Aseptic processing of health care products - Part 6: Isolator systems (ISO 13408-6:2021)

Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 6: Isolatorensysteme (ISO 13408-6:2021)

Dieses Dokument legt die Anforderungen für Isolatorensysteme fest und stellt einen Leitfaden zur Spezifikation, Auswahl, Qualifizierung, Biodekontamination, Validierung, zum Betrieb und zur Kontrolle von Isolatorensystemen im Zusammenhang mit der aseptischen Herstellung von Produkten für die Gesundheitsfürsorge und der Herstellung von zellbasierten Produkten für die Gesundheitsfürsorge zur Verfügung.
Dieses Dokument legt keine Anforderungen für Barrieresysteme mit beschränktem Zugang (RABS, en: restricted access barrier system) fest.
Dieses Dokument ersetzt keine nationalen behördlichen Anforderungen, wie z. B. Gute Herstellungspraktiken (GMP, en: Good Manufacturing Practices) und/oder Anforderungen von Arzneibüchern, die insbesondere nationale oder regionale Zuständigkeiten betreffen.
Dieses Dokument legt keine Anforderungen für Isolatoren fest, die für Sterilitätsprüfungen verwendet werden, jedoch könnten einige der Grundsätze und Angaben in diesem Dokument auf diese Anwendung anwendbar sein.
Dieses Dokument definiert keine Eindämmungsanforderungen für die Biosicherheit.

Traitement aseptique des produits de santé - Partie 6: Systèmes isolateurs (ISO 13408-6:2021)

Aseptična proizvodnja izdelkov za zdravstveno nego - 6. del: Sistemi izolatorjev (ISO 13408-6:2021)

General Information

Status
Published
Public Enquiry End Date
04-Jul-2019
Publication Date
29-Jun-2021
Technical Committee
Current Stage
6060 - National Implementation/Publication (Adopted Project)
Start Date
11-Jun-2021
Due Date
16-Aug-2021
Completion Date
30-Jun-2021

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SLOVENSKI STANDARD
SIST EN ISO 13408-6:2021
01-september-2021
Nadomešča:
SIST EN ISO 13408-6:2011
SIST EN ISO 13408-6:2011/A1:2013
Aseptična proizvodnja izdelkov za zdravstveno nego - 6. del: Sistemi izolatorjev
(ISO 13408-6:2021)

Aseptic processing of health care products - Part 6: Isolator systems (ISO 13408-6:2021)

Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 6:
Isolatorensysteme (ISO 13408-6:2021)

Traitement aseptique des produits de santé - Partie 6: Systèmes isolateurs (ISO 13408-

6:2021)
Ta slovenski standard je istoveten z: EN ISO 13408-6:2021
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 13408-6:2021 en

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

---------------------- Page: 1 ----------------------
SIST EN ISO 13408-6:2021
---------------------- Page: 2 ----------------------
SIST EN ISO 13408-6:2021
EN ISO 13408-6
EUROPEAN STANDARD
NORME EUROPÉENNE
May 2021
EUROPÄISCHE NORM
ICS 11.080.01 Supersedes EN ISO 13408-6:2011
English Version
Aseptic processing of health care products - Part 6:
Isolator systems (ISO 13408-6:2021)

Traitement aseptique des produits de santé - Partie 6: Aseptische Herstellung von Produkten für die

Systèmes isolateurs (ISO 13408-6:2021) Gesundheitsfürsorge - Teil 6: Isolatorensysteme (ISO

13408-6:2021)
This European Standard was approved by CEN on 7 June 2020.

This European Standard was corrected and reissued by the CEN-CENELEC Management Centre on 9 June 2021.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this

European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references

concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN

member.

This European Standard exists in three official versions (English, French, German). A version in any other language made by

translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management

Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,

Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,

Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and

United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATIO N
EUROPÄISCHES KOMITEE FÜR NORMUN G
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels

© 2021 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 13408-6:2021 E

worldwide for CEN national Members.
---------------------- Page: 3 ----------------------
SIST EN ISO 13408-6:2021
EN ISO 13408-6:2021 (E)
Contents Page

European foreword ....................................................................................................................................................... 3

Annex ZA (informative) Relationship between this European Standard and the General

Safety and Performance requirements of Regulation (EU) 2017/745 aimed to be

covered................................................................................................................................................................ 5

Annex ZB (informative) Relationship between this European Standard and the General

Safety and Performance Requirements of Regulation (EU) 2017/746 aimed to be

covered................................................................................................................................................................ 7

---------------------- Page: 4 ----------------------
SIST EN ISO 13408-6:2021
EN ISO 13408-6:2021 (E)
European foreword

This document (EN ISO 13408-6:2021) has been prepared by Technical Committee ISO/TC 198

"Sterilization of health care products" in collaboration with Technical Committee CEN/TC 204

“Sterilization of medical devices” the secretariat of which is held by BSI.

