Rethinking Inhalation Risk Assessment: Integrating Respiratory Cell Models with Air-Liquid Interface Exposure?

Air-liquid-interface (ALI) exposure systems, combined with respiratory cell models, have been increasingly used for the past decades to assess the hazard of substances and for drug safety and efficacy testing. Further, these are being used for exploring disease mechanisms. Currently, on a global scale, there is a critical mass of scientific researchers conducting such experiments and using the technologies for ALI exposure. The methodology is already paramount within the training of the next generation of researchers, due to the concomitant necessity to develop alternative, human relevant models for regulatory risk assessment and accelerating drug development. There are many different ALI respiratory cell models and exposure systems available, but there is a lack of widely accepted standard operating procedures and pre-validation efforts for increasing confidence and acceptance by different stakeholders. However, how do we get there? The herein commentary intends to discuss the current situation of ALI-based experimentation, as well as consider the future challenges that must be overcome to establish these next-level testing strategies to be accepted in the regulatory arena.