Bsi bs en 01422 2014

This European Standard specifies requirements for ethylene oxide sterilizers EO-sterilizers working at super or sub-atmospheric pressure for: — the performance and design of sterilizers

BSI Standards Publication

Sterilizers for medical purposes

— Ethylene oxide sterilizers

— Requirements and test methods

© The British Standards Institution 2014.

Published by BSI Standards Limited 2014ISBN 978 0 580 76557 5

Amendments/corrigenda issued since publication

Date Text affected

NORME EUROPÉENNE

English Version

Sterilizers for medical purposes - Ethylene oxide sterilizers -

Requirements and test methods

Stérilisateurs à usage médical - Stérilisateurs à l'oxyde

d'éthylène - Exigences et méthodes d'essai

Sterilisatoren für medizinische Zwecke - Sterilisatoren - Anforderungen und Prüfverfahren

Ethylenoxid-This European Standard was approved by CEN on 17 April 2014

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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,

Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United Kingdom

EUROPEAN COMMITTEE FOR STANDARDIZATION

C O M I T É E U R O P É E N D E N O R M A L I S A T I O N

E U R O P Ä I S C H E S K O M I T E E F Ü R N O R M U N G

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels

© 2014 CEN All rights of exploitation in any form and by any means reserved

worldwide for CEN national Members

Ref No EN 1422:2014 E

2

Foreword 4

Introduction 5

1 Scope 6

2 Normative references 6

3 Terms and definitions 7

4 Technical requirements 12

4.1 General 12

4.1.1 Risk control and usability 12

4.1.2 Materials 13

4.2 Sterilizer chamber 13

4.2.1 Chamber size 13

4.2.2 Doors, closures and interlocks of the sterilizer chamber 13

4.2.3 Test connections 14

4.3 Design and construction 15

4.3.1 General 15

4.3.2 EO vaporizers 15

4.3.3 Pipework and fittings 15

4.3.4 Evacuation system 15

4.3.5 Control valves 16

4.3.6 Thermal insulation 16

4.3.7 Electrical and mechanical safety 16

4.3.8 Air or inert gas filter 16

4.3.9 Emission control 16

4.3.10 Framework and panelling 17

4.3.11 Loading equipment 17

4.3.12 Transport 17

4.4 Indicating, measuring, and recording instruments 17

4.4.1 General 17

4.4.2 Temperature sensor 18

4.4.3 Temperature indicating instruments 18

4.4.4 Pressure sensors 19

4.4.5 Timers and time indicating instruments 19

4.4.6 Sterilizing cycle counter 19

4.4.7 Relative humidity (RH) sensors 19

4.4.8 Ethylene Oxide (EO) concentration-measurement 19

4.4.9 Recording instruments 20

4.4.10 Indicating instruments 21

5 Process control 22

5.1 General 22

5.2 Software verification and validation 23

5.3 Sterilization cycle and automatic control 23

5.3.1 Automatic control 23

5.3.2 Sterilization cycle 24

5.4 Override of automatic control 27

5.5 Fault 27

6 Performance requirements 28

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6.1 Sterilizing performance 28

6.1.1 Loading configuration 28

6.1.2 Physical parameters 28

6.1.3 Microbiological efficacy 28

6.2 EO removal (flushing) 29

6.3 Aeration 29

7 Sound power 29

8 Packaging, marking and labelling 29

9 Information to be supplied by the manufacturer 30

10 Service and local environment 32

10.1 General 32

10.2 Electricity 33

10.3 Sterilant 33

10.4 Circulation systems 33

10.5 Steam 33

10.6 Water 34

10.7 Air and inert gasses 34

10.8 Drainage and discharges 34

10.9 Ventilation and environment 34

10.10 Lighting 34

Annex A (normative) Test instrumentation 35

Annex B (normative) Leak test cycle 36

Annex C (normative) Sterilizer chamber profile testing 37

C.1 Sterilizer chamber internal surfaces 37

C.2 Empty sterilizer chamber 37

Annex D (normative) Microbiological test for EO sterilizers 38

D.1 General 38

D.2 Test equipment 38

D.3 Procedure 39

D.4 Interpretation of results 40

Annex E (informative) Environmental aspects 41

E.1 Environmental aspects regarding the life cycle of EO sterilizers 41

E.2 EO (brief description) 41

E.3 Environmental impact 41

Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on medical devices 44

Bibliography 48

4

Foreword

This document (EN 1422:2014) has been prepared by Technical Committee CEN/TC 102 “Sterilizers for medical purposes”, the secretariat of which is held by DIN

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 2014 and conflicting national standards shall be withdrawn at the latest

by May 2017

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 1422:1997+A1:2009

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

For relationship with EU Directive, see informative Annex ZA, which is an integral part of this document