This European Standard shall be given the status of a national standard, either by publication of an

identical text or by endorsement, at the latest by November 2021, and conflicting national standards

shall be withdrawn at the latest by November 2021.

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. CEN shall not be held responsible for identifying any or all such patent rights.

This document supersedes EN ISO 13408-6:2011 + A1:2013.

This document has been prepared under a mandate given to CEN by the European Commission and the

European Free Trade Association, and supports essential requirements of EU Directive(s).

For the relationship with EU Directive(s) see informative Annex ZA and ZB which are an integral parts

of this document.

This document is an adoption of an International Standard. As the scope of the applicable regulatory

requirements differ from nation to nation and region to region, the scope of this document can differ

from the scope of the European Regulations that it supports. This document supports European

regulatory requirements only to the extent of the scope of the European regulations for medical devices

and in vitro diagnostic medical devices. For relationship with EU Regulations, see informative Annex ZA

and ZB, which are an integral part of this document.

The following referenced documents are indispensable for the application of this document. For

undated references, the latest edition of the referenced document (including any amendments) applies.

For dated references, only the edition cited applies. However, for any use of this standard ‘within the

meaning of Annexes ZA and ZB, the user should always check that any referenced document has not

been superseded and that its relevant contents can still be considered the generally acknowledged

state-of-art.

When an IEC or ISO standard is referred to in the ISO standard text, this should be understood as a

normative reference to the corresponding EN standard, if available, and otherwise to the dated version

of the ISO or IEC standard as listed below.

NOTE The way in which these referenced documents are cited in normative requirements determines the

extent (in whole or in part) to which they apply.
---------------------- Page: 5 ----------------------
SIST EN ISO 13408-6:2021
EN ISO 13408-6:2021 (E)
Table – Correlation between normative references and dated EN and ISO standards
Normative references Equivalent dated standard
as listed in Clause 2 of the ISO
EN ISO
standard
ISO 11139 EN ISO 11139:2018 ISO 11139:2018
ISO 13408-1:2008 EN ISO 13408-1:2015 ISO 13408-1:2008
ISO 13408-4 EN ISO 13408-4:2011 ISO 13408-4:2005
ISO 13408-7 EN ISO 13408-7:2015 ISO 13408-7:2012
ISO 14644-1:2015 EN ISO 14644-1:2015 ISO 14644-1:2015
ISO 14644-7 EN ISO 14644-7:2004 ISO 14644-7:2004
ISO 18362:2016 No equivalent ISO 18362:2016
ISO/IEC/IEEE 90003 No equivalent ISO/IEC/IEEE 90003:2018

According to the CEN-CENELEC Internal Regulations, the national standards organizations of the

following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,

Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,

Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of

North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the

United Kingdom.
Endorsement notice

The text of ISO 13408-6:2021 has been approved by CEN as EN ISO 13408-6:2021 without any

modification.
---------------------- Page: 6 ----------------------
SIST EN ISO 13408-6:2021
EN ISO 13408-6:2021 (E)
Annex ZA
(informative)
Relationship between this European Standard and the General Safety and
Performance requirements of Regulation (EU) 2017/745 aimed to be
covered

This European standard has been prepared under a Commission’s standardisation request to provide

one voluntary means of conforming to the General Safety and Performance Requirements of Regulation

(EU) 2017/745 of 5 April 2017 concerning medical devices [OJ L 117].

Once this standard is cited in the Official Journal of the European Union under that Regulation,

compliance with the normative clauses of this standard given in Table ZA.1 confers, within the limits of

the scope of this standard, a presumption of conformity with the corresponding General Safety and

Performance requirements of that Regulation, and associated EFTA regulations.

NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk

management process needs to be in compliance with Regulation (EU) 2017/745. This means that risks have to be

‘reduced as far as possible’, ‘reduced to the lowest possible level’, ‘reduced as far as possible and appropriate’,

‘removed or reduced as far as possible’, ‘eliminated or reduced as far as possible’, ’removed or minimized as far as

possible’, or ‘minimized’, according to the wording of the corresponding General Safety and Performance

Requirement.

NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety

and Performance Requirements 1, 2, 3, 4, 5, 8, 9, 10, 11, 14, 16, 17, 18, 19, 20, 21 and 22 of the Regulation.

NOTE 3 This Annex ZA is based on normative references according to the table of references in the European

Foreword, replacing the references in the core text.

NOTE 4 When a General Safety and Performance Requirement does not appear in Table ZA.1, it means that it is

not addressed by this European Standard.

Table ZA.1 — Correspondence between this European Standard and Annex I of Regulation (EU)

2017/745 [OJ L 117]
General Safety and Performance Clause(s)/sub-clause(s) Remarks/Notes
Requirements of Regulation (EU) of this EN
2017/745
11.3 4,5,6,7,8,9,10 This standard provides requirements for
the specification, selection, qualification,
bio-decontamination, validation, operation
and control of isolator systems related to
aseptic processing.
This General Safety and Performance
Requirement is addressed only with
regard to devices for which use of isolators
for aseptic processing is appropriate.
In conjunction with EN ISO 13408-1, this
relevant General Safety and Performance
Requirement is only partly addressed in
this European Standard. Design and
packaging for maintenance of sterility are
not covered. Aspects of manufacture other
---------------------- Page: 7 ----------------------
SIST EN ISO 13408-6:2021
EN ISO 13408-6:2021 (E)
than those related to maintenance of a
specific microbial state by aseptic
processing within an isolator are not
covered.
11.4 first sentence only 4,5,6,7,8,9,10 This standard provides requirements for
the specification, selection, qualification,
bio-decontamination, validation, operation
and control of isolator systems related to
aseptic processing.
This General Safety and Performance
Requirement is addressed only with
regard to devices for which use of isolators
for aseptic processing is appropriate.
In conjunction with EN ISO 13408-1, this
relevant General Safety and Performance
Requirement is only partly addressed in
this European Standard. Design and
packaging for maintenance of sterility are
not covered. Evidence that the integrity of
the packaging is maintained to the point of
use is not covered. Aspects of manufacture
other than those related to maintenance of
sterility during aseptic processing within
an isolator are not covered.
11.5 4,5,6,7,8,9,10 This standard provides requirements for
the specification, selection, qualification,
bio-decontamination, validation, operation
and control of isolator systems related to
aseptic processing.
This General Safety and Performance
Requirement is addressed only with
regard to devices for which use of isolators
for aseptic processing is appropriate.
In conjunction with EN ISO 13408-1, this
relevant General Safety and Performance
Requirement is only partly addressed in
this European Standard. Design and
packaging for maintenance of sterility is
not covered. Aspects of manufacture other
than those related to maintenance of
sterility during aseptic processing within
an isolator are not covered.

WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European

Standard is maintained in the list published in the Official Journal of the European Union. Users of this

standard should consult frequently the latest list published in the Official Journal of the European

Union.

WARNING 2 — Other Union legislation may be applicable to the product(s) falling within the scope of

this standard.
---------------------- Page: 8 ----------------------
SIST EN ISO 13408-6:2021
EN ISO 13408-6:2021 (E)
Annex ZB
(informative)
Relationship between this European Standard and the General Safety and
Performance Requirements of Regulation (EU) 2017/746 aimed to be
covered

This European standard has been prepared under a Commission’s standardisation request to provide

one voluntary means of conforming to the General Safety and Performance Requirements of Regulation

(EU) 2017/746 of 5 April 2017 concerning in vitro diagnostic medical devices [OJ L 117].

Once this standard is cited in the Official Journal of the European Union under that Regulation,

compliance with the normative clauses of this standard given in Table ZB.1 confers, within the limits of

the scope of this standard, a presumption of conformity with the corresponding General Safety and

Performance Requirements of that Regulation, and associated EFTA regulations.

NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk

management process needs to be in compliance with Regulation (EU) 2017/746. This means that risks have to be

‘reduced as far as possible’, ‘reduced to a level as low as reasonably practicable’, ‘reduced to the lowest possible

level’, ‘reduced as far as possible and appropriate’, ‘removed or reduced as far as possible’, ‘eliminated or reduced

as far as possible’, ‘prevented’ or ‘minimized’, according to the wording of the corresponding General Safety and

Performance Requirement.

NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety

and Performance Requirements 1, 2, 3, 4, 5, 8, 10, 11, 13, 15, 16, 17, 18 and 19 of the Regulation.

NOTE 3 This Annex ZB is based on normative references according to the table of references in the European

Foreword, replacing the references in the core text.

NOTE 4 When a General Safety and Performance Requirement does not appear in Table ZB.1, it means that it is

not addressed by this European Standard.

Table ZB.1 — Correspondence between this European standard and Annex I of Regulation (EU)

2017/746 [OJ L 117]
General Safety and Performance Clause(s)/sub-clause(s) of this Remarks/Notes
Requirements of Regulation (EU) EN
2017/746
11.2 4,5,6,7,8,9,10 This standard provides
requirements for the specification,
selection, qualification, bio-
decontamination, validation,
operation and control of isolator
systems related to aseptic
processing.
This General Safety and
Performance Requirement is
addressed only with regard to
devices for which use of isolators
for aseptic processing is
appropriate.
In conjunction with EN ISO 13408-
1, this relevant General Safety and
---------------------- Page: 9 ----------------------
SIST EN ISO 13408-6:2021
EN ISO 13408-6:2021 (E)
Performance Requirement is only
partly addressed in this European
Standard. Design and packaging for
maintenance of sterility are not
covered. Aspects of manufacture
other than those related to
maintenance of a specific microbial
state by aseptic processing within
an isolator are not covered.
11.3 4,5,6,7,8,9,10 This standard provides
requirements for the specification,
selection, qualification, bio-
decontamination, validation,
operation and control of isolator
systems related to aseptic
processing.
This General Safety and
Performance Requirement is
addressed only with regard to
devices for which use of isolators
for aseptic processing is
appropriate.
In conjunction with
EN ISO 13408-1, this relevant
General Safety and Performance
Requirement is only partly
addressed in this European
Standard. Design and packaging for
maintenance of sterility is not
covered. Aspects of manufacture
other than those related to
maintenance of sterility during
aseptic processing within an
isolator are not covered.

WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European

Standard is maintained in the list published in the Official Journal of the European Union. Users of this

standard should consult frequently the latest list published in the Official Journal of the European

Union.

WARNING 2 — Other Union legislation may be applicable to the product(s) falling within the scope of

this standard.
---------------------- Page: 10 ----------------------
SIST EN ISO 13408-6:2021
INTERNATIONAL ISO
STANDARD 13408-6
Second edition
2021-04
Aseptic processing of health care
products —
Part 6:
Isolator systems
Traitement aseptique des produits de santé —
Partie 6: Systèmes isolateurs
Reference number
ISO 13408-6:2021(E)
ISO 2021
---------------------- Page: 11 ----------------------
SIST EN ISO 13408-6:2021
ISO 13408-6:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© 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: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved
---------------------- Page: 12 ----------------------
SIST EN ISO 13408-6:2021
ISO 13408-6:2021(E)
Contents Page

Foreword ..........................................................................................................................................................................................................................................v

Introduction ................................................................................................................................................................................................................................vi

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

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

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

4 Quality system elements .............................................................................................................................................................................. 3

5 Basic principle of isolator systems .................................................................................................................................................... 3

5.1 General ........................................................................................................................................................................................................... 3

5.2 Negative pressure isolators .......................................................................................................................................................... 4

6 Isolator system specification ................................................................................................................................................................... 4

6.1 General .......................................................................................................................................................................................................... 4

6.2 Risk management ................................................................................................................................................................................. 4

6.2.1 General...................................................................................................................................................................................... 4

6.2.2 Negative pressure isolator systems ................................................................................................................. 5

6.3 User requirement specification ................................................................................................................................................ 5

7 Design of isolator systems .......................................................................................................................................................................... 5

7.1 General ........................................................................................................................................................................................................... 5

7.2 Materials of construction ............................................................................................................................................................... 6

