Biotechnology -- Biobanking -- General requirements for the validation and verification of processing methods for biological material in biobanks

This document specifies the validation and verification requirements applicable to a biobank to be able to demonstrate that it operates its processing of biological materials with validated and/or verified methods that are fit for purpose. This document is intended for use in the implementation and validation of processing methods for biological materials. This document covers method validation and verification for the production of all biological materials. This document does not apply to biological material intended for food/feed production, laboratories undertaking food/feed analysis, and/or therapeutic use. Reference material production is not covered in this document. For the production requirements for reference materials, see ISO 17034.

Biotechnologie -- Biobanques -- Exigences générales pour la validation et la vérification des méthodes de traitement du matériel biologique dans les biobanques

Le présent document spécifie les exigences de validation et de vérification applicables pour qu'une biobanque puisse démontrer qu'elle réalise le traitement des matériels biologiques selon des méthodes validées et/ou vérifiées qui sont adéquates ŕ l'usage prévu. Le présent document est destiné ŕ ętre utilisé pour la mise en place et la validation des méthodes de traitement des matériels biologiques. Le présent document couvre la validation et la vérification des méthodes de production de tous les matériels biologiques. Le présent document ne s'applique pas aux matériels biologiques destinés ŕ la production de denrées alimentaires/d'aliments pour animaux, aux laboratoires effectuant des analyses de denrées alimentaires/d'aliments pour animaux et/ou ŕ un usage thérapeutique. La production de matériaux de référence n'est pas couverte par le présent document. Pour les exigences liées ŕ la production des matériaux de référence, voir l'ISO 17034.

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Published
Publication Date
14-Jun-2020
Current Stage
6060 - International Standard published
Start Date
15-Jun-2020
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INTERNATIONAL ISO
STANDARD 21899
First edition
2020-06
Biotechnology — Biobanking —
General requirements for the
validation and verification of
processing methods for biological
material in biobanks
Biotechnologie — Biobanques — Exigences générales pour la
validation et la vérification des méthodes de traitement du matériel
biologique dans les biobanques
Reference number
ISO 21899:2020(E)
ISO 2020
---------------------- Page: 1 ----------------------
ISO 21899:2020(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2020

All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may

be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting

on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address

below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
---------------------- Page: 2 ----------------------
ISO 21899:2020(E)
Contents Page

Foreword ........................................................................................................................................................................................................................................iv

Introduction ..................................................................................................................................................................................................................................v

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 1

4 Abbreviated terms .............................................................................................................................................................................................. 5

5 General and resource requirements ................................................................................................................................................ 6

6 Selection of processing methods ......................................................................................................................................................... 6

7 Processing method implementation ............................................................................................................................................... 7

7.1 Targets for method implementation .................................................................................................................................... 7

7.2 Processing method implementation .................................................................................................................................... 7

8 Initial validation of a processing method ................................................................................................................................... 7

8.1 General ........................................................................................................................................................................................................... 7

8.2 Validation plan ........................................................................................................................................................................................ 8

8.3 Assays for properties of interest .............................................................................................................................................. 8

8.4 Validation execution ........................................................................................................................................................................... 9

8.4.1 General...................................................................................................................................................................................... 9

8.4.2 Validation site ..................................................................................................................................................................... 9

8.4.3 In-house or outsourced testing ........................................................................................................................... 9

8.5 Targets for processing method validation ....................................................................................................................10

8.5.1 General...................................................................................................................................................................................10

8.5.2 Fitness for purpose .....................................................................................................................................................10

8.5.3 Reproducibility ...............................................................................................................................................................10

8.5.4 Robustness .........................................................................................................................................................................10

8.5.5 Homogeneity ....................................................................................................................................................................11

8.5.6 Stability .................................................................................................................................................................................11

8.6 Review and approval of validation report ....................................................................................................................12

9 Further validation ............................................................................................................................................................................................12

10 Method verification ........................................................................................................................................................................................12

11 Ongoing monitoring of a processing method.......................................................................................................................13

11.1 General ........................................................................................................................................................................................................13

11.2 Frequency of the monitoring ...................................................................................................................................................13

11.3 Planning .....................................................................................................................................................................................................14

11.4 Procedure of the systematic monitoring .......................................................................................................................14

11.5 Procedure of the periodic monitoring .............................................................................................................................14

11.6 External quality assessments (EQA)/Interlaboratory exercises ..............................................................15

12 Record keeping and archiving .............................................................................................................................................................15

Annex A (informative) Processing and testing methods ...............................................................................................................16

Annex B (informative) Examples of validation plans .......................................................................................................................17

Bibliography .............................................................................................................................................................................................................................20

© ISO 2020 – All rights reserved iii
---------------------- Page: 3 ----------------------
ISO 21899:2020(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 276, Biotechnology.

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 2020 – All rights reserved
---------------------- Page: 4 ----------------------
ISO 21899:2020(E)
Introduction

Biobanks, producing viable and non-viable biological materials (human, animal, plant, microbial) for

research purposes, within biotechnology, use processing methods. Many biobanks include processing

laboratories where processing methods are performed and biological materials are produced as an

output. Examples of widely used processing methods, applied by biobank laboratories, include DNA,

RNA and protein extractions from blood, tissue, seeds, bacteria, or other biological material, or primary

cell cultures. An example for the validation of a processing method is provided in Reference [27].

Biobank laboratories are not always equipped to perform testing methods, which are required for

annotation or qualification of the biological material output.

This document sets out specific requirements for validation of processing methods. It is intended to

help biobank laboratories who perform processing of biological materials, whether they perform

themselves testing activities on the biological materials they have produced, or not. It enables validation

of processing methods, complements the quality management system of any biobank laboratory

performing processing of biological materials and gives more credibility to such an organization. It

is understood that while the term “method” used in ISO/IEC 17025 corresponds to “testing method”

or “calibration method”, a fundamental distinction exists between “processing methods” where the

output is a biological material and “testing methods” where the output is a test result (see Annex A). It

is understood that validation of processing methods performed by accredited testing laboratories, who

test the biological material output themselves, is already included in their accreditation scope.

Validation of a processing method encompasses confirmation of the fitness for purpose of the output

biological material, assessment of the homogeneity and stability of the biological material, and

assessment of the reproducibility and robustness of the processing method. This validation requires

testing in order to assess/measure the qualitative or quantitative properties of the biological material.

This testing will lead to the assessment of the fitness for purpose, the reproducibility, and the robustness

of the processing method. Examples of such properties are: viability, purity, pluripotency, molecular

integrity, concentration, growth capacity, etc.
© ISO 2020 – All rights reserved v
---------------------- Page: 5 ----------------------
INTERNATIONAL STANDARD ISO 21899:2020(E)
Biotechnology — Biobanking — General requirements for
the validation and verification of processing methods for
biological material in biobanks
1 Scope

This document specifies the validation and verification requirements applicable to a biobank to be able

to demonstrate that it operates its processing of biological materials with validated and/or verified

methods that are fit for purpose.

This document is intended for use in the implementation and validation of processing methods for

biological materials.

This document covers method validation and verification for the production of all biological materials.

This document does not apply to biological material intended for food/feed production, laboratories

undertaking food/feed analysis, and/or therapeutic use.

Reference material production is not covered in this document. For the production requirements for

reference materials, see ISO 17034.
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 20387, Biotechnology — Biobanking — General requirements for biobanking
3 Terms and definitions

For the purposes of this document, the terms and definitions given in ISO 20387 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 http:// www .electropedia .org/
3.1
aliquot

portion of a quantity of biological material which has been divided into separate parts at the same time

under identical conditions

Note 1 to entry: The aliquot is representative of the biological material with respect to the property or properties

being investigated.