Annexes A, B, C and D are normative and form part of this European Standard

Annexes E and ZA are for information only

The standard is a full technical revision of the previous version The following amendments have been made in comparison with EN 1422:1997+A1:2009:

— new specification of the scope of the standard, e.g explicit exclusion of sterilizers which employ the injection of

EO or mixtures containing EO directly into packages or into a flexible chamber and removal of different types A and B of EO-sterilizers ;

— normative references have been updated;

— layout of the standard brought in line with the standard for LTSF-sterilization (EN 14180);

— the additional requirements from the machinery directive, introduced by the revision of the medical devices directive 2007/47/EC have been addressed (see revised Annex ZA), i.e update of technical requirements and Tables ZA.1 and ZA.2;

— requirements have been rephrased to be performance requirements instead of design requirements;

— addition of an environmental checklist;

— Annex B has been thoroughly revised and Annex D has been deleted

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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom

Validation and routine control of sterilization processes are essential to ensure their efficacy This European Standard does not cover validation and routine control of EO processes (see prEN ISO 11135:2012) EO is a highly reactive chemical which can present a toxic, flammable or explosive hazard if incorrectly handled (see Annex E) The performance requirements specified in this document are not intended for the process to be effective in inactivating the causative agents of spongiform encephalopathies such as scrapie, bovine spongiform encephalopathy and Creutzfeld-Jakob disease

Planning and design of products complying with this standard should consider not only technical issues but also the environmental impact from the product during its life-cycle Environmental aspects are addressed in Annex E of this standard

By performing tests concurrently and/or in a logical sequence, the total number of tests carried out and waste arising from such tests, is reduced As a result the burden on the environment can be reduced (see also Annex E)

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1 Scope

This European Standard specifies the requirements and the relevant tests for automatically controlled sterilizers employing ethylene oxide (EO) gas as the sterilant, either as a pure gas or a mixture with other gases, being used for the sterilization of medical devices and their accessories

This European Standard specifies requirements for ethylene oxide sterilizers (EO-sterilizers) working at super or sub-atmospheric pressure for:

— the performance and design of sterilizers to ensure that the process is capable of sterilizing medical devices;

— the equipment and controls of these sterilizers necessary for the validation and routine control of the sterilization processes

The test loads described in this European Standard are selected to represent a number of loads for the evaluation

of the performance of EO sterilizers for medical devices However, specific loads may require the use of other test loads

This European Standard does not specify those tests which are necessary to determine the probability of a processed product being sterile, nor the routine quality control tests required prior to release of sterile product These topics are addressed in prEN ISO 11135:2012

This European Standard does not specify requirements for occupational safety associated with the design and operation of EO sterilization facilities

NOTE 1 For further information on safety, see examples in the Bibliography National or regional regulations can exist

This European Standard does not cover sterilizers which employ the injection of EO or mixtures containing EO directly into packages or into a flexible chamber

NOTE 2 See EN ISO 14937

This European Standard is not intended as a checklist for suitability of an existing EO sterilizer when assessing compliance with prEN ISO 11135:2012 This standard is not intended to be applied retrospectively

This European Standard does not cover analytical methods for determining levels of residual EO and/or its reaction products

NOTE 3 For further information see ISO 10993-7

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

EN 764-7, Pressure equipment - Part 7: Safety systems for unfired pressure equipment

EN 868-4, Packaging for terminally sterilized medical devices - Part 4: Paper bags - Requirements and test methods

EN 868–5, Packaging for terminally sterilized medical devices - Part 5: Sealable pouches and reels of porous materials and plastic film construction - Requirements and test methods

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EN 13445-3, Unfired pressure vessels - Part 3: Design

EN 13445-5, Unfired pressure vessels - Part 5: Inspection and testing

EN 14222, Stainless steel shell boilers

EN 61010–1:2010, Safety requirements for electrical equipment for measurement, control and laboratory use — Part 1: General requirements (IEC 61010-1:2010)

EN 61010-2-040:2005, Safety requirements for electrical equipment for measurement, control and laboratory use — Part 2-040: Particular requirements for sterilizers and washer-disinfectors used to treat medical materials (IEC 61010-2-040:2005)

EN 61326-1:2006, Electrical equipment for measurement, control and laboratory use — EMC requirements — Part 1: General requirements (IEC 61326-1:2005)

EN ISO 3746:2010, Acoustics - Determination of sound power levels and sound energy levels of noise sources using sound pressure - Survey method using an enveloping measurement surface over a reflecting plane (ISO 3746:2010)

EN ISO 10993-7:2008, Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals (ISO 10993-7:2008)

prEN ISO 11135:2012, Sterilization of health-care products — Ethylene oxide — Requirements for the development, validation and routine control of a sterilization process for medical devices (ISO/DIS 11135:2012)

