ISO/TS 23565:2021

Biotechnology — Bioprocessing — General requirements and considerations for equipment systems used in the manufacturing of cells for therapeutic use

This document specifies minimum requirements and general considerations for equipment, consisting of hardware, software and consumables, used in the manufacturing of cells for therapeutic use. This includes equipment for processing cells for therapeutic use starting from cell isolation/selection, expansion, washing and volume reduction, from cell finish through to cryopreservation for the storage of cells for therapeutic use. This document gives guidance on the design, use and maintenance of equipment and equipment systems to both suppliers and users from aspects including the target parties, i.e. supplier or user, and phase of involved task, i.e. design, use or maintenance. This document is applicable to any unit operation system that is used, alone or in combination, for the manufacturing of cells for therapeutic use, meeting user requirements. It is applicable to devices used for the purpose of monitoring equipment status. It does not apply to: processing equipment for cells for therapeutic use used at the point of care; devices used for analytical purposes; biosafety cabinets, general cell culture equipment (such as CO2 incubators, etc.), and software to control multiple equipment systems or multiple unit operations.

Biotechnologie — Bioprocédés — Exigences et considérations générales pour les systèmes d'équipement utilisés dans la fabrication de cellules à usage thérapeutique

General Information

• Status: Published
• Publication Date: 30-Sep-2021
• ICS: 07.080 - Biology. Botany. Zoology
• Technical Committee: ISO/TC 276 - Biotechnology
• Drafting Committee: ISO/TC 276/WG 4 - Bioprocessing
• Current Stage: 9092 - International Standard to be revised
• Completion Date: 26-Jun-2024

Standards Content (Sample)

TECHNICAL ISO/TS
SPECIFICATION 23565
First edition
2021-10
Biotechnology — Bioprocessing
— General requirements and
considerations for equipment systems
used in the manufacturing of cells for
therapeutic use
Biotechnologie — Bioprocédés — Exigences et considérations
générales pour les systèmes d'équipement utilisés dans la fabrication
de cellules à usage thérapeutique
Reference number
© ISO 2021
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: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii
Contents Page
Foreword .iv
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 General considerations .4
4.1 General . 4
4.2 Incorporating equipment and testing into the manufacturing workflow of cells for
therapeutic use . 5
4.3 Unit operation equipment systems . 6
4.4 Connecting to upstream or downstream processing equipment, or both . 6
4.5 Monitoring and surveillance software . 6
4.6 Impurity and toxicity contribution to final cells for therapeutic use . 6
4.7 Sterility and non-pyrogenicity . 6
5 Equipment overall performance characteristics and evaluation .7
5.1 General . 7
5.2 Description of performance characteristics . 7
5.3 Performance parameters and correlation to cell quality attributes . 8
6 Components of the equipment system . 8
6.1 Hardware . 8
6.1.1 General . 8
6.1.2 Physical integrity . 8
6.1.3 Physical strength . 9
6.1.4 Packaging . 9
6.1.5 Recovery of cells . 9
6.1.6 Validation of performance qualification . 9
6.1.7 Physical evaluation of equipment and cell sample interaction . 9
6.1.8 Damage to cells . 9
6.1.9 Impact to clean room environment . 10
6.1.10 Monitoring . 10
6.2 Equipment software for manufacturing of cells for therapeutic use . 10
6.3 Consumables . . . 11
6.3.1 General . 11
6.3.2 Biocompatibility . 11
6.3.3 Toxicity of chemical sterilants . 11
6.3.4 Toxicity of extracted and leached materials .12
6.3.5 Particulates .12
6.3.6 Stability of disposable single-use components .13
7 Documentation and notification of changes .13
7.1 Documentation . 13
7.1.1 General .13
7.1.2 Documentation for off-the-shelf equipment or instruments .13
7.1.3 Custom-designed supplier documentation package for equipment or
instruments . 14
8 Use and maintenance of equipment .14
8.1 Use of equipment . 14
8.2 Maintenance of equipment .15
Bibliography .16
iii
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
TECHNICAL SPECIFICATION ISO/TS 23565:2021(E)
Biotechnology — Bioprocessing — General requirements
and considerations for equipment systems used in the
manufacturing of cells for therapeutic use
1 Scope
This document specifies minimum requirements and general considerations for equipment, consisting
of hardware, software and consumables, used in the manufacturing of cells for therapeutic use. This
includes equipment for processing cells for therapeutic use starting from cell isolation/selection,
expansion, washing and volume reduction, from cell finish through to cryopreservation for the storage
of cells for therapeutic use.
This document gives guidance on the design, use and maintenance of equipment and equipment systems
to both suppliers and users from aspects including the target parties, i.e. supplier or user, and phase of
involved task, i.e. design, use or maintenance.
This document is applicable to any unit operation system that is used, alone or in combination, for the
manufacturing of cells for therapeutic use, meeting user requirements. It is applicable to devices used
for the purpose of monitoring equipment status.
It does not apply to:
— processing equipment for cells for therapeutic use used at the point of care;
— devices used for analytical purposes;
— biosafety cabinets, general cell culture equipment (such as CO incubators, etc.), and software to
control multiple equipment systems or multiple unit operations.
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
batch
quantity of material regarded as a single unit, and having a unique reference
Note 1 to entry: Batch is primarily a processing term.
[SOURCE: ISO 15270:2008, 3.3]
3.2
cells for therapeutic use
product containing cells as the active substance
EXAMPLE A cell therapy medicinal product (allogenic, autologous, somatic, genetically modified), tissue
engineered product.
Note 1 to entry: For the purpose of this document, “cells” mean human cells and tissues of autologous as well as
allogeneic.
[SOURCE: ISO 21973:2020, 3.1, modified — The example has been replaced. Notes 2 and 3 to entry have
been deleted.]
3.3
consumable
tubing, filter, culture vessel, bag or bottle used to transfer, culture or act as a container for the biologics
or another consumable used in the production of cells for therapeutic use (3.2)
3.4
corrective action
action to eliminate the cause of a nonconformity and to prevent recurrence
Note 1 to entry: There can be more than one cause for a nonconformity.
Note 2 to entry: Corrective action is taken to prevent recurrence whereas preventive action (3.15) is taken to
...

