ABSTRACT
Combination drug therapy is an important tool to treat complex diseases. However, with enhanced efficacy comes the risk for greater toxicity. This chapter discusses the nonclinical safety strategy for the combination of drug products (either as a combination product or a combination regimen), focusing on the specific scientific drivers as well as the regulatory considerations for combinations that include at least one biopharmaceutical with a small molecular weight compound or two biopharmaceuticals together and how these considerations drive this strategy. Regulatory guidance that provide a framework for the strategy are reviewed. Owing to the unique nature of biopharmaceuticals, special considerations that can impact and complicate the study design for a repeat-dose combination toxicity study or other specialty assessment when warranted are also discussed. Several case studies that illustrate examples of combination toxicity strategies that have been conducted are also presented.