EN ISO 11138-1, Sterilization of health care products - Biological indicators - Part 1: General requirements (ISO 11138-1)

EN ISO 11138-2, Sterilization of health care products - Biological indicators - Part 2: Biological indicators for ethylene oxide sterilization processes (ISO 11138-2)

EN ISO 11607-1, Packaging for terminally sterilized medical devices - Part 1: Requirements for materials, sterile barrier systems and packaging systems (ISO 11607-1)

EN ISO 14971:2012, Medical devices - Application of risk management to medical devices (ISO 14971:2007, Corrected version 2007-10-01)

3 Terms and definitions

For the purposes of this document, the following terms and definitions apply

3.1

aeration

part of the sterilization process during which ethylene oxide and/or its reaction products desorb from the medical device until predetermined levels are reached

Note 1 to entry: This can be performed within the sterilizer and/or in a separate chamber or room

[SOURCE: prEN ISO 11135:2012, 3.1]

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3.2

air admission stage

stage of the cycle beginning with the attainment of the pre-set pressure on the last evacuation of the flushing stage

or sterilant removal stage when filtered air is admitted to allow the chamber pressure to equilibrate with ambient pressure

set of operations that establish, under specified conditions, the relationship between values of a quantity indicated

by a measuring instrument or measuring system, or values represented by a material measure or a reference material, and the corresponding values realized by standards

ethylene oxide exposure time

the period of the sterilization cycle between the end of EO injection and the beginning of EO removal

3.10

fault

one or more of the process parameters lying outside of its/their specified tolerance(s)

[SOURCE: ISO/TS 11139:2006, 2.19]

any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calibrator, software, material

or other similar or related article, intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the specific purpose(s) of

— diagnosis, prevention, monitoring, treatment or alleviation of disease,

— diagnosis, monitoring, treatment, alleviation of or compensation for an injury,

— investigation, replacement, modification or support of the anatomy or of a physiological process,

— supporting or sustaining life,

— control of conception

— disinfection of medical devices,

— providing information for medical purposes by means of in vitro examination of specimens derived from the human body,

and which does not achieve its primary intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means

collecting and storing data

Note 1 to entry: Data storing can be realised electronically or by hard copy

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3.24

services

supplies from an external source, needed for the function of equipment

EXAMPLE Electricity, water, compressed air, drainage

treatment in a sealed chamber comprising air removal, conditioning (if used), injection of ethylene oxide, exposure

to ethylene oxide, removal of ethylene oxide and flushing (if used), and air/inert gas admission

[SOURCE: prEN ISO 11135:2012, 3.48]

Note 1 to entry: EO sterilization cycle does not include aeration (if required)

usable chamber volume

defined space within the sterilizer chamber, which is not restricted by fixed or mobile parts and which is available to accept the sterilization load

EXAMPLE The available space on a pallet of defined dimensions

Note 1 to entry: The maximum load volume is likely to be less than the usable chamber volume as space is required to allow for circulation of sterilant gasses

[SOURCE: prEN ISO 11135:2012, 3.56]

series of tests performed prior to delivery to demonstrate compliance of equipment with its specification

Note 1 to entry : In accordance with EN ISO 15883-1:2009

4 Technical requirements

4.1 General

If a pressure vessel according to the Pressure Equipment Directive (PED) is used for the sterilization, the vessel shall comply with EN 13445-3, EN 13445-5 and EN 764-7

If a shell boiler is used to generate the steam used in the sterilizer, it shall comply with EN 14222

NOTE 1 See Council Directive concerning pressure equipment (97/23/EEC) [3]

NOTE 2 Sterilizer chambers that run sterilization cycles designed to operate completely below 1,5 bar, do not fall under the Pressure Vessel Directive (PED) Appropriate pressure relief valves can used to ensure over pressurisation does not occur NOTE 3 Other European directives can apply Examples of directives that can apply include, but are not restricted to, the LVD [5], EMC [4], ATEX [2], REACH [10]

4.1.1 Risk control and usability

4.1.1.1 Risk assessment and risk control for sterilizer design and software shall be performed following the procedures and requirements given in EN ISO 14971:2012, Clauses 5, 6 and 7

4.1.1.2 Risk analysis shall address the specific EO-sterilizer design and features Measures taken for risk reduction shall consider aspects as user knowledge, experience, training, ergonomics and usability

— are not corroded by EO, its diluent gasses or potential contaminants or steam and/or be subject to metallic corrosion;

— will not react with EO, its diluent gasses or potential contaminants or steam;

— will not promote the polymerization or decomposition of EO;

— will not allow diffusion of EO to an extent which impairs their safe operation

Due attention should be paid to the effects of mechanical effects and differential expansion when dissimilar metals are used in contact

NOTE 1 When selecting materials for construction, the material safety data sheet for EO can be referenced

