SIST EN ISO 13408-4:2011

Aseptic processing of health care products - Part 4: Clean-in-place technologies (ISO 13408-4:2005)

ISO 13408-4:2005 specifies the general requirements for clean-in-place (CIP) processes applied to product contact surfaces of equipment used in the manufacture of sterile health care products by aseptic processing and offers guidance on qualification, validation, operation and control.
ISO 13408-4:2005 is applicable to processes where cleaning agents are delivered to the internal surfaces of equipment designed to be compatible with CIP, which may come in contact with the product.
ISO 13408-4:2005 is not applicable to processes where equipment is dismantled and cleaned in a washer.
ISO 13408-4:2005 does not supersede or replace national regulatory requirements, such as Good Manufacturing Practices (GMPs) and/or compendial requirements that pertain to particular national or regional jurisdictions.

Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 4: Reinigung vor Ort (ISO 13408-4:2005)

Der vorliegende Teil von ISO 13408 legt die allgemeinen Anforderungen an die Verfahren zur Reinigung vor Ort (CIP-Verfahren) fest, die auf die Produktkontaktflächen der Ausrüstung angewendet werden, welche bei der Herstellung steriler Produkte für die Gesundheitsfürsorge durch aseptische Herstellung eingesetzt wird, und stellt einen Leitfaden zur Qualifizierung, Validierung, zum Arbeitsablauf und zur Kontrolle zur Verfügung.
Der vorliegende Teil von ISO 13408 ist anwendbar auf Verfahren, bei denen Reinigungsmittel auf die innenliegenden Oberflächen der für das CIP-Verfahren ausgelegten Ausrüstung, die in Kontakt mit dem Produkt kommen können, aufgebracht werden.
Der vorliegende Teil von ISO 13408 ist nicht anwendbar auf Verfahren, bei denen die Ausrüstung demontiert und in einer Waschanlage gereinigt wird.
Der vorliegende Teil von ISO 13408 ersetzt keine behördlichen Anforderungen, wie z. B. Gute Herstellungs-praktiken (GMP) und/oder Anforderungen von Arzneibüchern, die insbesondere nationale oder regionale Zuständigkeiten betreffen.

Traitement aseptique des produits de santé - Partie 4: Technologies de nettoyage sur place (ISO 13408-4:2005)

L'ISO 13408-4:2005 spécifie les exigences générales relatives au nettoyage sur place (NSP) appliqué aux surfaces de l'équipement utilisé pour la fabrication de produits de santé stériles et se trouvant en contact avec le produit en procédant à un traitement aseptique. Elle propose également des directives relatives à la qualification, à la validation, à l'exploitation et au contrôle.
L'ISO 13408-4:2005 s'applique aux processus dans lesquels des agents nettoyants sont appliqués sur les surfaces internes de l'équipement qui peuvent être nettoyées sur place, et qui peuvent entrer en contact avec le produit.
L'ISO 13408-4:2005 ne s'applique pas aux processus dans lesquels l'équipement est démonté et nettoyé dans une laveuse.
L'ISO 13408-4:2005 ne emplace pas ni n'annule des exigences réglementaires nationales, telles que les bonnes pratiques de fabrication (BPF) et/ou les exigences officielles, qui relèvent des juridictions nationales ou régionales particulières.

Aseptična proizvodnja izdelkov za zdravstveno nego - 4. del: Tehnologija čiščenja na mestu proizvodnje (ISO 13408-4:2005)

Ta del ISO 13408 določa splošne zahteve za procese čiščenja na mestu proizvodnje, uporabljene za površine opreme, ki je v stiku s proizvodi, uporabljanimi v proizvodnji sterilnih izdelkov za zdravstveno nego z aseptično proizvodnjo, in ponuja smernice za kvalifikacijo, validacijo, delovanje in nadzor. Ta del ISO 13408 velja za procese, kjer se čistilna sredstva nanašajo na notranje površine opreme, skladne s CIP, ki lahko pride v stik s proizvodom. Ta del ISO 13408 ne velja za procese, kjer se oprema razstavi in opere v pralnem stroju. Ta del ISO 13408 ne nadomešča ali zamenjuje nacionalnih regulatornih zahtev, kot so dobre prakse proizvodnje (GMP) in/ali strnjene zahteve, ki se nanašajo na nekatere državne ali regijske pristojnosti.

