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)
Modified by
- Commission Implementing Regulation (EU) 2021/810of 20 May 2021amending Implementing Regulation (EU) 2021/808 as regards transitional provisions for certain substances listed in Annex II to Decision 2002/657/EC(Text with EEA relevance)Corrigendum to Commission Implementing Regulation (EU) 2021/810 of 20 May 2021 amending Implementing Regulation (EU) 2021/2021/808 as regards transitional provisions for certain substances listed in Annex II to Decision 2002/657/EC(Official Journal of the European Union L 180 of 21 May 2021), 32021R081032021R0810R(01), May 21, 2021
Corrected by
- Corrigendum to Commission Implementing Regulation (EU) 2021/810 of 20 May 2021 amending Implementing Regulation (EU) 2021/2021/808 as regards transitional provisions for certain substances listed in Annex II to Decision 2002/657/EC, 32021R0810R(01), May 27, 2021
(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 ISO 3534-1: 2006 Statistics – Vocabulary and symbols – Part 1: General statistical terms and terms used in probability (Chapter 1). (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 Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products (OJ L 311, 28.11.2001, p. 1 ).(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 JCGM 200:2008, International vocabulary of metrology – Basic and general concepts and associated terms (VIM), Third Edition 2008: https://www.iso.org/sites/JCGM/VIM-JCGM200.htm (Chapter 5 Measurement standards (Etalons)). (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: (a) at the maximum residue level or maximum level for authorised substances; (b) at the reference points for action (RPA) for prohibited or unauthorised substances, for which a reference point for action is established; (c) 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: (a) 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; (b) 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: (a) the maximum residue level or maximum level for authorised substances in accordance with Commission Regulation (EC) No 124/2009 Commission Regulation (EC) No 124/2009 of 10 February 2009 setting maximum levels for the presence of coccidiostats or histomonostats in food resulting from the unavoidable carry-over of these substances in non-target feed (OJ L 40, 11.2.2009, p. 7 ).Commission Regulation (EU) No 37/2010 of 22 December 2009 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin (OJ L 15, 20.1.2010, p. 1 ).(b) 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; (c) 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 Codex Alimentarius Commission, Food and Agriculture Organization of the United Nations/World Health Organization, Guidelines on analytical terminology (CAC/GL 72-2009). (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 ISO 5725-1:1994 Accuracy (trueness and precision) of measurement methods and results – Part 1: General principles and definitions (Chapter 3). (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 ISO 80000-1:2009 Quantities and units – Part 1: General (Introduction). Council Directive 80/181/EEC of 20 December 1979 on the approximation of the laws of the Member States relating to units of measurement and on the repeal of Directive 71/354/EEC (OJ L 39, 15.2.1980, p. 40 ).(48) "validation" means the demonstration by examination and the provision of effective evidence that the particular requirements of a specific intended use are fulfilled ISO/IEC 17025:2017 General requirements for the competence of testing and calibration laboratories (Chapter 3). (49) "within-laboratory reproducibility" or "intermediate precision/in-house reproducibility" means measurement precision under a set of within-laboratory conditions in a specific laboratory.
(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 ISO 78-2: 1999 Chemistry – Layouts for standards – Part 2: Methods of chemical analysis (Annexes). (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.
| Mass Fraction | Range |
|---|---|
| ≤ 1 μg/kg | –50 % to +20 % |
| > 1 μg/kg to 10 μg/kg | –30 % to +20 % |
| ≥ 10 μg/kg | –20 % to +20 % |
| 16 (adapted from Horwitz equation) | |
| 22 (adapted from Horwitz equation) | |
| 25 | |
| 30 |
1. recording full scan (FS) mass spectra; 2. selected ion monitoring (SIM); 3. sequential mass spectrometry (MS n ) techniques such as Selected Reaction Monitoring (SRM);4. a combination of mass spectrometry (MS) or sequential mass spectrometry (MS n ) techniques with appropriate ionisation modes.