NOTE 2 The compatibility of materials with ethylene oxide has been addressed in literature (e.g.[6])

4.1.2.2 The admissible pressure and temperature range (see 9.2) shall be specified when selecting materials for construction

c) for other configurations the chamber shall be specified in analogy to a) or b)

4.2.2 Doors, closures and interlocks of the sterilizer chamber

4.2.2.1 After closing the sterilizer door, it shall be possible to open it before a cycle has been started

4.2.2.4 In case of an interrupted cycle (e.g due to a fault), the sterilizer shall be brought to a condition that presents no hazard to the operator or ancillary equipment, taking into account EO and inert gases being used during the process Opening of the door shall require the use of a special key, code or tool as specified by the manufacturer

4.2.2.5 Provision shall be made to permit access to the contact surfaces for the purposes of cleaning and replacing the door seal

4.2.2.6 For dedicated test or maintenance cycles, the records shall clearly indicate that this is not a routine sterilization cycle The ‘cycle complete’ indication on the sterilizer may be different from the normal cycle complete indication and/or opening the unloading door may require the use of a special key, code or tool as specified by the manufacturer

4.2.2.7 The device used to start the automatic operating cycle shall be located at the loading side of the sterilizer or in the control room

4.2.2.8 For maintenance purposes it shall be possible to open both doors simultaneously on double-ended sterilizers using a special key, code or tool as specified by the manufacturer

4.2.2.9 For double-ended sterilizers both ends of the sterilizer shall be fitted with a device to indicate whether the door at that end can be opened In addition, if there is a control room, an indication of which door can be opened shall also be provided in the control room

If the doors are controlled from a control room, no indications at the doors whether a door can be opened, are required

4.2.2.10 The indication ‘cycle complete’ shall be cancelled when a door is opened

NOTE After the ‘cycle complete’ indication, additional degassing/aeration could be required to achieve safe conditions for the operators

4.2.2.11 The door closing and locking mechanism shall be designed in such a way that the operator is not endangered, such as a safety edge or an auto reverse function

4.2.2.12 If a powered chamber door is fitted, systems shall be provided to permit the removal of persons or objects entrapped by the moving door before the pressure, force and temperature specified in EN 61010-1:2010,10.1 and EN 61010-2-040:2005, 7.1.101, 7.101 and 7.102 are exceeded

NOTE This can be achieved, e.g by reversing the direction of the door movement

4.2.3 Test connections

4.2.3.1 The number and types of test connections shall be specified It shall be specified how test equipment can be introduced into the sterilizer chamber Test connection(s) (if fitted) shall be designed in such a way that all areas of the chamber can be reached in a suitable manner with suitable measurement techniques

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NOTE 1 If the measurement of EO-concentration or RH is required, this needs to be taken into account when specifying the dimensions for the test connections to allow easy access for the measuring systems

NOTE 2 Increasing the number of test connections increases the risk of leakage

NOTE 3 Failure to provide test connections could complicate the performance of validation

4.2.3.2 Test connections shall be at points of easy access, but not in pipes for media transport (e.g steam,

EO, air), and the test connections shall be specified

4.2.3.3 The test connections shall be provided with caps and sealed with EO proof and mechanically resistant seals

NOTE It is recommended to keep the number of test connections to a minimum for reasons of safety

4.3 Design and construction

4.3.1 General

Components, including ancillary vessels that are connected to sterilizer chamber and that are required to contain the admissible design pressure of the chamber or higher, may need to comply with the requirements of the PED or other relevant directives

All components in the piping network shall be marked and/or identified according to their functions (see EN 60073) The maintenance or replacement frequency for all components of the equipment shall be established and documented

4.3.2 EO vaporizers

EO vaporizers shall be constructed so that the heating surface in contact with EO is cleanable by the method specified by the manufacturer

4.3.3 Pipework and fittings

4.3.3.1 Pipework shall be designed to prevent accumulation of condensate

NOTE Insulation of pipework can reduce the amount of condensate formed

4.3.3.2 All pipework and fittings carrying EO shall be made by welding or brazing unless the joint is intended to

be demountable for maintenance purposes

NOTE Flexible hoses which are designed to, or can inadvertently, carry EO are preferably constructed from stainless steel

or stainless steel internally lined with polytetrafluoroethylene (PTFE), nitrile rubber, or other material of demonstrated equivalent performance

4.3.4 Evacuation system

4.3.4.1 Sterilizers shall be provided with means to evacuate the chamber to meet process specifications

NOTE 1 Minimization of the amount of water used is a consideration when designing evacuation (see also Annex E)

NOTE 2 EO can dissolve in water and oil

4.3.4.2 The sterilizer shall be provided with a means for leak testing which shall include the sterilizer chamber and all relevant connected pipeworks and fittings

