Navigating the Regulatory Landscape to Develop Pediatric Oncology Drugs: Expert Opinion Recommendations.

Regulatory changes have been enacted in the United States (US) and European Union (EU) to encourage the development of new treatments for pediatric cancer. Here, we review some of the factors that have hampered the development of pediatric cancer treatments and provide a comparison of the US and EU regulations implemented to address this clinical need. We then provide some recommendations for each stage of the oncology drug development pathway to help researchers maximize their chance of successful drug development while complying with regulations. A key recommendation is the engagement of key stakeholders such as regulatory authorities, pediatric oncologists, academic researchers, patient advocacy groups, and a Pediatric Expert Group early in the drug development process. During drug target selection, sponsors are encouraged to consult the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the FDA target list, in addition to relevant US and European consortia that have been established to characterize and prioritize oncology drug targets. Sponsors also need to carefully consider the resourcing requirements for preclinical testing, which include ensuring appropriate access to the most relevant databases, clinical samples, and preclinical models (cell lines and animal models). During clinical development, sponsors can account for the pharmacodynamic (PD)/pharmacokinetic (PK) considerations specific to a pediatric population by developing pediatric formulations, selecting suitable PD endpoints, and employing sparse PK sampling or modeling/simulation of drug exposures where appropriate. Additional clinical considerations include the specific design of the clinical trial, the potential inclusion of children in adult trials, and the value of cooperative group trials.