The PDE represents a substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed at or below this dose daily for lifetime. Establishment of PDE also known as Acceptable Daily Exposure (ADE) has become an integral part of cleaning validation program due to the risks of possible carryover contamination of residual active substances so as to comply with various Regulatory or cGMP requirements.
The PDE calculation involves complex steps such as systemic hazard identification through organized, strategized literature search; identification of critical effects; establishment of NOEL (no observed effect level)/NOAEL (no-observed-adverse-effect level) for critical effects and application of adjustment factors including bioavailability correction factors for route to route extrapolation as per the EMA, 2014, ICH Q3C, ISPE and VICH GL18. The PDE/ADE values are used in cleaning validation in manufacturing facilities to further determine the maximum acceptable carryover (MACO values).
Occupational Exposure Limit (OEL) refers to the maximum airborne concentration of a chemical to which most workers could be exposed, without consequent adverse health effect or impact. OELs are a measure for minimizing the worker exposure to hazardous substances in the workplace. The OEL calculation is set considering, all available data on the hazards of a substance, particularly with respect to its acute and/or chronic toxicity, carcinogenicity, mutagenicity and toxicity to reproduction.
Though not mandated for pharmaceuticals, the OEL calculation has been recommended by several Agencies including, Occupational Safety and Health Administration (OSHA), American Conference of Governmental Industrial Hygienists (ACGIH), National Institutes of Occupational Safety and Health (NIOSH), Japan Society for Occupational Health (JSOH) and European Chemical Agency (ECHA).