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New ISO standards for medical
biology laboratories,
prescriptions and deviations
Marco Pradella, MD, Italian Society of Clinical Pathology and Laboratory Medicine, National
Commission for Quality and Accreditation. SIPMeL, Via Ponchini 17/int.7 - 31033
Castelfranco Veneto (TV) - Tel. 0423 738098 - Fax 0423 740715. E-mail:
labmedico@labmedico.it.
Keywords: ISO 15189; ISO 17025; accreditation, medical biology laboratory
Abstract
ISO published the draft for final approval of the revision of ISO 15189 standard. Following
ISO directives, ISO 15189 must be aligned with ISO/IEC 17025:2017 and should be less
prescriptive. Draft ISO/DIS 15189 deviates in some points from ISO 17025 and the ISO
indications to limit prescriptiveness: equipment, uncertainty, quality control. This do not seem
to be justified by medical specificities and could complicate the understanding of the new
requirements in medical laboratories.
Introduction
We have recently read some contributions on the topic of accreditation according to ISO
15189.[1],[2] Since January 16 2010, the French legislation requires that the medical
laboratories must be accredited according to ISO 15189 standards.[3] Thus, all medical
laboratories in France must be accredited for at least part of their biological tests before the
end of October 2013.
The order no. 2010-49 of January 13, 2010 has made the accreditation of medical biology
laboratories in France mandatory, using international standards: NF EN ISO 15189 for
medical biology laboratories and NF EN ISO 22870 for point-of-care testing. The NF EN ISO
15189:2012 standard [4] is an adaptation of the requirements relating to the quality
management system according to the NF EN ISO 9001:2008 standard,[5] to improve delivery
performance. Medical biology laboratories will have to deal with a new version of ISO 15189
in the coming years. it is therefore useful to be able to discuss some of the critical points of
the new standard that have already emerged in the preparatory stages.
ISO published the draft for final approval of the revision of ISO 15189 standard.[6] Following
ISO directives, ISO 15189 must be aligned with ISO/IEC 17025:2017[7] and should be less
prescriptive.[8]
Language of the new standard
ISO 17025 point 6.4.1 includes in the equipment necessary to laboratory activities several
items: instruments, software, reference materials, reagents, and consumables. ISO/DIS 15189,
without any medical reason, has two chapters, Equipment and Reagents. Therefore, many
points are duplicated in Reagent and in Equipment chapters.
Section 3 of draft ISO/DIS 15189 contains several synonymous terms. In general, it is not
good policy to use two or more words for the same object. However, some duplications do not
lead to serious ambiguities: 3.2 biological reference interval/reference interval, 3.4
commutability of a reference material/commutability, 3.13 internal quality control
(IQC)/quality control (QC), 3.18 measurement accuracy/accuracy of measurement/accuracy,
3.20 medical laboratory/laboratory, 3.29 trueness/measurement trueness.
At least one of these (3.25 primary sample/specimen) instead introduces an ambiguity, which
a huge mass of ISO documents and those of other authoritative bodies (CLSI, IMDRF, WHO)
have resolved, assigning "specimen" to collection and "sample" to measurement in the
laboratory (next to "aliquot") or in statistical activities, thus abandoning "primary sample".[9]
Ambiguities that the SIPMeL Recommendations proposed to resolve, in the context of
activities to harmonise terms used in ISO documents.[10]
Metrology in the new standard
ISO 17025 deals with the assessment of measurement uncertainty (MU, clause 7.6). ISO
17025 finds the fundamentals of uncertainty in ISO/IEC Guide 98-3:2008 (GUM)[11], ISO
21748:2017 (precision)[12] and ISO 5725 (trueness and precision)[13]. ISO 17025 does not
distinguish between quantitative and qualitative methods, emphasizes the role of the precision
(repeatability and reproducibility) and considers that an estimate shall always be made even
when a rigorous statistical-mathematical approach is difficult, using the skill and experience
of the laboratory.
