The document discusses the concept of traceability in laboratory medicine. It provides an overview of how traceability developed through the work of organizations like NIST and NCCLS. Traceability means relating measurement values to international standards through an unbroken chain of comparisons. This ensures accuracy and comparability of results across laboratories and diagnostic methods. The key aspects of traceability include certified reference materials, reference measurement procedures, and qualified reference laboratories. Traceability is important for standardization in laboratory medicine and compliance with regulations like the EU IVD directive.

1. THE CONCEPT OF TRACEABILITY
IN LABORATORY MEDICINE - A
TOOL FOR STANDARDISATION
BY
Prof. MOUSTAFA RIZK
CLINICAL PATHOLOGY DEPAR.
ALEX UNIVERSITY

2. This talk provides:
1 - An overview of the development of the
traceability concept, with focus on the
traceability chain.
2 - Analytical discussion of the problems that
once hampered the performance quality of
clinical diagnostic tests.

4. What is Traceability?
In the context of laboratory medicine, the term
traceability means metrological traceability.
Definition:
‘the value of a standard or result whereby it , can
be related to stated references, usually
national or international standards, through an
unbroken chain of comparisons all having
stated uncertainties’
VIM 6.10 – ref: BIPM, IEC, IFCC, ISO, IUPAC, IUPAP, OIML, International Vocabulary of Basic and
General Terms in Metrology, 2nd edition, Geneva, 1993)

5. Metrological Traceability
Concept :
􀂉 Each calibrator value or test result must
come from a calibrated test method
􀂉 Each calibrator must have a value
assigned by a calibrated test method.

6. Traceability is not really a new concept for in vitro
diagnostics.
Many years before traceability was mentioned
in connection with general chemical metrology,
reference measurement procedures and
reference materials had been established in
clinical chemistry.

7. Primary Standards
A primary standard is a reagent that is extremely pure,
stable, has no waters of hydration, and has a high
molecular weight.
Some primary standards for titration of acids:
sodium carbonate: Na2CO3 ,
tris-(hydroxymethyl)aminomethane (TRIS)
Some primary standards for titration of bases:
potassium hydrogen phthalate (KHP): KHC8H4O4
potassium hydrogen iodate: KH(IO3)2
Some primary standards for redox titrations:
potassium dichromate: K2Cr2O7.

8. Secondary Standards
A secondary standard is a standard
that is prepared in the laboratory for a
specific analysis. It is usually
standardized against a primary
standard.

9. Why all the fuss about Traceability ?
Traceability is an Essential Requirement of
the European Union (EU) Directive on in
vitro diagnostic medical devices.
- No long term stable references
- No comparability between
measurements produced by different
manufacturers
- repeated measurements cost a fortune.
- wrong measurements results in wrong
medical treatment

10. What is meant by Essential Requirement ?
“ The traceability of values assigned to
calibrators and control materials must be
assured through available reference
measurement procedures and/or available
reference materials of a higher order”.
Official Journal of European Communities (1998)

11. Traceability is ….
not accuracy.
a tool to ensure accurate results.
not showing equivalence to a reference st.
a process that relates measurement
values to a reference standard

12. Traceability requires…..
1-Higher order Reference Measurement
Procedures
ISO 15193
2-Qualified Reference Materials
ISO 15194
3-Suitable Reference Laboratories
ISO 15195

13. DEVELOPMENT OF THE CONCEPT OF TRACEABILITY
Scientists at the National Institute of Standards and
Technology (NIST)
The National Committee for Clinical Laboratory
Standards (NCCLS)
Both had an important influence on the development of
the concept of traceability in general chemical metrology.
Some basic experimental work toward the development of reference
measurement procedures and reference materials had already been
undertaken in Europe.

14. JOINT COMMITTEE FOR TRACEABILITY IN
LABORATORY MEDICINE
JCTLM
MAIN STAKEHOLDERS
• International Federation of Clinical Chemists(IFCC)
• World Health Organisation(WHO)
• International Laboratory Accreditation Cooperation(ILAC)
• BUREAU INTERNATIONAL DES POIDS MESURES (BIPM)

15. The Traceability Chain
Traceability of a value attributed to a routine sample, a
calibrator, or a control material is established by a series of
comparative measurements using measurement procedures
and reference materials in a chain of decreasing hierarchical
order.
Since each link in the traceability chain contributes to the
uncertainty of the result, it is advisable to omit as many
steps as possible.
In metrological terms it would be ideal to omit all in-between steps of the
traceability chain and to measure the routine sample directly by use of a
primary reference procedure. This, of course, is not feasible

16. The Traceability Chain
The complete traceability chain is valid only for
those measurable quantities that can have a
value expressed in SI units .
When primary or secondary calibrators are not
available, the traceability chain for many
measurements in laboratory medicine ends at a
lower level, for example, at the manufacturer's
selected measurement procedure.

17. The Traceability Chain
In a case where a manufacturer detects a new
diagnostic marker and defines the measurable
quantity by establishing a measurement
procedure for the marker, the manufacturer's
measurement procedure will form the top of the
traceability chain.
Nevertheless, even in this simple situation the principles
of traceability are applicable.

18. The Traceability Chain
An inevitable precondition for
establishing results traceable to
calibrators and control materials is the
specificity of the measurement
procedures applied.
Results of measurement cannot be traceable
when the procedure applied , partially detects
components that are not consistent with the
definition of the measurand.

