PdD (Starting Point)

The starting point is based on the toxicological value associated with the critical effect. This is defined as the adverse effect observed at the lowest dose when a population is exposed to a certain substance. [5]​Normally, NOAEL (No Observable Adverse Effect Level) values ​​are used as a starting point, although different guidelines also consider appropriate the use of other values, such as: NOEL (No Observable Adverse Effect Level), LOAEL (Minimum Observable Toxic Effect Level) or LOEL (Minimum Observable Effect Level).

According to the ICH Q3C guideline, the PDE value is preferably obtained from a NO(A)EL, if this is not possible, the LO(A)EL value can be used.[4]​ Alternative approaches to the NOAEL can also be used, such as the reference dose (BMD).[1]​.

Initially, the use of other types of values ​​based on acute exposures was also supported, such as LD (Mean Lethal Dose) values. However, the European Medicines Agency (EMA) no longer considers them suitable to derive these limits.[6]​.

BW (Body Weight)

When the value used as a starting point is expressed in mg/kg body weight, the EMA guideline indicates that a standard body weight of 50 kg should be used for medicinal products for human use. The application of this factor will not be necessary when the target population is humans and the starting point is based on human doses expressed in mg/day.

This factor will not be applicable to the calculation of veterinary values ​​either, since the doses of veterinary medicines are generally expressed in mg/kg of body weight.[1]​.

FA (Adjustment Factors)

These factors can also be called safety factors, uncertainty factors, evaluation factors or modifiers. Depending on the guide that describes the calculation of the PDE, the number of factors to be used and their names may vary slightly. In any case, their purpose is the same and is to address various uncertainties and allow reliable and robust extrapolation to the target population (whether in humans or animals).[1]​.

Justification of each uncertainty factor is necessary, even if default values ​​are used, as this forms part of the risk assessment.[2]​ To cover all possible uncertainties, the Q3C guide establishes the following factors:[4]​.

PDE (Permitted Daily Exposure)

It is expressed in milligrams/day to derive limits in humans; although it can be expressed in mg/kg/day for pediatric populations or calculation of limits for veterinary drugs.

PdD (Starting Point)

The starting point is based on the toxicological value associated with the critical effect. This is defined as the adverse effect observed at the lowest dose when a population is exposed to a certain substance. [5]​Normally, NOAEL (No Observable Adverse Effect Level) values ​​are used as a starting point, although different guidelines also consider appropriate the use of other values, such as: NOEL (No Observable Adverse Effect Level), LOAEL (Minimum Observable Toxic Effect Level) or LOEL (Minimum Observable Effect Level).

According to the ICH Q3C guideline, the PDE value is preferably obtained from a NO(A)EL, if this is not possible, the LO(A)EL value can be used.[4]​ Alternative approaches to the NOAEL can also be used, such as the reference dose (BMD).[1]​.

Initially, the use of other types of values ​​based on acute exposures was also supported, such as LD (Mean Lethal Dose) values. However, the European Medicines Agency (EMA) no longer considers them suitable to derive these limits.[6]​.

BW (Body Weight)

When the value used as a starting point is expressed in mg/kg body weight, the EMA guideline indicates that a standard body weight of 50 kg should be used for medicinal products for human use. The application of this factor will not be necessary when the target population is humans and the starting point is based on human doses expressed in mg/day.

This factor will not be applicable to the calculation of veterinary values ​​either, since the doses of veterinary medicines are generally expressed in mg/kg of body weight.[1]​.

FA (Adjustment Factors)

These factors can also be called safety factors, uncertainty factors, evaluation factors or modifiers. Depending on the guide that describes the calculation of the PDE, the number of factors to be used and their names may vary slightly. In any case, their purpose is the same and is to address various uncertainties and allow reliable and robust extrapolation to the target population (whether in humans or animals).[1]​.

Justification of each uncertainty factor is necessary, even if default values ​​are used, as this forms part of the risk assessment.[2]​ To cover all possible uncertainties, the Q3C guide establishes the following factors:[4]​.