7.3 Air-handling system ........................................................................................................................................................................... 6

7.3.1 General...................................................................................................................................................................................... 6

7.3.2 Air change rate ...................................................................... ............................................................................................. 6

7.3.3 Airflow pattern .................................................................................................................................................................. 6

7.3.4 Temperature/humidity .............................................................................................................................................. 7

7.3.5 Particulate air specifications ................................................................................................................................. 7

7.3.6 Recirculation of air ......................................................................................................................................................... 7

7.3.7 Pressure differentials ................................................................................................................................................... 7

7.4 Operator interface ................................................................................................................................................................................ 7

7.4.1 Isolator gloves/sleeves ............................................................................................................................................... 7

7.4.2 Suits/half-suits .................................................................................................................................................................. 8

7.4.3 Access to the isolator/transfer systems....................................................................................................... 8

7.4.4 Devices acting as transfer ports .......................................................................................................................... 8

7.5 Ancillary isolator equipment ...................................................................................................................................................... 9

7.5.1 Portable and mobile equipment ......................................................................................................................... 9

7.6 Surrounding room classification ............................................................................................................................................. 9

7.7 Process utilities ...................................................................................................................................................................................... 9

8 Validation ..................................................................................................................................................................................................................... 9

8.1 General ........................................................................................................................................................................................................... 9

8.2 Design qualification .........................................................................................................................................................................10

8.2.1 General...................................................................................................................................................................................10

8.2.2 Product/process application ..............................................................................................................................10

8.2.3 Ergonomics ........................................................................................................................................................................10

8.2.4 Cleaning ................................................................................................................................................................................10

8.2.5 Bio-decontamination ................................................................................................................................................11

8.2.6 Selection of bio-decontamination agent ...................................................................................................11

8.2.7 Development and validation of bio-decontamination processes .......................................12

8.2.8 Bio-decontamination agent generation and testing .......................................................................12

8.2.9 Bio-decontamination parameters ..................................................................................................................13

8.2.10 Aeration and residue limits .................................................................................................................................13

8.2.11 Log reduction ...................................................................................................................................................................13

8.2.12 Surface bio-decontamination of items .......................................................................................................14

8.2.13 Development and validation of sterilization processes .............................................................14

© ISO 2021 – All rights reserved iii
---------------------- Page: 13 ----------------------
SIST EN ISO 13408-6:2021
ISO 13408-6:2021(E)

8.3 Installation qualification .............................................................................................................................................................14

8.3.1 General...................................................................................................................................................................................14

8.3.2 Installation .........................................................................................................................................................................14

8.4 Operational qualification ............................................................................................................................................................15

8.5 Performance qualification ..........................................................................................................................................................16

8.5.1 General...................................................................................................................................................................................16

8.5.2 Cleaning ................................................................................................................................................................................16

8.5.3 Bio-decontamination ................................................................................................................................................16

8.5.4 Process simulation t
...

SLOVENSKI STANDARD
oSIST prEN ISO 13408-6:2019
01-julij-2019
Aseptična proizvodnja izdelkov za zdravstveno nego - 6. del: Sistemi izolatorjev
(ISO/DIS 13408-6:2019)

Aseptic processing of health care products - Part 6: Isolator systems (ISO/DIS 13408-

6:2019)
Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 6:
Isolatorensysteme (ISO/DIS 13408-6:2019)

Traitement aseptique des produits de santé - Partie 6: Systèmes isolateurs (ISO/DIS

13408-6:2019)
Ta slovenski standard je istoveten z: prEN ISO 13408-6
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
oSIST prEN ISO 13408-6:2019 en

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

---------------------- Page: 1 ----------------------
oSIST prEN ISO 13408-6:2019
---------------------- Page: 2 ----------------------
oSIST prEN ISO 13408-6:2019
DRAFT INTERNATIONAL STANDARD
ISO/DIS 13408-6
ISO/TC 198 Secretariat: ANSI
Voting begins on: Voting terminates on:
2019-04-03 2019-06-26
Aseptic processing of health care products —
Part 6:
Isolator systems
Traitement aseptique des produits de santé —
Partie 6: Systèmes isolateurs
ICS: 11.080.01
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
ISO/CEN PARALLEL PROCESSING
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 13408-6:2019(E)
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 SUPPORTING DOCUMENTATION. ISO 2019
---------------------- Page: 3 ----------------------
oSIST prEN ISO 13408-6:2019
ISO/DIS 13408-6:2019(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2019

