On June 1, 2015, the European Medicines Agency's Guideline on setting health-based exposure limits (HBEL) for use in risk identification in the manufacture of different medicinal products in shared facilities came into effect. In this guideline there is the requirement to perform permitted daily exposure (PDE*) calculations.

The general process for performing these calculations is as follows:

1. Develop and document a literature search strategy.
2. Execute the strategy by searching both public and private scientific databases, scientific and medical journals, and internal pre-clinical and clinical records.
3. Select and review the key studies that provide relevant data.
4. Determine the point of departure (PoD), and any dosage or pharmacokinetic (PK) factors.
5. Perform the calculations using the equation shown in Fig. 1 and apply the appropriate uncertainty factors.
6. Prepare the documentation.

The calculation for acceptable daily exposure (ADE) (mg/day) = (NOAEL x BW) / (UF_c x MF x PK)

It should be noted, that while the equation for calculating the ADE seems simple, the determination of the appropriate PoD and the selection of the uncertainty factors requires an expert toxicologist.

Here at Affygility Solutions, we have a large catalog of occupational exposure limit monographs for generic pharmaceutical compounds. Many of these monographs also contain the ADE value and the necessary documentation to comply with the EMA Guideline. If you have a proprietary compound, we can also develop an OEL monograph with the ADE value.

Please contact us for additional information.

All monographs are prepared by industry experts with advance degrees, decades of industry experience, and professional certifications.

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* It should be noted that the EMA has stated that the terms PDE and ADE are effectively synonymous.

Published September 17, 2015 , Updated December 7, 2021

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