Working Group

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Joint Committee on Traceability in Laboratory
Medicine
Working Group2 Reference Measurement
Laboratories
Prof Dr LM Thienpont
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WG2 Reference Measurement Laboratories

• Co-chaired by

• Prof. Dr. Lothar SIEKMANN (DGKC, Germany)
• Prof. Dr. Linda THIENPONT (Ugent, Belgium)

• Members are (Organisation)

• IFCC (co-chairs)
• CIPM
• NMIs and related institutes such as CDC, IRMM
• ILAC
• IVD Industry (EDMA, AdvaMed and JACR)

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Context in which the establishment of WG2 fits

• European Directive 98/79/EC
• ? Requiring assurance/demonstration of
  metrological traceability of IVD medical devices

• CEN mandated standards
• prEN ISO 17511 (2002)
• Metrological traceability of values assigned to
  calibrators and control materials
• prEN ISO 18153 (2002)
• Metrological traceability of values for
  catalytic concentration of enzymes
• ? Guidance on how to implement traceability

-Application of a metrological traceability chain
-Ideally with the SI-unit as end-point
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The SI-traceability chain
Reference Measurement Laboratories
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Terms of Reference of WG2

• Collect information on existing candidate
  Reference Measurement Laboratories (RMLs)

• Encourage and facilitate the formation of
  Networks of RMLs for different groups of
  measurable quantities (concerning electrolytes,
  substrates/metabolites, enzymes, HbA1c, low
  molecular hormones, ..)

• Establish a procedure for the approval of RMLs
  on the basis of their metrological level
  according to ISO 15195 and their performance as
  demonstrated in interlaboratory comparisons

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Different steps in the activities of WG2

• Ask for nomination of candidate Reference
  Measurement Laboratories (RMLs) and collect data
  (deadline Nov. 28, 2002)

• Ask for adequate information from candidate RMLs
  (measurand?, SI-traceable?, principle of
  analytical procedure?, primary calibrator?,
  CRM/SRM for accuracy/trueness control?, status of
  RML?, etc) (deadline Febr. 24, 2003)

• Develop a basis for approval of RMLs

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Current status

• With respect to steps 1 2
• Data collected in an Excel spreadsheet and
  available for internal use
• - 310 laboratory-measurand combinations
• Combined responses sorted according to group
  measurands

• Check against decisions made by WG1 with respect
  to approved Reference Measurement Procedures
  (RMP) ISO 15193 (2002)
• ? Appeal to Review Teams of WG1

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Review Team Leaders
Electrolytes, Elements Dr. R.
MillerEnzymes Dr. M. PanteghiniMetabolites
and Substrates Dr. M. WelchProteins Dr. D.
SoginDrugs (therapeutic, abuse) Dr. A.
HenrionCoagulation Factors Dr. E.
GrayHormones Dr. H. SchimmelGlycated
Hemoglobin/ HbA1c Dr. K. WeykampVitamins Dr.
W. Lambert
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Approval of RMLs
Step 3 Develop a basis for approval

• prEN (ISO/FDIS) 15195 (2003)
• Requirements for Reference Laboratories

• 3.6
• Reference Measurement Laboratory
• Laboratory that performs a Reference Measurement
  Procedure and provides results with stated
  uncertainties.