1. All mass spectrometric analyses shall be combined with a separation technique that shows sufficient separation power and selectivity for the specific application. Suitable separation techniques are amongst others liquid and gas chromatography, capillary electrophoresis (CE) and supercritical fluid chromatography (SFC). In the case of analyte which presents any isobar or isomer compound, the acceptability of the retention time (i.e. ± 0,5 % in GC and ± 1 % in LC and SFC) is mandatory to confirm its identity. 2. A maximum of three separate techniques can be combined to achieve the minimum number of identification points. 3. Different ionisation modes (e.g. electron ionisation and chemical ionisation) are considered as different techniques. Table 3 Identification points per technique Technique Identification Points Separation (mode GC, LC, SFC, CE) 1 LR-MS ion 1 Precursor ion selection at <±0,5 Da mass range 1 (indirect) LR-MS n product ion1,5 HR-MS ion 1,5 HR-MS n product ion2,5 Table 4 Examples of the number of identification points specific techniques and combinations of techniques (n = an integer) No additional identification point is obtained for the precursor ion selection, if this precursor ion is the same ion (or an adduct or isotope) as the HRMS ion monitored in full scan. Technique(s) Separation Number of ions Identification points GC-MS (EI or CI) GC n 1 + n GC-MS (EI and CI) GC 2 (EI) + 2 (CI) 1 + 4 = 5 GC-MS (EI or CI) 2 derivates GC 2 (Derivate A) + 2 (Derivate B) 1 + 4 = 5 LC-MS LC n (MS) 1 + n GC- or LC-MS/MS GC or LC 1 precursor + 2 products 1 + 1 + 2 × 1,5 = 5 GC- or LC-MS/MS GC or LC 2 precursor + 2 products 1 + 2 + 2 × 1,5 = 6 GC- or LC-MS 3 GC or LC 1 precursor + 1 MS 2 product + 1 MS3 product1 + 1 + 1,5 + 1,5 = 5 GC- or LC-HRMS GC or LC n 1 + n × 1,5 GC- or LC-HRMS/MS GC or LC 1 precursor (<±0,5 Da mass range) + 1 product 1 + 1 + 2,5 = 4,5 GC- or LC-HRMS and HRMS/MS GC or LC 1 full scan ion + 1 HRMS product ion 1 + 1,5 + 2,5 = 5 GC- and LC-MS GC and LC 2 ions (GCMS) + 1 ion (LCMS) 1 + 1 + 2 + 1 + 1 = 6
1. full-scan diode array detection spectrophotometry (DAD) in case used with HPLC; 2. fluorescence detection spectrophotometry (FLD) in case used with HPLC.
| Method | Confirmation | Screening | |||
|---|---|---|---|---|---|
| Qualitative | Quantitative | Qualitative | Semi-quantitative | Quantitative | |
| Substances | A | A, B | A, B | A, B | A, B |
| Identification in accordance with 1.2 | x | x | |||
| CCα | x | x | |||
| CCβ | - | x | x | x | |
| Trueness | x | x | |||
| Precision | x | (x) | x | ||
| Relative matrix effect/absolute recovery | x | x | |||
| Selectivity/Specificity | x | x | x | x | |
| Stability | x | x | x | x | |
| Ruggedness | x | x | x | x | |
1. Analyse six replicates of the CRM in accordance with the test instructions for the method; 2. Determine the concentration of the analyte present in each sample of the replicates; 3. Calculate the mean, the standard deviation and the coefficient of variation (%) for these six replicates ;4. Calculate the trueness by dividing the detected mean concentration by the certified value (measured as concentration) and multiply by 100, to express the result as a percentage.
1. For methods validated from the date of entry into force of this Regulation, select blank material and fortify at a concentration of: (a) 0,5 Where, for a non-allowed pharmacologically active substance validation of a concentration of 0,5 times the RPA is not reasonably achievable, the concentration of 0,5 times the RPA can be replaced by the lowest concentration between 0,5 times and 1,0 times the RPA, which is reasonably achievable. (b) 0,1 Where, for a specific pharmacologically active substance validation of a concentration of 0,1 times the MRL is not reasonably achievable, the concentration of 0,1 times the MRL can be replaced by the lowest concentration between 0,1 times and 0,5 times the MRL, which is reasonably achievable. (c) 1,0, 2,0 and 3,0 times the LCL for unauthorised substances (for which no RPA has been established).
2. At each level, the analysis shall be performed with six replicates. 3. Analyse the samples. 4. Calculate the concentration detected in each sample. 5. Calculate the trueness for each sample using the equation below and subsequently calculate the mean trueness and coefficient of variation for the six results at each concentration level.
(a) 0,5 Where, for a non-allowed pharmacologically active substance validation of a concentration of 0,5 times the RPA is not reasonably achievable, the concentration of 0,5 times the RPA can be replaced by the lowest concentration between 0,5 times and 1,0 times the RPA, which is reasonably achievable. (b) 0,1 Where, for a specific pharmacologically active substance validation of a concentration of 0,1 times the MRL is not reasonably achievable, the concentration of 0,1 times the MRL can be replaced by the lowest concentration between 0,1 times and 0,5 times the MRL, which is reasonably achievable. (c) 1,0, 2,0 and 3,0 times the LCL for unauthorised or prohibited substances in case no RPA is applicable.
