WORKSHOP ON PRINCIPLES AND PRACTICES OF METHOD VALIDATION
November 4-6, 1999, Budapest,
- IUPAC Project 501/8/97
"Protocol for In-house Method Validation"
- IUPAC Project 5/2/99
"Preparation and Harmonisation of Internationally Harmonised Guidelines
for In-house Method Validation"
The International Workshop on "Principles and Practices of Method
Validation" took place between 4 and 6 November 1999 in Budapest,
Hungary. This workshop was organised jointly by the FAO, IAEA, AOAC
Int. and IUPAC. It resulted from the internationally recognised fact
that the full method validation carried out through interlaboratory
method performance study is an very expensive but also a limited exercise.
It is impossible to organise interlaboratory studies for all analytical
methods in use for determination of analytes in various analyte/matrix
combinations. A formal basis for the workshop organisation were:
In all three cases the in-house method validation (single laboratory
method validation) is scientifically/technically presented as an alternative
to the current internationally accepted method validation practice,
namely interlaboratory method performance studies. It is described
in the IUPAC, AOAC Int. and ISO in 1988 developed guidance. In this
respect, the present workshop might be seen as an important event,
actually discussing and establishing technical guidelines to be followed
within a single laboratory performing method validation. The process
required to elaborate all technical details and to change the "philosophy"
and consequently the international legislation may take some years.
In this process the present workshop was an important milestone.
The aim of the workshop was to bring together scientists and representatives
of different agencies, governments, standardisation organisations
and accreditation bodies involved in method validation in general
or in the acceptance of analytical methods for legislative purposes.
Around 120 participants from 34 countries attended the workshop. International
organisations, i.e. AOAC Int., FAO, IAEA, IUPAC, European Commission,
EURACHEM, etc. were also formally represented. 14 participants have
received the IUPAC financial support to attend the meeting. They have
all actively participated in preparation of the workshop documents
or have delivered a presentation (oral or poster). The first day of
the workshop was dedicated to presentations (lectures and posters),
while on the second day two draft documents were introduced and explained:
- IUPAC Harmonised Guidelines for the In-house Validation of Methods
of Analysis (Technical Report), prepared by R. Wood, M. Thompson and
S. Ellison; and
- the "Practical Procedures to Validate Method Performance and Results
of Analysis of Pesticide and Veterinary Drug Residues, and Trace Organic
Contaminants in Food", a discussion document, prepared by A. Ambrus,
FAO/IAEA. (Both documents are available upon request.)
The third day of the workshop was dedicated to general discussion
regarding the quality requirements to be met when analytical methods
are validated and specifically to comments and recommendations regarding
the two draft documents presented. From logistical reasons, a discussion
was mainly oriented to the methods applied for pesticide, veterinary
drug residues and trace organic contaminants in food. These are the
fields were the use of standardised methods has a strong legislative
basis. Nevertheless, single laboratory method validation approach
is important also for all other analytical methods. In this respect
specific guidance on (minimum) quality criteria and other requirements
will need to be prepared.
Major topics related to the validation and subsequent use of analytical
methods discussed by the present workshop were the following:
- the 'harmonised guidelines';
- the 'practical procedure';
- proficiency testing;
- use of collaboratively studied methods;
- uncertainty of analytical measurement; and
- role of LOD/LOQ.
The following are recommendations resulting from the workshop:
The IUPAC Harmonised Guidelines for the In-house Validation of
Methods of Analysis:
- The term 'single laboratory validation' is preferred to 'in-house
- Validation criteria recommended should be the minimum necessary
to assure method performance for the intended purpose.
- A single laboratory validation cannot assess between laboratory
variation and will provide an optimistic assessment of inter-laboratory
- Quality control (QC) procedures should be used within a laboratory
to monitor on-going conformance to the performance characteristics
estimated during validation. These results can be used to refine the
estimated performance characteristics of the method.
- Participation in inter-laboratory studies enhances method validation
and supports comparability of analytical results.
- Analysis of fortified test portions provides an estimate of precision
and bias of the analytical method.
- Analysis of samples containing incurred residues provides an estimate
of analyte homogeneity after sample processing.
- Where certified reference materials containing incurred residues
are not available, the determination of efficiency of extraction is
beyond the capability of most laboratories.
