|
| ||
|
|
||
Biopharmaceutical Products (biopharmaceutical + products)
Selected AbstractsNanofiltration of plasma-derived biopharmaceutical productsHAEMOPHILIA, Issue 1 2003T. Burnouf Summary. This review presents the current status on the use and benefits of viral removal filtration systems , known as nanofiltration , in the manufacture of plasma-derived coagulation factor concentrates and other biopharmaceutical products from human blood origin. Nanofiltration of plasma products has been implemented at a production scale in the early 1990s to improve margin of viral safety, as a complement to the viral reduction treatments, such as solvent,detergent and heat treatments, already applied for the inactivation of human immunodeficiency virus, hepatitis B and hepatitis C virus. The main reason for the introduction of nanofiltration was the need to improve product safety against non-enveloped viruses and to provide a possible safeguard against new infectious agents potentially entering the human plasma pool. Nanofiltration has gained quick acceptance as it is a relatively simple manufacturing step that consists in filtering protein solution through membranes of a very small pore size (typically 15,40 nm) under conditions that retain viruses by a mechanism largely based on size exclusion. Recent large-scale experience throughout the world has now established that nanofiltration is a robust and reliable viral reduction technique that can be applied to essentially all plasma products. Many of the licensed plasma products are currently nanofiltered. The technology has major advantages as it is flexible and it may combine efficient and largely predictable removal of more than 4 to 6 logs of a wide range of viruses, with an absence of denaturing effect on plasma proteins. Compared with other viral reduction means, nanofiltration may be the only method to date permitting efficient removal of enveloped and non-enveloped viruses under conditions where 90,95% of protein activity is recovered. New data indicate that nanofiltration may also remove prions, opening new perspectives in the development and interest of this technique. Nanofiltration is increasingly becoming a routine step in the manufacture of biopharmaceutical products. [source] Anion exchange chromatography provides a robust, predictable process to ensure viral safety of biotechnology productsBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009Daniel M. Strauss Abstract The mammalian cell-lines used to produce biopharmaceutical products are known to produce endogenous retrovirus-like particles and have the potential to foster adventitious viruses as well. To ensure product safety and regulatory compliance, recovery processes must be capable of removing or inactivating any viral impurities or contaminants which may be present. Anion exchange chromatography (AEX) is a common process in the recovery of monoclonal antibody products and has been shown to be effective for viral removal. To further characterize the robustness of viral clearance by AEX with respect to process variations, we have investigated the ability of an AEX process to remove three model viruses using various combinations of mAb products, feedstock conductivities and compositions, equilibration buffers, and pooling criteria. Our data indicate that AEX provides complete or near-complete removal of all three model viruses over a wide range of process conditions, including those typically used in manufacturing processes. Furthermore, this process provides effective viral clearance for different mAb products, using a variety of feedstocks, equilibration buffers, and different pooling criteria. Viral clearance is observed to decrease when feedstocks with sufficiently high conductivities are used, and the limit at which the decrease occurs is dependent on the salt composition of the feedstock. These data illustrate the robust nature of the AEX recovery process for removal of viruses, and they indicate that proper design of AEX processes can ensure viral safety of mAb products. Biotechnol. Bioeng. 2009;102: 168,175. © 2008 Wiley Periodicals, Inc. [source] Technological progresses in monoclonal antibody production systemsBIOTECHNOLOGY PROGRESS, Issue 2 2010Maria Elisa Rodrigues Abstract Monoclonal antibodies (mAbs) have become vitally important to modern medicine and are currently one of the major biopharmaceutical products in development. However, the high clinical dose requirements of mAbs demand a greater biomanufacturing capacity, leading to the development of new technologies for their large-scale production, with mammalian cell culture dominating the scenario. Although some companies have tried to meet these demands by creating bioreactors of increased capacity, the optimization of cell culture productivity in normal bioreactors appears as a better strategy. This review describes the main technological progresses made with this intent, presenting the advantages and limitations of each production system, as well as suggestions for improvements. New and upgraded bioreactors have emerged both for adherent and suspension cell culture, with disposable reactors attracting increased interest in the last years. Furthermore, the strategies and technologies used to control culture parameters are in constant evolution, aiming at the on-line multiparameter monitoring and considering now parameters not seen as relevant for process optimization in the past. All progresses being made have as primary goal the development of highly productive and economic mAb manufacturing processes that will allow the rapid introduction of the product in the biopharmaceutical market at more accessible prices. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] Antibodies and Genetically Engineered Related Molecules: Production and PurificationBIOTECHNOLOGY PROGRESS, Issue 3 2004A. Cecília A. Roque Antibodies and antibody derivatives constitute 20 % of biopharmaceutical products currently in development, and despite early failures of murine products, chimeric and humanized monoclonal antibodies are now viable therapeutics. A number of genetically engineered antibody constructions have emerged, including molecular hybrids or chimeras that can deliver a powerful toxin to a target such as a tumor cell. However, the general use in clinical practice of antibody therapeutics is dependent not only on the availability of products with required efficacy but also on the costs of therapy. As a rule, a significant percentage (50,80%) of the total manufacturing cost of a therapeutic antibody is incurred during downstream processing. The critical challenges posed by the production of novel antibody therapeutics include improving process economics and efficiency, to reduce costs, and fulfilling increasingly demanding quality criteria for Food and Drug Administration (FDA) approval. It is anticipated that novel affinity-based separations will emerge from the development of synthetic ligands tailored to specific biotechnological needs. These synthetic affinity ligands include peptides obtained by synthesis and screening of peptide combinatorial libraries and artificial non-peptidic ligands generated by a de novo process design and synthesis. The exceptional stability, improved selectivity, and low cost of these ligands can lead to more efficient, less expensive, and safer procedures for antibody purification at manufacturing scales. This review aims to highlight the current trends in the design and construction of genetically engineered antibodies and related molecules, the recombinant systems used for their production, and the development of novel affinity-based strategies for antibody recovery and purification. [source] | ||||||||||