4.3.7 Electrical and mechanical safety

4.3.7.1 Safety of the design shall be based on risk assessment Technical solutions shall consider applicable standards

NOTE 1 For general design see EN 61010–1 and EN 61010–2–040

NOTE 2 Additional guidance is given in EN ISO 12100

NOTE 3 For guidance regarding specific design aspects, EN 60204–1 can apply The guidance in EN 60204–1 can reduce testing

4.3.7.2 Sterilizers shall comply with EN 61326-1 regarding electromagnetic compatibility (EMC)

Sterilizers operating in areas intended for medical electrical equipment or in the vicinity of other sensitive equipment shall be regarded as Class B equipment as specified in EN 61326-1

The immunity performance criteria selected shall ensure that sterilizer performance as specified in 5.2 is met when exposed to disturbance phenomena of EN 61326-1:2006, Table 2

4.3.8 Air or inert gas filter

4.3.8.1 Microbial (re)contamination of the sterilization load shall be prevented

4.3.8.2 When filters are fitted to prevent (re)contamination, they shall be readily accessible for replacement The filter shall retain not less than 99,5 % of particles greater than 0,3 μm

Air filters should be constructed from materials resistant to corrosion and biodegradation

NOTE 1 A readily detachable pre-filter designed to retain dust particles greater than 25 μm is recommended to prolong the life of the filter

NOTE 2 It is recommended that the filter material is supported in a manner which restricts its distortion and movement during use in order to minimise damage to the filter medium

4.3.8.3 Each filter shall have a control valve fitted directly between the filter and chamber, to isolate the filter

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4.3.10 Framework and panelling

4.3.10.1 If the sides of the sterilizer need not to be accessible for normal operation, they shall be enclosed with panelling

NOTE Some types of large industrial sterilizers and sterilizers designed to be recessed into existing walls providing a continuous joint with the sterilizer front panelling, do not need to be provided with side panelling

4.3.10.2 Removal or opening of a panel used as a physical barrier to provide protection (guard) shall require the use of an access device

The panelling shall be long-term corrosion-resistant Instructions for cleaning of the panelling shall be provided

NOTE Ventilation openings can be provided in the panelling

4.3.10.3 The panelling of the sterilizer shall allow access for maintenance work Such panelling shall be demountable or the dimensions of any personal access shall be not less than 500 mm wide and not less than

1500 mm high, and the access shall not be obstructed

Fixings for these panels shall remain attached to either the panels or to the body of the sterilizer when panels are removed

The access for maintenance should be positioned so that it will not compromise the safety of either the product or persons

NOTE Requirements for access are specified in EN 61010–2-040:2005, 7.3.2 and 7.3.5

The sterilizer and it’s components (if applicable) shall be packed for transportation and storage in a way that, when handled or transported, all parts of the sterilizer shall remain in their position and orientation so that the sterilizer remains stable and no moving part can cause a hazard

4.4 Indicating, measuring, and recording instruments

4.4.1 General

4.4.1.1 Indicating and measuring and recording instruments shall be identified as to their function They shall

be readily accessible, clearly and durably marked with their function and designed to be easy to operate and read

4.4.1.2 The instruments shall be positioned and/or protected such that their performance is within the specified tolerances during the operation of the sterilizer

4.4.1.3 If an indicating instrument is connected in turn to more than one sensing point, there shall be a continuous indication of the active sensor that is being monitored

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4.4.1.4 Indicating and operating instruments shall be readable when viewed at a distance of (250 ± 25) mm with normal or corrected vision in an illumination of (215 ± 15) lx

4.4.1.5 Indicating, measuring and recording instruments shall have means to adjust in situ by the use of a key,

code or tool without dismantling the instrument

NOTE Where digital pressure indicators are used, an additional mechanical pressure gauge can be fitted for safety

reasons Where an analogue instrument is provided only for this purpose, the requirement for adjustment in situ is waived

4.4.1.6 Additional functions fitted at recording or indicating instruments shall not jeopardise the accuracy

4.4.1.7 When used for process control, indicating or recording purposes, means shall be provided to indicate a sensor failure

4.4.2 Temperature sensor

4.4.2.1 When used for process control, indicating or recording purposes, temperature sensors shall have maximum permissible errors of 1 °C or less over the scale range 20 °C to 10 °C above the highest process temperature The data sampling rate shall be high enough to ensure valid representation of the sterilization process and the response time of the sensor shall be 1 s or less

NOTE The required sampling rate will be dependent upon the rate of change of temperature within the process In large industrial sized chambers, the sampling rate can be once a minute In smaller chambers, this rate will need to be increased

4.4.2.2 A minimum of two probes to measure chamber temperature shall be used Large volume chambers can be fitted with more than two probes so as to ensure that the system captures data that reflects the temperature throughout the chamber during use Temperature probes should be located in the area specified as the reference measurement point and shall be easily removable for calibration purposes if necessary

