Biologics are often produced in or derived from matrices that harbor the potential for introduction of adventitious agents to the drug product. This potential is not strictly theoretical, as viruses such as hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), porcine circovirus (PCV), and minute virus of mice (MVM) have been detected in biological products in the past. From a regulatory and safety perspective, assurance that adventitious agents are not present in the drug product is a critical measure of product quality. Guidelines for assuring safety, with respect to adventitious agents in blood-derived products and products produced in mammalian cell culture, are addressed in specific guidances from the Food and Drug Administration (FDA) and the Committee for Proprietary Medicinal Products (CPMP). These guidance documents suggest that safety is best assured through screening donor material or production cell lines, by controlling animal-derived raw materials used during manufacture, incorporating viral removal and inactivation steps in the production process, and protecting the product from the environment during manufacture. Even though Medicago develops products that are produced in plants, a host that does not support the replication of viruses that infect mammals, various regulatory agencies have advised that the production process should contain one or more operations that remove or inactivate adventitious agents. Medicago has investigated multiple methodologies to accomplish this goal, and has found ultraviolet C (UVC) irradiation treatment to be effective for adventitious agent inactivation in the production process used to manufacture their quadrivalent influenza vaccine without detrimental impact to the product…
Tag: <span>plant-based protein production</span>
Regulatory agencies such as the FDA require the structure and amino acid sequence characterization of recombinant monoclonal antibodies (MAbs) to grant marketing approval. Characterizing such complex, inherently heterogeneous molecules is a significant analytical challenge that requires a broad array of physicochemical tests. Mass spectrometry (MS) is an essential tool for characterizing protein identity, functions, substrate specificity and amino acid sequence (AAS) of recombinant MAb biotherapeutics as it complements, or in some cases supersedes the utility of traditional biological methods. For some of the most important proteomic applications, the high sensitivity and accuracy provided by modern MS has allowed the unequivocal protein characterization…
Biopharmaceuticals are predicted to become the main driving force of the pharmaceutical market in the near future. Other than blockbuster products such as erythropoietin, an increasing number of approved recombinant therapeutic proteins are based on antibody technology (e.g., fusion proteins or monoclonal antibodies [MAbs]). In contrast to relatively simple products produced in Escherichia coli bacteria (e.g., insulin), proteins which require complex posttranslational modifications such as glycosylation have to be produced in eukaryotic cells. In this context, production systems have been dominated by mammalian cell culture. Nevertheless, alternative eukaryotic expression technologies based on yeast, insect cells, transgenic animals, or transgenic plants are under development. Plants are a particularly promising alternative to mammalian cell culture because of their excellent safety aspects and estimated cost-efficient upstream/cultivation processes. In addition, plants are well known for their ability to express biologically functional monoclonal antibodies. In comparison to the seed plants most widely used for transgenic protein expression — tobacco, corn, and rice — mosses provide unique, beneficial features…
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…
More than 130 drug and vaccine approvals for 95 entities over the last 20 years have generated roughly $30 billion in revenue for the biotech industry. The vast majority of this revenue comes from 30 proteins that have manufacturing bottlenecks resulting from the complexities of consistent protein production. The lag times involved in constructing mammalian cell fermentation facilities keeps supply of immensely successful high-volume drugs like Enbrel, Rituxan, and Remicade well below estimated demand. In other cases, the complexities of peptide synthesis threaten the potential of soon-to-be-launched or recently approved drugs like Fuzeon. The Pharmaceutical Research and Manufacturers of America (PhRMA) has documented more than 371 new biotech drugs in development, supporting the view that demand for many biopharmaceuticals will continue to outstrip supply. That number does not include the multitude of biotech drugs still in research stages…