(a) 0,5( 5 ), 1,0 and 1,5 times the RPA, or(b) 0,1( 6 ), 1,0 and 1,5 times the MRL or ML for authorised substances, or(c) 1,0, 2,0 and 3,0 times the LCL for unauthorised or prohibited substances in case no RPA is applicable.
| Factor | I | II | III | IV | V | VI | VII |
|---|---|---|---|---|---|---|---|
| Run 01 | A | A | A | A | A | A | A |
| Run 02 | A | A | B | A | B | B | B |
| Run 03 | A | B | A | B | A | B | B |
| Run 04 | A | B | B | B | B | A | A |
| Run 05 | B | A | A | B | B | A | B |
| Run 06 | B | A | B | B | A | B | A |
| Run 07 | B | B | A | A | B | B | A |
| Run 08 | B | B | B | A | A | A | B |
1. Select a range of chemically related compounds or other substances likely to be encountered with the compound of interest that may be present in the samples and verify whether they could interfere with the analysis of the target analyte(s). 2. Analyse an appropriate number of representative blank samples e.g. different lots or lots of different animal species (n ≥ 20) and check for any interferences of signals, peaks or ion traces in the region of interest where the target analyte is expected to elute. 3. Fortify representative blank samples at a relevant concentration with substances that could possibly interfere with the identification and/or quantification of the analyte and investigate whether the added substance: (a) may lead to a false identification; (b) hinders the identification of the target analyte; (c) influences the quantification notably.
(a) Solutions of the analyte, which are used for fortification; (b) Analyte solutions, used for the final analysis; (c) Any other solution that is of interest (e.g. derivatised standards).
| –20 °C | +4 °C | +20 °C | |
|---|---|---|---|
| Dark | 10 aliquots | 10 aliquots | 10 aliquots |
| Light | 10 aliquots |
1. For unauthorised or prohibited pharmacologically active substances , the CCα shall be calculated as follows:(a) Method 1: by the calibration curve procedure according to ISO 11843-1:1997 ISO 11843-1:1997 Capability of detection – Part 1: Terms and definitions. (b) Method 2: by analysing at least 20 representative blank materials per matrix to be able to calculate the signal to noise ratio at the time window in which the analyte is expected. Three times the signal-to-noise ratio can be used as the decision limit. This is applicable to quantitative and qualitative assays. Decision limits obtained with this approach shall be verified by analysing blank matrix fortified at the calculated decision limit. (c) Method 3: CCα = LCL + k(one-sided, 99 %) × (combined) standard measurement uncertainty at LCL For unauthorised or prohibited pharmacologically active substances, depending on the validation experiment (and its respective degrees of freedom) the t-distribution might be reasonably applied, or – if the Gaussian distribution (one-sided, n=∞) is taken as a basis – a k-factor of 2,33 shall be used. The within-laboratory reproducibility and the trueness are suitable to define the (combined) standard measurement uncertainty, if determined by taking into account all relevant influencing factors.
Method 2 for the calculation of CCα can only be used until 1 January 2026 in case of methods validated before the date of entry into force of this Regulation. For the methods validated after the entry into force of this Regulation, only Methods 1 or 3 shall be used.2. For authorised substances, the CCα shall be calculated as follows: (a) For authorised substances in matrix/species combinations for which an MRL or ML has been set:(i) Method 1: by the calibration curve procedure according to ISO 11843-1:1997 (here referred to as critical value of the net state variable). In this case, blank material shall be used, which is fortified at and above the MRL or ML in equidistant steps. Analyse the samples. After identification, plot the signal, where possible, or the recalculated concentration, against the added concentration. The corresponding concentration at the MRL or ML plus 1,64 times the standard deviation of the within-laboratory reproducibility at the permitted limit equals the decision limit (α = 5 %). (ii) Method 2: CCα = MRL (or ML) + k(one-sided, 95 %) × (combined) standard measurement uncertainty at the MRL or ML.
For authorised substances, depending on the validation experiment (and its respective degrees of freedom) the t-distribution might be reasonably applied, or – if the Gaussian distribution (one-sided, n=∞) is taken as a basis, a k-factor of 1,64 shall be used. The within-laboratory reproducibility and the trueness are suitable to define the (combined) standard measurement uncertainty, if determined by taking into account all relevant influencing factors. For pharmacologically active substances for which the MRL is established for the sum of different substances, the CCα of the substance with the highest concentration in the sample shall be used as the CCα to assess the sum of substances in the measured sample. (b) For authorised substances in matrix/species combinations for which no MRL has been set, no residues shall be present unless an authorised treatment in accordance with Article 11 of Directive 2001/82/EC took place. For authorised substances, for which no MRL has been set, the cascade MRL, established under Commission Implementing Regulation (EU) 2018/470Commission Implementing Regulation (EU) 2018/470 of 21 March 2018 on detailed rules on the maximum residue limit to be considered for control purposes for foodstuffs derived from animals which have been treated in the EU under Article 11 of Directive 2001/82/EC (OJ L 79, 22.3.2018, p. 16 ).
