Contamination by viruses

In the aquatic environment, viruses pathogenic to man, animals, plants and microorganisms (especially bacteriophages) can be found. The greatest attention is given to viruses pathogenic to man. Wastewater can be most frequently contaminated by viruses which may penetrate also surface water and even drinking water. Water can be most often contaminated by viruses excreted in faeces (enteroviruses, adenoviruses, rheoviruses and probable hepatitis viruses). 

Inspired by the broad substrate range of porcine liver esterase, cloning and overexpression of PLE isoenzymes was persued over the past few years in order to overcome imperfect stereoselectivities of crude PLE preparations and to provide a reliable enzyme source [244-246]. In addition, for industrial applications the use of enzymes from animal sources are often undesirable due to the risk of contaminations by viruses and prions and due to the fact that products derived from pigs are considered impure by several world religions. 

The risk of viral contamination in plant-based medicinal products, and requirements for strategies to ensure that the product is consistently free of contaminating viruses, is discussed in detail in the EMEA document, while it is not addressed by the FDA. In addition to contamination by insect, bird and animal excreta or carcases, organic fertilizer, production personnel and equipment, the EMEA document lists plant virus infection as a source of contamination and claims that "... freedom from contamination with all types of viruses, irrespective of natural tropism, should be demonstrated. ... 

The starting material will likely be contaminated by intact, viable hepatitis B viral particles (and perhaps additional viruses, such as HIV). This necessitates introduction of stringent purification procedures to ensure complete removal of any intact viral particles from the product stream. A final product QC test to confirm this entails a 6-month safety test on chimpanzees. 

Hepatitis A is common, particularly in areas of poor sanitation, and is transmitted by food or drink contaminated by a sulferer/carrier. Clinical symptoms include jaundice, and are usually mild. A full recovery is normally recorded. Hepatitis B is transmitted via infected blood. Symptoms of acute hepatitis B include fever, chill, weakness and jaundice. Most sufferers recover from such infection, although acute liver failure and death sometimes occur 5-10% of sufferers go on to develop chronic hepatitis B. Acute hepatitis C is usually mild and asymptomatic. However, up to 90% of infected persons go on to develop a chronic form of the condition. Hepatitis D is unusual in that it requires the presence of hepatitis B in order to replicate. It thus occurs in some persons concomitantly infected with hepatitis B virus. Its clinical symptoms are usually severe, and can occur in acute or chronic form. 

The records are handled by authorized personnel to ensure security and control possible contamination with viruses... 

JTru.vr.v. There are epidemics caused by viruses, which occur periodically in the inseel populations and llius naturally help tn check their spread, Entomologists would like to lind ways of infecting pesi insects before they can cause serious damage. Most inseel viruses are specitie for a Tevs closely related hosts. The general sirueture of ihe viral particles includes UNA plus protein, all imbedded in a protein matrix. They arc termed nuclear polyhedrosis virus tNPVi The viruses spread when larvae eat contaminated loliuge. 

E. coli and enterococci have been isolated front citrus juices, and apple juice has been associated with Cryptosporidiosis. Contamination by hepatitis A and Norwalk-like viruses has been reported in fruit juices (Vasavada, 2003). 

The norms for medicinal production are particularly stringent. Biological products are composed of complex molecules, produced by cell lines with a relatively recent history, and difficult to characterize. Tests performed only on the final product do not guarantee consistency of production. The purification procedures should be planned and validated for the removal of potential contaminants from diverse sources cells, culture media, equipment, and reagents used in the purification or even degradation products derived from the protein itself. There are examples of products with unexpected risks that have caused serious problems such as blood contamination by HIV-1 virus between 1980 and 1985 (Bloom, 1984) or the presence of residual infectious viruses in the poliomyelitis vaccine due to inefficient inactivation (Lubiniecki et al., 1990). 

Contamination of biologicals by viruses is not just a theoretical possibility. This has been documented throughout the history of biologicals production. Human growth hormone, blood-derived products, and monoclonal antibodies are typical examples. 

Arindam Bose (Pfizer Central Research) further discussed the ICH documents and presented a rationale for the recommended combination of test procedures and process clearance validations required to demonstrate that marketed biopharmaceuticals are free of adventitious agents. He showed that testing of Pre-Seed Stock (PSS), the Master Cell Bank (MCB), and the Working Cell Bank (WCB) is required to demonstrate that they are free from contamination by mycoplasma, bacteria, molds, and yeasts. In addition, viral clearance validation studies must be performed on scaled down versions of each chromatographic step and the viral inactivation/removal step employed in the product purification scheme. Finally, clearance studies must be conducted with a panel of relevant and model viruses (typically three to four) to establish that the purification scheme will indeed purge any viruses that may be inadvertently introduced during processing. 

The presence of pVIII in empty capsid confirms that the viral particle is at an early stage of virus assembly. Based on this finding and the uniqueness of pVIII to the empty capsid of the adenovirus, an assay was developed to quantify the empty capsid contaminants by measuring the amount of pVIII detected in SDS-PAGE during the recombinant adenovirus preparation [136]. 

Screening and selection of the source plasma will only avoid contamination by known pathogens. The protein purification steps and specific virus reduction methods used in production processes, however, will inactivate and/or remove both known and unknown viruses. Terminal virus inactivation treatments are applied to product in final container and must balance virus inactivation with any modifications to protein immunogenicity, activity, and yield. While many upstream virus inactivation steps rely on chemical methods that involve the addition and subsequent removal of toxic agents (e.g., solvent/detergent), physical methods for virus inactivation, such as pH and heat, are used for terminal steps. 

A freshwater stream may look sparkling and clean, but it s probably not safe for drinking. Many rivers and lakes in the United States are polluted. Bacteria and viruses enter water supplies through contamination by sewage and industrial wastes. Wastes from landfills and mines leak into groundwater reservoirs. Pesticides, herbicides, and fertilizers are picked up by rainwater and carried into streams. Streams flow into rivers, and rivers empty into oceans. In addition, coastal cities pump waste directly into the oceans. For this reason, much of the oceans pollution is found along the coasts of continents. 

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