Regulatory perspective on the importance of ADME assessment of nanoscale material containing drugs.

The promise of nanoscale material containing drug products to treat complex diseases is mounting. According to the literature, in addition to the liposomes, micelles, emulsions, there are novel drug delivery systems such as dendrimers and metal colloids at different stages of pre-clinical and clinical development. With the anticipation that more nanoscale material containing drug products will be submitted to the Food and Drug Administration (FDA) for approval in the future, FDA formed a Nanotechnology Task Force in 2006 to determine the critical regulatory issues regarding nanomaterials. As a result, all centers within the FDA are considering the development of guidance documents to address nanomaterial specific issues. It is well established in the literature that physico-chemical characterization (PCC) studies are crucial for nanomaterial containing drug products. However, this paper addresses the equally important topic of Absorption, Distribution, Metabolism and Excretion (ADME) studies for nanomaterials and provides examples of how physical properties affect biodistribution (i.e. the state of agglomeration, or aggregation, surface characteristics, stability of PEG). This paper also attempts to highlight some of the ADME study design issues related to nanomaterials such as the need for conducting biodistribution studies on each moiety of the multifunctional nanoparticles, dual labeled pharmacokinetic (PK) studies, and comparative PK studies on the free versus encapsulated drugs. In addition, this paper underlines the importance of long-term biodistribution and mass balance studies to understand the nanoparticle accumulation profile which may help to assess the safety and efficacy of the nanomaterial containing drug products. This review also lists some of the pre-clinical guidance documents that may help sponsors get started in developing data for inclusion in an initial investigational new drug application package for nanoscale material containing drug products.