General Information

• Status: Published
• Public Enquiry End Date: 14-Apr-2011
• Publication Date: 15-Sep-2011
• ICS: 11.080.01 - Sterilization and disinfection in general
• Technical Committee: VAZ - Healthcare
• Current Stage: 6060 - National Implementation/Publication (Adopted Project)
• Start Date: 29-Jul-2011
• Due Date: 03-Oct-2011
• Completion Date: 16-Sep-2011
• Directive: 90/385/EEC - Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning medical devices
• Directive: 98/79/EC - Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices
• Mandate: M/BC/CEN/89/9 - Joint Standardization request to CEN/CENELEC concerning harmonized standards relating to horizontal aspects in the field of medical devices
• Ref Project: EN ISO 13408-4:2011 - Aseptic processing of health care products - Part 4: Clean-in-place technologies (ISO 13408-4:2005)

Relations

• Replaces: SIST EN 13824:2005 - Sterilization of medical devices - Aseptic processing of liquid medical devices - Requirements
• Effective Date: 01-Oct-2011
• Replaces: SIST EN 13824:2005 - Sterilization of medical devices - Aseptic processing of liquid medical devices - Requirements
• Effective Date: 08-Jun-2022

Standards Content (Sample)

SLOVENSKI STANDARD
SIST EN ISO 13408-4:2011
01-oktober-2011
1DGRPHãþD
SIST EN 13824:2005
$VHSWLþQDSURL]YRGQMDL]GHONRY]D]GUDYVWYHQRQHJRGHO7HKQRORJLMDþLãþHQMD
QDPHVWXSURL]YRGQMH,62
Aseptic processing of health care products - Part 4: Clean-in-place technologies (ISO
13408-4:2005)
Aseptische Herstellung von Produkten für die Gesundheitsfürsorge - Teil 4: Reinigung
vor Ort (ISO 13408-4:2005)
Traitement aseptique des produits de santé - Partie 4: Technologies de nettoyage sur
place (ISO 13408-4:2005)
Ta slovenski standard je istoveten z: EN ISO 13408-4:2011
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 13408-4:2011 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 13408-4:2011

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SIST EN ISO 13408-4:2011


EUROPEAN STANDARD
EN ISO 13408-4

NORME EUROPÉENNE

EUROPÄISCHE NORM
June 2011
ICS 11.080.01 Supersedes EN 13824:2004
English Version
Aseptic processing of health care products - Part 4: Clean-in-
place technologies (ISO 13408-4:2005)
Traitement aseptique des produits de santé - Partie 4: Aseptische Herstellung von Produkten für die
Technologies de nettoyage sur place (ISO 13408-4:2005) Gesundheitsfürsorge - Teil 4: Reinigung vor Ort (ISO
13408-4:2005)
This European Standard was approved by CEN on 10 June 2011.

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, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.





EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2011 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 13408-4:2011: E
worldwide for CEN national Members.

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SIST EN ISO 13408-4:2011
EN ISO 13408-4:2011 (E)
Contents Page
Foreword .3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices .4
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices .5
Annex ZC (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices .6

2

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SIST EN ISO 13408-4:2011
EN ISO 13408-4:2011 (E)
Foreword
The text of ISO 13408-4:2005 has been prepared by Technical Committee ISO/TC 198 “Sterilization of health
care products” of the International Organization for Standardization (ISO) and has been taken over as
EN ISO 13408-4:2011 by 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 December 2011, and conflicting national standards shall be withdrawn
at the latest by December 2011.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN 13824:2004.
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 Directives.
For relationship with EU Directives, see informative Annexes ZA, ZB, or ZC, which are integral parts of this
document.
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, Romania, Slovakia, Slovenia, Spain,
Sweden, Switzerland and the United Kingdom.
Endorsement notice
The text of ISO 13408-4:2005 has been approved by CEN as a EN ISO 13408-4:2011 without any
modification.
3

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SIST EN ISO 13408-4:2011
EN ISO 13408-4:2011 (E)
Annex ZA
(informative)

Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical
Devices
This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 90/385/EEC on active implantable medical devices.

Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the 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 Essential Requirements of that Directive and associated EFTA regulations.

Table ZA.1 — Correspondence between this European Standard and Directive 90/385/EEC
Clauses of this EN Essential Requirements (ERs) of Qualifying remarks/Notes
Directive 90/385/EEC
4,5,6,7,8,9,10 7 This relevant Essential Requirement is
only partly addressed in this European
Standard and only in conjunction with
EN ISO 13408-1
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this Standard.
4

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SIST EN ISO 13408-4:2011
EN ISO 13408-4:2011 (E)
Annex ZB
(informative)

Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices
This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 93/42/EEC on medical devices.

Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the 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 Essential Requirements of that Directive and associated EFTA regulations.

Table ZB.1 — Correspondence between this European Standard and Directive 93/42/EEC
Clauses of this EN Essential Requirements (ERs) of Qualifying remarks/Notes
Directive 93/42/EEC
4,5,6,7,8,9,10 8.3 This relevant Essential Requirement is
only partly addressed in this European
Standard and only in conjunction with
EN ISO 13408-1
4,5,6,7,8,9,10 8.4 This relevant Essential Requirement is
addressed in this European standard
only in conjunction with
EN ISO 13408-1
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this Standard.
5

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SIST EN ISO 13408-4:2011
EN ISO 13408-4:2011 (E)
Annex ZC
(informative)

Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical
devices
This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to Essential Requirements of the
New Approach Directive 98/79/EC on in vitro diagnostic medical devices.

Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the clauses of this
standard given in Table ZC.1 confers, within the limits of the scope of this standard, a presumption of
conformity with the corresponding Essential Requirements of that Directive and associated EFTA regulations.

Table ZC.1 — Correspondence between this European Standard and Directive 98/79/EC
Clauses of this EN Essential Requirements (ERs) of Qualifying remarks/Notes
Directive 98/79/EC
4,5,6,7,8,9,10 B.2.3 This relevant Essential Requirement is
only partly addressed in this European
Standard and only in conjunction with
EN ISO 13408-1
4,5,6,7,8,9,10 B.2.4 This relevant Essential Requirement is
addressed in this European standard
only in conjunction with
EN ISO 13408-1
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this Standard.

6

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SIST EN ISO 13408-4:2011


INTERNATIONAL ISO
STANDARD 13408-4
First edition
2005-11-01


Aseptic processing of health care
products —
Part 4:
Clean-in-place technologies
Traitement aseptique des produits de santé —
Partie 4: Technologies de nettoyage sur place




Reference number
ISO 13408-4:2005(E)
©
ISO 2005

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SIST EN ISO 13408-4:2011
ISO 13408-4:2005(E)
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©  ISO 2005
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or
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ii © ISO 2005 – All rights reserved

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SIST EN ISO 13408-4:2011
ISO 13408-4:2005(E)
Contents Page
Foreword. iv
Introduction . v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions. 1
4 Quality system elements. 2
4.1 General. 2
4.2 Management responsibility . 2
4.3 Design control. 2
4.4 Measuring instruments and measuring systems . 2
5 Process and equipment characterization .3
5.1 General concepts. 3
5.2 Effectiveness of CIP . 3
5.3 Equipment . 4
6 Cleaning agent characterization . 5
6.1 Selection of cleaning agent(s). 5
6.2 Quality of cleaning agent(s). 5
6.3 Safety and the environment. 6
7 CIP process . 6
7.1 Process parameters. 6
7.2 Process control. 6
7.3 Residues of cleaning agent(s). 8
8 Validation. 8
8.1 Validation protocol . 8
8.2 Evaluation of the CIP process . 8
8.3 Design qualification. 8
8.4 Installation qualification. 8
8.5 Operational qualification. 9
8.6 Performance qualification. 9
8.7 Review and approval of validation. 10
8.8 Requalification . 10
9 Routine monitoring and control . 10
9.1 CIP process control. 10
9.2 Procedures . 10
9.3 CIP process records. 11
9.4 Change control. 11
9.5 Maintenance and calibration . 11
10 Personnel training . 11
Annex A (informative) Description of sampling methods. 12
Annex B (informative) Calculation examples for acceptance criteria. 13
Bibliography . 14