Note 2 to entry: The term aliquot most commonly refers to liquid or semi-liquid biological materials.

3.2
biobank laboratory

processing (3.15) laboratory under the control of a biobank where processing methods (3.16) are

performed for the output/production of biological materials
© ISO 2020 – All rights reserved 1
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ISO 21899:2020(E)
3.3
exploratory processing method

processing method (3.16) or adaptation/modification of a processing method, at an early stage of

development by the biobank laboratory (3.2) and for which further assessment is needed to determine if

it is useful for a specified application
3.4
external provider

body that undertakes aspects of the collection, transportation, preparation (3.14), handling,

homogeneity (3.7) and stability (3.21) assessment, testing or storage of the biological materials under

its own management system, on behalf of the biobank, on a contractual basis, or in the context of the

validation (3.25) of a processing method (3.16)
Note 1 to entry: A body can be an organization or a company, public or private.
3.5
feasibility

assessment of whether the processing method (3.16) can be applied to produce the desired type of

biological material output, independently from the properties of interest of this output biological

material
3.6
fit for purpose
fitness for the intended purpose
in-line with prearranged requirements for an intended use

Note 1 to entry: The definition of such requirements can take place within the biobank itself and/or in

collaboration with users and should consider analytical and other relevant criteria.

Note 2 to entry: These requirements correspond to the feasibility (3.5) of the downstream intended use and the

satisfaction of predefined performance (3.12) criteria of the intended use.
[SOURCE: ISO 20387:2018, 3.24, modified — Note 2 to entry has been added.]
3.7
homogeneity

uniformity of a specified, quantitative or qualitative, property value throughout a defined portion [or

among different aliquots (3.1)] of a biological material
3.8
installation qualification

process of establishing by objective evidence that all key aspects of the process equipment and ancillary

system installation comply with the approved specification
[SOURCE: ISO 11139:2018, 3.220.2]
3.9
measurand
quantity intended to be measured

[SOURCE: ISO/IEC Guide 99:2007, 2.3, modified — Notes to entry and examples were deleted.]

3.10
measurement

process of experimentally obtaining one or more quantity values that can reasonably be attributed to a

quantity
Note 1 to entry: Measurement does not apply to nominal properties.

Note 2 to entry: Measurement implies comparison of quantities or counting of entities.

2 © ISO 2020 – All rights reserved
---------------------- Page: 7 ----------------------
ISO 21899:2020(E)

Note 3 to entry: Measurement presupposes a description of the quantity commensurate with the intended use of

a measurement result, a measurement procedure, and a calibrated measuring system operating according to the

specified measurement procedure, including the measurement conditions
[SOURCE: ISO/IEC Guide 99:2007, 2.1]
3.11
operational qualification

process of obtaining and documenting evidence that installed equipment operates within predetermined

limits when used in accordance with its operational procedures
[SOURCE: ISO 11139:2018, 3.220.3]
3.12
performance

set of properties of interest of a biological material, produced by a processing method (3.16), e.g. yield,

purity, integrity, viability, functionality
3.13
performance qualification

process of establishing by objective evidence that the process, under anticipated conditions, consistently

produces a product which meets all predetermined requirements
[SOURCE: ISO 11139:2018, 3.220.4]
3.14
preparation

activities, taking place in a laboratory after acquisitioning, to make biological material ready for further

use in the life cycle, storage or distribution

Note 1 to entry: These activities can include, e.g. determination of volume or weight, centrifugation,

homogenization, purification, isolation, fixation, stabilization, filtration, sorting, culture, vacuum drying, freeze

drying, fractionation, aliquoting, removing tissues, cutting / milling / shaping, washing / soaking with antibiotic

or antimicrobial solutions, volume reduction / concentration, demineralization, glycerolisation, sterilization,

controlled or uncontrolled freezing, vitrification, cryopreservation.

[SOURCE: ISO 20387:2018, 3.37, modified — Note 1 to entry was modified by adding more details.]

3.15
processing

performing any activity on biological material and associated data during all stages of the life cycle

[SOURCE: ISO 20387:2018, 3.36]
3.16
processing method

procedure, applied to biological material and/or associated data during processing (3.15), with potential

to impact the intrinsic properties of the biological material and/or associated data produced as output

Note 1 to entry: A processing method can include, but is not limited to, activities belonging to: collection,

preparation (3.14), preservation, storage.

Note 2 to entry: The whole or part of a processing method can be a standard method.

Note 3 to entry: The term “standard” in this instance refers to the broader definition of “standard” — i.e., an

agreed-upon set of requirements.

Note 4 to entry: A simple processing method is a processing method that requires a simple laboratory

manipulation (e.g. centrifugation of collection tubes or mechanical disruption of tissues) without the addition of

chemical substances by the biobank laboratory (3.2) operator, and without cell disruption or cell selection as part

of a multi-step process (e.g. preparation of plasma, serum, buffy coat).
© ISO 2020 – All rights reserved 3
---------------------- Page: 8 ----------------------
ISO 21899:2020(E)

Note 5 to entry: A complex processing method is a processing method that requires usage of multiple steps and/

or addition of chemical substances by the biobank laboratory operator (e.g. preparation of DNA, RNA, proteins,

nuclei and other organelles, cell lines).

Note 6 to entry: Qualitative or quantitative tests for the examination of properties/quality/quantity attributes of

the produced biological material are outside of the scope of the “processing method” itself. However, a qualitative

or quantitative test can be part of a “processing method” if it is necessary as an “in-process control” step during

the processing method.
[SOURCE: ISO 20387:2018, 3.38, modified — The notes to entry were added.]
3.17
proficiency testing

evaluation of participant performance (3.12) against pre-established criteria by means of interlaboratory

comparisons
[SOURCE: ISO/IEC 17043:2010, 3.7, modified — Notes to entry have been deleted.]
3.18
property of interest

physical, chemical, biological, or microbiological property or characteristic that describes or is an

indicator of quality
3.19
reproducibility

coefficient of variation (CV %) of a property value being measured in biological

materials which are the processing (3.15) output from aliquots (3.1) of the same input biological material

(e.g. volume, weight, concentration)

Note 1 to entry: The reproducibility of a processing method (3.16) includes components arising from the processing

method itself and from the analytical uncertainty of the testing method used to assess the reproducibility.

Note 2 to entry: In general, for a given set of information, it is understood that the reproducibility of a processing

method is associated with a stated measurand (3.9). A modification of this measurand and the testing method

results in a modification of the associated reproducibility.
3.20
robustness

capacity of a processing method (3.16) to produce biological materials whose

properties remain within defined limits despite deviations from the experimental conditions that are

described in the standard operating procedure (SOP) (3.22) of the processing method

3.21
stability

ability of a biological material, when stored under specified conditions, to maintain a specified property

value within specified limits for a specified period of time

[SOURCE: ISO Guide 30:2015, 2.1.15, modified — The words “reference material” have been replaced by

“biological material" and Note 1 to entry has been deleted.]
3.22
standard operating procedure
SOP

written procedure prescribed for repetitive use as a practice, in accordance with agreed-upon

specifications aimed at obtaining a desired outcome
4 © ISO 2020 – All rights reserved
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ISO 21899:2020(E)
3.23
standard processing method

method officially accepted and recognized described in unambiguous details and validated for a

stated purpose

Note 1 to entry: Standard processing methods include e.g. methods published by a standardization body or

approved by regulatory authorities or published in peer-reviewed scientific literature, dedicated, at least partly,

to the validation (3.25) of the method.

