SPECLOG - the Specificity Log An underpinning documentation tool to transparently demonstrate the reliability of a specificity, confirmation and/or identification claim for an analytical method used in regulatory testing for residues of veterinary drugs in food and food related materials.
Regulatory inspection for use of veterinary drugs in food animals Zero tolerance ( A ) drugs: the regulatory offence is the treatment of animals MRL ( B ) drugs: the regulatory offence is the non-compliance with the MRL in edible tissues ( like muscle, fat, liver, kidney, milk or eggs)
Organization Residue Control European Union Community Reference Laboratory ( 4 CRL ) Member State National Reference Laboratory ( 37 NRL* in 15 MS ) Regional (Field) Laboratories (RFL) Private Laboratories inclusive European Union Community Reference Laboratory ( 4 CRL ) Member State National Reference Laboratory ( 37 NRL* in 15 MS ) Regional (Field) Laboratories (RFL) Private Laboratories inclusive * status October 2003
Primary objectives of the CRLs > to assure comparability of national control programmes > to assure their effectiveness : adequate methods and procedures testing for the right compounds > to assure the quality of the work > to assist and advice the Commission a.o. about testing and its consequences
Supportive analytical tools are not validated methods but Critical Analytical Modules (CAMs) like: critical reagents like standards ( parent compound, metabolites, conjugates, isotopes, derivatives, etcetera ), immunochemicals or micro-organisms critical Quality Control samples ( e.g. representative blanks, incurred samples, reference samples ) critical information ( e.g. chromatographic behaviour, solvent partitition data, stability and storage data, spectroscopic data, known interferences, lab safety data ).
Methods in relation to the purpose of the test result > Screening methods no false compliant results > Confirmatory methods reliable identification reliable quantification ( if applicable ) no false non-compliant results > Arbitration (reference) methods confirmatory methods with improved validation status (not longer defined as such in 2002/657/EC)
Confirmation To make sure that the test result is true beyond reasonable doubt –Is the residue detected indeed present? –Does the mass content exceed any action level ? (not applicable for zero tolerance residues)
EU MRPLs EU MRPLs are performance criteria for laboratories who test for the presence of residues of A (zero tolerance) substances MRPLs are quality bench marks QBMs MRPLs are quality bench marks (QBMs) targetting fitness-for-purpose
Decrease of EU QBMs since 1987 Year QBM ( ppb ) ~ 1987 10 ~ 1990 5 ~ 1993 2 - 5 2002 (MRPL) 0,3 - 2
What error probabilities are tolerated at the EU MRPL? are tolerated at the EU MRPL? Directive 2002/657/EC Alpha error requirements are laid down for all methods : 1% or lower for A substances. Beta error requirements are laid down for screening only : 5 % or lower for all substances.
What laboratory performance is required at the EU MRPL? is required at the EU MRPL? A laboratory has to demonstrate that the probability (beta error) is (e.g.) at least 95 out of 100 that it can detect and properly can identify a zero tolerance residue present in samples at a content equal to the residue MRPL
Cumulative probability (%) for a correct test result by two laboratories with a sample containing a residue at the MRPL or at half the MRPL lab-1 >lab-2 > confirmed MRPL 95 %95 %90 % half MRPL40 %60 %24 % A correct test result is the proof of presence in the sample of the zero tolerance residue according to 2002/657/EC. No quantitative information is given with this test result
EU MRPLs harmonize consumer protection decrease the incidence of false compliance testing decrease the incidence of ambiguous non-compliance testing consider metabolism & excretion of drug
EU MRPLs improve cost / effectiveness ratio are drafted by the CRL-NRL community are legalized by the Member States by voting and are laid down in Commission Decisions might be formally adapted according to the-state-of-art
Why lower EU MRPLs ? present MRPL is not adequate to track misuse lower health risk for consumers protection of trade ambition and chauvinism improve cost / effectiveness ratio new analytical improvements
CONCLUSIONS The EU control programmes to test for residues in food of animal origin DO NOT rely on standardized test methods because in the past decades this approach has proven in practice to be rely on standardized test methods because in the past decades this approach has proven in practice to beUNFITfor-the-purpose
CONCLUSIONS The EU control programmes to test for residues in food of animal origin are based mandatory on > Minimum quality criteria for test methods > QA / QC based at minimum on ISO 17025 > A hierarchical network of Reference Labs
CONCLUSIONS > The RFL + NRL + CRL system is effective as an efficient basis for residue control programmes > The system has proven to be fit-for-the-purpose > However, the system cannot do without scientific, financial, administrative nor legal quality
Whats new for residues ? Proposal COM(2003) 52 final of 5 February 2003 for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on official feed and food controls A 116 pages proposal a.o. enforcing more strictly the CRL- NRL network and its mandates