prEN ISO 13408-1

Aseptic processing of health care products - Part 1: General requirements (ISO/DIS 13408-1:2021)

Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 1: Allgemeine Anforderungen (ISO/DIS 13408-1:2021)

Der vorliegende Teil von ISO 13408 legt die allgemeinen Anforderungen an Verfahren, Programme und Verfahrensweisen zur Entwicklung, Validierung und routinemäßigen Kontrolle der aseptischen Herstellung von Produkten für die Gesundheitsfürsorge fest und stellt einen Leitfaden dafür zur Verfügung.
Der vorliegende Teil von ISO 13408 umfasst Anforderungen und einen Leitfaden in Bezug auf das Gesamtthema der aseptischen Herstellung.
Besondere Anforderungen und ein Leitfaden für verschiedene spezielle Prozesse und Verfahren in Bezug auf Sterilfiltration, Lyophilisierung, Technologien der Reinigung vor Ort (en: cleaning in place, CIP), Sterilisation vor Ort (en: sterilization in place, SIP) und Isolatorensysteme sind in anderen Teilen von ISO 13408 angeführt.

Traitement aseptique des produits de santé - Partie 1 : Exigences générales (ISO/DIS 13408-1:2021)

Aseptična proizvodnja izdelkov za zdravstveno nego - 1. del: Splošne zahteve (ISO/DIS 13408-1:2021)

General Information

• Status: Not Published
• Publication Date: 23-Oct-2023
• ICS: 11.080.01 - Sterilization and disinfection in general
• Technical Committee: CEN/TC 204 - Sterilization of medical devices
• Drafting Committee: CEN/TC 204 - Sterilization of medical devices
• Current Stage: 4599 - Dispatch of FV draft to CMC - Finalization for Vote
• Start Date: 21-Nov-2022
• Directive: 2017/745 - Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC
• Directive: 2017/746 - Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU
• Mandate: M/575 - Medical devices in support of Regulation (EU) 2017/745 and in vitro diagnostic medical devices in support of Regulation (EU) 2017/746
• Ref Project: oSIST prEN ISO 13408-1:2022 - Aseptic processing of health care products - Part 1: General requirements (ISO/DIS 13408-1:2021)

Relations

• Revises: EN ISO 13408-1:2015 - Aseptic processing of health care products - Part 1: General requirements (ISO 13408-1:2008, including Amd 1:2013)
• Effective Date: 19-Jan-2023

Standards Content (Sample)

SLOVENSKI STANDARD
oSIST prEN ISO 13408-1:2022
01-februar-2022
Aseptična proizvodnja izdelkov za zdravstveno nego - 1. del: Splošne zahteve
(ISO/DIS 13408-1:2021)

Aseptic processing of health care products - Part 1: General requirements (ISO/DIS

13408-1:2021)

Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 1: Allgemeine

Anforderungen (ISO/DIS 13408-1:2021)

Traitement aseptique des produits de santé - Partie 1 : Exigences générales (ISO/DIS

13408-1:2021)
Ta slovenski standard je istoveten z: prEN ISO 13408-1
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
oSIST prEN ISO 13408-1:2022 en,fr,de

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

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oSIST prEN ISO 13408-1:2022
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oSIST prEN ISO 13408-1:2022
DRAFT INTERNATIONAL STANDARD
ISO/DIS 13408-1
ISO/TC 198 Secretariat: ANSI
Voting begins on: Voting terminates on:
2021-12-16 2022-03-10
Aseptic processing of health care products —
Part 1:
General requirements
Traitement aseptique des produits de santé —
Partie 1: Exigences générales
ICS: 11.080.01
This document is circulated as received from the committee secretariat.
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENT AND APPROVAL. IT IS
ISO/CEN PARALLEL PROCESSING
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
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 13408-1:2021(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 2021
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oSIST prEN ISO 13408-1:2022
ISO/DIS 13408-1:2021(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

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oSIST prEN ISO 13408-1:2022
ISO/DIS 13408-1:2021(E)
Contents Page

Foreword ....................................................................................................................................................................................................................................... vi

Introduction ...........................................................................................................................................................................................................................viii

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

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

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

4 General ........................................................................................................................................................................................................................... 8

5 Principles of aseptic processing ..........................................................................................................................................................8

5.1 General ........................................................................................................................................................................................................... 8

5.2 Use of an aseptic process ............................................................................................................................................................... 9

5.3 Core elements ....................................................................................................................................................................................... 10

5.4 Aseptic processing zones ........................................................................................................................................................... 10