NOTE The purpose of two separate probes is to prevent the failure of one sensor from causing an out-of-specification process from being erroneously accepted Comparing two separate temperature sensors will detect that one of the sensors has failed A dual element temperature probe can be used to meet this need

If there is an undetected failure of a control or monitoring function, a sterilization load could be released without having met its required processing parameters To prevent this from happening, it is general practice to have redundant sensors for many critical process parameters The common options for utilising these redundant sensors include:

a) use one sensor for control, and another sensor for monitoring and reporting;

b) use two sensors, or their average value, for both monitoring and control; this system needs to generate an automatic fault condition if the difference between the two sensors exceeds a defined value;

c) use dual element sensors for both monitoring and control; this system needs to generate an automatic fault condition if the difference between the two elements exceeds a defined value

4.4.3 Temperature indicating instruments

In addition to the requirements in 4.4.2.1, the temperature indicating instruments shall:

a) be graduated in degrees Celsius;

b) have a scale, which includes at least 10 °C below the lowest process temperature and 10 °C above the highest process temperature;

c) for analogue instruments be graduated in divisions not greater than 2 °C;

4.4.5 Timers and time indicating instruments

4.4.5.1 Time periods within the process shall have an uncertainty of measurement of ± 2 % or less of the process stage duration

NOTE In some regions, the frequency of the public electrical supply is unstable and can therefore not be used to establish

a time base for cycle control and recording purposes

4.4.5.2 If dates and times are indicated, the formats dd:mm:yyyy or yyyy:mm:dd and hh:mm:ss shall be used

as applicable

4.4.6 Sterilizing cycle counter

A counter shall be provided to indicate the cumulative number of all cycles started, including those cycles in which a fault occurred The cycle counter shall display a minimum of four digits and shall not be capable of being reset inadvertently Additional data entry fields may be used for cycle identification

4.4.7 Relative humidity (RH) sensors

The RH instrumentation, if fitted, shall cover the range 0 % RH to 100 % RH In the range 30 % - 80 %, the accuracy shall be ± 10 % or better The data sampling rate shall be high enough to ensure valid representation of the sterilization process and the response time shall be not more than 1 min If the RH is measured it shall be recorded

NOTE Other methods to measure humidity (e.g gas chromatography and spectroscopy) can be used and under such circumstances, the above requirement for response time will not apply

4.4.8 Ethylene Oxide (EO) concentration-measurement

The range for EO-concentration measurement instrument, if fitted, shall cover 0 mg/l up to 10 % over the maximum concentration specified for the process The accuracy shall be ± 5 % If the EO-concentration is measured, it shall

be recorded

NOTE EO-measurement is a requirement for parametric release of the load (see prEN ISO 11135:2012, 10.5)

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4.4.9 Recording instruments

4.4.9.1 General

4.4.9.1.1 The recording instrumentation shall be independent from the automatic controller

NOTE 1 This does not exclude the transfer of informative data from the automatic controller to the recorder and vice versa, via a combined system for data transfer

NOTE 2 Sterilizer identification, cycle number and load identification can be recorded automatically

4.4.9.1.2 For operational inspection as well as for batch documentation, analogue or digital recording

instrumentation shall record pressure and temperature and, if measured, RH and EO-concentration data versus time The records shall allow evaluation of the data for compliance with process specifications (see 9.2)

NOTE The data records can consist of digital records, analogue curves or both

4.4.9.1.3 The recording system shall produce a record which will remain readable for a period specified by the

user

NOTE 1 The record can be printed or in electronic format

NOTE 2 The retention period can depend on local requirements and regulations

4.4.9.1.4 The recorder shall be either

a) a fixed and integral part of the sterilizer, or

b) as an external system connected to the sterilizer by a data link via a specified interface using specified data format

4.4.9.1.5 If used, the data link shall allow the external system to generate records, which are compliant to all

applicable specifications of 4.4.9

4.4.9.1.6 Unless the power supply is interrupted or the instrument itself malfunctions, the instrument shall

continue to operate after a fault occurs

4.4.9.1.7 Recording instrumentation shall have a sampling interval sufficient to provide an accurate

representation of the process, taking into account the dynamics of the process (see [9])

4.4.9.1.8 Records shall be readable when viewed at a distance of (250 ± 25) mm with a normal or corrected

vision in an illumination of (215 ± 15) lx

4.4.9.1.9 When a fully digital system is used for recording, means shall be provided to ensure that data are

secure and cannot be altered from their original state (see 5.2)

4.4.9.2 Recording instrumentation (analogue format)

4.4.9.2.1 If two or more variables are recorded in an analogue format, the displayed scale markings shall be

common for all the variables recorded and the major marked interval shall be marked sequentially for each of the variables recorded

