ANNEX IIIU.K.REQUIREMENTS FOR THE DOSSIER TO BE SUBMITTED FOR THE AUTHORIZATION OF A PLANT PROTECTION PRODUCT
PART AU.K.Chemical preparations
[5. Analytical methods U.K.
Introduction U.K.
The provisions of this section only cover analytical methods required for post-registration control and monitoring purposes.
For analytical methods used for generation of data as required in this Directive or for other purposes the applicant has to provide a justification for the method used; where necessary separate guidance will be developed for such methods on the basis of the same requirements as defined for methods for post-registration control and monitoring purposes.
Descriptions of methods must be provided and include details of equipment, materials and conditions used.
As far as practicable these methods must employ the simplest approach, involve the minimum cost, and require commonly available equipment.
For this section the following applies:
| Impurities | Any component other than the pure active substance which is present in the active substance as manufactured (including non-active isomers) originating from the manufacturing process or from degradation during storage |
| Relevant impurities | Impurities of toxicological and/or ecotoxicological or environmental concern |
| Metabolites | Metabolites include products resulting from degradation or reaction of the active substance |
| Relevant metabolites | Metabolites of toxicological and/or ecotoxicological or environmental concern |
On request the following samples must be provided:
(i)
samples of the preparation;
(ii)
analytical standards of the pure active substance;
(iii)
samples of the active substance as manufactured;
(iv)
analytical standards of relevant metabolites and all other components included in the residue definition;
(v)
if available, samples of reference substances for the relevant impurities.
For definitions see Annex II, Section 4, points 4.1 and 4.2.
5.1. Methods for the analysis of the preparation U.K.
5.1.1. Methods, which must be described in full, must be provided for the determination of the active substance in the preparation. In the case of a preparation containing more than one active substance a method capable of determining each, in the presence of the other, should be provided. If a combined method is not submitted, the technical reasons must be stated. The applicability of existing Cipac methods must be reported. U.K.
5.1.2. Methods must also be provided for the determination in the preparation of relevant impurities, if the composition of the preparation is such that — on the basis of theoretical consideration — such impurities may be formed by its manufacturing process or from degradation during storage. U.K.
If required, methods for the determination of formulants or constituents of formulants in the preparation must be submitted.
5.1.3. Specificity, linearity, accuracy and repeatability U.K.
5.1.3.1. Specificity of methods submitted, must be demonstrated and reported. In addition the extent of interference by other substances present in the preparation must be determined. U.K.
While interferences due to other components may be identified as systematic errors in the assessment of the accuracy of methods proposed, an explanation must be provided for any interference occurring which contribute more than ± 3 % to the total quantity determined.
5.1.3.2. The linearity of proposed methods over an appropriate range, must be determined and reported. The calibration range must extend (by at least 20 %) the highest and lowest nominal content of the analyte in relevant analytical solutions of the preparation. Duplicate calibration determinations must be made at three or more concentrations. Alternatively, five concentrations, each as single measurements, are acceptable. Reports submitted must include the equation of the calibration line and the correlation coefficient and representative and properly labelled documentation from the analysis, e.g. chromatograms. U.K.
5.1.3.3. Accuracy will normally only be required for methods for the determination of pure active substance and relevant impurities in the preparation. U.K.
5.1.3.4. For the repeatability in principle a minimum of five determinations must be made. The relative standard deviation (% RSD) must be reported. Outliers identified through an appropriate method (e.g. Dixons or Grubbs test), may be discarded. Where outliers have been discarded, that fact must be clearly indicated. An explanation as to the reason for the occurrence of individual outliers, must be attempted. U.K.
5.2. Analytical methods for the determination of residues U.K.
Analytical methods for the determination of residues must be submitted unless it is justified that the methods already submitted according to the requirements of Annex II, Section 4, point 4.2 can be applied.
The same provisions as provided in Annex II, Section 4, point 4.2 apply.]