Regulatory advice and support
Sometimes, the biggest hurdle is knowing where to start. With the specialist knowledge provided by Enviresearch’s expert regulatory team, all options can be considered, and the most appropriate, timely and cost-effective approach can be identified. This includes requirements outside, or in addition to, biocidal product regulations, such as REACH registration and CLP obligations (covering safety data sheet authoring, label compliance, PCN submissions, etc.). Potential requirements for products outside of the standard BPR routes, such as treated articles and borderline products, can also be reviewed to ensure compliance. Enviresearch offers a full project management service, from initial advice, strategy discussions and establishing obligations through to dossier preparation and submission and ongoing compliance activities.
Data gap analysis and product authorisation strategies
BPR registrations must include a data package that sufficiently addresses the data requirements, as laid down in the BPR regulations. If registering a new product, then gathering and presenting this data is the responsibility of the applicant. Via a comprehensive data gap analysis service, Enviresearch offers a completeness check against mandatory data requirements to determine which studies need to be performed and the necessary details to be presented to ensure the submission of a compliant data package. Enviresearch can assist with all aspects of filling in the identified data gaps from study design to commissioning, study monitoring and authoring study summaries for submission. Enviresearch can also assist in the sourcing or preparation of all supporting documentation to accompany a dossier submission. This includes documentation such as product safety data sheets, product labels, letters of access and a summary of product characteristics (SPC).
Preparation of active substance and product dossiers using IUCLID software
Biocidal product and active substance dossiers must be completed as both a Word document, such as a product assessment report (PAR), and an electronic dossier in IUCLID. The IUCLID dossier (includes the same information as the PAR plus copies of all referenced studies and supporting documentation) is self-validated to ensure there are no obvious data gaps before submission. Submission of the IUCLID dossier and the selection of relevant countries for mutual recognition is completed via the R4BP3 platform, where ongoing information requests and liaising with authorities are also done.
Biocidal product family concept
A biocidal product family (BPF) is a group of biocidal products that have similar uses and contain the same active substances. The biocidal product family concept is a key element of the Biocidal Products Regulation (EU) No 528/2012 (BPR), helping to bring products to the market more easily by enabling them to be assessed together and registered under a single authorisation.
BPR Article 3(1)(s) specifies that biocidal products in a BPF should fulfil all the following criteria
- similar uses
- the same active substance(s)
- similar composition within specified variations
- similar levels of risk
- similar levels of efficacy.
Using the risk envelope approach ensures that the maximum risks to both human/animal health and the environment are assessed for the product family. In addition, the minimum level of efficacy is also established. While this allows a range of products to be authorised under one application, the interpretation of “similar” between manufacturer and authorities can be very different. Enviresearch can assist with BPF concept design to ensure that the proposed family structure has the highest likelihood of being accepted by authorities.
Human health and environmental risk assessment
Risk assessment from both a human and environmental perspective forms a large section of dossier preparation. Although there is extensive guidance available from the European Chemicals Agency (ECHA), generally, the requirements will vary on a case-by-case basis and are heavily dependent on the use scenario; consequently, identifying the correct approach to cover the worst-case scenario (the most biocide exposure in this case) encompassing all possible uses and composition variance within the biocidal product family is necessary. A “risk envelope” approach can be taken if planned appropriately. Each active substance and substance of concern present must be assessed. Assuming that an appropriate Letter of Access is available, the active substance competent authority report (CAR, the active substance approval document) can provide all required active substance properties and established endpoints for risk assessment (such as predicted no effect concentrations). The CAR is also useful to indicate standard use scenarios and indicates previously approved approaches to risk assessments for the chosen product type. It is, however, important to note that the data requirements and approach will vary depending on the product type and specific use patterns required.
For environmental risk assessments, there are standard emission scenario documents (ESD) to indicate which environmental compartments are relevant (soil, water, groundwater, sewage treatment plant, air, etc.). Emission estimations are made using ESD spreadsheets and modelling software, such as EUSES and MAMPEC, to give predicated environmental concentrations that a risk quotient (PEC/PNEC) can be calculated and must be <1. If the risk quotient (RQ) is >1 then refinements to the risk assessment are required (e.g., make the PEC more accurate, as tier 1 approaches can overestimate emissions) and the proposal of bespoke risk mitigation measures if this is not possible. For human health risk assessments, there are product-type-specific guidelines that may require some amendment to the specific use patterns required. Risk assessments can be carried out using modelling software asuch as ConsExpo. Both acute (short-term) and chronic (long-term) exposure must be considered as well as exposure via dermal (skin) absorption, inhalation and ingestion. As with environmental risk assessments, some refinements can be carried out and risk mitigation measures suggested to reduce exposure, such as PPE for professional users.
Design and management of efficacy trials
Each product type under the BPR has a specific set of mandatory efficacy tests and/or trials to support any efficacy claims made by the product. It is essential that there is a robust and representative efficacy data set upon which the product registration is founded and consequently, the careful study design, timely execution and review of efficacy data form an integral part of dossier authoring and ongoing product support. The regulatory affairs team at Enviresearch includes an experienced regulatory efficacy specialist who can offer expert opinions and author study summaries on existing studies, as well as designing a study plan to fill any identified data gaps. This ensures that a submitted data set will be as comprehensive as is required for evaluation by authorities.
Technical equivalence applications
Article 54 of the BPR outlines the requirements for technical equivalence between active substances. The purpose is to establish, via a tiered process, if an active substance from an alternative source is equivalent to the reference active substance (as included on the Union list of approved active substances). This is to ensure that the chemical composition and hazard profile, from both a human health and environmental aspect, are consistent, regardless of source. The need for technical equivalence can arise when there is an additional manufacturer or the original manufacturer but a new process or different manufacturing location. Technical equivalence should be applied after the original active substance approval but before completing a biocidal product application.
The areas included in technical equivalence cover substance identification, analytical data (five-batch analysis) and sometimes information on relevant toxicological and ecotoxicological endpoints. Impurities should be considered and their status as significant and relevant should be covered. Enviresearch can assist with the data gap analysis, guide the commissioning of missing data and author a technical equivalence application in IUCLID, with submission via R4BP3. It is worth noting that suppliers of active substances covered by the BPR must also be Article 95 compliant. This also applies to national submissions to Member States where one or more active substances is under transitional measures. If in any doubt, it is essential that applicants have confirmation of Article 95 compliance from their active substance supplier.
Quantitative structure-activity relationship (QSAR) models are mathematical models that can be used to predict the chemical properties of compounds from the knowledge of their chemical structure. This is an effective way to evaluate, identify and manage potential risks linked to substances placed on the market. This analysis can be used for chemical substances as well as any relevant impurities or metabolites. QSAR is particularly useful to avoid testing on animals and to gain an early indication of experimental results, and when used as part of a weight-of-evidence approach, QSAR may be sufficient to fulfil regulatory information requirements. To support your technical equivalence, plant protection product, biocidal product and REACH applications, Enviresearch performs QSAR analysis using a variety of QSAR software platforms. This can be tailored to your needs, utilising our regulatory knowledge and our expertise in QSAR analysis of physicochemical, toxicological, ecotoxicological and environmental fate properties.
Registrations under national schemes
For products containing active substances still in the Review Programme, “national transitional measures” or pre-BPR registrations may be required. These are the requirements in place in each Member State before the BPR applied to the whole of the EU, therefore the required approach varies between countries. National transitional measures may apply for three reasons, when the active substances contained in (or generated by) your product are not approved under the EU BPR, not listed in Annex I of the BPR or listed under Article 93 of the BPR. Owing to the variation between transitional measure requirements between member states, from requiring no notification to needing a full BPR data set and dossier submission, a bespoke approach is required depending on product type, use and the target market area. Costs range from no fees to hundreds of euros, so it is important to ensure that the approach is correct.
EU authorisation holding
As it is a requirement of a BPR registration that the holder is an EU legal entity, Enviresearch offers this service to those clients that are based outside of the EU via our Portuguese office. Enviresearch can submit, monitor and maintain dossier submissions on behalf of those companies that do not have a presence in the EU.