Viral contamination

The early immunoglobulin products prepared by cold-ethanol fractionation were found to be free from transmitting hepatitis infection (106,108) this was not the case with products prepared by alternative methods (109). Subsequentiy, some batches of intravenous immunoglobulin transmitted hepatitis infection (110), emphasizing the importance of estabHshing vaHdated procedures for dealing with potential viral contaminants (111). 

Vimses are obligate intracellular parasites. They only exhibit activity by infecting other living organisms, thus they are not a practical concern in industrial microbiological fields. The exception is where viral contamination of the product or process represents a threat of transmission of disease. Microscopic insects and protozoans are also not addressed in this article (see Insectcontroltechnology). 

Semm is expensive, the 1992 price was 400/L, and supply depends on cattie supply. Use of this semm also poses significant difficulties in vahdating processes for absence of viral contamination. Hence, a goal in cell culture technology is to develop semm-free media for cell culture. Much work has gone into developing semm-free media and a sizable portion of cell culture research is devoted to this project. A detailed discussion of semm-free media development is available (5). 

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. ... 

In addition to the urgent problem of capacity, manufacturers have to cope with the operating costs of production, which are increased by the need for skilled personnel and expensive media components. Another cost driver is the inherent contamination risk when using mammalian cell culture systems. All materials must be checked closely for bacterial and viral contamination, and the presence of prions and endotoxins. This affects not only the manufacturing process, but also downstream materials and even human semm albumin (HSA) used for formulations. In the end, production costs add up to 100-1000 per gram of therapeutic protein. 

Biopharmaceutical products are also subjected to screening for the presence of viral particles prior to final product release. Although viruses could be introduced, for example, via infected personnel during downstream processing, proper implementation of GMP minimizes such risk. Any viral particles found in the finished product are most likely derived from raw material sources. Examples could include HIV or hepatitis viruses present in blood used in the manufacture of blood products. Such raw materials must be screened before processing for the presence of likely viral contaminants. 

A prime practical consideration in the use of the IP route for acute testing should be the utilization of aseptic techniques to preclude bacterial or viral contamination. If these are not exercised, the resulting infected and compromised animals cannot be expected to produce either valid or reproducible indications or actual chemical toxicity. 

Currently, all donors and blood preparations undergo multistage and expensive control to ensure the absence of viral contamination In this respect, the development of affordable methods of inactivation of viruses could be an important step toward safety in hemotransfusion. Currently used treatments such as UV irradiation damage therapeutic components of the blood (Williamson and Cardigan, 2003), so alternative selective approaches are needed for this purpose. Among them, chemotherapy, photochemotherapy (PCT), and photodynamic antibacterial therapy should be noted (Mohr, 2000). 

To date the Occupational Safety and Health Administration (OSHA) has had little involvement with GLP labs other than as a part of normal workplace safety evaluations. Increasingly however, OSHA has expressed concerns about the possible exposure of workers to biological and viral contaminants in laboratory environments. No doubt a good deal of this concern is a result of concerns following the September 11 disaster, and subsequent (so far unrealized) fears of related biological warfare. 

Clinical trials have demonstrated excellent efficacy with recombinant human factor VIII concentrates available as Recombinate and Kogenate. These recombinant factor VIII products are purified from the cell culture of plasmids, not viral DNA-transfected hamster cells and therefore do not express viral sequences. The addition of human serum albumin for stabilization, constitutes the sole possible source for human viral contamination. More recently recombinant factor IX has been genetically engineered by insertion of the human factor IX gene into a Chinese hamster ovary cell line. It has been proved to be safe and effective in the treatment of patients with hemophilia B. 

F. Role in therapy Somatropin (rDNA origin) is a safe alternative to growth hormone derived from human pituitary glands, which carries the risk of viral contamination. Pituitary-derived growth hormone has been withdrawn from the... 

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