Technical equivalence

Date: 1 June 2020

For every active substance, a specification is set during the evaluation process which includes the minimum purity of the active substance and the maximum contents of impurities. Impurities are divided into significant (content of 1 g/kg or more in the technical material) and relevant impurities (substances of (eco-)toxicological concern; max. content is set based on their (eco-)toxicological properties). A specification is generally based on the results of a 5 batch study. The limits for the individual components are derived from the found mean values minus (for the active substance) or plus (for impurities) three standard deviations. A five batch study must include data of 5 representative batches from the manufacturing plant (also called source) and the selected batches must not be older than 5 years. The specification which is set based on the source evaluated during the EU review is referred to as the reference specification and the evaluated manufacturing plant as the reference source.

If an applicant wants to use technical active substance produced at further manufacturing plant(s), a 5 batch study must be provided for each additional plant. This is also required if a change from a pilot to industrial scale is undertaken or if the manufacturing process is changed. It must be shown that the material from the additional plants does not exhibit a greater (eco-)toxicological concern than that of the reference source. The evaluation of material from additional sources is called the evaluation of technical equivalence. The guideline for this assessment is SANCO/10597/2003 –rev. 10.1 which is based on Article 38 of Regulation (EC) 1107/2009. The evaluation of technical equivalence is process is divided into two steps: Tier 1 and Tier 2.

The Tier 1 evaluation is a comparison of the content of the individual components in the technical material. The evaluation is completed if the following criteria are fulfilled:

• The minimum purity of the new source is not lower than that of the reference source
• No new impurities are present
• The increase of significant impurities is not more than 3 g/kg (if the max. content is 6 g/kg or less) or not more than 50% (if the max. content is higher than 6 g/kg)

If these points are met, no further evaluation is required and the new source is technically equivalent to the reference source.

If equivalence cannot be shown based on a Tier 1 assessment alone, a Tier 2 assessment becomes necessary. In this case the toxicity of the new (or increased) impurities must be assessed by additional data. Depending on the identity of impurities under discussion (for example, whether or not it is a known substance of concern) the additional data to be provided can be limited to a theoretical assessment (e.g. quantitative structure-activity relationship (QSAR) models) or new studies must be provided (e.g. an AMES test either with the technical material from the new source or the impurity). If the additional data shows that the technical material from the new source does not possess higher toxicity than that of the reference source, technical equivalence is shown based on the Tier 2 assessment.

Alexander Feyrer