Note 2 to entry: The term “standard” in this instance refers to the broader definition of “standard”—i.e., an

agreed-upon set of requirements.
3.24
stress

intentional exposure of biological material to conditions that are different from the predefined routine

conditions or procedures and that can affect the properties of the biological material

3.25
validation

confirmation, through the provision of objective evidence, that the requirements for a specific intended

use or application have been fulfilled

Note 1 to entry: The objective evidence needed for a validation is the result of a test or other form of determination

such as performing alternative calculations or reviewing documents.

Note 2 to entry: The word "validated" is used to designate the corresponding status.

Note 3 to entry: The use conditions for validation can be real or simulated.

Note 4 to entry: Validation is the confirmation that the specifications announced by the biobank laboratory (3.2)

are met.
[SOURCE: ISO 9000:2015, 3.8.13, modified — Note 4 to entry was added.]
3.26
verification

confirmation, through the provision of objective evidence, that specified requirements have been

fulfilled

Note 1 to entry: Verification is the confirmation that the specifications announced by a supplier, a publication or

another external source are met.

Note 2 to entry: The objective evidence needed for a verification can be the result of an inspection or of other

forms of determination such as performing alternative calculations or reviewing documents.

Note 3 to entry: The activities carried out for verification are sometimes called a qualification process.

Note 4 to entry: The word “verified” is used to designate the corresponding status.

[SOURCE: ISO 9000:2015, 3.8.12, modified — Note 1 to entry was added.]
4 Abbreviated terms
Abbreviated term Explanation
CPT cell preparation tube
CV coefficient of variation
Hly hemolysin
n number of samples
M mean square
OD optical density
© ISO 2020 – All rights reserved 5
---------------------- Page: 10 ----------------------
ISO 21899:2020(E)
Abbreviated term Explanation
PBMC peripheral blood mononuclear cells
PCA principal component analysis
RT room temperature
u variance
S standard deviation
SOP standard operating procedure
5 General and resource requirements

The biobank shall establish, implement and maintain a documented quality management system. (See

e.g. ISO 9001 or ISO 20387:2018, Clause 8.)

Requirements relative to personnel, infrastructure and environmental conditions, and processing

equipment are described in ISO 20387 and shall be followed.
6 Selection of processing methods

6.1 The methods for processing of biological materials shall meet the specified requirements for the

intended use and/or the needs of the customer (depositor or recipient). When the intended use is not

known beforehand, the biobank laboratory shall define a perimeter of intended uses (e.g. DNA-based tests).

6.1.1 When the customer (depositor or recipient) does not specify the processing method to be used,

the biobank laboratory shall select processing methods that have been published either in international,

regional or national standards, or by reputable technical organizations, or in relevant scientific texts or

journals, or as specified by the manufacturer of the equipment / commercial kit, and that are deemed fit

for purpose.

6.1.2 The biobank laboratory shall ensure that it uses the latest valid edition of a standard and/or

user manual, unless it is not appropriate or feasible to do so. Whenever necessary, the standard shall be

supplemented with additional details to ensure consistent application.

6.2 Biobank laboratory-developed methods or methods adopted by the biobank laboratory can also

be used if they are appropriate for the intended use and are validated. The customer shall be informed,

upon their request, as to the specifications of the method chosen, which constitute critical elements of

the method, and as to the scope of its validation by the biobank laboratory.

When a customer requests implementation of an exploratory processing method, or the implementation

of a method of processing for rare biological material types, the customer can accept that the method

is not validated or that the method is validated using surrogate materials. Such acceptance shall be

documented. If any report based on an exploratory processing method or methods that otherwise lack

conclusive validation evidence is issued by the biobank, the lack of assurance of its fitness for purpose

and the acceptance of the processing method by the client shall be stated.

6.3 The biobank shall inform the customer when the method proposed by the customer is considered

to be inappropriate for the intended use or out of date.

6.4 A description and the performance specifications of the selected processing methods shall be

documented.
6 © ISO 2020 – All rights reserved
---------------------- Page: 11 -
...

FINAL
INTERNATIONAL ISO/FDIS
DRAFT
STANDARD 21899
ISO/TC 276
Biotechnology — Biobanking —
Secretariat: DIN
General requirements for the
Voting begins on:
2020­03­10 validation and verification of
processing methods for biological
Voting terminates on:
2020­05­05
material in biobanks
Biotechnologie — Biobanques — Exigences générales pour la
validation et la vérification des méthodes de traitement du matériel
biologique dans les biobanques
RECIPIENTS OF THIS DRAFT ARE INVITED TO
SUBMIT, WITH THEIR COMMENTS, NOTIFICATION
OF ANY RELEVANT PATENT RIGHTS OF WHICH
THEY ARE AWARE AND TO PROVIDE SUPPOR TING
DOCUMENTATION.
IN ADDITION TO THEIR EVALUATION AS
Reference number
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO­
ISO/FDIS 21899:2020(E)
LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
OCCASION HAVE TO BE CONSIDERED IN THE
LIGHT OF THEIR POTENTIAL TO BECOME STAN­
DARDS TO WHICH REFERENCE MAY BE MADE IN
NATIONAL REGULATIONS. ISO 2020
---------------------- Page: 1 ----------------------
ISO/FDIS 21899:2020(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2020

All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may

be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting

on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address

below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH­1214 Vernier, Geneva
Phone: +41 22 749 01 11
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
---------------------- Page: 2 ----------------------
ISO/FDIS 21899:2020(E)
Contents Page

Foreword ........................................................................................................................................................................................................................................iv

Introduction ..................................................................................................................................................................................................................................v

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 1

4 Abbreviations........................................................................................................................................................................................................... 5

5 General and resource requirements ................................................................................................................................................ 6

6 Selection of processing methods ......................................................................................................................................................... 6

7 Processing method implementation ............................................................................................................................................... 7

7.1 Targets for method implementation .................................................................................................................................... 7

7.2 Processing method implementation .................................................................................................................................... 7

8 Initial validation of a processing method ................................................................................................................................... 7

8.1 General ........................................................................................................................................................................................................... 7

8.2 Validation plan ........................................................................................................................................................................................ 8

8.3 Assays for properties of interest .............................................................................................................................................. 8

8.4 Validation execution ........................................................................................................................................................................... 9

8.4.1 General...................................................................................................................................................................................... 9

8.4.2 Validation site ..................................................................................................................................................................... 9

8.4.3 In­house or outsourced testing ........................................................................................................................... 9

8.5 Targets for processing method validation ....................................................................................................................10

8.5.1 General...................................................................................................................................................................................10

8.5.2 Fitness for purpose .....................................................................................................................................................10

8.5.3 Reproducibility ...............................................................................................................................................................10

8.5.4 Robustness .........................................................................................................................................................................10

8.5.5 Homogeneity ....................................................................................................................................................................11

8.5.6 Stability .................................................................................................................................................................................11

8.6 Review and approval of validation report ....................................................................................................................12

9 Further validation ............................................................................................................................................................................................12

10 Method verification ........................................................................................................................................................................................12

11 Ongoing monitoring of a processing method.......................................................................................................................13

11.1 General ........................................................................................................................................................................................................13

11.2 Frequency of the monitoring ...................................................................................................................................................13

11.3 Planning .....................................................................................................................................................................................................14

11.4 Procedure of the systematic monitoring .......................................................................................................................14

11.5 Procedure of the periodic monitoring .............................................................................................................................14

11.6 External quality assessments (EQA)/Interlaboratory exercises ..............................................................15

12 Record keeping and archiving .............................................................................................................................................................15

Annex A (informative) Processing and testing methods ...............................................................................................................16

Annex B (informative) Examples of validation plans .......................................................................................................................17

Bibliography .............................................................................................................................................................................................................................20

© ISO 2020 – All rights reserved iii
---------------------- Page: 3 ----------------------
ISO/FDIS 21899:2020(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 non­governmental, 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 276, Biotechnology.

