Contamination by adventitious agents (bacteria, fungi, mycoplasma, and viruses) represents potential safety risks for biologics produced in mammalian cells. Bacterial and fungal contaminations are usually easy to detect in culture medium due to changes in pH and visual indicators such as color and opacity. Mycoplasma contamination has been detected in 15–35% of cell lines deposited in some cell culture collection. This is because mycoplasma contaminations often cause little changes that can be readily detected by visual inspection. However, bacterial, fungal, and mycoplasma contamination can be more effectively controlled than viral contamination by careful screening of initial parental cell banks, proper environmental monitoring, along with ongoing testing…
Tag: <span>mammalian cell culture</span>
Enriched or pure oxygen is increasingly being used to improve mammalian and microbial cell culture productivity. Sterilizing filtration of the process gas stream is required to remove all microbial contaminants. The filters used to sterilize the gas stream must meet demanding requirements. They must be capable of withstanding sterilization and integrity testing after each use. Oxygen challenges filters because filter components may suffer corrosion and filter materials can potentially ignite under extreme conditions. So the components of filters used with pure oxygen should be tested and rated for pure oxygen service. This article will delve into the main issues involved in sterilizing enriched or pure oxygen gas streams…
In today’s biopharmaceutical pipeline, monoclonal antibodies are a predominant modality for a broad range of clinical indications, including inflammatory disorders, oncology, and infectious diseases. More than two dozen antibody-based products are commercially available. In 2004, six of the 12 new biopharmaceutics that gained approval in the United States and Europe were antibody-based products. Most antibody therapies require high doses over a long period of time, which requires large amounts of purified product per patient. Therefore, manufacturing capacity to meet the demands of antibody production is a real challenge. It is desirable to have highly productive and consistent manufacturing processes. In addition, speed to market is critical to deliver health benefits to patients quickly and to achieve business success…
In the last few years, we have seen many biotech products approved by FDA. These products have gained public awareness because of their ability to treat several debilitating diseases with very minimal side effects, and thereby impact the quality of life for many people. As a result, the biotech industry is constantly in the news for its successes and programs to develop new therapeutics for many unmet medical needs. Immunomedics, Inc., a New Jersey biotechnology company, recently completed an expansion project that included new bioreactor manufacturing suites and support laboratories. Building on the company’s existing headquarters site and fully integrating the new capacity into the existing operational facility, the project spanned two years and was completed in 2003…
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…
Total market share of biopharmaceuticals is estimated to increase from $33 billion now to more than $45 billion in 2007. These numbers are accounted for by the 64 products approved by European and US regulators and some of the 500 products currently under clinical evaluation. More than 2,000 products are in discovery and preclinical development. Monoclonal antibodies (MAbs) and recombinant glycoproteins constitute a major part of these new biotech leads. The estimated demands for MAbs alone are more than 6,000 kg per year in 2006. Currently, 16 MAbs are licensed by the U.S. Food and Drug Administration (FDA) for pharmaceutical use and more than 130 are in clinical trials. This fast-growing class of biotherapeutics is expected to reach worldwide sales of more than $15 billion per year in 2008. In the coming years, mammalian cell culture technology will remain the production system of choice for MAbs and other recombinant glycoproteins. Therefore, efficient, cost-effective production systems need to be in place to meet the demands…
Within the biopharmaceutical industry, mammalian cell culture is extensively used to manufacture a various biopharmaceutics uncluding antibodies, interferons, hormones, crythropoietin, clotting factors, immunoadhesins, and vaccines. The market for monoclonal antibodies (MAbs) alone is expected to grow 30% a year and reach sales of nearly $6.5 billion in 2004. The vast majority of these biotherapeutics are secreted glycoproteins obtained from mammalian cell lines such as: Chinese hamster ovary (CHO), human embryonic kidney 293 (HEK-293 or 293). NS0, and baby hamster kidney (BHK). As is the goal with most commercial products, biotechnologists strive to generate these valuable proteins in the highest yields possible in order to utilize mammalian bioreactor facilities efficiently…
The biopharmaceutical manufacturing sector is rapidly gearing up production capacity to satisfy the steadily escalating global demand for complex biologics to combat a number of treatable illnesses. Frequently, the biotherapeutics in demand are too complicated to be chemically synthesized and thus are beyond the reach of traditional pharmaceutical approaches. To effectively address this issue, these products must be developed and produced using viable and robust biological systems…
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…
Cell culture was first devised at the beginning of the 20th century as a method for studying the behavior of animal cells free of systemic variations that might arise in the animal both during normal homeostasis and under the stress of an experiment. During the past thirty, thousands of academic and for-profit organizations have come to rely on cultivation of animal cells as the basic foundation to perform biomedical research and large-scale biomanufacturing. Their success is directly dependent upon the reproducible production of high quality cell culture products. The complexity of the mammalian cell, its growth and storage requirements, and the need to maintain pure and uncontaminated cultures is a constant challenge to those involved with in vitro cell culture…