NOTE An analogue format can be a graph and/or a chart, which can be produced either electromechanically or electronically

4.4.9.2.2 If the recorded data are printed, the scales used shall reflect the accuracy and resolution required for

the indicating instruments

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4.4.9.3 Recording instrumentation producing alphanumerical print-outs (digital format)

4.4.9.3.1 Recorders producing alphanumerical print-outs shall use alphanumeric characters and define data by

text

4.4.9.3.2 Recorders producing alphanumerical print-outs shall have a paper width with a space for a minimum of

15 characters/line

4.4.9.3.3 Temperature recorders producing alphanumerical print-outs shall have:

— a range which includes 0 °C to 100 °C;

— maximum permissible errors of 1 °C or less over the range 20 °C to 10 °C above the highest process temperature

4.4.9.3.4 Pressure recorders producing alphanumerical print-outs shall have:

— a range which includes 0 kPa (0 bar) to at least 10 % above the maximum process operating pressure;

— maximum permissible errors of the record of 1,6 % or less over the scale range

4.4.9.3.5 RH recorders producing alphanumerical print-outs shall have:

— a range which included 0 % −100 %

— maximum permissible errors of 10 % over the range 30 % - 80 %

4.4.9.3.6 EO-concentration recorders producing alphanumerical print-outs shall have:

— a range which includes 0 mg/l up to 10 % over the maximum concentration specified for the process;

— maximum permissible errors ± 5 %

4.4.10 Indicating instruments

4.4.10.1 Sterilizer instrumentation shall make available at least the following information:

a) indication of the chamber pressure;

b) indication of the chamber temperature;

c) indication of, if measured, relative humidity;

d) indication of the jacket/chamber wall temperature and pressure (if the sterilizer is fitted with a pressurized jacket);

e) indication of condition of the services (e.g steam, nitrogen, compressed air);

f) indication of the sterilizer being in the state of alert (standby);

g) indication of sterilizer “door(s) locked”;

h) indication of the cycle selected;

i) indication of sterilizer “in progress”;

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j) indication of the sterilization cycle stage;

k) indication of “cycle complete”;

l) indication of “fault” when occurring (see 5.5);

m) indication of when the sterilizer door can be opened;

n) cycle counter (see 4.4.6);

o) confirmation that gaseous EO was injected into the chamber and, if measured, an indication of it’s concentration

NOTE The required information outlined above can be integrated into a single system or a combination of individual systems

4.4.10.2 In addition, instrumentation at double-ended sterilizers shall provide the following visual information at the unloading side in case information a) to e) is not already displayed in the control room:

a) indication of the chamber pressure;

b) indication of sterilizer “in progress”;

c) indication of “cycle complete”;

d) indication of when the unloading door can be opened;

e) indication of “fault”

5 Process control

5.1 General

5.1.1 The sterilizer and the sterilization cycle shall be operated by an automatic controller

5.1.2 The sterilizer cycle shall operate with pre-set programmes Any change of the pre-set programme or its

parameters shall require the use of a key, code or tool and shall be documented

5.1.3 The parameters of the variables programmed into the automatic controller and the tolerances that will still

enable the performance requirements of Clause 6 to be met shall be specified (see also 9.2)

5.1.4 The automatic controller shall be protected against short circuit in components or equipment, which are

directly or indirectly connected to the controller

5.1.5 The automatic controller shall be located such that the maximum values of temperature and humidity

specified for the automatic controller are not exceeded

NOTE Widely used maximum values for the temperature and humidity in the vicinity of the control system are 50 °C and

85 % relative humidity respectively

5.1.6 The position of the temperature sensor used to control the process shall be selected in such a way that

throughout the exposure time the temperature at this point correlates with the temperature in the usable chamber volume

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5.1.7 Means shall be provided to ensure that failure in a control function does not lead to failure in recording of

process parameters such that an ineffective process appears effective

NOTE This can be achieved either by the use of independent systems for control and monitoring or by a cross-check between control and monitoring which identifies any discrepancies or indicates a fault

5.2 Software verification and validation

5.2.1 Software for automatic controllers shall be demonstrated to function as intended The classification of

software with respect to safety shall be established through risk assessment

5.2.2 Software parts related to safety of patients, users or any other persons shall be verified and validated using

methods according to the state of art The methods used in the validation and verification process shall be justified and documented

NOTE EN 61508–1, EN 62304 and EN 62061 can support activities to be performed

5.3 Sterilization cycle and automatic control

5.3.1 Automatic control

5.3.1.1 The automatic controller shall be capable of being programmed with parameters and tolerances for each stage of a sterilization cycle Programming the automatic controller shall require a special key, code or tool Where a cycle has been programmed for qualification purposes, the user shall have appropriate controls over it’s use Qualification cycles shall be clearly indicated