1. For unauthorised or prohibited pharmacologically active substances , a maximum β error of 5 % shall be ensured. The CCβ shall be calculated as follows:(a) Method 1: The calibration curve procedure according to ISO 11843-1:1997 (here referred to as minimum detectable value of the net state variable). In this case, representative blank material shall be used, which is fortified at and below the RPA, or if no RPA has been established, around the STC in equidistant steps. Analyse the samples. Plot the signal against the added concentration. The corresponding concentration at the STC plus 1,64 times the standard deviation of the within-laboratory reproducibility of the mean measured content at the STC equals the detection capability. Extrapolation far below the lowest fortification level (< 50 % of lowest fortification level) shall be confirmed by experimental data at the validation step. (b) Method 2: Investigation of fortified blank material at concentration levels at and above the STC. For each concentration level 20 fortified blanks shall be analysed in order to ensure a reliable basis for this determination. The concentration level, where only ≤ 5 % false compliant results remain, equals the detection capability of the method. (c) Method 3: CCβ = STC + k(one-sided, 95 %) × (combined) standard measurement uncertainty at or above the STC. For unauthorised or prohibited pharmacologically active substances, depending on the validation experiment (and its respective degrees of freedom) the t-distribution might be reasonably applied, or if the Gaussian distribution (one-sided, n=∞) is taken as a basis, a k-factor of 1,64 shall be used. The within-laboratory reproducibility and the trueness are suitable to define the (combined) standard measurement uncertainty, if determined by taking into account all relevant influencing factors.
2. For authorised substances , a maximum β error of 5 % shall be ensured. The CCβ shall be calculated as follows:(a) Method 1: by the calibration curve procedure according to ISO 11843-1:1997 (here referred to as a minimum detectable value of the net state variable). In this case, representative blank material shall be used, which is fortified at and below the permitted limit, starting from the STC in equidistant steps. Analyse the samples and identify the analyte(s). Calculate the standard deviation of the mean measured content at the STC. The corresponding concentration at the STC plus 1,64 times the standard deviation of the within-laboratory reproducibility of the mean measured content at the STC equals the detection capability, (b) Method 2: by investigation of fortified blank material at concentration levels below the permitted limit. For each concentration level 20 fortified blanks shall be analysed in order to ensure a reliable basis for this determination. The concentration level, where only ≤ 5 % false compliant results remain, equals the detection capability of the method. (c) Method 3: CCβ = STC + k(one-sided, 95 %) × (combined) standard measurement uncertainty at or above STC. For authorised substances, depending on the validation experiment (and its respective degrees of freedom) the t-distribution might be reasonably applied, or if the Gaussian distribution (one-sided, n=∞) is taken as a basis, a k-factor of 1,64 shall be used (whatever under cascade use or under regular MRL use). The within-laboratory reproducibility and the trueness are suitable to define the (combined) standard measurement uncertainty, if determined by taking into account all relevant influencing factors.
For pharmacologically active substances for which the MRL is established for the sum of different substances, the CCβ of the substance with the highest concentration in the sample shall be used as the CCβ to assess the sum of substances in the measured sample.
(1) at least five preferably equidistant levels (including zero level) should be used in the construction of the curve; (2) the working range of the curve shall be described; (3) the mathematical formula of the curve and the goodness-of-fit of the data (coefficient of determination R 2 ) to the curve shall be described;(4) acceptability ranges for the parameters of the curve shall be described.
1. For the screening step: For each series (batch) of analyses performed, a set of the following quality control samples shall be simultaneously analysed: (a) control sample for system suitability of the instrument, ideally method specific; (b) quality control samples which are fortified at a concentration close to the STC and ideally at the CCβ of screening for authorised pharmacologically active substances as well as for the prohibited or unauthorised substances); (c) compliant control sample (blank samples), and when relevant, reagent blanks.
2. For the confirmatory step: For each series (batch) of analyses performed, a set of the following quality control samples shall be simultaneously analysed: (a) control sample for system suitability of the instrument, ideally method specific; (b) quality control samples which are fortified at a concentration close to the MRL or ML for authorised pharmacologically active substances or close to the RPA or LCL for prohibited or unauthorised substances (non-compliant control samples); (c) compliant control sample (blank samples), and when relevant, reagent blanks.
1. at the farm from the collection tank; 2. at the level of the dairy industry, before the milk has been discharged.
1. address of the competent authorities; 2. name of the inspector or identification code; 3. official code number of the sample; 4. sampling date; 5. name and address of the owner or the person having charge of the animals or the animal products; 6. name and address of the animal’s farm of origin (when sampling on farm); 7. registration number of the establishment-slaughterhouse number; 8. animal or product identification; 9. animal species; 10. sample matrix; 11. where relevant, medication within the last four weeks before sampling (when sampling on farm); 12. substance or substance groups for examination; 13. particular remarks.
