Practical implementation of the ED guidance: Q&A with Michael Werner, knoell Germany
Ahead of his presentation at this year's Biocides Symposium, we caught up with Michael Werner, Senior Expert Regulatory Toxicology Biocides at knoell Germany. He gave us his thoughts on the guidance document released by Echa and Efsa last year on identifying endocrine disruptors, as well as some practical tips for applicants.
Q) Echa and Efsa have published a mammoth guidance document to support the implementation of the criteria for identifying endocrine disruptors (EDs). What is your verdict on the paper?
A) The word ‘mammoth guidance’ reflects very much our very first impression when reviewing the new ED guidance document. Without any question, it is science-based, in-depth guidance covering all facets for the assessment of potential endocrine disrupting properties with a focus on EATS endpoints.
Nevertheless, the room for escape clauses or ‘waivers’ is very limited and it is evident that the guidance is only applicable to data-rich substances with a complete data package, consisting of studies which comply with the most recent guidelines (OECD, OPPTS, etc.) and which have investigated the required ED endpoints. To date, this is only applicable to a few substances and concerns mostly actives which have already been suspected to possess ED properties.
Our initial experiences demonstrate that assessing the ED properties of a substance according to the guidance is very time consuming and presents a substantial cost factor in active substance approval/renewal processes and biocidal product authorisations.
Q) What would you highlight as a particularly important element of the guidance?
A) Those concerned with ED assessments have quickly realised that, due to the focus of the guidance, most cases will require an in-depth re-evaluation of all available (eco)tox studies. In this context, the Annex E table is clearly a central element and is the basic tool for data gathering and the subsequent assessment of potential ED properties. In my experience, existing evaluations and summaries of good-quality guideline studies can only be transferred into this table to a limited extent, so a great deal of manual work is still required.
Q) There are some concerns that the testing foreseen to investigate ED properties will conflict with the BPR’s goal to minimise animal testing. How will we be able to strike a balance?
A) The ED assessment should be performed on the basis of the data available, and testing should not be foreseen in the first instance. This approach is in accordance with the principles of the biocidal products Regulation (BPR), where animal testing should be the last resort.
The biggest issue we’ve encountered to date is, however, that even for data-rich substances with a complete (eco)tox data package consisting of good-quality guideline studies, the relevant endpoints/targets and the information needed for a proper ED assessment have not sufficiently been investigated.
From a strict science perspective, these data gaps need to be filled, and in vitro studies alone will not be sufficient. If further animal studies are needed, the applicant should discuss the testing strategy with the evaluating competent authority, and possibly also the ED expert group of Echa.
Q) Non-active substances may also lead to the conclusion that a biocidal product has ED properties. How do the approaches to identifying actives or non-actives differ?
A) Following the adoption of the ED criteria and the ED guidance, the implications of Art. 19 (4)(d) of the BPR are obvious, as they relate to the ED properties of the whole biocidal product rather than just those of the active substance(s).
In the context of biocidal product authorisation procedures, applicants will regularly receive a request from the evaluating competent authority to assess the potential ED properties of non-actives (so called ‘co-formulants’) according to the ED guidance. The most important (and justified) question is indeed whether or not the database for non-actives is sufficient for an ED assessment according to the ED guidance.
Our experience shows this is not the case, which in fact hampers the application of the guidance. In contrast to the BPR, where the data requirements are identical for all active substances, non-actives are usually within the scope of the REACH Regulation and the data sets provided are dependent on the tonnage, in the first instance. Thus, while the ED guidance is mostly applicable for a biocidal active substance with a complete data package, this is not feasible for co-formulants due to the limited (eco)tox data available.
Therefore, for co-formulants, a pragmatic approach should be taken considering in parallel that some biocidal products/product families contain a multitude of co-formulants. In accordance with the CA document CA-March18-Doc.7.3.b-final, the first step is, therefore, to investigate whether or not there is an indication for potential ED properties of non-actives.
If non-actives are identified as an ED, the legal consequences of the BPR apply. Non-actives with ED properties do not fall under the exclusion criteria of Art. 5(1) of the BPR but are rather regarded as substances of concern (SoC) for which a (quantitative systemic) risk assessment will be required.
Q) Assessing and generating data for ED properties is new ground for many applicants. What is your top tip for companies approaching this area for the first time?
A) If you haven’t gained in-depth experience or have been trained in (eco)toxicological evaluations in general – and in ED assessments in particular – expert advice is indispensable. If you’re dealing with this particular assessment for the very first time, I highly recommend getting expert support from someone who has already built up comprehensive knowledge in this area in order to avoid a waste of time and resources.
With respect to data generation, it is of the utmost importance to discuss and align the testing strategy with the competent authority. This is in case the generation of further data is required to draw a definitive conclusion on the presence or absence of potential ED properties during the ED assessment. At any rate, based on the principles of the BPR, animal testing should not be the favoured option in the first instance.
Q) What advice do you have for companies concerned that a substance in their biocidal product might be classified as an endocrine disruptor? How can they prepare for that possibility?
A) When talking about biocidal products, it’s important to differentiate between the ED properties of the active substance and those of non-actives. If an active substance is identified as an ED, it fulfils the BPR exclusion criteria. In this situation, the active substance can no longer be used in biocidal products and the applicant needs to withdraw the products from the EU market and find alternative solutions. This is unless the applicant is able to show that the derogation options according to Art. 5 (2) of the BPR apply.
Non-active substances in the biocidal product identified as being EDs do not fall under the exclusion criteria of the BPR but are considered as substances of concern. They can still be used as co-formulants in biocidal products if it can be demonstrated that no unacceptable health risks are identified during intended use. Most importantly, biocidal products identified as being potential EDs may not be sold to the general public and can only be applied by professional users. In this instance, market factors need to be carefully weighted to decide upon the replacement of a co-formulant against a safer alternative or restricting the market. Thus, for precautionary and responsible care reasons, the applicant should undertake considerations on safer alternatives.
You can hear Michael speak during day two of the Biocides Symposium, which takes place on 23-24 May in Rome. Click here or on the banner below to find out more and to book your place.