Process of PDE Calculation
- Hazard Identification through comprehensive literature search
- Identification of Critical effects
- Determination of Point Of Departure (POD)
- PDE Calculation with uncertainty factors
- Drafting the PDE Monograph
Permitted Daily Exposure (PDE/ADE)
(PDE/ADE)
When different medicinal products are produced in shared facilities, the potential for cross contamination is a concern. Hence, the presence of such contaminants should be managed according to the risk posed which in turn are related to levels that can be considered safe for all populations. PDE value represents a dose that is not expected to cause an adverse effect in an individual, even with a lifetime of exposure. This is synonymous to the term ‘Acceptable Daily Exposure (ADE)’. The derived PDE values should be well justified with expert rationale in such a way that even non-toxicologists (such as GMP inspector) are able to interpret and evaluate its content. (addition)
EMA Guidance
The form and content of the report are outlined in the EMA Guideline “Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities. Further, the objective of this guideline is to recommend an approach to review and evaluate pharmacological and toxicological data of individual active substances and thus enable determination of threshold levels as referred to in the GMP guideline. These levels can be used as a risk identification tool and can also be used to justify carry over limits used in cleaning validation. The guideline further stresses to include a CV by the expert writing the report.