ISO/DIS 15189 (Section 7.3.4) addresses only MU of quantitative values, without considering
nominal and ordinal results. In ISO/DIS 15189 MU can be estimated for the quantitative
measurement phases of methods giving nominal results. The draft relies for practical
application on ISO/TS 20914:2019[14] (now under revision). ISO/DIS 15189 allows the
laboratory to avoid MU estimation, if it documents the reasons, and leaves optional the use of
MU in the validation and verification of methods. Therefore, ISO/DIS 15189 on MU is both
more prescriptive and more restrictive than ISO 17025. After the publication of the
EURACHEM/CITAC Guide[15] and the ISO 27877 document[16], it is no longer possible to
restrict the field to numerical quantitative results only. EURACHEM/CITAC Guide on
Uncertainty of Qualitative Results is very important, even if it should be integrated with
evaluation of precision, and the nominal results obtained from quantitative measurements,
described by ISO documents.[17] Finally, the optionality of MU estimation opens up the
possibility of conflict between laboratory and accreditation inspectors.
The SIPMeL Recommendations on Measurement Uncertainty,[18] taking guidance from both
ISO 20914 and other documents such as ISO/TS 16393 [19] and ISO 5725-2 [20], also cover
nominal and qualitative ordinal results.[21]
Monitoring of results and/or comparison of methods
ISO 17025 in section 7.7.1 states that the laboratory must have a procedure to monitor the
validity of results, and can use multiple approaches, such as reference or quality control
materials, in-house comparisons, and review of results. In 7.7.2 the laboratory should make
comparisons with the results of other laboratories. ISO/DIS 15189 has three separate parts for
result monitoring: Internal quality control, External quality assessment, and Comparability of
examination results. This leads to more prescriptive guidance, beyond the general ISO rules,
and may conflict with recognized guidelines. The presence of different instruments for the
same examination is typical of medical laboratories, not often seen in other laboratories.
Therefore, the scientific community has worked to produce recommendations and guidelines
on the subject, Indeed, comparability has no recognized guideline and statistical rule for the
purpose of monitoring results, but only for the validation or verification of the methods,
requires costly experiments not compatible with monitoring.[22],[23]
Conclusions
The combination of the key values, their benefits and the positive emotions they give to the
team members was used to draft a reference text or common language for quality
management. The common language was written by the quality manager and approved by the
laboratory staff.[1] The language shared by the members of the laboratory team will constitute
a basis for the development of the quality culture. The rigour of the language is an
indispensable tool for effective implementation of the measures dictated by ISO requirements.
Many ISO documents contain a 'terms and definitions' section or make use of words defined
in other ISO documents. Over time, differences between words and between definitions have
stratified, so that the need for harmonization work is emerging, both between and within ISO
committees. The words equipment, instruments and reagents, verification, comparability, and
monitoring of results, uncertainty of measurements, sample, and specimen, must be used
avoiding redundancies and misunderstandings.
In the analytical phase, there is no difference between medical and forensic, anti-doping,
veterinary or food safety laboratories, so the ISO 17025 requirements are suitable. Limiting
the prescriptivity of the requirements we leave room for the natural, sometimes rapid,
evolution of scientific knowledge and professional skills in individual fields.
Medical biology laboratories should not be afraid of metrology. Metrology texts can
sometimes be difficult to read and understand. However, derived from extensive research,
they provide the correct solutions to problems encountered by laboratories of all types,
including those of medical biology. Carefully researched and applied with practical sense in
our realities, they can provide solutions that reduce difficulties instead of increasing them.
Draft ISO/DIS 15189 deviates in some points from ISO 17025 and the ISO indications to
limit prescriptiveness. This do not seem to be justified by medical specificities.
