The Acceptable Daily Exposure (PDE) is derived based on the complete clinical and non-clinical data available and is a dose at which adverse reactions are unlikely to occur if a person is exposed daily for a lifetime. by any route at that dose or less. When different drugs are manufactured in shared facilities, the potential for cross-contamination is an issue. Therefore, the presence of such contaminants must be managed according to risk, which in turn is related to levels that can be considered safe for all population groups.
FTI Incorporation is Permitted Daily Exposure (PDE) Certification Company.
The PDE value represents a dose that is not expected to cause an adverse effect in 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 even non-toxicologists (e.g. GMP inspectors) can 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 the baseline (PoD) and any dosing or pharmacokinetic (PK) factors.
- Carry out the calculations using the equation shown in Fig. 1 and apply the appropriate uncertainty factors.
- Prepare documentation.
Acceptable Daily Exposure (ADE) Calculation (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 various 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 that they are used appropriately and effectively in the risk assessment process.
First, a toxicologist should always perform a thorough analysis of all available data on the human and animal safety of a contaminant, 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 score overall systemic toxicity and not necessarily local tolerability 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 appropriate for reproductive toxicity endpoints.
Finally, PDE values should never be considered as analytical limits or acceptable levels of an impurity in a DS or DP as this does not take quality considerations into account. 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 are happy to create a new one to add to the list for additional API if needed.
Our focus is on the quality of each individual report. While not all reports may be available for instant download, we can make sure you get exactly what you need for the situation at hand, and at the best possible quality.
To ensure this, our quality promise includes:
- active membership of FTI Incorporation into the EUROTOX Corporate Program
- an experienced and multidisciplinary team of toxicologists certified by EUROTOX
- Compliance with the official EMA guideline
- PDE reports with a comprehensive structure so that all information is easily accessible
- PDE reports based on the toxicological properties and pharmacology of the specific active ingredient
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