CA-Sept10-Doc.
/ EUROPEAN COMMISSIONDIRECTORATE-GENERAL
ENVIRONMENT
Directorate D - Water, Chemicals & Biotechnology
ENV.D.3 - Chemicals & Nanomaterials
Technical Notes for Guidance
Frame formulations
These Technical Notes for Guidance were endorsed during the 40th CA meetingand will apply from 1 June 2011 for application for product authorisation.
1
/ EUROPEAN COMMISSIONDIRECTORATE-GENERAL
ENVIRONMENT
Directorate D - Water, Chemicals & Biotechnology
ENV.D.3 - Chemicals &Nanomaterials
Members States Competent Authorities for the implementation of Directive 98/8/EC concerning the placing of biocidal products on the market
Notes for Guidance
Frame formulations
This paper gives an overview of the approach to handling frame formulations and authorisation of products covered by a frame formulation. This practical approach has been developed in light of the first applications received so far but isalso likely to evolve with experience.
The frame formulation concept
The concept of frame formulation as laid down in Directive 98/8/EC (the Directive) is provided to underpin and allow for a streamlined and simplified procedure for granting authorisations to very similar products which only vary in terms of relatively minor differences in composition and have the same use and user type. To this end a frame formulation is essentially just a generic specification which encapsulates a group of highly related biocidal products.
The primary use of frame formulations is to expedite the evaluation and authorisation of such related products. In the first instance a frame formulation is established by carrying out an assessment of the risks to health and the environment and of the efficacy and by concluding that there are no unacceptable risks and that efficacy is demonstrated. Once established, any real product falling within the frame formulation can be taken to be acceptable without any formal evaluation necessary.
Frame formulations are considered to be an important tool in facilitating the efficient operation of product authorisation and are particularly useful for certain types of product that are often produced in subtle variations (e.g. in different colours/shades).
Formal definition of a frame formulation and practical interpretation
The formal definition of a frame formulation provides the general indication for the use and applicability of frame formulations.
Specifications for a group of biocidal products having the same use and user type
This group of products must contain the same active substances of the same specifications, and their compositions must present only variations from a previously authorised biocidal product, which do not affect the level of risk associated with them and their efficacy.
In this context, a variation is the allowance of a reduction in the percentage of the active substance and/or an alteration in percentage composition of one or more non-active substances and/or the replacement of one or more pigments, dyes, perfumes by others presenting the same or lower risk, and which do not decrease the efficacy.
The interpretation of this definition is that a frame formulation is a generic specification of a series of products for a given use and user type. The specification of the products is in terms of the active- and non-active substances present and the allowable range in the concentration at which each may be present.
A frame formulation has to be established in connection to an authorisation, either at the same time or later. According to the definition, the products must only present variations from a previously authorised biocidal product. In most cases it will however make more sense in practice to establish the frame formulation in the first instance, and then to assess individual products falling within the frame formulation for authorisation.
The frame formulation is based on data owned by a company and may not be used by others unless they have a letter of access.
The definition does not give much indication on the magnitude of the allowable variations in concentration, other than they should not affect the level of risk or decrease efficacy. However, although it is not explicitly stated in the Directive, one would expect other properties, such as the type of formulation, the instructions for use, not to be affected by the variations in concentration.
The definition also indicates that pigments, dyes and perfumes can be replaced by alternatives, with the implication that the alternatives could be present at different concentrations.
The specification of a frame formulation is presented graphically in Figure 1. Each component is specified with its allowable concentration range (see also the annex). What is an acceptable concentration range will depend on the nature of the substance and its properties and how its concentration may affect the product overall. The allowable range will be smaller for components with hazardous properties as changing the concentration significantly will potentially impact on the risk level. The classification of any product within the frame formulation should normally be the same.
Figure 1. Composition of a frame formulation.
Evaluating and establishing frame formulations
A frame formulation will be assessed according to the same criteria as for a single product, namely in relation to risks to health and the environment and efficacy. In general terms the assessment of the frame formulation will be conducted to assess the maximum risks to health and environment and the minimum level of efficacy over the whole potential range of composition of the frame formulation as specified.
For risks to health and the environment the maximum risk will usually be where the active substance(s) and any other components with hazardous properties are present at their highest allowable concentrations. Products with lower levels of these substances present will necessarily be of equal or lower risk. Similarly for efficacy, it will be necessary to demonstrate that a product containing the lowest allowable concentration of the active substance(s) is sufficient to achieve the label claims. Products with higher levels of the active substance(s) would be of at least equal efficacy. To help with this assessment it should be clearly indicated what the function (e.g. surfactant, emulsifier, stabiliser) of each component in the product is.
There are no definitive data requirements for establishing a frame formulation. The assessment is conducted using available data on the component substances and possibly products within the frame formulations, utilising to a large extent expert judgement, to make an informed judgement on the frame formulation as a whole. Requiring a considerable amount of extra testing to establish the frame formulation defeats the intention of frame formulations to expedite authorisation of related products. Where additional testing is needed, it may be useful to test products which are at the “low end” and at the “high end” of the frame formulation so that data are available that fully cover the range of product compositions allowed in the frame formulation.
The evaluation of the frame formulation would be documented in an assessment report, and, by definition, this assessment would be applicable to any individual product within that frame formulation.
Authorisation of products within frame formulations
A typical application will include a justification for establishing a frame formulation and application for authorisation of one or more products (with all the associated data, Letters of Access etc). The exact composition of each product in the application needs to be specified along with its name. Once the frame formulation has been evaluated and judged to be acceptable each individual product specified in the application can be authorised.