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 2020 – All rights reserved
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ISO/FDIS 21899:2020(E)
Introduction

Biobanks, producing viable and non­viable biological materials (human, animal, plant, microbial) for

research purposes, within biotechnology, use processing methods. Many biobanks include processing

laboratories where processing methods are performed and biological materials are produced as an

output. Examples of widely used processing methods, applied by biobank laboratories, include DNA,

RNA and protein extractions from blood, tissue, seeds, bacteria, or other biological material, or primary

cell cultures. An example for the validation of a processing method is provided in Reference [27].

Biobank laboratories are not always equipped to perform testing methods, which are required for

annotation or qualification of the biological material output.

This document sets out specific requirements for validation of processing methods. It is intended to

help biobank laboratories who perform processing of biological materials, whether they perform

themselves testing activities on the biological materials they have produced, or not. It enables validation

of processing methods, complements the quality management system of any biobank laboratory

performing processing of biological materials and gives more credibility to such an organization. It

is understood that while the term “method” used in ISO/IEC 17025 corresponds to “testing method”

or “calibration method”, a fundamental distinction exists between “processing methods” where the

output is a biological material and “testing methods” where the output is a test result (see Annex A). It

is understood that validation of processing methods performed by accredited testing laboratories, who

test the biological material output themselves, is already included in their accreditation scope.

Validation of a processing method encompasses confirmation of the fitness for purpose of the output

biological material, assessment of the homogeneity and stability of the biological material, and

assessment of the reproducibility and robustness of the processing method. This validation requires

testing in order to assess/measure the qualitative or quantitative properties of the biological material.

This testing will lead to the assessment of the fitness for purpose, the reproducibility, and the robustness

of the processing method. Examples of such properties are: viability, purity, pluripotency, molecular

integrity, concentration, growth capacity, etc.
© ISO 2020 – All rights reserved v
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FINAL DRAFT INTERNATIONAL STANDARD ISO/FDIS 21899:2020(E)
Biotechnology — Biobanking — General requirements for
the validation and verification of processing methods for
biological material in biobanks
1 Scope

This document specifies the validation and verification requirements applicable to a biobank to be able

to demonstrate that it operates its processing of biological materials with validated and/or verified

methods that are fit for purpose.

This document is intended for use in the implementation and validation of processing methods for

biological materials.

This document covers method validation and verification for the production of all biological materials.

This document does not apply to biological material intended for food/feed production, laboratories

undertaking food/feed analysis, and/or therapeutic use.

Reference material production is not covered in this document. For the production requirements for

reference materials, see ISO 17034.
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 20387, Biotechnology — Biobanking — General requirements for biobanking
3 Terms and definitions

For the purposes of this document, the terms and definitions given in ISO 20387 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 http:// www .electropedia .org/
3.1
aliquot

portion of a quantity of biological material which has been divided into separate parts at the same time

under identical conditions

Note 1 to entry: The aliquot is representative of the biological material with respect to the property or properties

being investigated.

Note 2 to entry: The term aliquot most commonly refers to liquid or semi-liquid biological materials.

3.2
biobank laboratory

processing (3.15) laboratory under the control of a biobank where processing methods (3.16) are

performed for the output/production of biological materials
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ISO/FDIS 21899:2020(E)
3.3
exploratory processing method

processing method (3.16) or adaptation/modification of a processing method, at an early stage of

development by the biobank laboratory (3.2) and for which further assessment is needed to determine if

it is useful for a specified application
3.4
external provider

body that undertakes aspects of the collection, transportation, preparation (3.14), handling,

homogeneity (3.7) and stability (3.21) assessment, testing or storage of the biological materials under

its own management system, on behalf of the biobank, on a contractual basis, or in the context of the

validation (3.25) of a processing method (3.16)
Note 1 to entry: A body can be an organization or a company, public or private.
3.5
feasibility

assessment of whether the processing method (3.16) can be applied to produce the desired type of

biological material output, independently from the properties of interest of this output biological

material
3.6
fit for purpose
fitness for the intended purpose
in-line with prearranged requirements for an intended use

Note 1 to entry: The definition of such requirements can take place within the biobank itself and/or in

collaboration with users and should consider analytical and other relevant criteria.

Note 2 to entry: These requirements correspond to the feasibility (3.5) of the downstream intended use and the

satisfaction of predefined performance (3.12) criteria of the intended use.
[SOURCE: ISO 20387:2018, 3.24, modified — Note 2 to entry has been added.]
3.7
homogeneity

uniformity of a specified, quantitative or qualitative, property value throughout a defined portion [or

among different aliquots (3.1)] of a biological material
3.8
installation qualification

process of establishing by objective evidence that all key aspects of the process equipment and ancillary

system installation comply with the approved specification
[SOURCE: ISO 11139:2018, 3.220.2]
3.9
measurand
quantity intended to be measured

[SOURCE: ISO/IEC Guide 99:2007, 2.3, modified — Notes to entry and examples were deleted.]

3.10
measurement

process of experimentally obtaining one or more quantity values that can reasonably be attributed to a

quantity
Note 1 to entry: Measurement does not apply to nominal properties.

Note 2 to entry: Measurement implies comparison of quantities or counting of entities.

2 © ISO 2020 – All rights reserved
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ISO/FDIS 21899:2020(E)

Note 3 to entry: Measurement presupposes a description of the quantity commensurate with the intended use of

a measurement result, a measurement procedure, and a calibrated measuring system operating according to the

specified measurement procedure, including the measurement conditions
[SOURCE: ISO/IEC Guide 99:2007, 2.1]
3.11
operational qualification

process of obtaining and documenting evidence that installed equipment operates within predetermined

limits when used in accordance with its operational procedures
[SOURCE: ISO 11139:2018, 3.220.3]
3.12
performance

set of properties of interest of a biological material, produced by a processing method (3.16), e.g. yield,

purity, integrity, viability, functionality
3.13
performance qualification

process of establishing by objective evidence that the process, under anticipated conditions, consistently

produces a product which meets all predetermined requirements
[SOURCE: ISO 11139:2018, 3.220.4]
3.14
preparation

activities, taking place in a laboratory after acquisitioning, to make biological material ready for further

use in the life cycle, storage or distribution

Note 1 to entry: These activities can include, e.g. determination of volume or weight, centrifugation,

homogenization, purification, isolation, fixation, stabilization, filtration, sorting, culture, vacuum drying, freeze

drying, fractionation, aliquoting, removing tissues, cutting / milling / shaping, washing / soaking with antibiotic

or antimicrobial solutions, volume reduction / concentration, demineralization, glycerolisation, sterilization,

controlled or uncontrolled freezing, vitrification, cryopreservation.

[SOURCE: ISO 20387:2018, 3.37, modified — Note 1 to entry was modified by adding more details.]

3.15
processing

performing any activity on biological material and associated data during all stages of the life cycle

[SOURCE: ISO 20387:2018, 3.36]
3.16
processing method

procedure, applied to biological material and/or associated data during processing (3.15), with potential

to impact the intrinsic properties of the biological material and/or associated data produced as output

Note 1 to entry: A processing method can include, but is not limited to, activities belonging to: collection,

preparation (3.14), preservation, storage.

