharmaceutical formulations and specify that these types of compounds be quantified using a validated analytical method…
Since the first gene therapy trials were conducted 25 years ago, there have been high expectations from the public, and much attention from investors, that previously incurable diseases would be cured by gene therapy. Still, despite numerous gene therapy clinical trials for many different indications, there are no approved gene therapy drugs in the United States. In 1999, one gene therapy patient died during clinical trials, the first ever. This highly publicized event led to heightened regulatory scrutiny over all such trials. Then in 2003 and 2005, three subjects developed leukemia as a direct consequence of gene therapy; one of them eventually passed away. The regulatory response stemming from these incidents led to greater regulatory oversight in gene therapy, as compared to other investigational drugs and biologics…
Optimal process development creates unit operations that effectively generate, separate, and concentrate a broad array of products. Historically, tangential flow filtration (TFF) process capabilities have been limited by technological and flow restrictions. Recent innovations in TFF module design have dramatically increased the capabilities of TFF to better achieve processing objectives. NCSRT has established a best practices protocol for developing clarification, fractionation, and concentration processes for mammalian, bacteria, yeast, insect, and virus based production systems. This article presents the development platform, supplemented with application-specific expertise…
Baculoviruses have found many uses in the field of biology, including as a control strategy for major insect pests such as the gypsy moth, the corn earworm, and the velvetbean caterpillar, for high level expression of recombinant proteins in insect cells, and, more recently, as gene delivery vehicles into mammalian cells. Some of these uses entail the need for isolation of baculoviral DNA for molecular biology studies. Currently, there are three ways in which baculoviral DNA can be obtained: 1) from the infection of insect larvae or cell cultures and the recovery of occlusion bodies (OB) containing viral particles, from which the DNA is then extracted; 2) from the recovery of extracellular virus (ECV) or budded virus (BV), usually from infected cell cultures; or 3) from total intracellular DNA harvested from infected cell cultures early in the infection cycle…
The developing biotechnology community may offer solutions and hope for recent world events that have focused attention on the vulnerability of the world’s population. Concerns about new pandemics have been raised by the emergence of new influenza strains and the re-emergence of older and even more highly virulent strains. In addition, there are fears that bioterrorism could involve agents such as anthrax or smallpox, and these threats become even more of a concern when you consider the increased mobility of such organisms via today’s commercial aviation. The ability of the biomedical community to respond rapidly to these shifting threats is more important than ever…