Biological Products (biological + products)

Distribution by Scientific Domains

Selected Abstracts

Pathogen safety of manufacturing processes for biological products: special emphasis on KOGENATE® Bayer

D. C. Lee
Summary., Manufacturers of human therapeutic proteins derived from biological sources continuously strive to improve the pathogen safety profiles of these products. Efforts to improve pathogen safety margins for these biological products are directed towards several areas within the manufacturing processes including: (a) sourcing and screening of raw materials (b) determining the potential for manufacturing processes to reduce pathogen titres, and (c) incorporating methods designed specifically to remove or inactivate contaminating pathogens. Methods that could potentially reduce pathogen titres are a major focus for many manufacturers. In general, these methods are grouped into two categories, pathogen clearance and pathogen inactivation. Assessments are performed on small-scale, laboratory simulations of the manufacturing process of interest that are spiked with a known amount of a selected pathogen. These studies provide estimates of the potential for a process step to remove or inactivate a particular pathogen. There are several pathogen clearance/inactivation methods that are inherent in manufacturing processes, however, some methods are intentionally incorporated into manufacturing for the sole purpose of reducing putative pathogen titres. Not only are well-known pathogens such as viruses targeted, but also suspected pathogens such as those associated with the transmissible spongiform encephalopathies (TSEs). The production processes for the isolation of several biological products, including recombinant KOGENATE® Bayer (Kogenate®FS), have been evaluated for the ability to reduce pathogen titres and/or have been designed to incorporate methods for reducing potential pathogen safety risks. Several processing steps with the potential to reduce pathogen titres have been identified. [source]

Aqueous two-phase systems strategies for the recovery and characterization of biological products from plants

Oscar Aguilar
Abstract The increasing interest of the biopharmaceutical industry to exploit plants as economically viable production systems is demanding the development of new downstream strategies to maximize product recovery. Aqueous two-phase systems (ATPSs) are a primary recovery technique that has shown great potential for the efficient extraction and purification of biological compounds. The present paper gives an overview of the efficient use of ATPS-based strategies for the isolation and partial purification of bioparticles from plant origin. Selected examples highlight the main advantages of this technique, i.e. scaling-up feasibility, process integration capability and biocompatibility. An overview of the recent approach of coupling ATPSs with traditional techniques to increase bioseparation process performance is discussed. A novel approach to characterization protein from plants combining ATPSs and two-dimensional electrophoresis (2-DE) is introduced as a tool for process development. In the particular case of products from plant origin, early success has demonstrated the potential application of ATPS-based strategies to address the major disadvantages of the traditional recovery and purification techniques. This literature review discloses the relevant contribution of ATPSs to facilitate the establishment of bioprocesses in the growing field of high-value products from plants. Copyright © 2010 Society of Chemical Industry [source]

Dipteran predators of Simuliid blackflies: a worldwide review

D. Werner
Abstract., Haematophagous female blackflies (Diptera: Simuliidae) are serious biting pests and obligate vectors of vertebrate pathogens, namely filarial Dirofilaria, Mansonella, Onchocerca and protozoal Leucocytozoon. Immature stages of Simuliidae inhabit lotic waterways, the sessile larvae filter-feeding and often forming a large proportion of the benthic biomass, usually aggregated in well-oxygenated sections of streams, rivers, waterfalls and spillways. Simuliid control practices depend on larvicidal chemicals, biological products (bacteria, nematodes) and environmental modification. The potential use of predators for biological control of Simuliidae has not been exploited. Predators of Simuliidae include examples of at least 12 families of Diptera and other predaceous arthropods (Crustacea and insects: Coleoptera, Odonata, Plecoptera, Trichoptera), invertebrates (notably Turbellaria), as well as browsing fish. Diptera impacting upon simuliid populations comprise mainly Chironomidae, Empididae and Muscidae, although several other families (Asilidae, Dolichopodidae, Phoridae, Drosophilidae, Scathophagidae) play a significant role as predators. Details of predator and prey species and life stages are presented, by zoogeographical region, including the prevalence of cannibalism among Simuliidae. [source]

Risk assessment of drugs, biologics and therapeutic devices: present and future issues,

B. L. Strom
Abstract Purpose The current US system for detecting adverse effects of therapeutics (drugs, devices and biological products) is suboptimal. This report presents the results of an expert workshop on assessing therapeutic risks. This is the second of five workshops coordinated by the Centers for Education and Research on Therapeutics (CERTs) to address the management of therapeutic risks relative to potential benefits. Methods The workshop included academic, industry, government and constituency-based leaders. The focus was on the postapproval phase and procedures in the US, but relevant international issues and attendees were included. Results Substantial deficiencies in the current US system for risk assessment were delineated. Improving the system will involve research into methods to improve risk assessment, enhancement and consolidation of data-handling systems, education of healthcare workers, allocation of financial resources and building of constituencies. Conclusions We need leadership on multiple levels for global coordination of risk assessment. We can then begin to fill gaps and produce benefits for industry, health authorities, government agencies, healthcare providers, and most important, the public. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Microarray-based gene expression analysis as a process characterization tool to establish comparability of complex biological products: Scale-up of a whole-cell immunotherapy product

Min Wang
Abstract Whole-cell immunotherapies and other cellular therapies have shown promising results in clinical trials. Due to the complex nature of the whole cell product and of the sometimes limited correlation of clinical potency with the proposed mechanism of action, these cellular immunotherapy products are generally not considered well characterized. Therefore, one major challenge in the product development of whole cell therapies is the ability to demonstrate comparability of product after changes in the manufacturing process. Such changes are nearly inevitable with increase in manufacturing experience leading to improved and robust processes that may have higher commercial feasibility. In order to comprehensively assess the impact of the process changes on the final product, and thus establish comparability, a matrix of characterization assays (in addition to lot release assays) assessing the various aspects of the cellular product are required. In this study, we assessed the capability of DNA-microarray-based, gene-expression analysis as a characterization tool using GVAX cancer immunotherapy cells manufactured by Cell Genesys, Inc. The GVAX immunotherapy product consists two prostate cancer cell lines (CG1940 and CG8711) engineered to secrete human GM-CSF. To demonstrate the capability of the assay, we assessed the transcriptional changes in the product when produced in the presence or absence of fetal bovine serum, and under normal and hypoxic conditions, both changes intended to stress the cell lines. We then assessed the impact of an approximately 10-fold process scale-up on the final product at the transcriptional level. These data were used to develop comparisons and statistical analyses suitable for characterizing culture reproducibility and cellular product similarity. Use of gene-expression data for process characterization proved to be a reproducible and sensitive method for detecting differences due to small or large changes in culture conditions as might be encountered in process scale-up or unanticipated bioprocess failures. Gene expression analysis demonstrated that cell products of representative lots under the same production process and at the same production scale were statistically identical. Large process changes that resulted from the artificial stress conditions used (absence of FBS and induction of hypoxia) displayed profoundly different gene expression patterns. We propose the use of simple t -test analysis in combination with the herein introduced expression ratio with mean intensity (ERMI) analysis as useful tools for process characterization by global gene expression analysis. Biotechnol. Bioeng. 2009; 104: 796,808 © 2009 Wiley Periodicals, Inc. [source]