Risk assessment of plant-based pharmaceuticals and biologics

Abstract

Biotechnology is evolving to produce pharmaceutical proteins in plants. Plantbased pharmaceutical production creates concerns of exposure in an open environment and contamination of the food supply. Consequently, quantitative human health and ecological risk assessments were conducted for aprotinin, gastric lipase, and LT-B expressed in maize. A comparative, qualitative risk assessment was conducted for conventionally derived and plant-cell derived Newcastle disease virus vaccine. Effect and exposure scenarios were modeled for each quantitative risk assessment and each scenario was based on a tiered approach in which inadvertent exposure through ingestion were examined to determine a risk characterization of the plant-based pharmaceuticals. The qualitative Newcastle disease virus vaccine risk assessment characterized risks based on the potential exposures to the poultry being vaccinated, to humans administering the vaccine, and to non-target birds. For the human-health risk assessment, the dietary exposure evaluation model (DEEM) was used to estimate the inadvertent dietary intake of the pharmaceutical proteins in food. The ecological risk assessment used Monte Carlo simulations to evaluate the exposure of each protein in maize for four receptor species.

The human-health risk assessments revealed that the most conservative scenario produced higher risk quotients (RQ's) than the other two scenarios. The difference in risks was attributable to the differences in toxic endpoints of the proteins. Although the protein expressions and dietary consumption were assumed to be the same, dietary risks between the proteins varied by more than 56,000 times. The human-health risk assessment revealed that risks will vary dramatically and depend on factors such as the specific pharmaceutical protein, protein expression, and exposure scenarios. The assessments reinforced the need for case-by-case assessments. The ecological risk assessment demonstrated that risks will vary between species and between proteins, based primarily on differences in toxic endpoint and consumption rates. It shows the utility of probabilistic, quantitative risk assessment methodologies and supports the human dietary risk assessment by demonstrating the importance of assessing risks from plant-based pharmaceuticals on a case-by-case basis. The qualitative assessment illustrated that fewer effects and contamination issues were associated with the use of the plant-cell derived Newcastle disease virus vaccine compared to conventionally derived vaccines.