Note 2 to entry: The whole or part of a processing method can be a standard method.

Note 3 to entry: The term “standard” in this instance refers to the broader definition of “standard” — i.e., an

agreed-upon set of requirements.

Note 4 to entry: A simple processing method is a processing method that requires a simple laboratory

manipulation (e.g. centrifugation of collection tubes or mechanical disruption of tissues) without the addition of

chemical substances by the biobank laboratory (3.2) operator, and without cell disruption or cell selection as part

of a multi-step process (e.g. preparation of plasma, serum, buffy coat).
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ISO/FDIS 21899:2020(E)

Note 5 to entry: A complex processing method is a processing method that requires usage of multiple steps and/

or addition of chemical substances by the biobank laboratory operator (e.g. preparation of DNA, RNA, proteins,

nuclei and other organelles, cell lines).

Note 6 to entry: Qualitative or quantitative tests for the examination of properties/quality/quantity attributes of

the produced biological material are outside of the scope of the “processing method” itself. However, a qualitative

or quantitative test can be part of a “processing method” if it is necessary as an “in-process control” step during

the processing method.
[SOURCE: ISO 20387:2018, 3.38, modified — The notes to entry were added.]
3.17
proficiency testing

evaluation of participant performance (3.12) against pre-established criteria by means of interlaboratory

comparisons
[SOURCE: ISO/IEC 17043:2010, 3.7, modified — Notes to entry have been deleted.]
3.18
property of interest

physical, chemical, biological, or microbiological property or characteristic that describes or is an

indicator of quality
3.19
reproducibility

coefficient of variation (CV %) of a property value being measured in biological

materials which are the processing (3.15) output from aliquots (3.1) of the same input biological material

(e.g. volume, weight, concentration)

Note 1 to entry: The reproducibility of a processing method (3.16) includes components arising from the processing

method itself and from the analytical uncertainty of the testing method used to assess the reproducibility.

Note 2 to entry: In general, for a given set of information, it is understood that the reproducibility of a processing

method is associated with a stated measurand (3.9). A modification of this measurand and the testing method

results in a modification of the associated reproducibility.
3.20
robustness

capacity of a processing method (3.16) to produce biological materials whose

properties remain within defined limits despite deviations from the experimental conditions that are

described in the standard operating procedure (SOP) (3.22) of the processing method

3.21
stability

ability of a biological material, when stored under specified conditions, to maintain a specified property

value within specified limits for a specified period of time

[SOURCE: ISO Guide 30:2015, 2.1.15, modified — The words “reference material” have been replaced by

“biological material" and Note 1 to entry has been deleted.]
3.22
standard operating procedure
SOP

written procedure prescribed for repetitive use as a practice, in accordance with agreed­upon

specifications aimed at obtaining a desired outcome
4 © ISO 2020 – All rights reserved
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ISO/FDIS 21899:2020(E)
3.23
standard processing method

method officially accepted and recognized described in unambiguous details and validated for a

stated purpose

Note 1 to entry: Note to entry 1: Standard processing methods include e.g. methods published by a standardization

body or approved by regulatory authorities or published in peer-reviewed scientific literature, dedicated, at least

partly, to the validation (3.25) of the method.

Note 2 to entry: Note to entry 2: The term “standard” in this instance refers to the broader definition of

“standard”—i.e., an agreed-upon set of requirements.
3.24
stress

intentional exposure of biological material to conditions that are different from the predefined routine

conditions or procedures and that can affect the properties of the biological material

3.25
validation

confirmation, through the provision of objective evidence, that the requirements for a specific intended

use or application have been fulfilled

Note 1 to entry: The objective evidence needed for a validation is the result of a test or other form of determination

such as performing alternative calculations or reviewing documents.

Note 2 to entry: The word "validated" is used to designate the corresponding status.

Note 3 to entry: The use conditions for validation can be real or simulated.

Note 4 to entry: Validation is the confirmation that the specifications announced by the biobank laboratory (3.2)

are met.
[SOURCE: ISO 9000:2015, 3.8.13, modified — Note 4 to entry was added.]
3.26
verification

confirmation, through the provision of objective evidence, that specified requirements have been

fulfilled

Note 1 to entry: Verification is the confirmation that the specifications announced by a supplier, a publication or

another external source are met.

Note 2 to entry: The objective evidence needed for a verification can be the result of an inspection or of other

forms of determination such as performing alternative calculations or reviewing documents.

Note 3 to entry: The activities carried out for verification are sometimes called a qualification process.

Note 4 to entry: The word “verified” is used to designate the corresponding status.

[SOURCE: ISO 9000:2015, 3.8.12, modified — Note 1 to entry was added.]
4 Abbreviations
Abbreviation Explanation
CPT cell preparation tube
CV coefficient of variation
Hly hemolysin
n number of samples
M mean square
OD optical density
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ISO/FDIS 21899:2020(E)
Abbreviation Explanation
PBMC peripheral blood mononuclear cells
PCA principal component analysis
RT room temperature
u variance
S standard deviation
SOP standard operating procedure
5 General and resource requirements

The biobank shall establish, implement and maintain a documented quality management system. (See

e.g. ISO 9001 or ISO 20387:2018, Clause 8.)

Requirements relative to personnel, infrastructure and environmental conditions, and processing

equipment are described in ISO 20387 and shall be followed.
6 Selection of processing methods

6.1 The methods for processing of biological materials shall meet the specified requirements for the

intended use and/or the needs of the customer (depositor or recipient). When the intended use is not

known beforehand, the biobank laboratory shall define a perimeter of intended uses (e.g. DNA-based tests).

6.1.1 When the customer (depositor or recipient) does not specify the processing method to be used,

the biobank laboratory shall select processing methods that have been published either in international,

regional or national standards, or by reputable technical organizations, or in relevant scientific texts or

journals, or as specified by the manufacturer of the equipment / commercial kit, and that are deemed fit

for purpose.

6.1.2 The biobank laboratory shall ensure that it uses the latest valid edition of a standard and/or

user manual, unless it is not appropriate or feasible to do so. Whenever necessary, the standard shall be

supplemented with additional details to ensure consistent application.

6.2 Biobank laboratory-developed methods or methods adopted by the biobank laboratory can also

be used if they are appropriate for the intended use and are validated. The customer shall be informed,

upon their request, as to the specifications of the method chosen, which constitute critical elements of

the method, and as to the scope of its validation by the biobank laboratory.

When a customer requests implementation of an exploratory processing method, or the implementation

of a method of processing for rare biological material types, the customer can accept that the method

is not validated or that the method is validated using sur
...

