Abstract

Determining Adversity in Toxicology Studies - A Toxicologist’s Perspective

Venkatesha Udupa, Senior General Manager, Glenmark Pharmaceuticals Limited

A biochemical, morphological or physiological change (in response to a stimulus) that either singly or in combination adversely affects the performance of the whole organism or reduces the organism’s ability to respond to an additional environmental challenge is called ‘adverse effect’ in a repeat dose toxicology studies.  Adversity assessment represent empirical measurements (i.e., objective data), and integrated with well-informed subjective and professional judgments, and consequent designation of the No Adverse Effect Level (NOAEL) is the pivotal endpoint of repeat dose toxicology studies in animals which require analysis of results of all parameters evaluated in the particular study.  Differences in approaches and opinions related to using adverse effect data and NOAEL affect the assessment of human risk by regulators who may apply more conservative approaches to human dosing than otherwise necessary with better prepared discussion and application of the concepts of adversity.    Clarity achieved through more consistent and transparent application of the adversity concept within nonclinical reports will improve communications in regulatory submissions, benefitting both clinicians and regulators charged with protecting human health. It is the ultimate responsibility of each organization to ensure that toxicology study documents and nonclinical overview regulatory documents for a given product include clear and cohesive interpretation of study findings, adversity and their relevance to humans.