5.4.1 General ..................................................................................................................................................................................... 10

5.4.2 Critical processing zone ............................................................................................................................................ 11

5.4.3 Direct support zones .................................................................................................................................................... 11

5.4.4 Indirect support zones ............................................................................................................................................... 11

6 Risk based process design, development and risk management ..................................................................11

6.1 General ........................................................................................................................................................................................................ 11

6.2 Process design ..................................................................................................................................................................................... 13

6.3 Risk assessment .................................................................................................................................................................................. 13

6.4 Identification of critical control points and process parameters .......................................................... 14

6.5 Handling and processing ............................................................................................................................................................ 14

6.6 Environment and air handling .............................................................................................................................................. 14

6.7 Materials ................................................................................................................................................................................................... 15

6.8 Personnel .................................................................................................................................................................................................. 15

6.8.1 General .....................................................................................................................................................................................15

6.8.2 Training ................................................................................................................................................................................... 16

6.8.3 Cleanroom clothing systems ................................................................................................................................ 16

6.8.4 Health ........................................................................................................................................................................................ 17

6.8.5 Service personnel ........................................................................................................................................................... 17

6.9 Aseptic processing equipment............................................................................................................................................... 18

6.9.1 General ..................................................................................................................................................................................... 18

6.9.2 Automated processes and robotics ................................................................................................................. 18

6.9.3 Single use systems and connecting devices ............................................................................................ 18

6.9.4 Auxiliary equipment and utilities .................................................................................................................... 18

6.10 Components ............................................................................................................................................................................................ 19

6.10.1 General ..................................................................................................................................................................................... 19

6.10.2 Integrity test ....................................................................................................................................................................... 19

6.11 Product ....................................................................................................................................................................................................... 19

6.11.1 Containment ........................................................................................................................................................................ 19

6.11.2 Aseptic Final Packaging Process ....................................................................................................................... 19

6.12 Flow management ............................................................................................................................................................................ 20

6.12.1 Containment ........................................................................................................................................................................20

6.12.2 Cross contamination .................................................................................................................................................... 20

6.12.3 Item introduction ...................................................................... ...................................................................................... 20

6.12.4 Egress ........................................................................................................................................................................................ 21

6.12.5 Waste management ....................................................................................................................................................... 21

6.13 Manufacturing process duration ......... ................................................................................................................................ 21

7 Contamination control strategy .......................................................................................................................................................21

7.1 General ........................................................................................................................................................................................................ 21

7.2 Cleaning and disinfection programs ................................................................................................................................ 22

7.2.1 General .....................................................................................................................................................................................22

7.2.2 Cleaning ................................................................................................................................................................................... 22

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7.2.3 Disinfection .......................................................................................................................................................................... 23

7.2.4 Equipment used for cleaning and disinfection in APA ...................................................................23

7.2.5 Cleaning process validation .................................................................................................................................. 24

7.2.6 Disinfection process validation .......................................................................................................................... 24

7.2.7 Cleaning and disinfection of equipment ..................................................................................................... 24

7.2.8 Cleaning and disinfection procedures ......................................................................................................... 25

7.3 Sterilization ............................................................................................................................................................................................ 25

7.3.1 General ..................................................................................................................................................................................... 25

7.3.2 Sterilization processes ...............................................................................................................................................25

7.3.3 Sterilization equipment ............................................................................................................................................. 25

7.3.4 Sterilization procedures ........................................................................................................................................... 26

7.3.5 Endotoxin control ...........................................................................................................................................................26

7.3.6 Depyrogenation process ........................................................................................................................................... 26

7.3.7 Maintenance of sterility ............................................................................................................................................ 27

7.4 Maintenance and calibration programs ........................................................................................................................29

7.4.1 Service personnel ...........................................................................................................................................................29

7.4.2 Planned maintenance activities .........................................................................................................................29

7.4.3 Unplanned maintenance ........................................................................................................................................... 30

7.4.4 Calibration of equipment ......................................................................................................................................... 30

7.5 Environmental monitoring ....................................................................................................................................................... 30

7.5.1 General .....................................................................................................................................................................................30

7.5.2 Sampling for non-viable particulate monitoring ................................................................................ 31

7.5.3 Sampling for microbiological environmental monitoring .......................................................... 31

7.6 Containment of potent or toxic substances................................................................................................................ 32

8 Demonstration of the effectiveness ..............................................................................................................................................32

8.1 Equipment qualification and validation........................................................................................................................ 32

8.1.1 General ..................................................................................................................................................................................... 32

