Commission Implementing Regulation (EU) 2021/808 of 22 March 2021 on the performance of analytical methods for residues of pharmacologically active substances used in food-producing animals and on the interpretation of results as well as on the methods to be used for sampling and repealing Decisions 2002/657/EC and 98/179/EC (Text with EEA relevance)Text with EEA relevance

This Regulation lays down rules concerning the methods of analysis used for sampling and for laboratory analyses in relation to residues of pharmacologically active substances in live food-producing animals, their body parts and fluids, excrements, tissues, products of animal origin, animal by-products, feed and water. It also lays down rules for the interpretation of analytical results of these laboratory analyses.

This Regulation applies to official controls aimed at verifying compliance with the requirements on the presence of residues of pharmacologically active substances.

For the purposes of this Regulation, the definitions in Article 2 of Commission Delegated Regulation (EU) 2019/2090⁽¹⁾, in Commission Regulation (EU) 2019/1871⁽²⁾, in Article 2 of Regulation (EC) No 470/2009 of the European Parliament and of the Council⁽³⁾ and in Council Regulation (EEC) No 315/93⁽⁴⁾ shall apply.

The following definitions shall also apply:

1. ‘absolute recovery’ means the yield of the final stage of an analytical process for an analyte divided by the amount of the analyte in the original sample, expressed as a percentage;

2. ‘accuracy’ means the closeness of agreement between a test result and the accepted true reference value, determined by estimating trueness and precision⁽⁵⁾;

3. ‘alpha (α) error’ means the probability that the tested sample is compliant, even though a non-compliant measurement result has been obtained;

4. ‘analyte’ means the component of a system to be analysed;

5. ‘authorised substance’ means a pharmacologically active substance authorised for use in food-producing animals in accordance with Directive 2001/82/EC of the European Parliament and of the Council⁽⁶⁾;

6. ‘beta (β) error’ means the probability that the tested sample is truly non-compliant, even though a compliant measurement result has been obtained;

7. ‘bias’ means the difference between the estimated value of the test result and an accepted reference value;

8. ‘calibration standard’ means a traceable reference for measurements that represents the quantity of substance of interest in a way that ties its value to a reference base;

9. ‘certified reference material’ (CRM) means a reference material, accompanied by documentation issued by a delegated body and providing one or more specified property values with associated uncertainties and traceabilities, using valid procedures⁽⁷⁾;

10. ‘co-chromatography’ means a technique in which an unknown substance is applied to a chromatographic support together with one or more known compounds, in the expectation that the relative behaviour of the unknown and known substances will assist in the identification of the unknown one;

11. ‘collaborative study’ means analysing the same sample(s) by using the same method to determine performance characteristics of the method in different laboratories, where the study allows to calculate the random measurement error and laboratory bias for the method used;

12. ‘confirmatory method’ means a method that provides full or complementary information enabling the substance to be unequivocally identified and if necessary quantified in one of the following manners:

    1. at the maximum residue level or maximum level for authorised substances;

    2. at the reference points for action (RPA) for prohibited or unauthorised substances, for which a reference point for action is established;

    3. at a concentration as low as reasonably achievable for prohibited or unauthorised substance, for which no reference point for action is established;

13. ‘coverage factor (k)’ means a number which expresses the desired level of confidence and which is associated with the expanded measurement uncertainty;

14. ‘decision limit for confirmation (CCα)’ means the limit at and above which it can be concluded with an error probability of α that a sample is non-compliant and the value 1 – α means statistical certainty in percentage that the permitted limit has been exceeded;

15. ‘detection capability for screening (CCβ)’ means the smallest content of the analyte that may be detected or quantified in a sample with an error probability of β:

    1. in the case of prohibited or unauthorised pharmacologically active substances, the CCβ is the lowest concentration at which a method is able to detect or quantify, with a statistical certainty of 1 – β, samples containing residues of prohibited or unauthorised substances;

    2. in the case of authorised substances, the CCβ is the concentration at which the method is able to detect concentrations below the permitted limit with a statistical certainty of 1 – β;

16. ‘fortified sample material’ means a sample enriched with a known amount of the analyte to be detected or quantified;

17. ‘inter-laboratory study’ means the organisation, performance and evaluation of tests on the same sample(s) by two or more laboratories in accordance with predetermined conditions to evaluate testing performance, either as a collaborative study or a proficiency test;

18. ‘internal standard (IS)’ means a substance not contained in the sample and having physico-chemical properties as similar as possible to those of the analyte to be identified or quantified;

19. ‘level of interest’ means the concentration of a substance or analyte in a sample that is significant to determine its compliance with the legislation as regards:

    1. the maximum residue level or maximum level for authorised substances in accordance with Commission Regulation (EC) No 124/2009⁽⁸⁾ and Commission Regulation (EU) No 37/2010⁽⁹⁾;

    2. reference points for action for prohibited or unauthorised substances, for which a reference point for action is established in accordance with Regulation (EU) 2019/1871;

    3. a concentration as low as analytically achievable for prohibited or unauthorised substance, for which no reference point for action is established;

20. ‘lowest calibrated level’ (LCL) means the lowest concentration on which the measuring system has been calibrated;

21. ‘matrix’ means the material from which a sample is taken;