NORME ISO
INTERNATIONALE 21899
Première édition
2020-06
Biotechnologie — Biobanques —
Exigences générales pour la validation
et la vérification des méthodes de
traitement du matériel biologique
dans les biobanques
Biotechnology — Biobanking — General requirements for the
validation and verification of processing methods for biological
material in biobanks
Numéro de référence
ISO 21899:2020(F)
ISO 2020
---------------------- Page: 1 ----------------------
ISO 21899:2020(F)
DOCUMENT PROTÉGÉ PAR COPYRIGHT
© ISO 2020

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ii © ISO 2020 – Tous droits réservés
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ISO 21899:2020(F)
Sommaire Page

Avant-propos ..............................................................................................................................................................................................................................iv

Introduction ..................................................................................................................................................................................................................................v

1 Domaine d’application ................................................................................................................................................................................... 1

2 Références normatives ................................................................................................................................................................................... 1

3 Termes et définitions ....................................................................................................................................................................................... 1

4 Termes abrégés ...................................................................................................................................................................................................... 6

5 Généralités et exigences relatives aux ressources ............................................................................................................ 6

6 Sélection des méthodes de traitement .......................................................................................................................................... 6

7 Mise en place d’une méthode de traitement ........................................................................................................................... 7

7.1 Objectifs de la mise en place d’une méthode ................................................................................................................ 7

7.2 Mise en place d’une méthode de traitement ................................................................................................................. 7

8 Validation initiale d’une méthode de traitement ............................................................................................................... 8

8.1 Généralités .................................................................................................................................................................................................. 8

8.2 Plan de validation ................................................................................................................................................................................. 8

8.3 Analyses des propriétés d’intérêt ........................................................................................................................................... 9

8.4 Exécution de la validation ............................................................................................................................................................. 9

8.4.1 Généralités ............................................................................................................................................................................ 9

8.4.2 Site de validation ............................................................................................................................................................. 9

8.4.3 Essais internes ou externalisés ........................................................................................................................... 9

8.5 Objectifs de la validation d’une méthode de traitement ..................................................................................10

8.5.1 Généralités .........................................................................................................................................................................10

8.5.2 Adéquation à l’usage prévu .................................................................................................................................10

8.5.3 Reproductibilité .............................................................................................................................................................11

8.5.4 Robustesse .........................................................................................................................................................................11

8.5.5 Homogénéité ....................................................................................................................................................................12

8.5.6 Stabilité .................................................................................................................................................................................12

8.6 Revue et approbation du rapport de validation ......................................................................................................13

9 Validation plus approfondie ..................................................................................................................................................................13

10 Vérification de la méthode ......................................................................................................................................................................13

11 Surveillance continue d’une méthode de traitement ..................................................................................................14

11.1 Généralités ...............................................................................................................................................................................................14

11.2 Fréquence de la surveillance ......... ...........................................................................................................................................14

11.3 Planification ............................................................................................................................................................................................15

11.4 Procédure de surveillance systématique.......................................................................................................................15

11.5 Procédure de surveillance périodique.............................................................................................................................15

11.6 Évaluations externes de la qualité (EQA)/exercices interlaboratoires ...............................................16

12 Conservation des enregistrements et archivage ..............................................................................................................16

Annexe A (informative) Méthodes de traitement et d’essai ......................................................................................................17

Annexe B (informative) Exemples de plans de validation ...........................................................................................................18

Bibliographie ...........................................................................................................................................................................................................................21

© ISO 2020 – Tous droits réservés iii
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ISO 21899:2020(F)
Avant-propos

L'ISO (Organisation internationale de normalisation) est une fédération mondiale d'organismes

nationaux de normalisation (comités membres de l'ISO). L'élaboration des Normes internationales est

en général confiée aux comités techniques de l'ISO. Chaque comité membre intéressé par une étude

a le droit de faire partie du comité technique créé à cet effet. Les organisations internationales,

gouvernementales et non gouvernementales, en liaison avec l'ISO participent également aux travaux.

L'ISO collabore étroitement avec la Commission électrotechnique internationale (IEC) en ce qui

concerne la normalisation électrotechnique.

Les procédures utilisées pour élaborer le présent document et celles destinées à sa mise à jour sont

décrites dans les Directives ISO/IEC, Partie 1. Il convient, en particulier, de prendre note des différents

critères d'approbation requis pour les différents types de documents ISO. Le présent document a été

rédigé conformément aux règles de rédaction données dans les Directives ISO/IEC, Partie 2 (voir www

.iso .org/ directives).

L'attention est attirée sur le fait que certains des éléments du présent document peuvent faire l'objet de

droits de propriété intellectuelle ou de droits analogues. L'ISO ne saurait être tenue pour responsable

de ne pas avoir identifié de tels droits de propriété et averti de leur existence. Les détails concernant

les références aux droits de propriété intellectuelle ou autres droits analogues identifiés lors de

l'élaboration du document sont indiqués dans l'Introduction et/ou dans la liste des déclarations de

brevets reçues par l'ISO (voir www .iso .org/ brevets).

Les appellations commerciales éventuellement mentionnées dans le présent document sont données

pour information, par souci de commodité, à l’intention des utilisateurs et ne sauraient constituer un

engagement.

Pour une explication de la nature volontaire des normes, la signification des termes et expressions

spécifiques de l'ISO liés à l'évaluation de la conformité, ou pour toute information au sujet de l'adhésion

de l'ISO aux principes de l’Organisation mondiale du commerce (OMC) concernant les obstacles

techniques au commerce (OTC), voir www .iso .org/ avant -propos.

Le présent document a été élaboré par le comité technique ISO/TC 276, Biotechnologie.

Il convient que l’utilisateur adresse tout retour d’information ou toute question concernant le présent

document à l’organisme national de normalisation de son pays. Une liste exhaustive desdits organismes

se trouve à l’adresse www .iso .org/ fr/ members .html.
iv © ISO 2020 – Tous droits réservés
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ISO 21899:2020(F)
Introduction

Les biobanques, qui gèrent des matériels biologiques viables et non viables (d’origine humaine, animale,

végétale, microbienne) pour la recherche dans le cadre de la biotechnologie, utilisent des méthodes de

traitement. De nombreuses biobanques abritent des laboratoires de traitement qui mettent en œuvre

ces méthodes de traitement et qui produisent des matériels biologiques en sortie. Comme exemples de

méthodes de traitement largement utilisées, appliquées par les laboratoires des biobanques, on peut

citer l’extraction d’ADN, d’ARN et de protéines à partir du sang, des tissus, des semences, des bactéries

ou d’autres matériels biologiques, ou les cultures de cellules primaires. Un exemple de validation d’une

méthode de traitement est fourni dans la Référence [27]. Les laboratoires des biobanques ne sont

pas toujours équipés pour mettre en œuvre les méthodes d’essai nécessaires à l’annotation ou à la

qualification des matériels biologiques obtenus.

Le présent document définit les exigences spécifiques relatives à la validation des méthodes de

traitement. Il est destiné à aider les laboratoires des biobanques qui effectuent le traitement de

matériels biologiques, qu’ils effectuent ou non eux-mêmes les activités d’essai des matériels biologiques

qu’ils ont produits. Il permet de réaliser la validation des méthodes de traitement et de compléter

le système de management de la qualité de tout laboratoire de biobanque effectuant le traitement

de matériels biologiques, donnant ainsi plus de crédibilité à cette organisation. Il est entendu que si

le terme « méthode » utilisé dans l’ISO/IEC 17025 désigne une « méthode d’essai » ou une « méthode

d’étalonnage », il existe une distinction fondamentale entre les « méthodes de traitement », pour

lesquelles l’élément de sortie est un matériel biologique, et les « méthodes d’essai », pour lesquelles

l’élément de sortie est un résultat d’essai (voir l’Annexe A). Il est entendu que la validation des méthodes

de traitement mises en œuvre par les laboratoires d’essais accrédités, qui soumettent eux-mêmes à

essai les matériels biologiques obtenus, est déjà comprise dans leur domaine d’accréditation.

