ISO/TS 20399-1:2018

Biotechnology — Ancillary materials present during the production of cellular therapeutic products — Part 1: General requirements

This document specifies definitions and general requirements for ancillary materials (AMs) used in cell processing of cellular therapeutic products. This document is applicable to cellular therapeutic products, including those gene therapy products whereby cells form part of the final product. It does not apply to products without cells. This document does not cover the selection, assessment or control of starting materials and excipients. NOTE International, regional or national regulations or requirements can also apply to specific topics covered in this document.

Biotechnologie — Matériaux auxiliaires présents lors de la production de produits thérapeutiques cellulaires — Partie 1: Exigences générales

General Information

• Status: Withdrawn
• Publication Date: 03-Dec-2018
• ICS: 07.080 - Biology. Botany. Zoology
• Technical Committee: ISO/TC 276 - Biotechnology
• Drafting Committee: ISO/TC 276/WG 4 - Bioprocessing
• Current Stage: 9599 - Withdrawal of International Standard
• Completion Date: 01-Dec-2022

Relations

• Revised: ISO 20399:2022 - Biotechnology — Ancillary materials present during the production of cellular therapeutic products and gene therapy products
• Effective Date: 23-Apr-2020

Standards Content (Sample)

TECHNICAL ISO/TS
SPECIFICATION 20399-1
First edition
2018-11
Biotechnology — Ancillary materials
present during the production of
cellular therapeutic products —
Part 1:
General requirements
Biotechnologie — Matériaux auxiliaires présents lors de la production
de produits thérapeutiques cellulaires —
Partie 1: Exigences générales
Reference number
ISO/TS 20399-1:2018(E)
©
ISO 2018

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ISO/TS 20399-1:2018(E)

COPYRIGHT PROTECTED DOCUMENT
© ISO 2018
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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Published in Switzerland
ii © ISO 2018 – All rights reserved

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ISO/TS 20399-1:2018(E)

Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviated terms . 3
5 Considerations . 3
5.1 General considerations . 3
5.2 Animal-derived components of AM . 3
5.2.1 General. 3
5.2.2 Levels of ADCF . 3
5.2.3 Key considerations in the use of animal-derived components . 4
5.2.4 Viral inactivation . 4
5.3 Mutual responsibilities for AMs . 4
5.4 Example workflow . 5
6 Ancillary material requirements . 6
6.1 Quality management system . 6
6.2 Information on ancillary material products and materials used to produce
ancillary materials . 6
Annex A (informative) Example of workflow from AM supplier to AM user .7
Annex B (informative) Information on AM products and materials used to produce AM .8
Bibliography .10
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ISO/TS 20399-1:2018(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.
A list of all parts in the ISO/TS 20399 series can be found on the ISO website.
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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ISO/TS 20399-1:2018(E)

Introduction
Ancillary materials (AMs) are materials that come into contact with the cellular therapeutic product
during the manufacturing process, but are not intended to be in the final product.
AMs include culture media and growth factors, among other biological and non-biological components.
They can be a complex mixture of many components, and a variation in their lot-to-lot composition can
hamper the ability to produce consistent cellular therapeutic products with specified quality attributes.
As such, AMs can have implications with regard to the safety and effectiveness of a cellular therapeutic
product. Appropriate control of ancillary materials is determined by a risk-based approach.
This document specifies definitions and general requirements for AMs and contributes to their control
by suppliers and users of such materials.
The ISO/TS 20399 series provides general requirements and guidance regarding ancillary materials
to maintain a high level of lot-to-lot consistency, as well as the accompanying documentation, so that
consistent ancillary materials products and documentation provided by the suppliers can help AM users.
It is intended to ensure the quality and consistency of AMs used in the manufacturing of cellular
therapeutic products. Good manufacturing practice (GMP) is taken into account, when necessary.
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TECHNICAL SPECIFICATION ISO/TS 20399-1:2018(E)
Biotechnology — Ancillary materials present during the
production of cellular therapeutic products —
Part 1:
General requirements
1 Scope
This document specifies definitions and general requirements for ancillary materials (AMs) used in cell
processing of cellular therapeutic products.
This document is applicable to cellular therapeutic products, including those gene therapy products
whereby cells form part of the final product. It does not apply to products without cells.
This document does not cover the selection, assessment or control of starting materials and excipients.
NOTE International, regional or national regulations or requirements can also apply to specific topics
covered in this document.
2 Normative references
There are no normative references in this document.
3 Terms and definitions
For the purposes of this document, the following terms and definitions 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
ancillary material
AM
material that comes into contact with the cell or tissue product during cell-processing, but is not
intended to be part of the final product formulation
Note 1 to entry: AMs exclude non-biological consumables (e.g. tissue culture flasks, bags, tubing, pipettes,
needles) and other plastic ware that comes into contact with the cell or tissue, but include consumables which
can have a biological component (e.g. coated dishes or beads).
Note 2 to entry: AMs exclude cells (e.g. feeder cells).
Note 3 to entry: In some cases AM is described as raw material.
3.2
AM user
entity who makes use of AM (3.1) and conducts cell-processing for cellular therapeutic product
3.3
AM supplier
entity who manufactures and/or supplies the AM (3.1) for AM user (3.2)
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ISO/TS 20399-1:2018(E)

3.4
animal-derived component free
ADCF
absence of animal or human origin material(s)
Note 1 to entry: The main purpose of defining ADCF is to provide necessary information for a user's risk
assessment of ancillary material.
Note 2 to entry: There are levels of ADCF, which are listed in 5.2.2.
Note 3 to entry: In some cases, animal-derived component free (ADCF) is described as animal origin free.
Note 4 to entry: In cases where there is absence of non-human animal components, the term xeno-free is
commonly used.
3.5
cellular therapeutic product
product containing cells as the active substance
EXAMPLE Cell therapy medicinal product, tissue engineered product.
3.6
chain of custody
responsibility for or control of materials as they move through each step of a process
Note 1 to entry: For the purpose of this document, “chain of custody” is the unbroken path of an AM product from
the production of AM to the end customer. It covers controls, distribution and logistics to the end-user.
3.7
excipient
material that is present in the cellular therapeutic product (3.5) administered to a patient(s), other than
the active substance(s)
EXAMPLE Cryopreservation components.
Note 1 to entry: For the purpose of this document, “active substance” corresponds to cellular therapeutic product.
3.8
maximum shelf life
period during which an AM (3.1) is expected to comply with the specifications, if stored under defined
conditions
3.9
specification
list of tests, references to analytical procedures, and appropriate acceptance criteria that would be
expected to be met to demonstrate suitability for its intended use definition
3.10
stability
characteristic of a material, when stored under specified conditions, to maintain a value(s) for stated
property(ies) within specified limits for a specified period of time
[SOURCE: ISO Guide 30:2015, 2.1.15, modified — “reference material” has been replaced by “material”,
“a specified property value” has been replaced by “a value(s) for stated property(ies)”, the Note 1 to
entry has been deleted.]
3.11
starting material
any substance of cellular origin that constitutes the cellular therapeutic product (3.5)
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ISO/TS 20399-1:2018(E)

4 Abbreviated terms
ADCF animal-derived component free
AM ancillary material
BSE bovine spongiform encephalopathy
CoA certificate of analysis
CoO
...