DIRECTORATE-GENERAL
ENVIRONMENT
Directorate D - Water, Chemicals & Biotechnology
ENV.D.3 - Chemicals & Nanomaterials
EU Evaluation Manual
for the Authorisation
of Biocidal Products
draft final
version 2.0
EU Evaluation Manual for the authorisation of biocidal products - draft final v 2.0
INDEX
I.About this manual
I.aFor who is this manual intended?
I.bWhy has this manual been compiled?
I.cHow should I use this manual?
I.dMaintenance of this manual
II. General principles of product authorisation
II.aLegal framework
II.bProcedure of approach (incl. exposure based approach)
II.cPrinciples behind data requirements for product authorisation
II.c.1 Data protection and product dossiers
II.c.2 Active substance
II.c.3 Substances of concern
II.c.4 Product
II.c.5 Waiving
II.dEfficacy
II.eExposure assessment: Basic principles
II.e.1 Human exposure
II.e.2 Exposure to live stock and pets
II.e.3 Environmental exposure
II.fEffect/hazard assessment: Basic principles
II.f.1 Physico-chemical hazards and effects
II.f.2 Human health hazards and effects
II.f.3 Environmental hazards and effects
II.gRisk assessment: Basic principles
Applicant
Identity (product)
2.1Active substance(s)
2.2Formulants
2.3Substances of concern
2.4Other aspects of identity
2.4.1.Multi-component products and products adhered to a carrier
3. Physico-chemical & technical properties (product)
3.1General requirements
3.2Waiving
3.3Special requirements
3.4Data requirements and evaluation
4. Analytical methods
4.1 Analytical methods for formulation analysis
Generally, analytical methods for the residue analysis of the active substance are described in the CA-Report.
5. Efficacy
5.1General introduction
5.2Intended use
5.3Efficacy
5.3.1 Data requirements
5.3.2 Norms and criteria
5.3.3 Resistance and other aspects that influence efficacy
5.3.4 Unacceptable effects
Appendix B (chapter 5): Paragraphs of the Common Principles (Annex VI of 98/8/EC) relevant for efficacy evaluation and decision making.
6. Human health assessment
6.1Combination toxicity
6.2Exposure assessment
6.2.1 Sources of information for exposure calculations
6.3Effect assessment
6.4Risk characterisation
6.4.1Tiered approach
6.4.2Risk reduction measures
Appendix A (chapter 6):
Appendix B (chapter 6):
Examples regarding data requirements for specific product types
Appendix C (chapter 6)
Encoded standard instruction phrases in the biocides procedure
7.1Mixture toxicity
7.2Exposure assessment
7.2.1 Exposure calculations
7.2.1.1 Aquatic compartment (water and sediment)
7.2.1.2 Sewage treatment plant
7.2.1.3 Marine compartment (water and sediment)
7.2.1.4 Soil compartment (including groundwater for drinking water production)
7.2.1.5Air
7.2.1.6 Birds and mammals (primary and secondary exposure)
7.3Effect assessment
7.3.1 Aquatic compartment (water and sediment)
7.3.1.1 Relevant toxicity data for PNEC derivation
7.3.1.2 PNEC derivation
7.3.2 Sewage treatment plant
7.3.2.1 Relevant toxicity data for PNEC derivation
7.3.2.2 PNEC derivation
7.3.3 Marine compartment (water and sediment)
7.3.3.1 Relevant toxicity data for PNEC derivation
7.3.3.2 PNEC derivation
7.3.4 Soil compartment
7.3.4.1 Relevant toxicity data for PNEC derivation
7.3.4.2 PNEC derivation
7.3.5 Birds and mammals
7.3.5.1 Relevant toxicity data for PNEC derivation
7.3.5.2 PNEC derivation
7.3.6 PBT/vPvB assessment
7.3.7 Endocrine disruption
7.4Risk characterisation
7.4.1 Tiered approach
7.4.1.1 Aquatic compartment (water and sediment)
7.4.1.2 Sewage treatment plant
7.4.1.3 Marine compartment (water and sediment)
7.4.1.4 Soil compartment (including groundwater for drinking water production)
7.4.1.5 Air
7.4.1.6 Birds and mammals (primary and secondary exposure)
7.4.2 Risk reduction measures
Appendix – ENV 1: Quality assessment of data
Classification, Labelling and Packaging
Packaging
8. Appendices
IRecord of changes to this Manual (including date of change)
IIGuidance to be included in future TNsGs
IIIFuture work
IVList of standard terms and abbreviations
VOverview of product types
VI Format PAR with SPC
VIIFrequently used internet links in the evaluation manual
I.About this manual
I.aFor who is this manual intended?