La validation d’une méthode de traitement comprend la confirmation de l’adéquation à l’usage prévu des

matériels biologiques obtenus, l’évaluation de l’homogénéité et de la stabilité des matériels biologiques

et l’évaluation de la reproductibilité et de la robustesse de la méthode de traitement. Cette validation

nécessite des essais visant à évaluer/mesurer les propriétés qualitatives ou quantitatives des matériels

biologiques. Ces essais permettront d’évaluer l’adéquation à l’usage prévu, la reproductibilité et la

robustesse de la méthode de traitement. Exemples de ces propriétés: viabilité, pureté, pluripotence,

intégrité moléculaire, concentration, capacité de croissance, etc.
© ISO 2020 – Tous droits réservés v
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NORME INTERNATIONALE ISO 21899:2020(F)
Biotechnologie — Biobanques — Exigences générales pour
la validation et la vérification des méthodes de traitement
du matériel biologique dans les biobanques
1 Domaine d’application

Le présent document spécifie les exigences de validation et de vérification applicables pour qu’une

biobanque puisse démontrer qu’elle réalise le traitement des matériels biologiques selon des méthodes

validées et/ou vérifiées qui sont adéquates à l’usage prévu.

Le présent document est destiné à être utilisé pour la mise en place et la validation des méthodes de

traitement des matériels biologiques.

Le présent document couvre la validation et la vérification des méthodes de production de tous les

matériels biologiques. Le présent document ne s’applique pas aux matériels biologiques destinés à la

production de denrées alimentaires/d’aliments pour animaux, aux laboratoires effectuant des analyses

de denrées alimentaires/d’aliments pour animaux et/ou à un usage thérapeutique.

La production de matériaux de référence n’est pas couverte par le présent document. Pour les exigences

liées à la production des matériaux de référence, voir l’ISO 17034.
2 Références normatives

Les documents suivants sont cités dans le texte de sorte qu’ils constituent, pour tout ou partie de leur

contenu, des exigences du présent document. Pour les références datées, seule l’édition citée s’applique.

Pour les références non datées, la dernière édition du document de référence s'applique (y compris les

éventuels amendements).

ISO 20387, Biotechnologie — «Biobanking» — Exigences générales relatives au «biobanking»

3 Termes et définitions

Pour les besoins du présent document, les termes et définitions donnés dans l’ISO 20387 ainsi que les

suivants, s’appliquent.

L’ISO et l’IEC tiennent à jour des bases de données terminologiques destinées à être utilisées en

normalisation, consultables aux adresses suivantes:

— ISO Online browsing platform: disponible à l’adresse https:// www .iso .org/ obp

— IEC Electropedia: disponible à l’adresse http:// www .electropedia .org/
3.1
aliquote

portion d’une quantité de matériel biologique qui a été divisée en plusieurs parties, en même temps,

dans des conditions identiques

Note 1 à l'article: L’aliquote est représentative du matériel biologique pour la ou les propriétés étudiées.

Note 2 à l'article: Le terme «aliquote» fait communément référence à des matériels biologiques liquides ou semi-

liquides.
© ISO 2020 – Tous droits réservés 1
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ISO 21899:2020(F)
3.2
laboratoire d’une biobanque

laboratoire de traitement (3.15) sous le contrôle d’une biobanque, dans lequel des méthodes de traitement

(3.16) sont mises en œuvre pour obtenir/produire des matériels biologiques
3.3
méthode de traitement exploratoire

méthode de traitement (3.16) ou adaptation/modification d’une méthode de traitement, qui en est à un

stade précoce de développement par le laboratoire de la biobanque (3.2) et pour laquelle une évaluation

plus approfondie est nécessaire afin de déterminer si elle est utile pour une application donnée

3.4
prestataire externe

entité qui entreprend des aspects du prélèvement, du transport, de la préparation (3.14), de la

manipulation, de l’évaluation de l’homogénéité (3.7) et de la stabilité (3.21), des essais ou du stockage

des matériels biologiques dans le périmètre de son propre système de management, au nom de la

biobanque, sur une base contractuelle, ou dans le contexte de la validation (3.25) d’une méthode de

traitement (3.16)

Note 1 à l'article: Une entité peut être une organisation ou une société, publique ou privée.

3.5
faisabilité

évaluation pour savoir si la méthode de traitement (3.16) peut être appliquée pour produire le type

souhaité de matériel biologique en sortie, indépendamment des propriétés d’intérêt de ce matériel

biologique
3.6
adapté à l’usage prévu
adéquation à l’usage prévu
conforme aux exigences préétablies pour un usage prévu

Note 1 à l'article: Ces exigences peuvent être établies dans le cadre de la biobanque elle-même et/ou en

collaboration avec les utilisateurs. Il convient qu’elles tiennent compte des critères d’analyse et autres critères

pertinents.

Note 2 à l'article: Ces exigences correspondent à la faisabilité (3.5) de l’usage prévu en aval et à la satisfaction de

critères de performance (3.12) prédéfinis pour l’usage prévu.
[SOURCE: ISO 20387:2018, 3.24, modifiée — Note 2 à l’article ajoutée]
3.7
homogénéité

uniformité d’une valeur de propriété quantitative ou qualitative spécifiée, dans une portion définie [ou

entre différentes aliquotes (3.1)] d’un matériel biologique
3.8
qualification de l’installation

processus visant à établir par des preuves objectives que tous les principaux aspects de l’installation de

l’équipement et du système auxiliaire du procédé sont conformes à la spécification approuvée

[SOURCE: ISO 11139:2018, 3.220.2]
3.9
mesurande
grandeur que l’on veut mesurer

[SOURCE: Guide ISO/IEC 99:2007, 2.3, modifiée — Notes à l’article et exemples supprimés]

2 © ISO 2020 – Tous droits réservés
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3.10
mesurage

processus consistant à obtenir expérimentalement une ou plusieurs valeurs que l’on peut

raisonnablement attribuer à une grandeur

Note 1 à l'article: Les mesurages ne s’appliquent pas aux propriétés qualitatives.

Note 2 à l'article: Un mesurage implique la comparaison de grandeurs ou le comptage d’entités.

Note 3 à l'article: Un mesurage suppose une description de la grandeur compatible avec l’usage prévu d’un

résultat de mesure, une procédure de mesure et un système de mesure étalonné fonctionnant selon la procédure

de mesure spécifiée, incluant les conditions de mesure.
[SOURCE: Guide ISO/IEC 99:2007, 2.1]
3.11
qualification opérationnelle

processus d’obtention de preuves documentées selon lesquelles l’équipement installé fonctionne dans

les limites prédéterminées, dans la mesure où il est utilisé conformément à son mode opératoire

[SOURCE: ISO 11139:2018, 3.220.3]
3.12
performance

ensemble des propriétés d’intérêt d’un matériel biologique, produit par une méthode de traitement

(3.16), par exemple rendement, pureté, intégrité, viabilité, fonctionnalité
3.13
qualification de performance

processus visant à établir par des preuves objectives que le procédé, dans les conditions anticipées,

produit de façon constante un produit conforme à toutes les exigences prédéterminées

[SOURCE: ISO 11139:2018, 3.220.4]
3.14
préparation

activités se déroulant dans un laboratoire après l’acquisition, visant à préparer des matériels biologiques

en vue d’une utilisation ultérieure au cours du cycle de vie, du stockage ou de la distribution

Note 1 à l'article: Ces activités peuvent inclure, par exemple, la détermination du volume ou du poids, la

centrifugation, l’homogénéisation, la purification, la séparation, la fixation, la stabilisation, la filtration, le tri, la

mise en culture, le séchage sous vide, la lyophilisation, le fractionnement, l’aliquotage, le prélèvement de tissus,

la découpe / le broyage / le modelage, le lavage / l’immersion ou l’humidification avec des solutions antibiotiques

ou antimicrobiennes, la réduction du volume / la concentration, la déminéralisation, la glycérolisation, la

stérilisation, la congélation contrôlée ou non contrôlée, la vitrification, la cryoconservation.