19. Use of calibration standards (calibrantsUse of calibration standards (calibrants))
Secondary
calibrator
Manufacturer’s
product calibrator
End user’s
laboratory primary
calibrator
sample
Manufacturer’s
working calibrator
Primary
calibrator
Working calibrator
End user’s
laboratory
sells to
Reference material producer
sells to

20. Analyte Classification
Type A
1 -Well defined compounds
2 -Results are not method dependent
3 -Concentrations can be expressed in SI Units
4 -Full traceability chain is possible
5 -Approx. 25-30 analytes (e.g. glucose,
electrolytes, urea, cholesterol, steroid hormones)

21. Analyte Classification
Type B
1- Not well defined (e.g. heterogeneous)
2- 400-600 analytes (e.g., tumor markers,
viral antigens, enzymes, glycoproteins,
coagulation factors)
3- Arbitrary or conventional units (e.g., WHO
International Units)
4- Full traceability chains not practical.

22. Copyright ©2000 American Association for Clinical Chemistry
Muller, M. M. Clin Chem 2000;46:1907-1909
Calibration hierarchy and traceability to the SI

23. Terminology related to CRMs
reference material certified reference
material
standard reference
material
standard secondary standard secondary reference
material
control sample laboratory control
sample
calibration standard
calibration solution calibrator measurement standard
(etalon)
international
(measurement) standard
national (measurement)
standard
primary standard
secondary standard reference standard working standard
transfer standard travelling standard multicomponent
standard
cocktail pure substance standard matrix reference
material

24. Primary methodPrimary method
• A primary method of measurement is a
method having the highest metrological
qualities, whose operation can be
completely described and understood, for
which a complete uncertainty statement
can be written down in terms of SI units
• A primary direct method measures the
value of an unknown without reference to
a standard of the same quantity

25. Examples of primary methods
• Coulometry
• Gravimetry
• Titrimetry
• Calorimetry
• Cavity Ring Down Spectroscopy

26. Primary ratio method
• A primary ratio method measures the
value of an unknown to a standard of the
same quantity; its operation must be
completely described by a measurement
equation
• In this case almost always use is made of
a high purity material (a “primary reference
material”)
• Thus, high purity analysis are crucial.

27. Certified Reference Materials (CRMs)
• Calibration
• Validation - Recovery factor (calibration)
• In general NOT the top of the chain
• Importance of pure reference materials
• Role when traceability to SI can not be
realized
• Limited availability
• Matrix problems

28. What is measurement uncertainty?
“A parameter associated with the result of a measurement, that
characterises the dispersion of the values that could reasonably
be attributed to the measurand”. (VIM definition)
X ± u
“The uncertainty represents the range of values that the
analyst believes could reasonably be attributed to the
measurand.”
“The uncertainty is a range in which we expect and claim
our result to lay in with a certain confidence.”
International Vocabulary of Basic and General Terms in Metrology

29. Characterisation
* (Uchar)
Lab
3
Lab
2
Lab
1
Transport
(Usts)
Storage
(Ults)
Between bottle
variation (Sbb)
UCR
M
FACTORS AFFECT CRM PROPERTIESFACTORS AFFECT CRM PROPERTIES
Need to ensure awareness of users that the properties
of CRMs can change, due to various factors, including
the effects of sample division (includes homogeneity),
storage, transport, ageing, etc.
Uncertainty of
the assigned
property
values

30. FACTORS AFFECT CRMs
PROPERTIES
• Matrix structure
• Instabilities and differences in
composition of (reference materials)
used .
• Lack of precise definition of
measurand.
• Measurement uncertainty
calculations

31. Results of NCCLS-AACC Survey of
problem Analytes – 2001
Clinical laboratory personnel were asked to rate problem analytes
based upon three criteria:
-Inconsistent results between different methods
-Results questioned by physician
-Lot-to-lot shifts
Rank order from respondents:
1. Troponin I 7. Glycated Hemoglobin
2. PSA 8. Free T4
3. Glucose 9. Bilirubin
4. Creatinine 10. Potassium
5. Calcium 11. Amylase
6. HCG 12. TSH

32. THE QUALITY OFFICER….HIS ROLE
• Operating the calibration system to all the
measurements performed and to be
traceable to the appropriate standard.
Responsible to guarantee that the calibration
programme is performed in the time due and as
it is described in the corresponding Operation
procedure

33. THE QUALITY OFFICER….HIS ROLE
• Obtaining the relevant calibration data
regarding the various items of laboratory
equipment in use from the manufacturers
and keeping to hand in the appropriate
files.
Labelling all measuring equipment to
indicate their calibration status.

34. THE QUALITY OFFICER….HIS ROLE
The calibration data has to meet the specifications
contained in test or equipment procedures.
Calibration frequencies are indicated in the
standard operating procedures.
The period for which calibration data has to be
retained is stated in the standard operating
procedures for each analyte .

35. THA QUALITY MANAGER …HIS ROLE
• To be sure that :
1 - The calibration system is designed and
operated in such a way that , all measurements
performed shall be traceable to the appropriate
national standard.
• 2 - Reference standards of measurement, are
stored separately and used only for calibration
purposes.
• 3 - The calibration programe is implemented at all
times.
• 4 - The retention time of periodical calibrations is
established in the document.

36. THA QUALITY MANAGER …HIS ROLE
• 5- The laboratory adhere to international
standards regarding the traceability of results.
• 6- The quality material is made of certificate
reference material and standard reference
material as supplied by the National Standards
Office and commercial suppliers.

37. THE DIRECTOR OF THE DEPARTMENT
• The Director of the Department is
the final responsible for the policy
and procedures of calibration of
analytical tests , equipments .

38. CONCLUSION
The concept of measurement traceability that has
been established in general chemical metrology
is now being introduced to the field of clinical
chemical analysis.
Traceability provides probably the most
important strategy for achieving standardization
in laboratory medicine, that is, the attainment of
comparable measurement results regardless of
the method or measurement procedure (test kit)
used, or of the laboratory in which analyses are
performed.

39. Merological traceability in chemistry
The Hubble telescope...
THANK YOU
Prof.Dr.Moustafa Rizk