The use of plants as protein expression hosts for human therapeutic proteins is emerging as a safe and cost-effective alternative to microbial and mammalian cell culture. Pharmaceutical protein production is typically carried out in microbes and mammalian cell culture because of their high production potential and/or ability to produce complex eukaryotic proteins. However, immense costs are typically required for production facilities to support their growth. To offset these costs, companies usually build and expand a production facility over several years. In fact, it has been predicted that the demand for high-value pharmaceuticals produced by cell culture will quickly surpass the ability of pharmaceutical companies to produce them…
BioProcessing Journal Posts
The first use of mammalian cell culture for the production of vaccines dates back to polio vaccine development in the 1950s. The development of hybridoma technology in the 1970s further stimulated the use of mammalian cells for the production of monoclonal antibodies. Together with developments in genetic engineering, it therefore became possible to produce a wide range of recombinant proteins as well as to improve cell metabolism. Animal cells are now widely used in industrial processes to obtain complex glycoproteins with correct posttranslational modifications and biological activity for diagnostic and therapeutic applications. Animal cells are the main source for commercially available recombinant proteins such as tissue plasminogen activator (tPa), erythropoietin (EPO), DNAse, factor VIII, interferon-ß, and monoclonal antibodies…
The modern age of blood transfusion began after the Second World War, as detailed in Douglas Starr’s book, Blood: An Epic History of Medicine and Commerce. During the war, it became apparent that early and aggressive medical treatment utilizing whole blood or plasma could increase the chances of survival for military personnel wounded in combat. In the United States, a national program to encourage blood donation was created to provide the needed blood, which was then shipped as whole blood or plasma to war zones. After the war, physicians were eager to apply surgical advances developed on and off the battlefield to the care of the general population. Because these advances relied on blood transfusion, for the public to realize their benefit, adequate supplies of whole blood and blood components needed to be available to hospitals across the country. This was often not the case…
Parvoviruses are one of the most prevalent infectious agents in the laboratory rodent. Their effect on research can range from immune dysfunction that may mislead researchers when interpreting results to lethal effects on animals. Until recently parvovirus infection in mice was thought to be caused by minute mouse virus (MMV) and in rats by rat viral agents in the KRV or H-1 serogroups. Relatively newly discovered viruses in these groups are mouse (MPV) and rat parvoviruses (RPV-1 and 2). Parvoviruses are 15–20 nm in diameter and are single-stranded DNA viruses of about 5,000 nucleotides, which replicate through a double-stranded DNA intermediate. The protein composition consists of three structural or capsid proteins providing the viral coat (VP-1, VP-2, and VP-3) and two non-structural proteins involved in viral replication (NS-1 and NS-2). Among the capsid proteins,VP-2 is the major protein…
At the onset of modern-day biotechnology, products typically fell into two distinct categories, the traditional high volume, low value products (e.g. beer and industrial enzymes) that had come to characterize the biotechnology industry, and low volume, high cost products. Recombinant proteins, the result of technological advances in molecular biology, have come to typify these latter products. Recombinant protein therapeutics have been hugely successful, potentially outstripping production capacity and continue to drive much of the biotechnology. Meanwhile, many recombinant proteins, those characterized as research tools and reagents, are governed by a price-volume relationship typical of industrial enzymes. In a competitive environment, they are fast becoming commodities — price sensitive, packaged as kits, coupled to instrumentation, and relying on heavy marketing and brand recognition. Ominously, the advantage protein therapeutics have enjoyed with patent protection and regulatory constraints on production is being threatened as patents expire and competition from generics increases…
In general, the industry has gone through another of its realignment periods, where much was learned, but a lot of restructuring and refocusing took place. Driven by the need to keep the doors open, small to medium sized firms had to do some severe belt tightening, or completely redefine themselves as to technologies, products, and personnel. Many of the larger firms reevaluated their product pipelines, and then made the changes they felt were necessary to assure future revenues, or to make themselves attractive merger partners. Numerous large mergers took place with some that were the largest the biopharmaceutical industry has ever seen. In addition, several medium-sized companies merged, or otherwise found strategic alliances that energized their product pipelines, or simply provided the cash they needed to keep going. Antibody products did very well with a number of blockbusters receiving license approval in 2003…
Xcyte Therapies has recently introduced a bioreactor-based process for the GMP manufacture of autologous activated T cells, Xcellerated T Cells™, for clinical trials. Using a single customized disposable 20-L Cellbag™ with a working volume of 10 L on a customized Wave Bioreactor platform (Wave Biotech, Bridgewater, NJ), the Xcellerate™ III Process has supplanted the 60-L static Xcellerate II Process that used 60 bags cultured in a standard incubator. Compared to the Xcellerate II™ Process, the Xcellerate III Process significantly reduces the overall labor, the number of culture containers, bag spikes, and sterile connections required, as well as reducing the process volume and the cost of goods, while more than quadrupling the final cell density and doubling the facility capacity. These process improvements are achieved without compromising final product composition or quality…