They could be different approaches for authorising a series of products covered by the same frame formulation: a first one, whereby the authorisation covers a single product (1-to-1 relation), resulting in several separate authorisations to authorise the different products covered by the frame formulation; a second one, whereby a single authorisation covers the series of products (1-to-many relation), as exemplified in the figure below.
Figure 2. Possible approaches to product authorisation
For the purpose of the first product authorisation and of mutual recognition, these different approaches would be compatible.
The authorisation and the summary of the product characteristics would include the name of the product, the name of the active substance and of any substance of concern. Where the authorisation covers several products, as many summary of product characteristics would need to be included in the authorisation.
The detailed composition of the frame formulation would be available in the assessment report of the frame formulation as well as in the R4BP and that of the individual products in the R4BP.
If the authorisation holder wishes to place on the market additional products and if these are covered by an established frame formulation, the authorisation holder will be required to make a notification to the relevant competent authorities. This notification should be a simple process, but would require, as a minimum, the authorisation holder to indicate the name and the detailed composition of the product.
This is considered acceptable because the frame formulation is established on the basis that any product falling within it is safe and efficacious and therefore any new product within the frame formulation can implicitly be taken to be acceptable without the need for a formal assessment. This approach is intended to give authorisation holders a considerable degree of freedom in managing their product lines without any unnecessary burden of submitting additional applications.
Similarly, if the composition of existing products are modified, but still covered by the frame formulation, then the authorisation would be updated accordingly after notification of the new composition of the product by the authorisation holder.
Lastly, if some products are no longer placed on the market, then the authorisation will be revoked (1-to-1 approach) or amended (1-to-many approach) as the case may be.
Mutual recognition of frame formulations
Where the authorisation holder intends to seek mutual recognition of the authorisation to place one of their products on the market, they will however need to ensure that the product is formally authorised by the Reference Member State.
In the approach outlined above, all of the products covered by a frame formulation would be authorised either through individual decisions or through a single decision. There would be an assessment report on the frame formulation. The detailed composition of the frame formulation would be available in the assessment report and in the R4BP and that of the individual products in the R4BP.
This should allow other Member States to consider the frame formulation and establish it for themselves, if they wish, and to consider the authorisation - through mutual recognition - of the product(s) within that frame.
As a requirement of mutual recognition is that the product is authorised in the Reference Member State, any product for which the authorisation holder intends to seek mutual recognition must be formally authorised by the Reference Member State. It does however not matter if a particular product is only formally authorised with the Reference Member State in order to facilitate mutual recognition by another Member State and is not actually placed on the market of the Reference Member State.
As an alternative, the applicant may prefer to apply for mutual recognition of products to be placed on the markets of both the Reference and Concerned Member States, to request the establishment of the same frame formulation by the Concerned Member States and then to notify the relevant Concerned Member States of additional products to be placed on their market and covered by the frame formulation.
Fees to be charged for the establishment of a frame formulation
The future rules on fees could include a fee for the establishment of a frame formulation as well as fees for the authorisations of individual products covered by a frame formulation. As the main part of the work will relate to the establishment of the frame formulation, the fee to cover the product authorisation would rather be a “top up” fee to cover the additional work involved in processing the application to completion.
In most cases an applicant will apply for authorisation of a product(s) and at the same time seek to establish a frame formulation which includes that product(s). The fee structure described above could however be applied. Thus, there could be a single fee for such an application which would cover both the work involved in establishing the frame formulation and in processing each individual product.
This should be considerably less than the fee for seeking the equivalent number of product authorisations in individual applications.
Any subsequent applications for authorisation of products within that frame formulation would attract an individual fee per product as some processing will be required for each application. This fee would however be similar to the 'top up' fee described above.
Alternative approaches to frame formulations
Frame formulations are of most use for groups of highly related products, for instance where a product is available in a range of colours. However, in cases where few products are involved, or where frame formulations may not be applicable, it may be more appropriate to use a read-across / bridging approach. Here, data principally on one product is used in the assessment of another similar product.
This could apply for instance to rodenticide baits containing the same active and non-active substances in different matrices (e.g. wheat, pasta, wax blocks etc), which can not be formally grouped within a frame formulation. Given that the risks to health and the environment of these products are expected to be more or less the same a read-across / bridging approach using data on one product to assess another product in a different matrix would be appropriate.
In practice, the read-across / bridging and frame formulation approach are very similar and achieve the same aim of expediting the authorisation of similar products with the minimum of extra testing and evaluation.
The future fee regulation should also include the possibility of a reduced fee whenever a read-across approach is used.
1
Annex
Composition of the frame formulation
NB: This information is confidential and should not be disclosed to third parties
Active substance(s) / ContentsMinimum / Maximum
Common name[1] / IUPAC name / CAS number / EC number / Concentration / Unit[2] / w/w (%) / Concentration / Unit / w/w (%) / minimum purity (% w/w) / Same source as for Annex I inclusion
yes no[3]
Add rows as necessary
Co-formulants / ContentsMinimum / Maximum
Common name / IUPAC name / Function[4] / CAS number / EC number / Concentration / Unit / w/w (%) / Concentration / Unit / w/w (%) / Classification / Substance of concern
yes no
Add rows as necessary
1
[1] Indicate the common name. Trade names alone are not accepted. For biological products, indicate the scientific name, strain/serovar, as appropriate.
[2] e.g. g/l, g/kg, other. For biological products, the concentration should state the number of activity units/units of potency (as appropriate) per defined unit of formulation (e.g. per gramme or per litre).
[3] If the source is different, information should be provided on the technical equivalence of the two sources. For further guidance, see note for guidance on the assessment of technical equivalence (CA-May08-Doc.6.7) available at: .
[4] e.g.: antioxidant, emetic, dispersing agent, other.