Reference Measurement Laboratories
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ISO/FDIS 15195
Requirements for Reference Measurement
Laboratories in Laboratory Medicine (cont.)
3.7 Reference Measurement Procedure Thoroughl
y investigated measurement procedure shown to
have an uncertainty of measurement commensurate
with the intended use, especially in assessing
the trueness of other measurement procedures for
the same quantity and in characterising reference
materials. NOTE 1 When several RMPs exist for a
given measurable quantity, it may be possible to
arrange them in a hierarchy according to size of
uncertainty of measurement
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ISO/FDIS 15195
Requirements for Reference Measurement
Laboratories in Laboratory Medicine (cont.)
5.5 Reference Measurement Procedures The
reference measurement procedures are usually
complex. They are generally developed and
published by individual laboratories and approved
by international organisations or national
metrology institutes. A procedure to be accepted
as a reference measurement procedure shall be
designed, , and applied so that traceability of
its results to a higher reference procedure or a
higher reference material is achieved with the
level of uncertainty of measurement as required
to meet the needs of the customer (see also prEN
ISO 17511).
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ISO/FDIS 15195
Requirements for Reference Measurement
Laboratories in Laboratory Medicine (cont.)
5.5 Reference Measurement Procedures The
presentation of a reference measurement procedure
shall follow ISO 15193. Before reference
measurements are offered to a customer, the
laboratory shall demonstrate, for example by
accreditation, that it can properly operate the
reference measurement procedure and that the
equipment and reagents used are appropriate.
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ISO/FDIS 15195
Requirements for Reference Measurement
Laboratories in Laboratory Medicine (cont.)
5.7 Quality assurance The analytical goals
shall be defined in relation to the customers
needs and shall take into consideration that the
metrological level is appropriate to enable the
customer to fulfil medical requirements.
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ISO/FDIS 15195
Requirements for Reference Measurement
Laboratories in Laboratory Medicine (cont.)
5.7 Quality assurance The way of assessing
conformity with quality control rules shall be
documented. Internal quality control shall be
performed by measuring a sufficient number of
matrix control samples in each analytical series
in order to provide sufficiently powerful control
rules to fulfil the customers requirements.
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ISO/FDIS 15195
Requirements for Reference Measurement
Laboratories in Laboratory Medicine (cont.)
5.7 Quality assurance The measurement
value obtained on the control material shall
agree with its assigned value within the
measurement capability claimed by the laboratory.
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ISO/FDIS 15195
Requirements for Reference Measurement
Laboratories in Laboratory Medicine (cont.)
5.7 Quality assurance In order to
supplement internal quality control, the
laboratory shall regularly check its performance
characteristics by taking part in interlaboratory
comparisons for relevant types of quantity
(preferably in a network of reference measurement
laboratories) organized by national metrology
institutes, accrediting bodies, or international
scientific organizations.
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Approval of RMLs
Conclusion The prEN (ISO/FDIS) 15195 forms an
ideal basis for approval of RMLs because it
defines/describes

• RML
• RMP and uncertainty
• Quality assurance

Reference Measurement Laboratories Reference
Measurement Procedure
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Criteria selected for approval of RMLs

• Metrological level of the Reference Measurement
  Procedure (RMP) applied
• a) Primary RMP
• b) Secondary RMP
• c) Internationally agreed conventional RMP

• Implementation of a Quality Management System
• according to ISO 17025 (as calibration
  laboratory) or in compliance with ISO 15195 (or
  existence of a link to a NMI)

• Ability to demonstrate competence
• in regular interlaboratory measurements
  (Networks)

Reference Measurement Laboratories
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Approval of RMLs current status

• Collected information from candidate RMLs is
  currently under investigation for approval by
  Review Teams
• Outcome will be discussed with WG2 co-chairs
• Organisation of proficiency testing of RMLs to
  demonstrate competence is currently in process
  (formation of a kind of Network of RMLs)

Reference Measurement Laboratories
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Demonstration of competence

• By regular interlaboratory measurements
• Currently, only few Networks of Reference
  Measurement Laboratories (RMLs) exist, i.e. the
  HbA1c enzyme Network (IFCC), the cholesterol
  Network (CDC)

• There is a need for additional Networks and/or,
  at least, for organisation of proficiency testing
  (PT) of RMLs, via which the latter indeed can
  demonstrate their competence on a regular basis

? The Reference Institute of Bioanalysis (Bonn)
will, on behalf of IFCC, organise PT of RMLs
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Demonstration of competence
By regular interlaboratory measurements
The ring trials for Reference Measurement
Laboratories will be organised according to the
following rules

• every 6th month
• groups of measurands, per trial a key measurand
• 2 samples/trial
• 4-month reply period
• overall evaluation individual report
• start next September

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Conclusion and perspectives

• The IVD Directive created a need to establish
  internationally recognized lists of higher order
  Reference Materials, Reference Measurement
  Procedures (RMPs) and competent Reference
  Measurement Laboratories (RMLs) in laboratory
  medicine

• Like JCTLM WG1, WG2 laid down procedures
  whereby RMLs are examined with respect to
  conformity with appropriate international
  standards

• The activities of both WGs will result in a
  database (publicly available on the BIPM/IFCC
  website) that can be used by the IVD Industry and
  other users to meet the requirements of national
  and international regulations