IAEA

IUPAC


INTERNATIONAL WORKSHOP ON PRINCIPLES AND PRACTICES OF METHOD VALIDATION

November 4-6, 1999, Budapest, Hungary

Workshop Report

Reference:

  • 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'.
  • 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 variability.
  • 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.

Proficiency Testing:

  • 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 participating laboratory.
  • 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 laboratory credibility.

Use of Collaboratively Studied Methods:

Collaboratively studied methods should be used when such methods are already available, suitable for purpose and required by clients or regulation.

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.
  • 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 Book

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 days.

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
E-mail: A.Fajgelj@iaea.org
Dr. Árpád Ambrus
FAO/IAEA Training and Reference Centre for Food and Pesticide Control
E-mail: a.ambrus@iaea.org

 

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