ISO 20399:2022

INTERNATIONAL ISO
STANDARD 20399
First edition
2022-12
Biotechnology — Ancillary materials
present during the production of
cellular therapeutic products and
gene therapy products
Biotechnologie — Matériaux auxiliaires présents lors de la production
de produits thérapeutiques cellulaires et de produits de thérapie
génique
Reference number
© ISO 2022
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Published in Switzerland
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Contents Page
Foreword .v
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviated terms . 4
5 Strategy . 5
5.1 Key concepts on AM . 5
5.2 AM-related responsibilities . 5
5.3 Qualification considerations of AM . 6
5.4 Animal-derived components of AM . 7
5.4.1 General . 7
5.4.2 Key considerations in the use of animal-derived components . 7
5.4.3 Viral inactivation . 8
6 Evaluation criteria and risk mitigation for AM containing biological material .8
6.1 Evaluation criteria for AM selection . 8
6.2 Mitigation of risk . 10
6.2.1 Scientific approach . 10
6.2.2 Supplier audit and questionnaires . 11
6.2.3 Risk assessment .12
7 AM characteristics and quality attributes .12
7.1 AM components, identity and purity .12
7.1.1 General .12
7.1.2 Identity and quantity of component(s) . 13
7.1.3 Purity and impurity .13
7.1.4 Lot-to-lot consistency for AMs containing proprietary components .13
7.2 AM storage and stability . 14
7.2.1 General . 14
7.2.2 Stability and storage conditions . 14
8 AM manufacturing and biosafety . .15
8.1 Quality management system . 15
8.2 Manufacturing process . 16
8.3 Container and closure systems . 16
8.4 Animal and human-derived components . 16
8.5 Safety to cells and humans . 17
9 AM performance .17
9.1 General . 17
9.2 Quality and testing . 18
9.3 Qualification activity . 18
9.4 Performance assay . 19
9.5 Performance assay results . 19
10 AM documentation .19
10.1 General . 19
10.2 Reporting requirements . 20
10.3 Certificate of analysis . 21
10.4 Additional certificates .22
10.4.1 Certificate of origin .22
10.4.2 Certificate of compliance . 22
10.4.3 Certificate of irradiation . 22
11 Managing changes to components .22
iii
11.1 Impact of changes to components . 22
11.2 Measures for managing changes to components . 22
Annex A (informative) Decision chart of AMs .24
Annex B (informative) Example workflow from AM supplier to AM user .26
Annex C (informative) Information on AM and materials used to produce AMs .27
Annex D (informative) Considerations for the characterization of AMs .29
Annex E (informative) Quality declarations for manufactured biological materials used in
the manufacture of a cell-based therapeutic product.30
Bibliography .31
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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.
This first edition cancels and replaces ISO/TS 20399-1:2018, ISO/TS 20399-2:2018 and
ISO/TS 20399-3:2018, which have been technically revised.
The main changes are as follows:
— merging of the three parts of the ISO 20399 series;
— change in definitions of key terms including “ancillary material” and “cellular therapeutic product”;
— addition of Clause 5 “Strategy”, including key concepts, animal-derived components, mutual
responsibilities and qualification;
— revision and rearrangement of requirements and recommendations with emphasis on clarifying
responsibility of involved parties and emphasis of a risk-based approach.
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.
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