The Acceptable Daily Exposure (PDE) is derived based on the full available clinical and non-clinical data and is a dose at which side effects are unlikely to occur if a person is exposed daily for life. by any means at that dose or less. When different medicines are manufactured in shared facilities, the possibility of cross-contamination is an issue. Therefore, the presence of such contaminants must be managed according to risk, which in turn relates to levels that can be considered safe for all population groups.
FTI Incorporation is a Permitted Daily Exposure (PDE) Certification Company.
The PDE value represents a dose that would be expected to have no adverse effects on a person even with lifetime exposure. This is synonymous with the term ‘Acceptable Daily Exposure (ADE)’. The derived PDE values must be justified with a technical justification so that non-toxicologists (e.g. GMP inspectors) can also interpret and evaluate their content.
The general process for performing these calculations is as follows:
Calculation of Permitted Daily Exposure (PDE)
- Develop and document a literature search strategy.
- Execute the strategy by searching public and private scientific databases, scientific and medical journals, and internal preclinical and clinical registries.
- Select and review key studies that provide relevant data.
- Determine baseline (PoD) and any dosing or pharmacokinetic (PK) factors.
- Perform the calculations using the equation shown in Fig. 1 and apply the appropriate uncertainty factors.
- Prepare documentation.
Calculation of Acceptable Daily Exposure (ADE) (mg/day) = (NOAEL x BW) / (UFc x MF x PK)
Permitted Daily Exposure Values
Acceptable Daily Exposure (PDE) values are used by some toxicologists to aid in the safety classification of different types of impurities found in a drug substance (DS) or pharmaceutical product (DP). Acceptable daily exposure levels are important tools for the toxicologist, but one must be aware of their limitations to ensure they are used appropriately and effectively in the risk assessment process.
First, a toxicologist should always conduct a thorough analysis of all available data on the safety of a pollutant for humans and animals, including identifying any data gaps that may exist.
Second, if sufficient data are available and there are no genotoxicity concerns, an appropriate and well-designed repeat-dose animal toxicity study should be selected to calculate the PDE.
It is important to note that PDE values assess overall systemic toxicity and not necessarily local tolerance endpoints such as irritation and sensitization, which are concentration rather than dose dependent. In addition, a PDE value calculated from a general animal toxicity study is not necessarily suitable for reproductive toxicological endpoints.
Finally, PDE values should never be considered as analytical limits or acceptable levels of an impurity in a DS or DP as this fails to address quality considerations. Using safety information for various chemicals as indirect contaminants, this article serves as an educational introduction to facilitate a better understanding of the development and use of PDE values in the risk assessment process.
Quality is crucial: our quality promise
We provide PDE reports for all active pharmaceutical ingredients (APIs). There are already a large number of existing reports to choose from, but we’re happy to create a new one to add to the list of additional APIs if needed.
Our focus is on the quality of each individual report. While not all reports may be available for instant download, we can ensure you get exactly what you need for the current situation and in the best possible quality.
To ensure this, our quality promise includes:
- active membership of FTI Incorporation in the EUROTOX Corporate Program
- an experienced and multidisciplinary team of EUROTOX-certified toxicologists
- Compliance with the official EMA guideline
- PDE reports with a comprehensive structure so that all information is easily accessible
- PDE reports are based on the toxicological properties and pharmacology of the specific active ingredient
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