Pharmaceutical Regulatory Affairs: Open Access

Conducting Preclinical Abuse Liability Screening in Only One Sex: Making a Case for “Reasonable Exclusion”

Abstract

David V Gauvin and Zachary J Zimmermann

The Animal Welfare Act (AWA; 1990) requires the reduction in use of purpose bred animal subjects in bona fide research conducted in drug development. The National Institutes of Health (NIH) Revitalization Act of 1993 also requires its Director to reduce the number of animals used in government funded research as well as promoting those specific study protocols that provide valid and reliable data using only one gender. The consensus between the pharmaceutical industry and FDA was that a valid and reliable set of abuse liability studies did NOT require the inclusion of both male and female subjects. In recent pre-study protocol reviews, FDA has required the inclusion of both males and female animals in all three core abuse liability assays, basically doubling the total number of animals used on a single study design. NIH/FDA policy does allow for exceptions to the new rule. We provide evidence to establish a defence of a more balanced approach to these study designs that complies with the AWA and the NIH Revitalization Act by reducing the use of laboratory animals in preclinical research and to align the study designs with current goals of the International Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC).