Preparation and submission of the application
General
The assessment report should meet the objectives of the assessment for the renewal of approval of active substances:
- 1) check if the active substance still meets the conditions of approval in accordance with Great Britain Biocidal Products Regulation (GB BPR) Article 12 (1, 2)
- 2) assess mandatory endpoints or criteria that have not been previously assessed
- 3) in light of new information and scientific and technical progress, consider possible change to the main conclusions and the reference values
You should identify any new information available on the active substance since the previous approval or review and include any relevant data in the renewal dossier, in particular notifications of adverse or unexpected effects. Likewise, you should use scientific literature or other publicly available information published since the previous approval assessment to evaluate whether there is new information questioning or confirming the conclusions of the previous approval. This should include endpoints not previously assessed (such as endocrine disruption (ED)).
Information on the test substance in open literature studies may be limited, and this may prevent the comparison with the reference specifications. Take this into account when selecting the studies to consider for the assessment. The reliability of the studies should be also considered and used in a weight of evidence approach, rather than for rejecting studies.
You need to anticipate the generation of data on ED properties, so that the necessary data is generated and included in the submission of the application. The relevant guidance to follow for the assessment of ED should be followed. However, in vivo testing on vertebrate animals should only be conducted as a last resort and not be repeated for the purposes of GB BPR. If you are considering carrying out such study work, you must contact HSE prior to taking any action.
Please note that any waivers to the ED assessment must be fully substantiated by scientifically robust arguments in line with Annex IV of GB BPR.
Submission of the dossier
The dossier should include the assessment on whether the conclusions of the initial or previous assessment on the active substance remain valid and any supportive information to substantiate this conclusion. Avoid changing the reference product and its uses, although there might be situations where replacing the representative product or its uses considered in the previous approval is appropriate, for example to adjust better to the products that are actually on the market.
The dossier should allow HSE to draw key conclusions on the renewal of the approval and on the exclusion criteria, considering the information requirements on Annexes II and III of GB BPR. Any generation of new data should be finalised by the time of the submission of the dossier.
You should include the following:
- For the endpoints where no new data or no revisions are provided, an assessment of why the conclusions of the initial or previous assessment(s) remain valid, and any supporting information (for example data requirements, guidance documents, and/or test guidelines not changed since initial approval or previous re-approval, and no new information is available)
- For the endpoints where new data or re-assessment are provided, an explanation for the new data or the reason for re-assessment. The justification could include among others:
- information that has become available on the active substance since its approval, including the related study summaries
- data requested or answers to issues raised and left open at the time of the initial approval
- change of data requirements
- changes to scientific and technical knowledge, development of guidance documents, updates to test guidelines
- necessity to amend or extend the conditions of approval, or to change the range of representative uses
Renewal risk assessment report (RAR)
A renewal risk assessment report (RAR) on whether the conclusions of the initial or previous assessments for the active substance remain valid should be submitted and attached in section 13 of IUCLID dossier.
If the active substance has not yet received a GB CLP (Classification, labelling and packaging of chemicals) mandatory classification, a proposal for mandatory classification and labelling is necessary.
The parts where the evaluation of previously submitted studies and the risk assessment has changed, alongside any new studies/information or assessment included, have to be clearly highlighted. You should highlight the new studies in the table of contents and in the reference list as well.
You should include the following in the RAR:
- for substances that meet the exclusion criteria, an assessment on whether at least one of the conditions set out in Article 5(2) is met. This assessment should also include appropriate risk mitigation measures to ensure that the exposure of humans, animals or the environment is minimised
- for active substances where no ED assessment was previously submitted, there should be either an assessment of ED properties or a justified statement that the conclusions of the latest assessment are still valid. You should also indicate whether you have generated or considered any new information for this purpose
- you should include the new studies in the list of studies submitted indicating whether they are considered relevant renewal data. HSE will take the final decision of whether a given study is considered relevant renewal data when the evaluation is finalised
Renewal document
You should provide a short summary on the application for renewal in a separate renewal document.
There is no specific GB template for this document, however it should include the following sections:
- Background:
- brief overview of dates and decisions related to the approval, early reviews or subsequent renewals, including in different product types
- intended uses included in the assessment
- details of the application for renewal
- brief overview of biocidal products authorised on the market
- The active substance and the biocidal product:
- identification of additional data needed for the reassessment, such as batch number and purity of test substance used for (old and new) toxicological and environmental studies
- justification for deviations from the profile of the active substance of the application for renewal
- identification of the reference specification
- information on the representative product if changed from previous approval.
- in case an ED assessment is needed, data gap analysis for the investigation of ED properties and a justification on the strategy to be followed to provide relevant ED data on the active substance
- Specific conclusions based on previous evaluations. It should cover the sections:
- efficacy
- identity, physical/chemical/technical properties and methods of analysis
- human health
- environment
- classification and labelling
For each of these sections, the document should include:
- a) brief overview of data available for the approval, early reviews or subsequent renewals of the active substance and the conclusions of the previous evaluation
- b) assessment by section of whether the conclusions of the initial or previous assessments of the active substance remain valid
- c) identification of potential data gaps
- d) guidance on what will be expected from the resubmission, with a view on new test methods and development of guidance since the approval or subsequent renewals
- List of new studies addressing data gaps identified in the previous sections that need to be finalised and included in dossier submission
- Identified areas for which updated reassessment is needed in the dossier: a list of proposed areas to be addressed in which there have been scientific and technical developments and implementation of new guidance since the previous assessment
- Conclusion on the extent of the evaluation: whether a full or partial evaluation is proposed
At the submission of the dossier, the final version of the document should be included in Section 13 of IUCLID dossier as an appendix to the RAR.
5-Batch analysis and reference specifications of the active substance
You must provide a new 5-batch analysis in cases where the previous batches provided are older than 10 years. If the previous batches provided are between 5 and 10 years old, you must provide quality control data.
For active substances that were approved without reference specifications or reference sources, a reference specification should be set at renewal.
For the rest of the substances, the reference sources of the active substance and the reference specifications will remain the same as in the initial approval. In exceptional situations, the reference specifications would be adapted if justified by safety concerns linked to the previous reference specifications.
If you do not support a reference source, no 5-batch analysis is required for the alternative source supported at the renewal. You can only use alternative sources that are assessed as being technically equivalent. Consequently, no new or updated reference specification will be established at renewal.
The alternative sources that have previously been assessed as technically equivalent will not need to be re-assessed following the renewal of the active substance as the set reference specification will not be changing during the renewal. If the reference specification changes further consideration may be required.
Pre-submission meetings
Pre-submission meetings with HSE, which can attract a fee, are available to applicants. Specifically, they may be of benefit to provide clarifications on issues that might lead to identify the substance as meeting the exclusion or substitution criteria.
The renewal document can serve as the basis of the discussion at the pre-submission meetings, since the RAR will not be available at that time. The document may undergo significant revisions pending on the outcome of the meetings and with the agreement of HSE.
If the initial approval of the substance for a given product type was granted based on derogation criteria, a discussion regarding whether the exclusion criteria are still met and whether the derogation conditions could still be satisfied could be carried out during the pre-submission meetings.
Detailed discussion may also be needed on parts of the assessment not addressed in the initial approval, previous renewal or review of the approval, such as assessment of ED properties. You should anticipate and discuss with HSE the need to generate new data to investigate ED properties.
It is advised that pre-submission meetings between the prospective applicant and HSE take place as early as possible, and sufficiently in advance of the submission to avoid delays due to missing data.
Evaluation by HSE
HSE will make an independent, objective and transparent assessment in the light of current scientific and technical knowledge. HSE will decide whether a full evaluation is needed considering:
- whether the dossier submitted meets the data requirements
- in case an assessment of ED properties is included, whether the data available is sufficient to support this assessment or additional information will be needed during the evaluation (such as for non-target organisms)
HSE will identify data gaps in the RAR, and it may then not be possible to propose the renewal of the approval of the active substance if there is no evidence that the conditions in Article 4 of GB BPR are met.
If a full evaluation is needed, it will not include extensive re-evaluation of all endpoints but focus on the assessment of the key conclusions. HSE will establish whether the exclusion criteria set out in Article 5(1) are met, as well as the appropriateness of risk mitigation measures for the related uses. If previous approval of the substance was granted based on derogation criteria, HSE will check whether the exclusion criteria are still met, and, if this is the case, whether the derogation conditions could still be satisfied.
Where the assessment of ED properties has not yet been completed, in the first renewal of the approval it is expected that the full evaluation will be undertaken to include the ED assessment.
Specific considerations for evaluations
Efficacy
HSE will not carry out an efficacy assessment at this stage except in situations where new risk assessment information would lead to reduce safe doses for the reference product, below the efficacious dose for the corresponding use.
Evaluation of efficacy data, when needed, will be done for the renewal of product authorisations and new product authorisations.
If no biocidal product is authorised on the GB market at the time of the renewal of the active substance, the efficacy of the representative product should be confirmed with reference to any changes in the applicable guidance. This situation could require the submission of new information.
If there are aspects not covered by previous guidance or requirements at the time of the first/previous approval that impact the conclusions of the previous efficacy evaluation, the efficacy of the representative product should be confirmed with reference to the applicable guidance. All information available related to the development of resistance should be provided, with particular emphasis on any further development of resistance since previous authorisation.
Analytical methods and physical-chemical properties (APCP)
Physical properties must be addressed using appropriate methods (for example; UN; EU; OECD; CIPAC).
Physical hazards must be addressed according to the requirements of GB CLP.
Methods of analysis must be submitted validated in accordance with appropriate SANCO guidance documents.
Human health
The human health assessment should include an evaluation of the human health hazards, a human exposure assessment and the resulting risk characterisation.
Human health hazards must be addressed according to the data requirements in Annex II of GB BPR. In addition, hazard classification should be addressed in line with the criteria of GB CLP.
HSE will consider the following elements when evaluating an application of renewal of approval of an active substance:
- an assessment of whether biological effects and parameters recorded in old non-GLP studies address sufficiently the requirements considering the current scientific knowledge. Deviations from new guidelines and their impact on the validity of the results should be clearly mentioned. HSE will consider whether the available studies have appropriate dose setting and not too low or overly toxic doses
- further to a quality check of the studies against current standards, old studies often lack investigation of parameters/endpoints that should be addressed according to the new data requirements (such as toxicokinetic data, potential neurotoxic and immunotoxic effects, micronuclei formation in short term studies and endocrine sensitive parameters in reproductive studies). In these cases, HSE will check the whole dossier to verify whether these endpoints have been investigated elsewhere before generation of new data is considered. The repeat or duplication of studies using vertebrate animals will only be considered as the last resort
- HSE will take into consideration changes in relevant guidance documents in the assessment of the exposure
- new legal requirements, like an ED assessment
Environment
Environmental hazards must be addressed according to the requirements of GB CLP.
HSE will consider these elements in the evaluation of environmental hazard, exposure assessment and risk characterisation under the application of renewal of approval of an active substance:
- an assessment of whether biological effects and parameters recorded in the old studies address sufficiently the assessment needs considering the current scientific knowledge. Deviations from new or updated guidelines that are considered to conclude on the validity of the results should be clearly mentioned
- any new guidance or updated models on exposure assessment relevant to exposure scenarios should be considered in the assessment of the exposure
- new legal requirements, like an ED assessment
- scientific knowledge influencing the assessment of relevant endpoints (for example new interpretation of data resulting in a necessary revision of predicted no effect concentration derivation)