22. ‘matrix effect’ means the difference in analytical response between a standard dissolved in the solvent and a matrix-matched standard either without a correction using an internal standard or with correction using an internal standard;

23. ‘matrix-matched standard’ means a blank (i.e. analyte-free) matrix to which the analyte is added at a range of concentrations after sample processing;

24. ‘matrix-fortified standard’ means a blank (i.e. analyte-free) matrix, which prior to solvent extraction and sample processing, is spiked with the analyte at a range of concentrations;

25. ‘measurand’ means the particular quantity subject to measurement;

26. ‘measurement uncertainty’ means a non-negative parameter associated with the result of measurement, which characterises the dispersion of values that could reasonably be attributed to the measurand, based on the information used;

27. ‘performance criteria’ means requirements for a performance characteristic according to which it can be judged that the analytical method is fit for the intended use and generates reliable results;

28. ‘precision’ means the closeness of agreement between independent test results obtained under stipulated conditions and is expressed as the standard deviation or coefficient of variation of the test results;

29. ‘qualitative method’ means an analytical method, which detects or identifies a substance or a group of substances on the basis of its chemical, biological or physical properties;

30. ‘quantitative method’ means an analytical method, which determines the amount or mass fraction of a substance so that it may be expressed as a numerical value of appropriate units;

31. ‘recovery’ means the recovery corrected amount of an analyte divided by the fortified amount of the analyte in the matrix sample, expressed as a percentage;

32. ‘recovery correction’ means the use of internal standards, the use of a matrix calibration curve as well as the use of a recovery correction factor and also a combination of these approaches;

33. ‘reference material’ means a material sufficiently homogeneous and stable with respect to one or more specified properties, which has been established to be fit for its intended use in a measurement process or in examination of nominal properties⁽¹⁰⁾;

34. ‘relative matrix effect’ means the difference in analytical response between a standard dissolved in the solvent and a matrix-matched standard with a correction using an internal standard;

35. ‘repeatability’ means precision under conditions, where independent test results are obtained with the same method on identical test items in the same laboratory by the same operator using the same equipment within short intervals of time;

36. ‘reproducibility’ means precision under conditions, where test results are obtained with the same method on identical test items in different laboratories with different operators using different equipment⁽¹¹⁾;

37. ‘ruggedness’ means the susceptibility of an analytical method to changes in experimental conditions under which the method can be applied as presented or with specified minor modifications;

38. ‘screening method’ means a method that is used for screening of a substance or class of substances at the level of interest;

39. ‘screening target concentration’ (STC) means the concentration lower than or equal to the CCβ at which a screening measurement categorises the sample as potentially non-compliant ‘Screen Positive’ and triggers a confirmatory testing;

40. ‘selectivity’ means the ability of a method to distinguish between the analyte being measured and other substances;

41. ‘single laboratory study’ or ‘in-house validation’ means an analytical study involving a single laboratory using one method to analyse the same or different test materials under different conditions over justified long time intervals;

42. ‘standard addition’ means a procedure in which one part of the sample is analysed as such and known amounts of the standard analyte are added to the other test portions before analysis;

43. ‘standard analyte’ means an analyte of known and certified content and purity to be used as a reference in the analysis;

44. ‘substance’ means matter of constant composition characterised by the entities which compose it and by certain physical properties;

45. ‘test portion’ means the quantity of material drawn from the sample on which the test or observation is carried out;

46. ‘trueness’ means the closeness of agreement between the average value obtained from a large series of test results and an accepted reference value;

47. ‘units’ means those units described in ISO 80000⁽¹²⁾ and Council Directive 80/181/EEC⁽¹³⁾;

48. ‘validation’ means the demonstration by examination and the provision of effective evidence that the particular requirements of a specific intended use are fulfilled⁽¹⁴⁾, through a single laboratory study or a collaborative study;

49. ‘within-laboratory reproducibility’ or ‘intermediate precision/in-house reproducibility’ means measurement precision under a set of within-laboratory conditions in a specific laboratory.

Member States shall ensure that the samples taken in accordance with Article 34 of Regulation (EU) 2017/625 are analysed using methods that comply with the following requirements:

1. they are documented in test instructions, preferably according to Annexes of ISO 78-2:1999 Chemistry-Layouts for standards – Part 2: Methods of chemical analysis⁽¹⁵⁾;

2. they comply with the performance criteria and other requirements for analytical methods laid down in Chapter 1 of Annex I to this Regulation;

3. they have been validated in accordance with the requirements laid down in Chapters 2 and 4 of Annex I to this Regulation;

4. they allow enforcement of the reference points for action laid down in Regulation (EU) 2019/1871, the identification of the presence of prohibited and unauthorised substances and the enforcement of maximum levels (MLs), which have been set on the basis of Regulation (EEC) No 315/93 and Regulation (EC) No 124/2009 and maximum residue limits (MRLs), which have been set on the basis of Regulations (EC) No 1831/2003 and (EC) No 470/2009.

Member States shall ensure the quality of the results of analyses performed pursuant to Regulation (EU) 2017/625, in particular by monitoring tests or calibration results in accordance with ISO/IEC 17025:2017 General requirements for the competence of testing and calibration laboratories and with the requirements for quality control during routine analysis as laid down in Chapter 3 of Annex I to this Regulation.