This manual is intended for experts working on the dossier evaluation of biocidal products under Directive 98/8/EC at the Competent Authorities of their EU Member State. In addition, the information in this manual may also be useful for industry.
I.bWhy has this manual been compiled?
Over the years, a lot of guidance on how to evaluate the (possible) risks of biocidal products and their constituents has been developed both inside and outside (e.g. OECD) the EU. This information is scattered over an ever increasing number of (guidance) documents.
Next to this, several member states currently have their own authorisation procedure (and sometimes their own guidance), while others do not have such a system, yet.
These factors can seriously hamper a consistent product evaluation within the EU.
Both the Biocidal Products Directive 98/8/EC and the upcoming Biocidal Products Regulation COM(2009)267 establish the principle of mutual recognition of authorisations within the EU. This means that a product which has been evaluated and authorised in one member state (reference member state, Ref-MS) should, in principle, also be authorised in another member state (concerned member state, CMS), provided that the authorisation holder wants to put it on the market in the CMS as well and that there are no specific national circumstances in the CMS that differ from those that were evaluated by the RMS.
In order to facilitate the mutual recognition process, it is essential that all member states perform their risk evaluation in a similar way and base their judgement on the same principles. This will also increase the trust between member states to rely on each other’s dossier evaluations. Harmonisation is the key issue in whether or not mutual recognition will work.
This manual intends to give direction on which information should be used in a certain part of the evaluation process, where this information can be found and how it can be used in the risk evaluation. It is not the intention of this manual to duplicate existing guidance already presented on the site of the European Commission.
In cases there is a relevant link available an asterisk (=*) is used. Frequently used links are presented in appendix VII (not an alphabetical list but in a sequence that was used).The site of the European Commission where most of the links can be found is:
I.cHow should I use this manual?
Chapter II gives a short and comprehensive overview of the general principles behind the product authorisation process and thus is advised as a starting point when using this manual. Subsequently, in Chapters 1 – 9, the different aspects of a risk evaluation are elaborated in more detail and can be used as guidance for specific aspects of biocide dossier evaluation.
The appendices contain a glossary of standard terms and abbreviations, an overview of the product types, a format for the Summary of Product Characteristics (SPC) including the summary of products characteristics (see product assessment report (PAR) in appendix VI) and an overview of helpful internet links. Furtherappendicesare dedicated to record changes to this Manual, guidance to be included in futureTNsG and agreements or text proposals for inclusion in future versions of this Manual.
I.dMaintenance of this manual
The Dutch Ministry of Housing, Spatial Planning and the Environment (VROM) provided the Dutch Board for the Authorisation of Plant Protection Products and Biocides (Ctgb) with funding for development of the Evaluation Manual. This includes the maintenance of the manual until 2013.
This manual is a living document, therefore maintenance will be performed once per year and will, where necessary, include updating the manual with newlyagreed upon guidance, removing old or redundant guidance and checking the hyperlinks.
It is crucial for the status of the manual that other member states actively contribute to this process. It is anticipated that maintenance of the manual will be taken over by the European Chemical Agency (ECHA) in Helsinki, Finland, as ECHA is expected to playan important role in the Biocidal Products Regulation which comes into force on September 1st 2013.
II. General principles of product authorisation
II.aLegal framework
Currently, the legal basis for biocidal product authorisation is the national legislation in each individual member state, which is based on the EU Biocidal Products Directive 98/8/EC (BPD).
This manual describes how to evaluate a biocidal product dossier in accordance with article 8 of the BPD and the Common Principles, which can be found in Annex VI of the BPD.