© ISO 2005 – All rights reserved iii

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SIST EN ISO 13408-4:2011
ISO 13408-4:2005(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
(ISO member bodies). The work of preparing International Standards is normally carried out through ISO
technical committees. Each member body interested in a subject for which a technical committee has been
established has the right to be represented on that committee. International organizations, governmental and
non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the
International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
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.
ISO 13408-4 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.
ISO 13408 consists of the following parts, under the general title Aseptic processing of health care products:
 Part 1: General requirements
 Part 2: Filtration
 Part 3: Lyophilization
 Part 4: Clean-in-place technologies
 Part 5: Sterilization in place
 Part 6: Isolator systems

iv © ISO 2005 – All rights reserved

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SIST EN ISO 13408-4:2011
ISO 13408-4:2005(E)
Introduction
During the process of preparing ISO 13408-1 several items, e.g. filtration, lyophilization drying and
sterilization-in-place technologies, were found to be in need of supplementary information that was too
voluminous to be given in corresponding annexes.
This part of ISO 13408 includes requirements and guidance that are to be observed during clean-in-place
processes. The purpose of this part of ISO 13408 is to achieve standardization in the field of validation and
routine control of clean-in-place processes used in the manufacture of health care products.
Clean-in-place processes allow parts of the equipment or an entire process system to be cleaned without
being dismantled, reducing the need for disassembling and connections under clean conditions. For example,
tanks, vessels, freeze-dryers piping and other processing equipment used for manufacture may be cleaned in
place.
The clean-in-place process is in most instances followed by sterilization-in-place process (described in
ISO 13408-5). While clean-in-place and sterilization-in-place methods differ considerably in technology, the
concept of in situ treatment is similar.
Design considerations of all systems are critical to ensure that clean-in-place technologies can be successfully
applied to clean manufacturing equipment to the desired level of cleanliness.

© ISO 2005 – All rights reserved v

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SIST EN ISO 13408-4:2011

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SIST EN ISO 13408-4:2011
INTERNATIONAL STANDARD ISO 13408-4:2005(E)

Aseptic processing of health care products —
Part 4:
Clean-in-place technologies
1 Scope
This part of ISO 13408 specifies the general requirements for clean-in-place (CIP) processes applied to
product contact surfaces of equipment used in the manufacture of sterile health care products by aseptic
processing and offers guidance on qualification, validation, operation and control.
This part of ISO 13408 is applicable to processes where cleaning agents are delivered to the internal surfaces
of equipment designed to be compatible with CIP, which may come in contact with the product.
This part of ISO 13408 is not applicable to processes where equipment is dismantled and cleaned in a washer.
This part of ISO 13408 does not supersede or replace national regulatory requirements, such as Good
Manufacturing Practices (GMPs) and/or compendial requirements that pertain to particular national or regional
jurisdictions.
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated
references, only the edition cited applies. For undated references, the latest edition of the referenced
document (including any amendments) applies.
ISO 13408-1, Aseptic processing of health care products ― Part 1: General requirements
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 13408-1 and the following apply.
3.1
cleaning agent
organic or inorganic chemical including water, detergent or mixture thereof, used as an aid in the cleaning
process for cleaning equipment
3.2
clean-in-place
CIP
method of cleaning of the internal surfaces of parts of the equipment or an entire process system without or
with minimal disassembly
NOTE CIP also includes the removal of remaining residual cleaning agent to an acceptable level which is defined
based on the nature of the product and the process tolerance.
© ISO 2005 – All rights reserved 1