1. address of the competent authorities or designated bodies; 2. name of inspector or identification code; 3. official code number of the sample; 4. sampling date; 5. animal species; 6. sample matrix; 7. substances or substance groups for examination; 8. particular remarks.
(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 ISO 3534-1: 2006 Statistics – Vocabulary and symbols – Part 1: General statistical terms and terms used in probability (Chapter 1). (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 Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products (OJ L 311, 28.11.2001, p. 1 ).(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 JCGM 200:2008, International vocabulary of metrology – Basic and general concepts and associated terms (VIM), Third Edition 2008: https://www.iso.org/sites/JCGM/VIM-JCGM200.htm (Chapter 5 Measurement standards (Etalons)). (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: (a) at the maximum residue level or maximum level for authorised substances; (b) at the reference points for action (RPA) for prohibited or unauthorised substances, for which a reference point for action is established; (c) 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: (a) 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; (b) 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: (a) the maximum residue level or maximum level for authorised substances in accordance with Commission Regulation (EC) No 124/2009 Commission Regulation (EC) No 124/2009 of 10 February 2009 setting maximum levels for the presence of coccidiostats or histomonostats in food resulting from the unavoidable carry-over of these substances in non-target feed (OJ L 40, 11.2.2009, p. 7 ).Commission Regulation (EU) No 37/2010 of 22 December 2009 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin (OJ L 15, 20.1.2010, p. 1 ).(b) 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; (c) 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 Codex Alimentarius Commission, Food and Agriculture Organization of the United Nations/World Health Organization, Guidelines on analytical terminology (CAC/GL 72-2009). (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 ISO 5725-1:1994 Accuracy (trueness and precision) of measurement methods and results – Part 1: General principles and definitions (Chapter 3). (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 ISO 80000-1:2009 Quantities and units – Part 1: General (Introduction). Council Directive 80/181/EEC of 20 December 1979 on the approximation of the laws of the Member States relating to units of measurement and on the repeal of Directive 71/354/EEC (OJ L 39, 15.2.1980, p. 40 ).(48) "validation" means the demonstration by examination and the provision of effective evidence that the particular requirements of a specific intended use are fulfilled ISO/IEC 17025:2017 General requirements for the competence of testing and calibration laboratories (Chapter 3). (49) "within-laboratory reproducibility" or "intermediate precision/in-house reproducibility" means measurement precision under a set of within-laboratory conditions in a specific laboratory.
(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 ISO 78-2: 1999 Chemistry – Layouts for standards – Part 2: Methods of chemical analysis (Annexes). (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.
| Mass Fraction | Range |
|---|---|
| ≤ 1 μg/kg | –50 % to +20 % |
| > 1 μg/kg to 10 μg/kg | –30 % to +20 % |
| ≥ 10 μg/kg | –20 % to +20 % |
| 16 (adapted from Horwitz equation) | |
| 22 (adapted from Horwitz equation) | |
| 25 | |
| 30 |
1. recording full scan (FS) mass spectra; 2. selected ion monitoring (SIM); 3. sequential mass spectrometry (MS n ) techniques such as Selected Reaction Monitoring (SRM);4. a combination of mass spectrometry (MS) or sequential mass spectrometry (MS n ) techniques with appropriate ionisation modes.