From September 1st 2013, the legal basis for biocidal product authorisations will be the Biocidal Products Regulation, which will be directly applicable in all EU Member States.
II.bProcedure of approach (incl. exposure based approach)
In short, the evaluation of a biocidal product dossier is based on the following approach:
- Check whether the active substance(s) within the product is/are included in Annex I of the BPD for the concerning Product Type (PT) and whether they are technically equivalent to the active substance(s) on Annex I.
- Check whether the applicant has access to the Annex I dossier(s) of the active substance(s), either directly (being the data owner) or indirectly (through a Letter of Access, LoA).
- Check whether the applicant is located in the EU
- Check whether the requested product is similar to the product evaluated in the Annex I dossier and whether the intended uses have been evaluated during the Annex I inclusion procedure.
- Check forsubstances of concern on the basis of classification and relevant concentration in the biocidal product.
- Check that the requested use(s) do not differ from the use(s) that are evaluated in the Annex I dossier.The Summary of Product Characteristics (SPC) provides information on the requested use(s).
- Check the Register for Biocidal Products (R4BP), as to whether there have already been evaluations of biocidal products with a similar use within the EU. This can provide you with useful information on how to proceed with the dossier evaluation.
- If there are uncertaintiesregarding the exact use of the biocidal product, ask the applicant for clarification (e.g.dosage, frequency, way of application, location of application). Subsequently, consider the exposure routes that result from this use and decide on which data are needed for the product (and, if necessary,for the active substance).
- Check that all the necessary data is available to begin the evaluation.
- The dossier evaluation should start from the perspective of the use and the corresponding exposure pattern. Next, the exposure is compared to the hazard, which will in the end lead to an appropriate risk assessment (and if necessary risk reduction measures).
II.cPrinciples behind data requirements for product authorisation
In the risk assessment for biocidal product authorisation, exposure is a result of the practical use of the product and itsintrinsic properties (e.g. water solubility, vapour pressure, etc.).Therefore, the dossier for product authorisation must contain information on both subjects. Prior to product authorisation the risks involved inthe use of the product need to be evaluated. Possible harmful components not only include the active substance, but also other components of the product with intrinsically harmful properties.Although active substances included in Annex I have been evaluated, the composition and actual use of the biocidal product for which authorisation is sought may differ from those evaluated in the Competent Authority Report (CAR) for Annex I inclusion.
For products containing Annex I substances, the testing criteria are laid down in the Biocidal Products Directive 98/8/EC*.The dossier of the biocidal product shouldmeet the requirements laid down in Annexes IIA, IIB and relevant parts IIIA and IIIB of this directive. Further explanations regarding data requirements are given in the TNsG*.The TNsG on Dossier Preparation provides a form (the Form for check for completeness and quality of data compiled in Doc.IIIB; in Appendix 4.3) that may be useful for evaluating the completeness of data
According to the TNsG on data requirements* for Active Substances and Biocidal Products “the applicant is responsible to search for data from all sources which he or she may reasonably be expected to have access to”. Generally, this could be achieved by a recent literature search, i.e. not older than one year.
A list of studies to be performed according to Applicability of Good Laboratory Practice (GLP) is available (Guidance regarding the Applicability of GLP to Data Requirements according to Annex IIB/IIIB of Directive 98/8/EC (PA&MRFG-Feb11-Doc.8a.i).
II.c.1 Data protection and product dossiers
Data protection is intended to prevent competitors to freely benefit from the investment that other applicants have put in their application. This protection has a time limit. After the period of data protection has expired, everyone has free access to the data. The use of protected data can be done by third party if a declaration of the owner or owners has been provided to the CA which states that for a given application the applicant may refer to their data (letter of access).
It must be noted that for data on animal studies, if an animal study is available in a dossier, that repetition of this study is prohibited. Applicants must provide (sell) letters of access to other applicants to this study. If necessary, the CA or judge can set the price of a letter of access.
A complete application dossier may therefore include:
1.study reports
2.statements
3.LOA for reference to other people's data
4.reference to other people whose data protection period has expired.
