Biopharmaceuticals risk analysis

Q Risk Analysis and Safety of Plant-Made Biopharmaceuticals... 

Risk analysis has been proven to retain the flexibility necessary to make it a useful model system for addressing the countless issues that are found to be associated with plant-derived pharmaceuticals (Wolt and Peterson, 2000). Over the past few years, a great deal of information and experience has steadily accumulated with respect to risk analysis of pharmaceuticals that are currently produced in bacterial and aifimal cell bioreactor systems. Risk analysis has also been performed on transgenic crops used for food production as well as for other applications. As a result, elements from each of these disciplines can be incorporated into the design of optimal production and testing policies and practices. Risk analysis has been employed to cover a series of important issues regarding the large-scale manufacture of plant-made biopharmaceuticals, and will continue to present serious issues for researchers in the academic, corporate, and public health arenas to address (Miele, 1997 Ciliberti and Molinelli, 2005). 

A number of potential risks are associated with plant-based pharmaceuticals these include allergen exposure to the public, pollen transfer to wild species, nontarget organism exposure due to persistence of genetically engineered material in the environment, interspecies gene flow, and contamination of nontransgenic crops intended for human consumption. The role of risk analysis with respect to the impact of plant-based biopharmaceuticals on human health and the environment are discussed in this chapter. 

Since risk analysis plays an important role in public policy decision making, efforts have been made to devise a means by which to identify, control, and communicate the risks imposed by agricultural biotechnology. A paradigm of environmental risk assessment was first introduced in the United States by Peterson and Arntzen in 2004. In this risk assessment, a number of assumptions and uncertainties were considered and presented. These include (1) problem formulation, (2) hazard identihcation, (3) dose-response relationships, (4) exposure assessment, and (5) risk characterization. Risk assessment of plant-made pharmaceuticals must be reviewed on a case-by-case basis because the plants used to produce proteins each have different risks associated with them. Many plant-derived biopharmaceuticals will challenge our ability to define an environmental hazard (Howard and Donnelly, 2004). For example, the expression of a bovine-specihc antigen produced in a potato plant and used orally in veterinary medicine would have a dramatically different set of criteria for assessment of risk than, as another example, the expression of a neutralizing nonspecihc oral antibody developed in maize to suppress Campylobacter jejuni in chickens (Peterson and Arntzen, 2004 Kirk et al., 2005). 

Finally, both assessments are combined, resulting in the assessment of the expected company-specific return versus the risk contribution to the overall portfolio. The analysis described could be done for several levels of a biopharmaceutical portfolio the overall portfolio or individual indications with a project assessment on the level of mechanism of action and/or targets. 

Purpose. As biopharmaceutical products are large and complex molecules and no single test method is sufficient, product analysis uses multiple, different analytical methods strategically designed to be complementary with respect to selectivity and specificity [4, 27]. More sensitive test methods allow proof of greater removal of a putative risk factor [12], and the more key parameters that can be measured assure that process variability is understood and controlled [66]. However, it is important... 

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