[SOURCE: ISO 20387:2018, 3.37, modifiée — Note 1 à l’article modifiée afin d’ajouter des informations

plus détaillées]
3.15
traitement

conduite de toute activité sur des matériels biologiques et les données associées à toutes les étapes du

cycle de vie
[SOURCE: ISO 20387:2018, 3.36]
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ISO 21899:2020(F)
3.16
méthode de traitement

procédure appliquée aux matériels biologiques et/ou aux données associées lors du traitement (3.15),

susceptible d’avoir une incidence sur les propriétés intrinsèques des matériels biologiques et/ou des

données associées produits en sortie

Note 1 à l'article: Une méthode de traitement peut comprendre, sans pour autant s’y limiter, des activités

appartenant aux domaines suivants: prélèvement, préparation (3.14), conservation, stockage.

Note 2 à l'article: La totalité ou une partie d’une méthode de traitement peut être une méthode normalisée.

Note 3 à l'article: Le terme «normalisée» dans cet exemple fait référence à la définition plus large de «norme» —

c’est-à-dire un ensemble d’exigences convenues.

Note 4 à l'article: Une méthode de traitement simple est une méthode de traitement qui nécessite une manipulation

simple en laboratoire (par exemple centrifugation de tubes de prélèvement ou broyage mécanique de tissus) sans

l’ajout de substances chimiques par le technicien de laboratoire de la biobanque (3.2) et sans lyse cellulaire ou

sélection de cellules au cours d’un processus multi-étapes (par exemple préparation du plasma, sérum, couche

leuco-plaquettaire).

Note 5 à l'article: Une méthode de traitement complexe est une méthode de traitement qui nécessite l’utilisation

de plusieurs étapes et/ou l’ajout de substances chimiques par le technicien de laboratoire de la biobanque (par

exemple préparation d’ADN, d’ARN, de protéines, de noyaux et autres organites, de lignées cellulaires).

Note 6 à l'article: Les essais qualitatifs ou quantitatifs pour l’examen des caractéristiques de propriétés/qualité/

quantité des matériels biologiques produits sont hors du domaine d’application de la «méthode de traitement»

proprement dite. Toutefois, un essai qualitatif ou quantitatif peut faire partie d’une «méthode de traitement»

s’il est nécessaire en tant qu’étape de «contrôle en cours de traitement» pendant la réalisation de la méthode de

traitement.
[SOURCE: ISO 20387:2018, 3.38, modifiée — Notes à l’article ajoutées]
3.17
essai d’aptitude

évaluation de la performance (3.12) d’un participant par rapport à des critères préétablis au moyen de

comparaisons interlaboratoires
[SOURCE: ISO/IEC 17043:2010, 3.7, modifiée — Notes à l’article supprimées]
3.18
propriété d’intérêt

propriété ou caractéristique physique, chimique, biologique ou microbiologique qui décrit la qualité ou

qui en est un indicateur
3.19
reproductibilité

coefficient de variation (CV en %) d’une valeur de propriété mesurée dans des

matériels biologiques qui constituent l’élément de sortie du traitement (3.15) d’aliquotes (3.1) provenant

du même matériel biologique d’entrée (par exemple volume, poids, concentration)

Note 1 à l'article: La reproductibilité d’une méthode de traitement (3.16) comprend des composantes provenant

de la méthode de traitement proprement dite et de l’incertitude analytique de la méthode d’essai utilisée pour

évaluer la reproductibilité.

Note 2 à l'article: En général, pour un ensemble donné d’informations, il est entendu que la reproductibilité d’une

méthode de traitement est associée à un mesurande (3.9) donné. Une modification de ce mesurande et de la

méthode d’essai entraîne une modification de la reproductibilité associée.
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3.20
robustesse

capacité d’une méthode de traitement (3.16) à produire des matériels

biologiques dont les propriétés restent dans des limites définies malgré les écarts par rapport aux

conditions expérimentales décrites dans la procédure opérationnelle normalisée (SOP) (3.22) de la

méthode de traitement
3.21
stabilité

capacité d’un matériel biologique, lorsqu’il est entreposé dans des conditions spécifiées, à conserver

une valeur de propriété donnée dans des limites spécifiées, pour une période de temps spécifiée

[SOURCE: Guide ISO 30:2015, 2.1.15, modifiée — Le terme « matériau de référence » a été remplacé

par « matériel biologique » et la Note 1 à l’article a été supprimée]
3.22
procédure opérationnelle normalisée
SOP

procédure écrite prescrite pour un usage répétitif en tant que pratique, conformément à des

spécifications convenues, visant à obtenir un résultat souhaité
3.23
méthode de traitement normalisée

méthode officiellement acceptée et reconnue, décrite en détail sans ambiguïté et validée pour un

objectif défini

Note 1 à l'article: Les méthodes de traitement normalisées comprennent, par exemple, les méthodes publiées

par un organisme de normalisation ou approuvées par les autorités réglementaires ou encore publiées dans la

littérature scientifique évaluée par des pairs, dédiées au moins partiellement à la validation (3.25) de la méthode.

Note 2 à l'article: Le terme «normalisée» dans cet exemple fait référence à la définition plus large de «norme» —

c’est-à-dire un ensemble d’exigences convenues.
3.24
contrainte

exposition intentionnelle d’un matériel biologique à des conditions qui diffèrent des conditions ou

procédures de routine prédéfinies et qui peuvent avoir un impact sur les propriétés du matériel

biologique
3.25
validation

confirmation par des preuves objectives que les exigences pour une utilisation spécifique ou une

application prévues ont été satisfaites

Note 1 à l'article: Les preuves objectives requises pour la validation peuvent être le résultat d’un essai ou d’une

autre forme de détermination, telle que la réalisation de calculs ou la revue de documents.

Note 2 à l'article: Le terme « validé » est utilisé pour désigner l’état correspondant.

Note 3 à l'article: Pour la validation, les conditions d’utilisation peuvent être réelles ou simulées.

Note 4 à l'article: La validation est la confirmation que les spécifications annoncées par le laboratoire de la

biobanque (3.2) sont respectées.
[SOURCE: ISO 9000:2015, 3.8.13, modifiée — Note 4 à l’article ajoutée]
3.26
vérification

confirmation par des preuves objectives que les exigences spécifiées ont été satisfaites

Note 1 à l'article: La vérification est la confirmation que les spécifications annoncées par un fournisseur, par une

publication ou par une autre source externe sont respectées.
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Note 2 à l'article: Les preuves objectives requises pour la vérification peuvent être le résultat d’un contrôle ou

d’autres formes de détermination, telles que la réalisation de calculs ou la revue de documents.

Note 3 à l'article: Les activités réalisées pour la vérification sont parfois appelées processus de qualification.

Note 4 à l'article: Le terme « vérifié » est utilisé pour désigner l’état correspondant.

[SOURCE: ISO 9000:2015, 3.8.12, modifiée — Note 1 à l’article ajoutée]
4 Termes abrégés
Terme abrégé Explication
CPT tube de préparation de cellules
CV coefficient de variation
Hly hémolysine
n nombre d’échantillons
M carré moyen
OD densité optique
PBMC cellules mononuclées de sang périphérique
PCA analyse en composantes principales
RT température ambiante
u variance
S écart-type
SOP procédure opérationnelle normalisée
5 Généralités et exigences relatives aux ressources

La biobanque doit établir, mettre en place et tenir à jour un système de management de la qualité

documenté. (Voir par exemple l’ISO 9001 ou l’ISO 20387:2018, Article 8.)

Les exigences relatives au personnel, à l’infrastructure et aux conditions environnementales, ainsi qu’au

...

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