Computational modeling approaches and regulatory pathways for drug combinations

Drug combinations offer several advantages over monotherapies, but identifying effective drug combinations while avoiding adverse effects is a major challenge. Computational network models are particularly useful for identifying mechanistically compatible drug combinations and generating hypotheses about their mechanisms of action. Here, we discuss the advantages and challenges of in silico discovery approaches for drug combinations. Obtaining regulatory approval during later stages of product development can be more complex for drug combinations than for single drugs. The regulatory pathway is mainly determined by the approval status of the individual compounds included in a combination. We provide an overview of the regulatory guidelines for drug combination development and discuss trends from previous approvals.