Molecular biomarker analysis - General guidelines for single-laboratory validation of qualitative real-time PCR methods (ISO/DIS 11781:2023)

This document describes the performance characteristics and minimum performance criteria which should be taken into account when conducting a single-laboratory validation study for qualitative (binary) real-time polymerase chain reaction (PCR) methods applied for the detection of specific DNA sequences present in foods.
The protocol was developed for qualitative real-time PCR methods for the detection of DNA sequences derived from genetically modified foodstuffs. It is applicable also for single-laboratory validation of qualitative PCR methods used for analysis of other food materials, e.g. for species detection and identification.
The document does not cover the evaluation of the applicability and the practicability with respect to the specific scope of the PCR method.

Molekulare Biomarker-Analyse - Allgemeine Anleitung für die Einzellaborvalidierung qualitativer Real-time-PCR Verfahren (ISO/DIS 11781:2023)

Analyse de biomarqueurs moléculaires - Lignes directrices générales pour la validation intralaboratoire des méthodes de PCR qualitative en temps réel (ISO/DIS 11781:2023)

Analiza molekulskih biomarkerjev - Splošne smernice za validacijo kvalitativnih metod PCR v realnem času v posameznem laboratoriju (ISO/DIS 11781:2023)

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Not Published
Publication Date
23-Jun-2025
Current Stage
4060 - Closure of enquiry - Enquiry
Start Date
21-Feb-2024
Completion Date
21-Feb-2024

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SLOVENSKI STANDARD
01-februar-2024
Analiza molekulskih biomarkerjev - Splošne smernice za validacijo kvalitativnih
metod PCR v realnem času v posameznem laboratoriju (ISO/DIS 11781:2023)
Molecular biomarker analysis - General guidelines for single-laboratory validation of
qualitative real-time PCR methods (ISO/DIS 11781:2023)
Molekulare Biomarker-Analyse - Allgemeine Anleitung für die Einzellaborvalidierung
qualitativer Real-time-PCR Verfahren (ISO/DIS 11781:2023)
Analyse de biomarqueurs moléculaires - Lignes directrices générales pour la validation
intralaboratoire des méthodes de PCR qualitative en temps réel (ISO/DIS 11781:2023)
Ta slovenski standard je istoveten z: prEN ISO 11781
ICS:
67.050 Splošne preskusne in General methods of tests and
analizne metode za živilske analysis for food products
proizvode
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

DRAFT INTERNATIONAL STANDARD
ISO/DIS 11781
ISO/TC 34/SC 16 Secretariat: ANSI
Voting begins on: Voting terminates on:
2023-11-29 2024-02-21
Molecular biomarker analysis — General guidelines for
single-laboratory validation of qualitative real-time PCR
methods
ICS: 67.050
This document is circulated as received from the committee secretariat.
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENT AND APPROVAL. IT IS
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NATIONAL REGULATIONS.
ISO/DIS 11781:2023(E)
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ISO/DIS 11781:2023(E)
DRAFT INTERNATIONAL STANDARD
ISO/DIS 11781
ISO/TC 34/SC 16 Secretariat: ANSI
Voting begins on: Voting terminates on:

Molecular biomarker analysis — General guidelines for
single-laboratory validation of qualitative real-time PCR
methods
ICS: 67.050
This document is circulated as received from the committee secretariat.
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENT AND APPROVAL. IT IS
© ISO 2023
ISO/CEN PARALLEL PROCESSING
THEREFORE SUBJECT TO CHANGE AND MAY
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
NOT BE REFERRED TO AS AN INTERNATIONAL
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on STANDARD UNTIL PUBLISHED AS SUCH.
the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below
IN ADDITION TO THEIR EVALUATION AS
or ISO’s member body in the country of the requester. BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
ISO copyright office
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CH-1214 Vernier, Geneva
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NATIONAL REGULATIONS.
Website: www.iso.org ISO/DIS 11781:2023(E)
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Published in Switzerland
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
ii
PROVIDE SUPPORTING DOCUMENTATION. © ISO 2023

ISO/DIS 11781:2023(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Principle . 2
5 Single-laboratory validation of the performance characteristics . 2
5.1 General . 2
5.2 Limit of detection (LOD ) . 2
95 %
5.3 Determining copies of DNA target sequences in DNA test materials . 3
5.4 Evaluation of data for the limit of detection (LOD ) . 3
95 %
5.5 PCR efficiency and variability of the measured copy number around the LOD . 4
95 %
5.6 Specificity . 4
5.6.1 General . 4
5.6.2 Bioinformatic (in silico) test for specificity . 4
5.6.3 Practical test for specificity . 4
5.6.4 Robustness . . 5
6 Validation report . 6
Annex A (informative) Estimation of the number of copies of the DNA target sequence .7
Annex B (informative) Determination of limit of detection, precision and PCR efficiency .9
Annex C (informative) Generalized linear mixed model (GLMM) with log-log link.13
Annex D (informative) Robustness testing .21
Bibliography .23
iii
ISO/DIS 11781:2023(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO’s adherence to
the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see
www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 34, Food products, Subcommittee SC 16,
Horizontal methods for molecular biomarker analysis.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.
iv
ISO/DIS 11781:2023(E)
Introduction
Qualitative real-time polymerase chain reaction (PCR) methods currently find broad application for
the detection of specific DNA sequences in food, e.g., for the detection and identification of genetically
modified organisms and the products derived thereof, for food authentication and speciation and
other purposes. It is important that a newly developed food analytical method is fit-for-purpose and
meets certain performance characteristics and quality criteria as demonstrated by a particular set of
validation experiments.
The data determined by the single laboratory validation are the basis for the decision to apply a method
in-house. Furthermore, it helps to decide whether the method in question should be fully validated in
[3]
the framework of a collaborative study. The statistical model described has been practically applied.
Other models can be applicable, see ISO/TS 16393.
The aim of this document is to provide a protocol for single-laboratory validation of qualitative real-
time PCR methods that are applied for food analysis. Procedures for DNA extraction from the food
matrix are not included in this document. The procedure described is a recommendation which is
underpinned by practical experience in several laboratories. Alternate approaches may be applied if
they can be shown to meet the performance criteria set in this document.
v
DRAFT INTERNATIONAL STANDARD ISO/DIS 11781:2023(E)
Molecular biomarker analysis — General guidelines for
single-laboratory validation of qualitative real-time PCR
methods
1 Scope
This document describes minimum requirements and minimum performance criteria for conducting a
single-laboratory validation study for qualitative (binary) real-time polymerase chain reaction (PCR)
methods applied to the detection of specific DNA sequences present in foods.
The document can be applied to any single-laboratory validation of a qualitative real-time PCR
method used for the detection of specific DNA sequences in food and food products, e.g. for detection
of genetically modified foodstuffs and for species determination, including species known to produce
allergenic proteins.
The document does not cover the evaluation of applicability and practicability with respect to the
specific scope of the PCR method.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 16577, Molecular biomarker analysis — Vocabulary for molecular biomarker analytical methods in
agriculture and food production
ISO 21571, Foodstuffs — Methods of analysis for the detection of genetically modified organisms and
derived products — Nucleic acid extraction
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 16577 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
probability of detection
POD
probability of a positive analytical outcome of a qualitative method for a given matrix at a given
concentration in a single laboratory
Note 1 to entry: For a qualitative real-time PCR method it describes the probability that, for a given number of
DNA copies of the target sequence, PCR amplification will take place.
[SOURCE: ISO 16577:2022, 3.9.12, modified — The notes have been removed and a new note 1 to entry
was added.]
ISO/DIS 11781:2023(
...

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