Considerations Regarding Nonhuman Primate Use in Safety Assessment of Biopharmaceuticals

Abstract

Selection of a pharmacologically responsive species can represent a major challenge in designing nonclinical safety assessment programs for many biopharmaceuticals (eg, monoclonal antibodies (mAbs)). Frequently, the only relevant species for nonclinical testing of mAbs is the non-human primate (NHP). This situation, coupled with a rapidly increasing number of mAb drugs in development, has resulted in a significant increase in the number of NHPs used in nonclinical safety assessment. Apart from ethical considerations related to responsible animal use, there is a clear need for more efficient and innovative approaches to drug discovery and development; these factors drive the need to investigate alternative approaches and strategies for the safety assessment. This review summarizes important scientific and regulatory perspectives derived from presentations and audience discussions in an educational forum at the 2010 annual American College of Toxicology meeting regarding opportunities for employing alternative approaches to minimize NHP use in mAb drug development.

The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals

“…In addition, increasing regulatory demands (for example, juvenile toxicity testing) are also thought to contribute to the increased use of NHPs (Buckley et al, 2011).…”

Considerations Regarding the Future Use of Nonhuman Primates to Support the Clinical Development of Biopharmaceuticals

“…Buckley et al [14] captured the opportunities to minimize (but not avoid) the use of NHPs provided by ICH S6 guidance. These included (1) incorporating safety pharmacology end points into repeat-dose toxicity studies, (2) minimizing the number of dose groups in chronic toxicity studies, (3) conducting a maximum of two general toxicology studies (i.e., 1 month and 3 or 6 months), (4) avoiding the conduct of multiple chronic toxicity studies (which have been requested based on the lack of achieving toxicity), and (5) the use of only the rodent for chronic toxicity studies when appropriate [34].…”

Science-based approaches to carcinogenicity risk assessment for large molecules

“…Identifying opportunities where other species can provide valuable data and also where study designs can be amended to reduce non-human primate use has scientific and business benefits. The NC3Rs has been working with 18 pharmaceutical, biotechnology and contract research organisations over the last 7 years to share data on species selection and study design for mAbs in development (Chapman et al, 2007, Chapman et al, 2009, Chapman et al, 2010, Buckley et al, 2011, Chapman et al, 2012. The evidence base has been used to develop a series of recommendations which have the potential to reduce non-human primate use and includesconsiderations for dose level selection and use ofrecovery animals.…”