1. All mass spectrometric analyses shall be combined with a separation technique that shows sufficient separation power and selectivity for the specific application. Suitable separation techniques are amongst others liquid and gas chromatography, capillary electrophoresis (CE) and supercritical fluid chromatography (SFC). In the case of analyte which presents any isobar or isomer compound, the acceptability of the retention time (i.e. ± 0,5 % in GC and ± 1 % in LC and SFC) is mandatory to confirm its identity. 2. A maximum of three separate techniques can be combined to achieve the minimum number of identification points. 3. Different ionisation modes (e.g. electron ionisation and chemical ionisation) are considered as different techniques. Table 3 Identification points per technique Technique Identification Points Separation (mode GC, LC, SFC, CE) 1 LR-MS ion 1 Precursor ion selection at <±0,5 Da mass range 1 (indirect) LR-MS n product ion1,5 HR-MS ion 1,5 HR-MS n product ion2,5 Table 4 Examples of the number of identification points specific techniques and combinations of techniques (n = an integer) No additional identification point is obtained for the precursor ion selection, if this precursor ion is the same ion (or an adduct or isotope) as the HRMS ion monitored in full scan. Technique(s) Separation Number of ions Identification points GC-MS (EI or CI) GC n 1 + n GC-MS (EI and CI) GC 2 (EI) + 2 (CI) 1 + 4 = 5 GC-MS (EI or CI) 2 derivates GC 2 (Derivate A) + 2 (Derivate B) 1 + 4 = 5 LC-MS LC n (MS) 1 + n GC- or LC-MS/MS GC or LC 1 precursor + 2 products 1 + 1 + 2 × 1,5 = 5 GC- or LC-MS/MS GC or LC 2 precursor + 2 products 1 + 2 + 2 × 1,5 = 6 GC- or LC-MS 3 GC or LC 1 precursor + 1 MS 2 product + 1 MS3 product1 + 1 + 1,5 + 1,5 = 5 GC- or LC-HRMS GC or LC n 1 + n × 1,5 GC- or LC-HRMS/MS GC or LC 1 precursor (<±0,5 Da mass range) + 1 product 1 + 1 + 2,5 = 4,5 GC- or LC-HRMS and HRMS/MS GC or LC 1 full scan ion + 1 HRMS product ion 1 + 1,5 + 2,5 = 5 GC- and LC-MS GC and LC 2 ions (GCMS) + 1 ion (LCMS) 1 + 1 + 2 + 1 + 1 = 6
1. full-scan diode array detection spectrophotometry (DAD) in case used with HPLC; 2. fluorescence detection spectrophotometry (FLD) in case used with HPLC.
| Method | Confirmation | Screening | |||
|---|---|---|---|---|---|
| Qualitative | Quantitative | Qualitative | Semi-quantitative | Quantitative | |
| Substances | A | A, B | A, B | A, B | A, B |
| Identification in accordance with 1.2 | x | x | |||
| CCα | x | x | |||
| CCβ | - | x | x | x | |
| Trueness | x | x | |||
| Precision | x | (x) | x | ||
| Relative matrix effect/absolute recovery | x | x | |||
| Selectivity/Specificity | x | x | x | x | |
| Stability | x | x | x | x | |
| Ruggedness | x | x | x | x | |
1. Analyse six replicates of the CRM in accordance with the test instructions for the method; 2. Determine the concentration of the analyte present in each sample of the replicates; 3. Calculate the mean, the standard deviation and the coefficient of variation (%) for these six replicates ;4. Calculate the trueness by dividing the detected mean concentration by the certified value (measured as concentration) and multiply by 100, to express the result as a percentage.
1. For methods validated from the date of entry into force of this Regulation, select blank material and fortify at a concentration of: (a) 0,5 Where, for a non-allowed pharmacologically active substance validation of a concentration of 0,5 times the RPA is not reasonably achievable, the concentration of 0,5 times the RPA can be replaced by the lowest concentration between 0,5 times and 1,0 times the RPA, which is reasonably achievable. (b) 0,1 Where, for a specific pharmacologically active substance validation of a concentration of 0,1 times the MRL is not reasonably achievable, the concentration of 0,1 times the MRL can be replaced by the lowest concentration between 0,1 times and 0,5 times the MRL, which is reasonably achievable. (c) 1,0, 2,0 and 3,0 times the LCL for unauthorised substances (for which no RPA has been established).
2. At each level, the analysis shall be performed with six replicates. 3. Analyse the samples. 4. Calculate the concentration detected in each sample. 5. Calculate the trueness for each sample using the equation below and subsequently calculate the mean trueness and coefficient of variation for the six results at each concentration level.
(a) 0,5 Where, for a non-allowed pharmacologically active substance validation of a concentration of 0,5 times the RPA is not reasonably achievable, the concentration of 0,5 times the RPA can be replaced by the lowest concentration between 0,5 times and 1,0 times the RPA, which is reasonably achievable. (b) 0,1 Where, for a specific pharmacologically active substance validation of a concentration of 0,1 times the MRL is not reasonably achievable, the concentration of 0,1 times the MRL can be replaced by the lowest concentration between 0,1 times and 0,5 times the MRL, which is reasonably achievable. (c) 1,0, 2,0 and 3,0 times the LCL for unauthorised or prohibited substances in case no RPA is applicable.
