a error : false positive ß error : false negative analytical limits consumer risk producer risk...
TRANSCRIPT
a ERROR : FALSE POSITIVE
ß ERROR : FALSE NEGATIVE
ANALYTICAL LIMITS
consumer risk
producer risk
non-compliant
compliantRef: H. De Brabander
Euro
~US $
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 Regulatory inspection for use of veterinary drugs in food animalsveterinary drugs in food animals
Zero tolerance ( “A” ) drugs:Zero tolerance ( “A” ) drugs:
• the regulatory offence is the treatment of animals
MRL ( “B” ) drugs: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 ControlOrganization 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 Primary objectives of the CRLsCRLs
> 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 Methods in relation to the purpose of the test resultthe test result
> Screening methodsScreening methods• “no” false compliant results
> Confirmatory methodsConfirmatory methods• reliable identification• reliable quantification ( if applicable )• “no” false non-compliant results
> Arbitration (“reference”) methodsArbitration (“reference”) methods• confirmatory methods with improved
validation status (not longer defined as such in 2002/657/EC)
ConfirmationConfirmation
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)
EUEU MRPL’s MRPL’s are performance criteria for laboratories who test for
the presence of residues of “A” (zero tolerance) substances
MRPL’sMRPL’s are quality bench marks are quality bench marks (QBM’sQBM’s)
targetting fitness-for-purpose
Decrease of EU Decrease of EU QBM’sQBM’s since 1987 since 1987
Year QBM ( ppb )
~ 1987 10
~ 1990 5
~ 1993 2 - 5
2002 (MRPL) 0,3 - 2
What error probabilitiesWhat error probabilities
are tolerated at the EU are tolerated at the EU MRPLMRPL??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 performanceWhat laboratory performance
is required at the EU is required at the EU MRPLMRPL??
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 Cumulative probability (%) for a
correct test result bycorrect test result by
two laboratories with a sample containingtwo laboratories with a sample containing
a residue at the MRPL or at half the MRPLa residue at the MRPL or at half the MRPL
lab-1 > lab-2 > confirmed
MRPL 95 % 95 % 90 %
half MRPL 40 % 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
EUEU MRPL’s MRPL’s• harmonize consumer protection
• decrease the incidence of false
compliance testing
• decrease the incidence of ambiguous
non-compliance testing
• consider metabolism & excretion of drug
EUEU MRPL’s MRPL’s
• 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”
WhyWhy lowerlower EU EU MRPL’s MRPL’s ??
• 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
CONCLUSIONSCONCLUSIONS
The EU control programmes to test for residues in The EU control programmes to test for residues in
food of animal origin food of animal origin
DO NOTDO NOT
rely on standardized test methods because in the rely on standardized test methods because in the
past decades this approach has proven in practice to past decades this approach has proven in practice to
be be
UNFITUNFIT
for-the-purposefor-the-purpose
CONCLUSIONSCONCLUSIONS
The EU control programmes to test for The EU control programmes to test for
residues in food of animal origin are residues in food of animal origin are
based mandatory onbased mandatory on
> Minimum quality criteria for test methodsMinimum quality criteria for test methods
> QA / QC based at minimum on ISO 17025QA / QC based at minimum on ISO 17025
> A hierarchical network of Reference LabsA hierarchical network of Reference Labs
CONCLUSIONSCONCLUSIONS
> The RFL + NRL + CRL system is effective as an The RFL + NRL + CRL system is effective as an
efficient basis for residue control programmesefficient basis for residue control programmes
> The system has proven to be The system has proven to be
fit-for-the-purposefit-for-the-purpose
> However, the system cannot do without However, the system cannot do without
scientific, financial, administrative nor legal scientific, financial, administrative nor legal
qualityquality
What’s new for residues ?What’s new for residues ?
Proposal COM(2003) 52 final of 5 February 2003
for aREGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCILon official feed and food controls
A 116 pages proposal a.o. enforcing more strictly the CRL- NRL network and its
mandates