Service Area

Permissible Daily Exposures

Permitted daily exposures (PDEs, also referred to as “permissible daily exposures”) are toxicology-based exposure limits for pharmaceutical impurities. PDE was originally developed in ICH Q3C as a risk assessment methodology for the qualification of residual solvents in pharmaceuticals. PDE methodology has since become an acceptable approach for deriving exposure limits for organic chemical impurities in pharmaceuticals. At Gradient, our team of board-certified toxicologists, health scientists, and chemists provide our clients with fit-for-purpose assessments to support PDE derivation. We are skilled in assessing data-poor chemicals and chemical classes through well-developed in silico and read-across methodologies, and we offer our clients responsive, expert advice and services.

  • Permitted Daily Exposure (PDE) monographs
  • ICH methodology (Q3C, Q3D, M7)
  • In silico predictions and expert review
  • Data gaps and read-across

We are skilled in assessing data poor chemicals and chemical classes through well developed in silico and read-across methodology.

Sample Projects

Toxicological Risk Assessments on Leachable Compounds from a Dermal Drug Container

For a pharmaceutical testing laboratory, Gradient derived a PDE and tolerable contact level (TCL) for several impurities in a dermally administered drug product in accordance with ICH methodology. Gradient relied on publicly available scientific literature and in silico tools to derive the PDEs and TCLs, which the drug manufacturer used to support and justify the manufacturing specification of the drug product.

Toxicological Risk Assessment on Leachable Compounds in Parenteral Drug Product

For a pharmaceutical testing laboratory, Gradient derived PDEs and toxicology-based exposure limits for potential leachable impurities in a parenterally administered drug product. We conducted a toxicological risk assessment of the identified chemicals for systemic toxicity, genotoxicity, carcinogenicity, and developmental and reproductive toxicity, and used read-across to analog chemicals where necessary. Based on the results of these evaluations, we proposed chemical-specific PDEs, as appropriate.

Our Team