(a) 0,5( 5 ), 1,0 and 1,5 times the RPA, or(b) 0,1( 6 ), 1,0 and 1,5 times the MRL or ML for authorised substances, or(c) 1,0, 2,0 and 3,0 times the LCL for unauthorised or prohibited substances in case no RPA is applicable.
| Factor | I | II | III | IV | V | VI | VII |
|---|---|---|---|---|---|---|---|
| Run 01 | A | A | A | A | A | A | A |
| Run 02 | A | A | B | A | B | B | B |
| Run 03 | A | B | A | B | A | B | B |
| Run 04 | A | B | B | B | B | A | A |
| Run 05 | B | A | A | B | B | A | B |
| Run 06 | B | A | B | B | A | B | A |
| Run 07 | B | B | A | A | B | B | A |
| Run 08 | B | B | B | A | A | A | B |
1. Select a range of chemically related compounds or other substances likely to be encountered with the compound of interest that may be present in the samples and verify whether they could interfere with the analysis of the target analyte(s). 2. Analyse an appropriate number of representative blank samples e.g. different lots or lots of different animal species (n ≥ 20) and check for any interferences of signals, peaks or ion traces in the region of interest where the target analyte is expected to elute. 3. Fortify representative blank samples at a relevant concentration with substances that could possibly interfere with the identification and/or quantification of the analyte and investigate whether the added substance: (a) may lead to a false identification; (b) hinders the identification of the target analyte; (c) influences the quantification notably.
(a) Solutions of the analyte, which are used for fortification; (b) Analyte solutions, used for the final analysis; (c) Any other solution that is of interest (e.g. derivatised standards).
| –20 °C | +4 °C | +20 °C | |
|---|---|---|---|
| Dark | 10 aliquots | 10 aliquots | 10 aliquots |
| Light | 10 aliquots |
1. For unauthorised or prohibited pharmacologically active substances , the CCα shall be calculated as follows:(a) Method 1: by the calibration curve procedure according to ISO 11843-1:1997 ISO 11843-1:1997 Capability of detection – Part 1: Terms and definitions. (b) Method 2: by analysing at least 20 representative blank materials per matrix to be able to calculate the signal to noise ratio at the time window in which the analyte is expected. Three times the signal-to-noise ratio can be used as the decision limit. This is applicable to quantitative and qualitative assays. Decision limits obtained with this approach shall be verified by analysing blank matrix fortified at the calculated decision limit. (c) Method 3: CCα = LCL + k(one-sided, 99 %) × (combined) standard measurement uncertainty at LCL For unauthorised or prohibited pharmacologically active substances, depending on the validation experiment (and its respective degrees of freedom) the t-distribution might be reasonably applied, or – if the Gaussian distribution (one-sided, n=∞) is taken as a basis – a k-factor of 2,33 shall be used. The within-laboratory reproducibility and the trueness are suitable to define the (combined) standard measurement uncertainty, if determined by taking into account all relevant influencing factors.
Method 2 for the calculation of CCα can only be used until 1 January 2026 in case of methods validated before the date of entry into force of this Regulation. For the methods validated after the entry into force of this Regulation, only Methods 1 or 3 shall be used.2. For authorised substances, the CCα shall be calculated as follows: (a) For authorised substances in matrix/species combinations for which an MRL or ML has been set:(i) Method 1: by the calibration curve procedure according to ISO 11843-1:1997 (here referred to as critical value of the net state variable). In this case, blank material shall be used, which is fortified at and above the MRL or ML in equidistant steps. Analyse the samples. After identification, plot the signal, where possible, or the recalculated concentration, against the added concentration. The corresponding concentration at the MRL or ML plus 1,64 times the standard deviation of the within-laboratory reproducibility at the permitted limit equals the decision limit (α = 5 %). (ii) Method 2: CCα = MRL (or ML) + k(one-sided, 95 %) × (combined) standard measurement uncertainty at the MRL or ML.
For authorised substances, depending on the validation experiment (and its respective degrees of freedom) the t-distribution might be reasonably applied, or – if the Gaussian distribution (one-sided, n=∞) is taken as a basis, a k-factor of 1,64 shall be used. The within-laboratory reproducibility and the trueness are suitable to define the (combined) standard measurement uncertainty, if determined by taking into account all relevant influencing factors. For pharmacologically active substances for which the MRL is established for the sum of different substances, the CCα of the substance with the highest concentration in the sample shall be used as the CCα to assess the sum of substances in the measured sample. (b) For authorised substances in matrix/species combinations for which no MRL has been set, no residues shall be present unless an authorised treatment in accordance with Article 11 of Directive 2001/82/EC took place. For authorised substances, for which no MRL has been set, the cascade MRL, established under Commission Implementing Regulation (EU) 2018/470Commission Implementing Regulation (EU) 2018/470 of 21 March 2018 on detailed rules on the maximum residue limit to be considered for control purposes for foodstuffs derived from animals which have been treated in the EU under Article 11 of Directive 2001/82/EC (OJ L 79, 22.3.2018, p. 16 ).
