Acceptable Daily Exposure (ADE) Limit Determination for Infusions

When our client wanted to determine the acceptable daily exposure (ADE) limits for endogenous compounds—those which originate within the human body including amino, fatty, and nucleic acids—they turned to our ChemRisk team to help. They tasked us to review clinical and nonclinical data for these classes of compounds and to establish a harmonized approach to identifying ADE limits for intravenous (IV) infusions.

We studied the information provided by our client along with available external data to derive patient exposure limits according to guidelines from the Federal Drug Administration and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). We identified several endogenous compound class-specific concerns such as cardiovascular-related health risks and the risk of fatty emboli based on critical concentrations.

Additionally, we developed a framework approach to determining ADE values for additional compounds that weren’t a focus of this current analysis. On behalf of the client, we are also collaborating with other pharmaceutical stakeholders to create a harmonized methodology for greater application. The resulting process will be published in peer-reviewed literature.