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SIST EN ISO 13408-4:2011
ISO 13408-4:2005(E)
3.3
dead leg
location which, by design, does not permit adequate accessibility of the cleaning agent
3.4
design qualification
documented verification that the proposed design of the facilities, equipment, or system is suitable for the
intended use
3.5
material safety data sheet
document specifying the properties of a material, its potential hazardous effects for humans and the
environment, and the precautions necessary to handle and dispose of the material safely
3.6
worst-to-clean
most difficult conditions for cleaning
EXAMPLES Materials to be removed, surface types to be cleaned, process parameters to be met or position(s) to be
reached.
4 Quality system elements
4.1 General
4.1.1 The requirements of ISO 13408-1 shall apply.
4.1.2 Documented procedures for each phase of the development, validation, routine monitoring and
control of the CIP process shall be prepared and implemented.
4.1.3 Documents required by this part of ISO 13408 shall be reviewed and approved by designated
personnel.
4.1.4 Records of development, validation, routine control and monitoring shall be maintained to provide
evidence of conformity to the requirements of this part of ISO 13408.
4.2 Management responsibility
4.2.1 The responsibilities and authority for implementing and performing the procedures described in this
part of ISO 13408 shall be specified.
4.2.2 If the requirements of this part of ISO 13408 are undertaken by organizations with separate quality
management systems, the responsibilities and authority of each party shall be specified.
4.3 Design control
Characterization of the cleaning agent(s), cleaning method, equipment to deliver CIP and the equipment
subject to CIP, shall be undertaken in accordance with a documented plan. At defined stages, design reviews
shall be planned, conducted and documented.
4.4 Measuring instruments and measuring systems
4.4.1 A documented system shall be specified for the calibration of all measuring instruments or measuring
systems.
4.4.2 The accuracy and tolerance of the measuring instrument shall be justified for the process to be
measured.
2 © ISO 2005 – All rights reserved

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SIST EN ISO 13408-4:2011
ISO 13408-4:2005(E)
5 Process and equipment characterization
5.1 General concepts
5.1.1 The specification for the CIP process shall include but not be limited to:
a) physical and chemical properties of the material to be removed and the strength of its adherence to the
surface from which it is to be removed;
b) physical and chemical properties and mechanism of action of cleaning agent(s);
c) compatibility of the equipment with the cleaning agents and processing conditions;
d) pre-cleaning period and conditions prior to cleaning;
e) the number of passes (single-pass cleaning, and/or multi-pass cleaning);
f) filling and immersing period with cleaning agent(s);
g) agitation or spraying of cleaning agent(s);
h) cleaning agent(s) elimination;
i) post-cleaning drying;
j) post-cleaning protection of the cleanliness of the equipment;
k) maximum post-cleaning hold period and conditions.
5.1.2 Cleaning agent(s) shall be reproducibly delivered in effective quantities and concentrations to all parts
of the system.
5.1.3 In order to ensure effective CIP, all parameters necessary to control the cleaning conditions shall be
established and documented. These conditions shall be maintained and monitored within specified limits.
5.1.4 When a large system is to be subjected to CIP, by dividing it into several segments, the segments
should overlap to ensure that all portions of the system are adequately and effectively cleaned.
NOTE Although the entire processing system can be cleaned as a single entity in CIP, it can be advantageous to
divide the system into several parts in order to simplify the cleaning procedures.
5.1.5 Complex sequences of opening and shutting of valves in the pipes of a system could be required.
Where this is controlled manually, detailed documentation of individual steps shall be established. Where
automation is used, electronic automation systems should be carefully designed and validated.
5.2 Effectiveness of CIP
5.2.1 The necessary level of cleanliness shall be established and documented. Justification of the process
parameters and the permitted levels of residual substances shall be included in the documentation. There
shall be no residue that poses a significant risk to patient safety.
NOTE Residual substances can include previous product or decomposition products thereof and/or cleaning agents.
5.2.2 Criteria for cleanliness are dependent in part, on the nature of the product that was previously
processed in the equipment to be cleaned taking into account potency, toxicity, biocompatibility,
carcinogenicity, mutagenicity, potential for tissue sensitization where equipment is not dedicated, etc. Where
removal of product is not possible with sufficient efficacy, it may be necessary to use dedicated equipment.
© ISO 2005 – All rights reserved 3

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SIST EN ISO 13408-4:2011
ISO 13408-4:2005(E)
5.3 Equipment
5.3.1 Equipment to be subjected to CIP
5.3.1.1 The equipment shall be designed and manufactured to ensure its cleanability by taking into
account ease of cleaning with regard to the characteristics of the products to be processed. Worst-to-clean
locations shall be minimized through the use of smooth, impervious, non-grooved, continuous and polished
surfaces.
NOTE Dead legs, locations with stagnant liquid in piping, shoulders of tanks, intricate irregular internal surfaces
...