8.1.2 User requirements specification ....................................................................................................................... 32

8.1.3 Design qualification ...................................................................................................................................................... 33

8.1.4 Installation qualification ......................................................................................................................................... 33

8.1.5 Operational qualification ......................................................................................................................................... 33

8.1.6 Performance qualification ...................................................................................................................................... 33

8.1.7 Requalification ..................................................................................................................................................................34

8.2 Aseptic process validation ........................................................................................................................................................34

8.2.1 General .....................................................................................................................................................................................34

8.2.2 Establishment and management of interventions.............................................................................34

8.2.3 Process simulation.........................................................................................................................................................34

8.2.4 Initial aseptic qualification .................................................................................................................................... 37

8.2.5 Periodic performance requalification .......................................................................................................... 37

8.2.6 Repeat of initial aseptic qualification ...........................................................................................................38

8.2.7 Documentation of process simulations .......................................................................................................39

8.2.8 Disposition of filled product ................................................................................................................................. 39

8.2.9 Aseptic process lifecycle considerations ...................................................................................................40

8.3 Maintenance of process ...............................................................................................................................................................40

8.3.1 General .....................................................................................................................................................................................40

8.3.2 R eview of the manufacturing process .........................................................................................................40

8.3.3 Changes or developments to the manufacturing process .......................................................... 41

8.3.4 R eview the risk assessment................................................................................................................................... 41

9 Product release ..................................................................................................................................................................................................41

9.1 General ........................................................................................................................................................................................................ 41

9.2 Testing for sterility .......................................................................................................................................................................... 41

9.3 Testing for bacterial endotoxins .......................................................................................................................................... 42

9.4 Rapid and alternative microbiological methods ................................................................................................... 42

Annex A (informative) Aseptic processing – typical elements .............................................................................................43

Annex B (informative) Specific risks to consider ............................................................................................................................... 44

Annex C (informative) Typical processing zones ................................................................................................................................50

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Annex D (informative) Comparison of classification of cleanrooms and filters ................................................55

Annex E (informative) Example of an aseptic process flow chart .....................................................................................57

Annex F (informative) Closed systems and robotics .......................................................................................................................58

Annex G (informative) Sterile cleanroom clothing system qualifications ...............................................................61

Annex H (informative) Rapid and alternative microbiological methods ..................................................................65

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

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

covered ........................................................................................................................................................................................................................67

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

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

covered ........................................................................................................................................................................................................................70

Bibliography .............................................................................................................................................................................................................................72

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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 198, Sterilization of health care products.

This third edition cancels and replaces the second edition (ISO 13408-1:2008) which has been

technically revised.
The main changes compared to the previous edition are as follows:
— a complete restructuring of the document;

— inclusion of a diagram to explain the relationship between the ISO 13408 series and ISO 18362;

— revision of the normative references;
— alignment of definitions with ISO 11139:2018;

— positioning of the document to recognize current and future advances in sterile manufacturing

technology, acknowledging that new approaches to aseptic processing are transforming classical

aseptic processing;

— promotion of aseptic processing principles and the systematic implementation of quality risk

management (QRM), including for aseptic process design, and microbiological contamination and

particulate contamination control;

— provision of guidance for different types of aseptic processing, for example, manual processing

systems through to automated robotic processing systems;

— deletion of tables from the previous edition of this document referring to acceptance criteria for

process simulation (media fill) qualification and requalification;

— encouraging adoption of advanced aseptic processing technologies and continuous process

improvement to improve assurance of sterility;
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— recognition that alternative or rapid microbiological methods provide timely microbiological data

vital for process monitoring and control, and for product release; and

inclusion of a series of informative annexes providing guidance on defining an aseptic process, including

risks to be considered, aseptic processing areas, classification of cleanrooms, aseptic process flow,

closed systems and robotics, and qualification of a cleanroom clothing system.
A list of all parts in the ISO 13408 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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Introduction

Wherever possible, healthcare products intended to be sterile should be terminally sterilized in their

final sealed container. Where a health care product is intended to be sterile and cannot withstand

terminal sterilization in its final container, aseptic processing provides an acceptable alternative for

product manufacture. Fundamentally, aseptic processing minimises the probability of a chance event of

microbial contamination occurring. The rationale to use aseptic processing is product dependent and is

not based solely on manufacturing considerations.

Aseptic processing produces a sterile product in its final container by the assembly of component parts

(e.g. product, container and container closure) that have been sterilized separately by validated and

controlled processes suitable for each component part. Each of these assembly processes can introduce

error that could result in produ
...