5.3.1.2 It shall not be possible to adjust the process parameters during the progress of a sterilization cycle

5.3.1.3 Access to control devices shall only be possible by use of a special key, code or tool

5.3.1.4 For maintenance, test purposes and in cases of emergency, means shall be provided to permit manual progression of the automatic controller The selection of this manual facility shall be by means of a special key, code or tool different from that specified in 5.3.1.3

5.3.1.5 The manual advance system shall not cause a safety hazard

5.3.1.6 On the successful completion of each specified sterilization cycle, the automatic controller shall indicate

“cycle complete”

5.3.1.7 The automatic controller shall provide for reproducible sterilization cycles within the specified tolerances for each stage of the cycle

5.3.1.8 Absolute pressure measurement systems shall be used for pressure control

5.3.1.9 The sterilizer chamber heating system shall be provided with an over-temperature cut-out which interrupts the chamber heating in order to prevent over-heating of the chamber The temperature at which the cut-out activates shall be specified The over-temperature cut-out shall be independent of the temperature control function of the automatic controller A fault shall be indicated

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5.3.2 Sterilization cycle

5.3.2.1 Automatic controller

The sterilizer shall perform the cycle stages given in 5.3.2.2 to 5.3.2.11 under the control of the automatic controller

NOTE 1 Provision can be required for treatment of goods prior to sterilization to ensure that the sterilization load is heated and humidified (see prEN ISO 11135:2012)

NOTE 2 The order and number of these stages can be different from that shown below

5.3.2.3 Stage 1: Air removal

Air shall be removed from the chamber and load, sufficient to permit the subsequent attainment of sterilizing conditions

NOTE High evacuation rate can damage the sterilization load The vacuum rate can be dependent upon the nature of the sterilization load and is a part of the sterilization parameters

5.3.2.4 Stage 2: Automatic Leak Rate Test

5.3.2.4.1 If the test is carried out prior to the commencement of the EO injection stage and prior to

commencement of the conditioning stage, the test shall be carried out at a pre-set pressure specified by the manufacturer and agreed by the user

NOTE 1 The automatic leak rate is a valuable indication of potential process failure and is regarded as industry best practice NOTE 2 The influence of the chamber temperature gradient on the chamber pressure and the degassing of the products need be taken into consideration when interpreting the results of the leak test

5.3.2.4.2 If the pressure in the sterilizer chamber is sub-atmospheric pressure at any stage of the sterilization

cycle, on attainment of the pressure specified by the manufacturer, the relevant valves shall be closed and the vacuum pump shall be stopped or isolated The pressure rise in the chamber shall be monitored for a pre-set period

of not less than 5 min, after an appropriate equilibration time allowing for a pressure stabilisation During this period the pressure rise shall not exceed the value specified by the manufacturer

NOTE 1 0,3 kPa/min has historically been a typical acceptance criteria

NOTE 2 Processes operating at sub-atmospheric pressures can be vulnerable to the ingress of air The automatic leak rate test can be an early indication of this problem

NOTE 3 A sub-atmospheric leak test can also be provided as a separate maintenance test (see 5.3.2.12)

NOTE 4 The duration of the monitoring period and the acceptable leak rate can be dependent upon the volume of the sterilizer and the product

NOTE 5 Initial load degassing can cause an initial pressure rise, which is not due to a chamber leak

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5.3.2.4.3 If the pressure in the sterilizer chamber is super-atmospheric pressure at any stage of the sterilization

cycle, on attainment of the pressure specified by the manufacturer, the relevant valves shall be closed and the vacuum pump shall be stopped or isolated The pressure decrease in the chamber shall be monitored for a pre-set period of not less than 5 min, after an appropriate equilibration time allowing for a pressure stabilisation During this period the pressure decrease shall not exceed the value specified by the manufacturer

NOTE 1 0,3 kPa/min has historically been a typical acceptance criteria

NOTE 2 Processes operating at super-atmospheric pressures can give rise to EO emissions if the chamber leaks The automatic leak rate test can be an early indication of this problem

NOTE 3 The duration of the monitoring period and the acceptable leak rate can be dependent upon the volume of the sterilizer and the product

5.3.2.5 Stage 3: conditioning (if used)

5.3.2.5.1 Means shall be provided to heat and, where necessary, humidify the load Steam shall be used for

humidification

5.3.2.5.2 If heating and humidification are not carried out concurrently, humidification shall not precede heating 5.3.2.5.3 The end of this stage shall be determined by elapsed time after attainment of the required temperature

and humidity in the chamber

NOTE Guidance on the determination of the time required for the humidification of load(s) is given in prEN ISO 11135:2012

NOTE 2 Gas-liquid sensors can also be used to differentiate between liquid and gaseous EO

NOTE 3 The injection rate can be controlled actively or passively by virtue of the system design