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 2019 – All rights reserved
---------------------- Page: 4 ----------------------
oSIST prEN ISO 13408-6:2019
ISO/DIS 13408-6:2019(E)
Contents Page

Foreword ..........................................................................................................................................................................................................................................v

Introduction ................................................................................................................................................................................................................................vi

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

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

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

4 Quality system elements .............................................................................................................................................................................. 2

5 Basic principal of Isolator systems .................................................................................................................................................... 2

5.1 General ........................................................................................................................................................................................................... 2

5.2 Negative pressure isolators .......................................................................................................................................................... 3

6 Isolator System Specification .................................................................................................................................................................. 3

6.1 General .......................................................................................................................................................................................................... 3

6.2 Risk management ................................................................................................................................................................................. 4

6.2.1 General...................................................................................................................................................................................... 4

6.2.2 Negative pressure isolators .................................................................................................................................... 4

6.3 User requirement specification ................................................................................................................................................ 4

7 Design of isolator systems .......................................................................................................................................................................... 5

7.1 General ........................................................................................................................................................................................................... 5

7.2 Materials of construction ............................................................................................................................................................... 5

7.3 Air-handling system ........................................................................................................................................................................... 6

7.3.1 General...................................................................................................................................................................................... 6

7.3.2 Air change rate ...................................................................... ............................................................................................. 6

7.3.3 Airflow pattern .................................................................................................................................................................. 6

7.3.4 Temperature/humidity .............................................................................................................................................. 6

7.3.5 Particulate air specifications ................................................................................................................................. 6

7.3.6 Recirculation of air ......................................................................................................................................................... 7

7.3.7 Pressure differentials ................................................................................................................................................... 7

7.4 Operator interface ................................................................................................................................................................................ 7

7.4.1 Isolator gloves/sleeves ............................................................................................................................................... 7

7.4.2 Suits/half-suits .................................................................................................................................................................. 7

7.4.3 Access to the isolator/Transfer systems ..................................................................................................... 7

7.4.4 Transfer ports ..................................................................................................................................................................... 8

7.5 Ancillary isolator equipment ...................................................................................................................................................... 8

7.5.1 Portable and mobile equipment ......................................................................................................................... 8

7.6 Surrounding room classification ............................................................................................................................................. 8

7.7 Process utilities ...................................................................................................................................................................................... 9

8 Validation ..................................................................................................................................................................................................................... 9

8.1 General ........................................................................................................................................................................................................... 9

8.2 Design qualification ............................................................................................................................................................................ 9

8.2.1 General...................................................................................................................................................................................... 9

8.2.2 Product/process application ................................................................................................................................. 9

8.2.3 Ergonomics ........................................................................................................................................................................10

8.2.4 Cleaning ................................................................................................................................................................................10

8.2.5 Bio-decontamination ................................................................................................................................................11

8.2.6 Development and validation of bio-decontamination processes .......................................11

8.2.7 Selection of bio-decontamination agent ...................................................................................................11

8.2.8 Bio-decontamination agent generation and testing .......................................................................12

8.2.9 Bio-decontamination parameters ..................................................................................................................12

8.2.10 Aeration and residue limits .................................................................................................................................12

8.2.11 Spore log reduction ....................................................................................................................................................13

8.2.12 Surface bio-decontamination of items .......................................................................................................13

8.2.13 Development and validation of sterilization processes .............................................................13

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8.3 Installation qualification .............................................................................................................................................................13

8.3.1 General...................................................................................................................................................................................13

8.3.2 Installation .........................................................................................................................................................................14

8.4 Operational qualification ............................................................................................................................................................14

8.5 Performance qualification ..........................................................................................................................................................15

8.5.1 General...................................................................................................................................................................................15

8.5.2 Cleaning ................................................................................................................................................................................15

8.5.3 Bio-decontamination ................................................................................................................................................16

8.5.4 Process simulation tests .........................................................................................................................................16

8.6 R eview and approval of validation .....................................................................................................................................16

8.7 Requalification .....................................................................................................................................................................................16

9 Routine monitoring and control .......................................................................................................................................................17