1. For unauthorised or prohibited pharmacologically active substances , a maximum β error of 5 % shall be ensured. The CCβ shall be calculated as follows:(a) Method 1: The calibration curve procedure according to ISO 11843-1:1997 (here referred to as minimum detectable value of the net state variable). In this case, representative blank material shall be used, which is fortified at and below the RPA, or if no RPA has been established, around the STC in equidistant steps. Analyse the samples. Plot the signal against the added concentration. The corresponding concentration at the STC plus 1,64 times the standard deviation of the within-laboratory reproducibility of the mean measured content at the STC equals the detection capability. Extrapolation far below the lowest fortification level (< 50 % of lowest fortification level) shall be confirmed by experimental data at the validation step. (b) Method 2: Investigation of fortified blank material at concentration levels at and above the STC. For each concentration level 20 fortified blanks shall be analysed in order to ensure a reliable basis for this determination. The concentration level, where only ≤ 5 % false compliant results remain, equals the detection capability of the method. (c) Method 3: CCβ = STC + k(one-sided, 95 %) × (combined) standard measurement uncertainty at or above the STC. For unauthorised or prohibited pharmacologically active substances, depending on the validation experiment (and its respective degrees of freedom) the t-distribution might be reasonably applied, or if the Gaussian distribution (one-sided, n=∞) is taken as a basis, a k-factor of 1,64 shall be used. The within-laboratory reproducibility and the trueness are suitable to define the (combined) standard measurement uncertainty, if determined by taking into account all relevant influencing factors.
2. For authorised substances , a maximum β error of 5 % shall be ensured. The CCβ shall be calculated as follows:(a) Method 1: by the calibration curve procedure according to ISO 11843-1:1997 (here referred to as a minimum detectable value of the net state variable). In this case, representative blank material shall be used, which is fortified at and below the permitted limit, starting from the STC in equidistant steps. Analyse the samples and identify the analyte(s). Calculate the standard deviation of the mean measured content at the STC. The corresponding concentration at the STC plus 1,64 times the standard deviation of the within-laboratory reproducibility of the mean measured content at the STC equals the detection capability, (b) Method 2: by investigation of fortified blank material at concentration levels below the permitted limit. For each concentration level 20 fortified blanks shall be analysed in order to ensure a reliable basis for this determination. The concentration level, where only ≤ 5 % false compliant results remain, equals the detection capability of the method. (c) Method 3: CCβ = STC + k(one-sided, 95 %) × (combined) standard measurement uncertainty at or above STC. For authorised substances, depending on the validation experiment (and its respective degrees of freedom) the t-distribution might be reasonably applied, or if the Gaussian distribution (one-sided, n=∞) is taken as a basis, a k-factor of 1,64 shall be used (whatever under cascade use or under regular MRL use). The within-laboratory reproducibility and the trueness are suitable to define the (combined) standard measurement uncertainty, if determined by taking into account all relevant influencing factors.
For pharmacologically active substances for which the MRL is established for the sum of different substances, the CCβ of the substance with the highest concentration in the sample shall be used as the CCβ to assess the sum of substances in the measured sample.
(1) at least five preferably equidistant levels (including zero level) should be used in the construction of the curve; (2) the working range of the curve shall be described; (3) the mathematical formula of the curve and the goodness-of-fit of the data (coefficient of determination R 2 ) to the curve shall be described;(4) acceptability ranges for the parameters of the curve shall be described.
1. For the screening step: For each series (batch) of analyses performed, a set of the following quality control samples shall be simultaneously analysed: (a) control sample for system suitability of the instrument, ideally method specific; (b) quality control samples which are fortified at a concentration close to the STC and ideally at the CCβ of screening for authorised pharmacologically active substances as well as for the prohibited or unauthorised substances); (c) compliant control sample (blank samples), and when relevant, reagent blanks.
2. For the confirmatory step: For each series (batch) of analyses performed, a set of the following quality control samples shall be simultaneously analysed: (a) control sample for system suitability of the instrument, ideally method specific; (b) quality control samples which are fortified at a concentration close to the MRL or ML for authorised pharmacologically active substances or close to the RPA or LCL for prohibited or unauthorised substances (non-compliant control samples); (c) compliant control sample (blank samples), and when relevant, reagent blanks.
1. at the farm from the collection tank; 2. at the level of the dairy industry, before the milk has been discharged.
1. address of the competent authorities; 2. name of the inspector or identification code; 3. official code number of the sample; 4. sampling date; 5. name and address of the owner or the person having charge of the animals or the animal products; 6. name and address of the animal’s farm of origin (when sampling on farm); 7. registration number of the establishment-slaughterhouse number; 8. animal or product identification; 9. animal species; 10. sample matrix; 11. where relevant, medication within the last four weeks before sampling (when sampling on farm); 12. substance or substance groups for examination; 13. particular remarks.
1. address of the competent authorities or designated bodies; 2. name of inspector or identification code; 3. official code number of the sample; 4. sampling date; 5. animal species; 6. sample matrix; 7. substances or substance groups for examination; 8. particular remarks.