Speaker Spotlight: Human Radiolabeled Mass Balance Studies- A Turn of a Kaleidoscope

Spotlight Speaker(s)

• 

  Shriram Pathak, PhD

  Associate Director
  Eisai Ltd.
  Hatfield, England, United Kingdom

Moderator(s)

• 

  Philip Kuehl, PhD

  Senior Scientist, Non-Clinical Drug Development
  Lovelace Biomedical
  Albuquerque, New Mexico

Radiolabeled mass balance studies undoubtedly provide the most direct and definitive understanding of the quantitative attributes of ADME of the new drug candidate in humans than any other known technique. By establishing how molecule gets absorbed, metabolized, and excreted after dosing and by identifying and quantifying its metabolites at an early stage can help researchers making some informed decisions, thereby de-risking the whole program. Not only sponsors but also regulators gain an extensive insight from these studies thus building confidence in the overall safety and efficacy of a potential drug.

Because of new technological advances, ever evolving regulatory expectations, and increasingly wider applications of these studies in novel areas such as mechanistic modelling techniques, an adequately designed mass balance study is very critical to further establish key clinical pharmacology aspects in a drug development program. In fact, federal agency has recently released its dedicated guidance providing recommendations or best practice considerations for planning and conducting mass balance studies.

Application of mass balance studies in drug development programs is probably quite well-established practice over the years, however, incremental complex drug pipelines has elicited a need to reinvent and future-proof our approach towards this immensely valuable technique. The changing paradigm of translational science, incremental role of complex drug transporters and evolved understanding of biliary as well as intestinal secretary clearance pathways have significantly renewed our interest in mass balance studies as a means of providing insights into the mechanisms and kinetics of drug disposition.

This presentation, thus, aims to introduce the current state of knowledge (including industry case study examples), highlight the gaps and the unique challenges the industry is currently facing and help exchanging of ideas to move this fundamental science further. This should be an interesting opportunity to reflect on where we are and where we are heading to!