- Laboratories should agree with clients the method performance to
be achieved, including reporting limits.
The basic concept of the document and the approach for in-house method
validation based on the evaluation of uncertainty sources associated
with each specific analytical method were largely accepted and after
revision will the document be sent to IUPAC, AOAC Int., ISO, EURACHEM,
and CITAC for endorsement. Its publication in the Journal of Pure
and Applied Chemistry is expected at the end of the year 2000.
As already mentioned, this will not be the end of the complete process.
The adoption of this new approach in the laboratories and its acceptance
by legislative authorities will require some more time.
The 'Practical Procedure':
In addition to the 'harmonised guideline', and the comments given
above, the following points are to be considered by the FAO/IAEA expert
consultation regarding the 'Practical Procedure':
- The redraft should contain a generic approach to single laboratory
method validation for organic trace analysis.
- Specific aspects relating to pesticide and veterinary drug residues
will be contained in appendices.
- The minimum list of analytes will be reconsidered to determine the
most appropriate analytes to be included in multi-residue method validation
(e.g. compounds which have caused problems in trade).
- The following issues should be considered within the context of
the intended use of method:
- parameters to be studied;
- criteria to be used;
- number of determination required to meet criteria.
- The terminology used in the document should be consistent with Codex,
ISO and IUPAC terms, as far as practical.
'Practical procedure' is under further elaboration by the experts
group of the FAO/IAEA. Publication of the document is foreseen for
the first half of the year 2000.
- The 'International harmonised protocol for proficiency testing of
(chemical) analytical laboratories' defines the criteria for design
and evaluation of proficiency tests.
- The participants raised some general concerns regarding the use
and interpretation of proficiency test results and asked to bring
them to the attention of accreditation authorities. These items were
not intended for inclusion in either 'the harmonised guideline' or
'the practical approach' final documents.
- Properly designed proficiency tests can provide information to reduce
the necessity for method collaborative studies. If laboratories can
demonstrate accurate measurement of test analytes in common samples,
acceptable method performance and equivalency of methods can be indicated.
- Proficiency testing and Q.C. are distinct procedures and cannot
take the place of each other.
- Proficiency test samples should represent the types of samples encountered
in actual practice, to the extent that is possible and practical.
- The scale of proficiency testing should be cost-effective for each
- Co-ordination of national testing plans or sample exchange schemes
can provide a greater range of samples and analytes for proficiency
testing. Such co-ordination is encouraged.
- Careful evaluation of proficiency tests is required to minimise
the possibility of misinterpretation of results. It is critical that
the limitations of proficiency testing be recognised since registration
and accreditation organisations may use results as a criterion of
Use of Collaboratively Studied Methods:
Collaboratively studied methods should be used when such methods
are already available, suitable for purpose and required by clients
Uncertainty of Analytical Measurement:
- A clear and unambiguous definition of uncertainty of measurement
in analytical chemistry is needed.
- Well-defined practical methodology is needed on how to develop meaningful
data to assess uncertainty, in trace analysis.
- It is especially important that the lay public and laboratory clients
understand what uncertainty means and does not mean in analytical
- Measurement uncertainty should be estimated, if required, and be
available to clients.
Use of LOD/LOQ:
LOD and LOQ are variable estimates, the values of which depend on
the conditions of measurement and the experience of the analyst. The
use of these estimates in client reports can be misleading. In view
of this, it was requested that the FAO/IAEA expert consultation following
the Workshop would consider as an alternative that the lowest calibrated
level of the analysis to be used in client reports.
Proceedings of the workshop, including most of the presentations
(lectures and posters) will be published in a special proceedings
series book by the Royal Society of Chemistry, Cambridge, UK within
the next half a year and might already be ordered. > View
The workshop was locally organised by the Plant Health and Soil Conservation
Station of Budapest in a very nice environment of the Hungarian Academy
of Sciences and has resulted in three very intensive and productive
The FAO/IAEA consultation report will soon be available on the http://www.iaea.org/trc/
|Dr. Ales Fajgelj
Chaiman, IUPAC Interdivisional WP on Harmonisation of Quality
Assurance Schemes for Analytical Laboratories
|Dr. Árpád Ambrus
FAO/IAEA Training and Reference Centre for Food and Pesticide
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