The product assessment will form the basis of a specific control strategy for elemental impurities and should be available to be presented to Regulators during an inspection upon request.
There are four options for the evaluation of elemental impurities: Option 1, 2A and 2B represent the "component-based approach", whereas Option 3 represents the "finished-product-based approach" for the elemental impurities risk assessment.
Option 1: Considers that all the components could be used in any proportion and that the product intake is not more than 10 g/day. For each elemental impurity, the concentration limit (CL) is calculated by dividing the PDE by 10 g/day.
Acceptance criteria: None of the components exceeds the calculated CL.
Option 2A: Considers that all the components could be used in any proportion and calculates the real maximum daily product intake (MDI). For each elemental impurity, the concentration limit (CL) is calculated by dividing the PDE by the MDI in grams.
Acceptance criteria: None of the components exceeds the calculated CL.
Option 2B: Considers the real quantitative composition of the product and the real maximum daily product intake. Calculate, for each component, the level of all elemental impurities. Then, for each elemental impurity, calculate the total level (aggregated from all the components).
Acceptance criteria: The total level does not exceed the PDE.
Option 3: Consists in the finished product analysis. The levels of the elemental impurities should be individually determined by appropriate techniques (ICP-MS) by analyzing 3 representative batches (industrial scale) or 6 representative batches (pilot scale). The total exposition to the elemental impurities is calculated with the maximum daily intake of the product.
Acceptance criteria: The total exposition does not exceed the PDE.