9.1 Procedures ...............................................................................................................................................................................................17

9.2 System integrity ..................................................................................................................................................................................17

9.3 Bio-decontamination process monitoring ...................................................................................................................17

9.4 Environmental monitoring ........................................................................................................................................................17

9.5 Change control .....................................................................................................................................................................................18

9.6 Maintenance and calibration ...................................................................................................................................................18

10 Personnel training ...........................................................................................................................................................................................18

Annex A (informative) Transfer ports for portable and mobile equipment ............................................................20

Annex B (informative) Isolator system – principal figure of term and flow diagram of air

and material ...........................................................................................................................................................................................................24

Annex C (informative) Isolator system – Critical surfaces in isolator system .........................................................25

Annex ZA (informative) Relationship between this European Standard and the essential

requirements of Directive 90/385/EEC [OJ L 189] aimed to be covered ................................................26

Annex ZB (informative) Relationship between this European Standard and the essential

requirements of Directive 93/42/EEC [OJ L 169] aimed to be covered ....................................................28

Annex ZC (informative) Relationship between this European Standard and the essential

requirements of Directive 98/79/EC [OJ L 331] aimed to be covered .......................................................30

Annex ZD (informative) Relationship between this European Standard and the General

Safety and Performance requirements of Regulation (EU) 2017/745 aimed to be

covered ......... ................................................................................................................................................................................................................32

Annex ZE (informative) Relationship between this European Standard and the General

Safety and Performance Requirements of Regulation (EU) 2017/746 aimed to be

covered ......... ................................................................................................................................................................................................................35

Bibliography .............................................................................................................................................................................................................................38

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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 on 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 the following URL: www .iso .org/iso/foreword .html.

This document was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.

This second edition cancels and replaces the first edition (ISO 13408-6:2005), which has been

technically revised.
The main changes compared to the previous edition are as follows:
— changes to the Introduction;
— changes to the Scope;
— addition of the new item No.5 Basic principle of Isolator system;

— addition of risk management approach in chapter 6 "Isolator system specification";

— addition of new informative Annex A "Transfer ports for portable and mobile equipment";

— addition of new informative Annex B "Isolator system – principal figure of term and flow diagram of

air and material";

— addition of new informative Annex C "Critical surface of Isolator systems(ex.)"

A list of all parts in the ISO 13408- series can be found on the ISO website.
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Introduction

A health care product that is labelled “sterile” is manufactured using suitably designed, validated and

controlled processes. Wherever possible, it is terminally sterilized in its final, sealed container. When

this is not possible, the product is aseptically processed.

Aseptic processing is an exacting and demanding discipline designed to maintain sterility through all

stages of preparation, manufacturing, filling and sealing in final containers. It relies on a number of

independent factors for prevention of recontamination of previously sterilized components during the

assembly or filling of product into a final container.

An effective risk management system addressing aseptic processing design (including the use of

barrier separation technology), validation and control, and which identifies, assesses, eliminates

(where applicable) and controls contamination risks is a prerequisite to provide assurance of sterility

for aseptically processed product.

Various separation systems exist to protect the critical processing zone of an aseptic processing area

from non-viable particulate and microbiological contamination and to separate process operators from

the critical processing zone.

These systems range from controlled airflow devices based on aerodynamic protection through

to separation barriers that combine physical and aerodynamic protection to separate the external

cleanroom environment from the critical processing zone, minimizing exposure of this zone to process

operators and thereby reducing the opportunities for contamination during processing.

Isolator systems provide physical separation whilst facilitating operator intervention into the

controlled processing environment under barrier conditions typically via sealed glove-sleeve systems

that are physically connected with glove-ports to the isolator barrier screen(s). To establish a controlled

environment, reduction of viable and non-viable particulates within isolators is achieved by validated

and reproducible cleaning and bio-decontamination processes, principally achieved through the use of

automated methods.

In addition to control of bio-contamination and non-viable particulates, isolator systems can include

control features, which together with operating practices provide product containment to control cross

contamination between process contaminants and product batches, and to manage risk to operators.

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oSIST prEN ISO 13408-6:2019
DRAFT INTERNATIONAL STANDARD ISO/DIS 13408-6:2019(E)
Aseptic processing of health care products —
Part 6:
Isolator systems
1 Scope

This document specifies the requirements for and provides guidance on the specification, selection,

qualification, bio-decontamination, validation, operation and control of isolator systems related to

aseptic processing of health care products and processing of cell based health care products.