Data protection periods may vary between dossiers, e.g. it varies between active substance dossiers of existing or new active substances. Data protection provisions of Directive 98/8/EC are contained in Article 12. A general note on data protection has been published by the commission to provide further guidance on the interpretation of Article 12*.
II.c.2 Active substance
The exact physical and chemical properties of the active substance and the possible risks of the active substance for specific uses havebeen evaluated in the CAR. Therefore the active substance for the application in question must bemanufactured at the same source as one considered at the time of the Annex I inclusion,or the applicant must prove that the active substance used is identical or technically equivalent to the active substance as evaluated in the CAR.
The applicant should provide the competent authority access to the active substance dossier which was the basis for the Annex I inclusion. Access can be either direct (the applicant is the data owner) or indirectly (through a Letter of Access (LoA) from the data owner). If the applicant for the product does not have access to the Annex I dossier, a full active substance dossier has to be submitted. The Rapporteur Member State (RMS) will subsequently compare the endpoints in this dossier to the endpoints of the existing List of Endpoints (LoEP) in the Annex I dossier. In principle, the List of Endpoints (LoEP) of the Annex I dossier should be used for product authorisation, as long as the endpoint is not product specific (i.e. related to formulation, use or inactive ingredients). Chapters 1 to 9 will specifically address this issue for the different aspects of the dossier.
A proposal for harmonisation and the creation of a level playing field for the authorisation of products based on active substances included in Annex I(A), but using another dossier, is discussed in PA/MRFG. Reference to the finalised document will be inserted once the document has officially been published.
In general, the data requirements for the active substance(s) have been elaborated in the TNsG on data requirements*. For several product types addenda are available (see chapter 1 Manual of Technical Agreements*). The basic principle is that the applicant submits all data or provides statements/justifications to meet the data requirements. In certain cases, data requirements may be waived by the non-submission of a study or by read-across or bridging. The applicant must explicitly justify such cases. More information about waiving is given in the TNsG on data requirements*(§1.4 and corresponding addenda) and the Manual of Technical Agreements*chapter 1.
At the time of submission of the application for product authorisation, the applicant has the obligation to verify that the data and the risk assessment submitted for Annex I/IA Inclusion of the active substance are also sufficient for the assessment of all intended uses of the biocidal product(s). Any data requirements laid down in the assessment report as well as in the specific provisions of the Inclusion Directive (in the CAR under Elements to be taken into account by MSs when authorising products) for the relevant active substance should be fulfilled for the national product authorisation.
Further data might be required if the exposure to the active substance resulting from the use(s) of the biocidal product to be authorised is higher or lasts longer than that considered at Annex I Inclusion, if exposure of other sub-populations occurs, or if there are additional routes of exposure.
Where justifications for non-submission of studies were submitted for Annex I inclusion, the applicant must confirm that the waiving arguments are also applicable to all intended uses of the biocidal product to be authorised. This applies in particular if non-submission of data was justified by the assessment of a dummy product or by reasons of negligible exposure.
The specific use conditions of the intended uses of the product to be authorised should be carefully considered.
If the applicant surmises that there are reasons for concern for certain endpoints, in the very least, data for those endpoints must be submitted. These requirements are further explained in chapter 4.3 of the TNsG on data requirements* for Active Substances and Biocidal Products. Access to these data could be gained by performing a recent literature search, i.e. not older than one year, and searching databases such as IUCLID.
If the product under evaluation has a different use pattern than the product that was evaluated for Annex I inclusion of the active substance, there might be different exposure routes. In that case, additional data on the active substance(s) could be considered necessary. If new data on active substance are submitted, the MS receiving the dossier of the product authorisations shall assess these.
II.c.3 Substances of concern
A substance of concern isany substance other than an active substance, which has an intrinsically harmful effect on people, animals or the environment and which is present in a biocidal product in sufficient amounts or which arises from the use of the product (Article 2, paragraph 1, under Directive 98/8/EC).
Currently, the PA&MRFG is discussing how to deal with these substances within the biocidal product evaluation. The outcome of this discussion will be inserted in this paragraph once a conclusion is reached.