An active substance may have various sources. Each source is linked to a production location of a given producer. Even if the production method is changed at a given location, the profile of an active substance may also change and this is then referred to as a ‘new source'.
During the approval of an active substance, a reference specification is determined based on the first approved source(s) (in other words a minimum level of purity of the active substance and maximum content of impurities). This/these initially examined source(s) is/are referred to as the reference source(s). For an application for a new source, or for modifications to existing sources (a.o. production from pilot to commercial scale, change in the manufacturing process), the specification of the new source is always compared with the reference specification. This is referred to as the equivalence assessment. A new source is declared to be equivalent and authorised if it does not have more harmful effects than the reference source (cfr. art. 29, 1, (b) of Regulation (EC) 1107/2009).
When an active substance is renewed, it is possible that the initial reference specification set for 1st approval is updated and that a new reference specification applies. In that case, each existing alternative source (for which equivalence was previously concluded) or each new source has to be assessed against the new reference specification of application on the basis of recent production data (new specifications dossier).
Generally, the RMS (Rapporteur Member State) of the active substance will carry out the equivalence assessment, but in principle any Member State can perform it. The conclusion is subject to an EU peer review. The terms for this assessment are laid down by art. 38 of Regulation (EC) 1107/2009 and are clarified in the EU guidance document SANCO/10597/2003 for synthetic active substance (chemical substances) and the EU guidance document SANCO/12823/2012 for micro-organisms.
Application for an equivalence assessment
The following data need to be submitted with the official request (letter/e-mail) asking the assessment of the technical equivalence:
- 1 electronic copy of the equivalence dossier, among which:
- The description of the production process and the information and discussion about the formation of any significant, relevant and potential (by-products resulting from the process, starting materials, solvents, etc.) impurities
- A declared specification of the source / Document J
- A GLP 5-batch analysis of recent batches (date of production not older than 5 years); including the analytical methods and their validation*, information about the batches (location, production date and size) and the results of a pre-screening study of the batches
- A complete description (name, CAS number, formulae, purity, etc) of the used starting materials and their MSDS files
- A letter of supply (when relevant)
- A letter of access (when relevant)
- Tier II studies (toxicological and ecotoxicological) if necessary
- An electronic copy of the assessment report template, completed with the specifications and analytical methods of the new source.
If necessary, more information and/or data can be requested in order to facilitate an assessment in Tier II (toxicology and ecotoxicology).
*For validation of the analytical methods, the last version of the EU guidance document SANCO/3030/99 should be used.
Use of an equivalent source in authorised products in Belgium
In order to be able to use a new, equivalent source in a plant protection product in Belgium, an application for an official approval must be submitted. For the equivalence assessment, reference can be made to the assessment which was carried out by the RMS and which was subjected to a peer review. The application has to be submitted in Belgium, along with following supporting data:
- A clear statement of the requested new source and in which plant protection products (commercial name, N number, authorization number, etc.) the new source will be used
- The complete equivalence dossier as mentioned above. If it is not available to the applicant, then the technical equivalence dossier will be directly sent to our service by the authorisation holder of the new source.
- The required letters of supply and letters of access (when relevant)
- An updated composition of the plant protection products, in case the purity of the new source is lower than the current source(s) currently authorised for the production of the plant protection products or if the purity of the new source is higher and it replaces definitely all other authorised sources of lower purity (with update of the part C of the dRR with mention of all the sources of active substances which are authorized together with their min. purity and the update of the composition based on the lowest min. purity of the approved sources).
Use of multiple equivalent sources of the same active substance
An authorisation holder may replace one source with an alternative source of the same active substance without notification, on condition that:
- the authorisation holder has already submitted an application for the use of the alternative source for the plant protection products in question
- both sources are approved and authorised in Belgium.
In all other cases, an application must be submitted to be able to use an alternative source.