Integrating Environmental Risks and Mitigation into Benefit- Risk Assessment of Veterinary Medicinal Products

The regulation for the authorization of veterinary medicinal products (VMPs) to the European market requires an environmental risk assessment (ERA). The ERA results are then included in a benefit-risk assessment. However, knowledge and experience in the benefit-risk assessment implementation is developing and current guidelines are vague on how environmental risks and risk mitigation measures (RMMs) are integrated into the benefit-risk assessment process. This study was therefore conducted to develop new approaches and knowledge for the integration of environmental risk assessment into the benefit-risk assessment process. Novel methodologies for the integration of ERA data into the benefit-risk assessment were initially developed. The main challenge of implementing a benefit-risk assessment is that benefits are measurements of animal health whereas the risks are environmental measurements therefore comparison is difficult. To address this challenge, categorization approaches for benefits and risks were developed in three different methodologies (i.e., a summative categorization, a visual scoring matrix and a comparative categorization). Work was then done, using available information from the literature to explore the environmental risks of the antibiotic tylosin. Modelling of exposure and toxicity to aquatic and terrestrial ecosystems concluded that a number of treatment scenarios have unacceptable risks and are therefore appropriate for benefit-risk consideration. The data generated for tylosin along with additional risk data for two VMPs of high environmental concern (i.e., ivermectin and diclofenac) were applied to the benefit-risk assessment methodologies previously developed. Valuable insights into differences in applicability, adaptability, sensitivity and transparency of the proposed categorization methodologies were found. Finally, a novel interview approach was employed to gain VMP user insights into users’ attitudes and perceptions of RMMs as well as on farm practicality. Overall, the sequential investigations presented in this thesis have built a foundation for the continued development of benefit-risk assessment process for VMPs has been lacking to date.