Nanoparticle Therapeutics: FDA Approval, Clinical Trials, Regulatory Pathways, and Case Study

The approval of drugs for human use by the US Food and Drug Administration (FDA) through the Center for Drug Evaluation and Research (CDER) is a time-consuming and expensive process, and approval rates are low (DiMasi et al., J Health Econ 22:151–185, 2003; Marchetti and Schellens, Br J Cancer 97:577–581, 2007). In general, the FDA drug approval process can be separated into preclinical, clinical, and postmarketing phases. At each step from the point of discovery through demonstration of safety and efficacy in humans, drug candidates are closely scrutinized. Advances in nanotechnology are being applied in the development of novel therapeutics that may address a number of shortcomings of conventional small molecule drugs and may facilitate the realization of personalized medicine (Ferrari, Curr Opin Chem Biol 9:343–346, 2005; Ferrari, Nat Rev Cancer 5:161–171, 2005; Ferrari and Downing, BioDrugs 19:203–210, 2005). Appealingly, nanoparticle drug candidates often represent multiplexed formulations (e.g., drug, targeting moiety, and nanoparticle scaffold material). By tailoring the chemistry and identity of variable nanoparticle constituents, it is possible to achieve targeted delivery, reduce side effects, and prepare formulations of unstable (e.g., siRNA) and/or highly toxic drugs (Ferrari, Curr Opin Chem Biol 9:343–346, 2005; Ferrari, Nat Rev Cancer 5:161–171, 2005; Ferrari and Downing, BioDrugs 19:203–210, 2005). With these benefits arise new challenges in all aspects of regulated drug development and testing.