A ERROR : FALSE POSITIVE ß ERROR : FALSE NEGATIVE ANALYTICAL LIMITS consumer risk producer risk non-compliant compliant Ref: H. De Brabander.

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