TECHNICAL ISO/TS
SPECIFICATION 23565
First edition
2021-10
Biotechnology — Bioprocessing
— General requirements and
considerations for equipment systems
used in the manufacturing of cells for
therapeutic use
Biotechnologie — Bioprocédés — Exigences et considérations
générales pour les systèmes d'équipement utilisés dans la fabrication
de cellules à usage thérapeutique
Reference number
© ISO 2021
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: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii
Contents Page
Foreword .iv
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 General considerations .4
4.1 General . 4
4.2 Incorporating equipment and testing into the manufacturing workflow of cells for
therapeutic use . 5
4.3 Unit operation equipment systems . 6
4.4 Connecting to upstream or downstream processing equipment, or both . 6
4.5 Monitoring and surveillance software . 6
4.6 Impurity and toxicity contribution to final cells for therapeutic use . 6
4.7 Sterility and non-pyrogenicity . 6
5 Equipment overall performance characteristics and evaluation .7
5.1 General . 7
5.2 Description of performance characteristics . 7
5.3 Performance parameters and correlation to cell quality attributes . 8
6 Components of the equipment system . 8
6.1 Hardware . 8
6.1.1 General . 8
6.1.2 Physical integrity . 8
6.1.3 Physical strength . 9
6.1.4 Packaging . 9
6.1.5 Recovery of cells . 9
6.1.6 Validation of performance qualification . 9
6.1.7 Physical evaluation of equipment and cell sample interaction . 9
6.1.8 Damage to cells . 9
6.1.9 Impact to clean room environment . 10
6.1.10 Monitoring . 10
6.2 Equipment software for manufacturing of cells for therapeutic use . 10
6.3 Consumables . . . 11
6.3.1 General . 11
6.3.2 Biocompatibility . 11
6.3.3 Toxicity of chemical sterilants . 11
6.3.4 Toxicity of extracted and leached materials .12
6.3.5 Particulates .12
6.3.6 Stability of disposable single-use components .13
7 Documentation and notification of changes .13
7.1 Documentation . 13
7.1.1 General .13
7.1.2 Documentation for off-the-shelf equipment or instruments .13
7.1.3 Custom-designed supplier documentation package for equipment or
instruments . 14
8 Use and maintenance of equipment .14
8.1 Use of equipment . 14
8.2 Maintenance of equipment .15
Bibliography .16
iii
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
TECHNICAL SPECIFICATION ISO/TS 23565:2021(E)
Biotechnology — Bioprocessing — General requirements
and considerations for equipment systems used in the
manufacturing of cells for therapeutic use
1 Scope
This document specifies minimum requirements and general considerations for equipment, consisting
of hardware, software and consumables, used in the manufacturing of cells for therapeutic use. This
includes equipment for processing cells for therapeutic use starting from cell isolation/selection,
expansion, washing and volume reduction, from cell finish through to cryopreservation for the storage
of cells for therapeutic use.
This document gives guidance on the design, use and maintenance of equipment and equipment systems
to both suppliers and users from aspects including the target parties, i.e. supplier or user, and phase of
involved task, i.e. design, use or maintenance.
This document is applicable to any unit operation system that is used, alone or in combination, for the
manufacturing of cells for therapeutic use, meeting user requirements. It is applicable to devices used
for the purpose of monitoring equipment status.
It does not apply to:
— processing equipment for cells for therapeutic use used at the point of care;
— devices used for analytical purposes;
— biosafety cabinets, general cell culture equipment (such as CO incubators, etc.), and software to
control multiple equipment systems or multiple unit operations.
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
batch
quantity of material regarded as a single unit, and having a unique reference
Note 1 to entry: Batch is primarily a processing term.
[SOURCE: ISO 15270:2008, 3.3]
3.2
cells for therapeutic use
product containing cells as the active substance
EXAMPLE A cell therapy medicinal product (allogenic, autologous, somatic, genetically modified), tissue
engineered product.
Note 1 to entry: For the purpose of this document, “cells” mean human cells and tissues of autologous as well as
allogeneic.
[SOURCE: ISO 21973:2020, 3.1, modified — The example has been replaced. Notes 2 and 3 to entry have
been deleted.]
3.3
consumable
tubing, filter, culture vessel, bag or bottle used to transfer, culture or act as a container for the biologics
or another consumable used in the production of cells for therapeutic use (3.2)
3.4
corrective action
action to eliminate the cause of a nonconformity and to prevent recurrence
Note 1 to entry: There can be more than one cause for a nonconformity.
Note 2 to entry: Corrective action is taken to prevent recurrence whereas preventive action (3.15) is taken to
...