Scientific progress does not rely on assertions, however authoritative, but on questions,
discussions and documentation of evidence. Whatever text appears in the final version of the
ISO standard, it is only fair that laboratory workers know that the process to get there has
been long and arduous, just as arduous and never concluded is the effort to develop scientific
progress.
References
1. Lathro HD, Sudrié-Arnaud B, Snanoudj-Verber S, Tebani A, Bekri S. A simple approach to
create a common language, a necessary element for the development of a quality culture in a
medical biology laboratory. Ann Biol Clin (Paris). 2021;79:83-7. doi:10.1684/abc.2021.1617
2. Giannoli JM, Albarede S, Avellan T, Bouilloux JP, Cartier R, Cohen R, Colard N,
Essemilaire L, Galinier JL, Kuentz M, Paris M, Portugal H, Scherrer F, Siest JP, Vassault A,
Vialle JM. Recommandations pour la mise en place et le suivi des contrôles de qualité dans
les laboratoires de biologie médicale. Ann Biol Clin (Paris). 2019;77:577-97.
doi:10.1684/abc.2019.1481
3. Ordonnance n◦ 2010-49 du 13 janvier 2010 relative à la biologie médicale. Journal officiel
du 15 janvier 2010 : 43
4. NF EN ISO 15189 : 2012. Laboratoire d’analyses de biologie médicale - Exigences
concernant la qualité et la compétence. Paris : AFNOR, 2012
5. NF EN ISO 9001:2008. Système de management de la qualité - Exigences. Paris : AFNOR,
2015.
6. ISO/DIS 15189:2021 Laboratoires de biologie médicale — Exigences concernant la qualité
et la compétence. Genève: ISO 2021.
7. NF EN ISO/IEC 17025:2017. Exigences générales concernant la compétence des
laboratoires d'étalonnages et d'essais. Paris : AFNOR, 2017.
8. NATA Team. ISO 15189 Revision Update. Media Releases. June 29, 2020. Available from
https://nata.com.au/news/iso-15189-revision-update/ [Accessed 1 Apr 2022]
9. Pradella M. "Specimen" is the Standard term for Collection, "Sample" is the Standard term
for Statistics and Measurement. 2022 AACC Annual Scientific Meeting July 24 - July 28,
2022, Chicago, IL. Poster Number: B-295
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11. NF ISO/IEC GUIDE 98-3 Incertitude de mesure - Partie 3 : guide pour l'expression de
l'incertitude de mesure (GUM : 1995).
12. NF ISO 21748:2017 Lignes directrices relatives à l'utilisation d'estimations de la
répétabilité, de la reproductibilité et de la justesse dans l'évaluation de l'incertitude de mesure.
13. NF ISO 5725-1:1994 Application de la statistique - Exactitude (justesse et fidélité) des
résultats et méthodes de mesure - Partie 1 : principes généraux et définitions.
14. XP ISO/TS 20914:2019 Laboratoires de biologie médicale - Recommandations pratiques
pour l'estimation de l'incertitude de mesure.
15. Bettencourt da Silva R, Ellison SRL (eds.) Eurachem/CITAC Guide: Assessment of
performance and uncertainty in qualitative chemical analysis. First Edition. Teddington
Middlesex: Eurachem; 2021.
16. ISO/TR 27877:2021 Analyse statistique pour l'évaluation de la fidélité des méthodes de
mesure binaire et de leurs résultats.
17. Pradella M. Criticalities of Eurachem/CITAC guide uncertainty of qualitative results.
Measurement, 2022;193:110911. https://doi.org/10.1016/j.measurement.2022.110911.
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raccomandazioni SIPMeL. Riv Ital Med Lab 2021;17:200-8
19. ISO 5725-2:2019. Accuracy (trueness and precision) of measurement methods and results
— Part 2: Basic method for the determination of repeatability and reproducibility of a
standard measurement method.
20. • ISO/TS 16393:2019. Molecular biomarker analysis — Determination of the performance
characteristics of qualitative measurement methods and validation of methods
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