What is PDE value of API?
PDE stands for permitted daily exposure. PDE value of API is having prime importance after implementation of European Medicines Agency’s (EMA’s), ‘Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities (EMA/CHMP/CVMP/SWP/169430/2012).
The importance of Health Based Exposure Limits (HBEL) through scientific toxicological risk assessment has got immense importance in the pharmaceutical industry.
The health-based exposure limit for a given API is the permitted daily exposure (PDE) value (also known as the allowable daily exposure, or ADE).
ADE stands for Allowable Daily Exposure.
Significance of PDE value of API
The Permitted Daily Exposure (PDE) values had been defined by the EMA in a new guideline in order to mathematically decide upon the dedicated or multi-purpose use of plants. The new health-based values influence the cleaning validation threshold values as well. In brief, it can be determined how much cross contamination may be tolerated from a health risk point of view by using the PDE values.
How PDE value is derived?
Derivation of a PDE value requires examination and interpretation of toxicology/safety data, pharmacology (efficacy) data, information on the route of administration, and other considerations. The PDE value is used to help establish cleaning validation requirements in manufacturing facilities (e.g., maximum allowable carryover values, or MACO values) and to assist with decisions regarding the use of dedicated equipment or facilities for certain APIs.
The potential risk of cross contamination can be controlled or restricted by use of PDE/ADE values derived by scientific and toxicological risk assessment of clinical and non-clinical data. The PDE calculation involves steps like hazard identification through structured and strategized literature search, identification of critical effects, establishment of NOEL/NOAEL 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). The PDE/ADE values of most hazardous substances like cytotoxic drugs, hormones and steroids etc., also help in determination of dedicated and separate equipment and facilities.
Thus, for pharmaceutical manufacturing facilities or Contract Manufacturing Organization (CMO), derivation and establishment of Permitted Daily Exposure (PDE) also known as Acceptable Daily Exposure (ADE) has become an integral part of cleaning validation program to comply with various Regulatory or cGMP requirements.