This document does not specify requirements for restricted access barrier systems (RABS).

This document does not supersede or replace national regulatory requirements such as Good

Manufacturing Practices (GMPs) and/or compendia requirements that pertain in particular to national

or regional jurisdictions.

This document does not specify requirements for isolators used for sterility testing; however, some of

the principles and information in this document could be applicable to this application.

This International Standard does not define biosafety containment requirements.
2 Normative references

The following documents, in whole or in part, are normatively referenced in this document and are

indispensable for its application. For dated references, only the edition cited applies. For undated

references, the latest edition of the referenced document (including any amendments) applies.

ISO 10648-1:1997, Containment enclosures — Part 1: Design principles

ISO 13408-1:2008, Aseptic processing of health care products — Part 1: General requirements

ISO 13408-1:2008/Amd, 1, Aseptic processing of health care products — Part 1: General requirements

ISO 13408-4, Aseptic processing of health care products — Part 4: Clean-in-place technologies

ISO 13408-5, Aseptic processing of health care products — Part 5: Sterilization in place

ISO 14644-7:2004, Cleanrooms and associated controlled environments — Part 7: Separative devices (clean

air hoods, gloveboxes, isolators and mini-environments)

ISO/IEC 90003, Software engineering — Guidelines for the application of ISO 9001:2000 to computer

software
3 Terms and definitions

For the purposes of this document, the terms and definitions given in ISO 11139:2018 and the

following apply.
3.1
ancillary isolator equipment

equipment that can be attached to or detached from the isolator whilst ensuring separation of the

internal and external environment
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3.2
bio-decontamination
removal and/or reduction of biological contaminants to an acceptable level
3.3
decontamination device
device used to deliver the agent for the decontamination process
3.4
isolator

enclosure capable of preventing ingress of contaminants by means of physical

separation of the interior from the exterior that is capable of being subject to reproducible interior bio-

decontamination and where operators always remain separated from the interior of the enclosure by

means of an absolute physical barrier

Note 1 to entry: If containment requirements apply (i.e. aseptic processing of hazardous materials) egress also

has to be prevented.
3.5
isolator system
isolator with transfer system(s), and ancillary isolator equipment
3.6
safety data sheet
SDS

document specifying the properties of a substance, its potential hazardous effects for humans and

the environment, and the precautions necessary to handle and dispose of the substance safely

3.7
transfer port

device acting as interface between the interiors of an isolator and ancillary isolator equipment

Note 1 to entry: See example figures in Annex A.
3.8
transfer system

equipment and process that allows ingress and/or egress of material to an isolator without

compromising its environmental quality
4 Quality system elements

Quality elements as defined in ISO 13408-1:2008, Clause 4 shall be implemented to assure control over

all activities affecting isolator systems.
5 Basic principal of Isolator systems
5.1 General

An isolator system comprises a piece of equipment, or collection of equipment that provides a

controlled environment suitable for aseptic processing that shall be separated from the operator and

the surrounding environment using barrier technologies. An isolator system consists of an isolator,

its utilities and its surrounding environment, and can include transfer systems and ancillary isolator

equipment.

Movement of materials in and out of the isolator is a principal risk in maintaining the quality of the

controlled environment. Materials are generally loaded into the isolator before bio-decontamination.

After bio-decontamination of the isolator and during operation, ingress of materials to and egress from

the isolator shall occur via transfer systems that maintain the quality of the controlled environment.

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Isolator systems shall be classified into open and closed systems according to the construction and

operation of their transfer systems.

Closed isolator systems shall exclusively incorporate transfer systems that separate the controlled

environment from the surrounding environment during operation through the use of a solid physical

barrier. A closed system shall restrict the movement of materials through the system to defined batches.

NOTE 1 Examples include autoclaves, pass-through chambers and rapid transfer port (RTP) containers.

Open isolator systems shall incorporate at least one transfer system that provides separation of the

controlled environment from the surrounding environment through use of a fluid barrier. Open systems

shall allow for the continuous movement of material through the isolator system.
NOTE 2 Examples include exit mouse holes, depyrogenation tunnels and electron b
...

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