CEN ISO/TS 11137-4:2023
(Main)Sterilization of health care products - Radiation - Part 4: Guidance on process control (ISO/TS 11137-4:2020)
Sterilization of health care products - Radiation - Part 4: Guidance on process control (ISO/TS 11137-4:2020)
This document provides additional guidance to that given in ISO 11137-3 on meeting the requirements specified in ISO 11137-1, ISO 11137-2 and ISO/TS 13004 for the establishment and control of a radiation sterilization process using gamma, electron beam, and X-irradiation.
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 4: Leitfaden zur Verfahrenssteuerung (ISO/TS 11137-4:2020)
Dieses Dokument liefert einen zusätzlichen Leitfaden zu der Anleitung in ISO 11137 3 zur Erfüllung der in ISO 11137 1, ISO 11137 2 und ISO/TS 13004 festgelegten Anforderungen für die Erarbeitung und Lenkung eines Strahlensterilisationsverfahrens mit Anwendung von Gamma-, Elektronen- oder XRay-Bestrahlung.
Stérilisation des produits de santé - Irradiation - Partie 4: Recommandations sur le contrôle de processus (ISO/TS 11137-4:2020)
Sterilizacija izdelkov za zdravstveno oskrbo - Sevanje - 4. del: Navodila za nadzor procesov (ISO/TS 11137-4:2020)
Ta dokument podaja dodatna navodila poleg navodil iz standarda ISO 11137‑3, ki se nanašajo na izpolnitev zahtev iz standardov ISO 11137‑1, ISO 11137‑2 in ISO/TS 13004, za vzpostavitev in nadziranje postopka sterilizacije z gama žarki, elektronskim žarkom in obsevanjem.
General Information
Standards Content (Sample)
SLOVENSKI STANDARD
01-september-2023
Sterilizacija izdelkov za zdravstveno oskrbo - Sevanje - 4. del: Navodila za nadzor
procesov (ISO/TS 11137-4:2020)
Sterilization of health care products - Radiation - Part 4: Guidance on process control
(ISO/TS 11137-4:2020)
Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Teil 4: Leitfaden zur
Verfahrenssteuerung (ISO/TS 11137-4:2020)
Stérilisation des produits de santé - Irradiation - Partie 4: Recommandations sur le
contrôle de processus (ISO/TS 11137-4:2020)
Ta slovenski standard je istoveten z: CEN ISO/TS 11137-4:2023
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
CEN ISO/TS 11137-4
TECHNICAL SPECIFICATION
SPÉCIFICATION TECHNIQUE
June 2023
TECHNISCHE SPEZIFIKATION
ICS 11.080.01
English Version
Sterilization of health care products - Radiation - Part 4:
Guidance on process control (ISO/TS 11137-4:2020)
Stérilisation des produits de santé - Irradiation - Partie Sterilisation von Produkten für die
4: Recommandations sur le contrôle de processus Gesundheitsfürsorge - Strahlen - Teil 4: Leitfaden zur
(ISO/TS 11137-4:2020) Verfahrenssteuerung (ISO/TS 11137-4:2020)
This Technical Specification (CEN/TS) was approved by CEN on 28 May 2023 for provisional application.
The period of validity of this CEN/TS is limited initially to three years. After two years the members of CEN will be requested to
submit their comments, particularly on the question whether the CEN/TS can be converted into a European Standard.
CEN members are required to announce the existence of this CEN/TS in the same way as for an EN and to make the CEN/TS
available promptly at national level in an appropriate form. It is permissible to keep conflicting national standards in force (in
parallel to the CEN/TS) until the final decision about the possible conversion of the CEN/TS into an EN is reached.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2023 CEN All rights of exploitation in any form and by any means reserved Ref. No. CEN ISO/TS 11137-4:2023 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
European foreword
The text of ISO/TS 11137-4:2020 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 CEN ISO/TS 11137-4:2023 by Technical Committee CEN/TC 204 “Sterilization of medical
devices” the secretariat of which is held by BSI.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
Any feedback and questions on this document should be directed to the users’ national standards body.
A complete listing of these bodies can be found on the CEN website.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and the
United Kingdom.
Endorsement notice
The text of ISO/TS 11137-4:2020 has been approved by CEN as CEN ISO/TS 11137-4:2023 without any
modification.
TECHNICAL ISO/TS
SPECIFICATION 11137-4
First edition
2020-06
Sterilization of health care products —
Radiation —
Part 4:
Guidance on process control
Stérilisation des produits de santé — Irradiation —
Partie 4: Recommandations sur le contrôle de processus
Reference number
ISO/TS 11137-4:2020(E)
©
ISO 2020
ISO/TS 11137-4:2020(E)
© ISO 2020
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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below or ISO’s member body in the country of the requester.
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Email: copyright@iso.org
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Published in Switzerland
ii © ISO 2020 – All rights reserved
ISO/TS 11137-4:2020(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms, definitions and symbols . 1
3.1 General . 1
3.2 Symbols . 3
4 Principles applied in validating and controlling an irradiation process .4
4.1 General . 4
4.2 Use of the dose measurement at the monitoring location . 4
4.2.1 General. 4
4.2.2 D as an indirect measurement of dose to product . 4
mon
4.2.3 D as a process monitor . 4
mon
4.2.4 D or D as a direct measurement of dose to product . 5
min max
4.3 Monitoring of critical process parameters . 5
5 Establishing process target doses . 6
5.1 Inputs and steps in establishing a process target dose . 6
5.1.1 General. 6
5.1.2 Process validation inputs (installation, operational and performance
qualification) . 7
5.1.3 Additional inputs . 7
5.1.4 Determine σ . 7
process
5.1.5 Product dose specifications . 8
5.1.6 Select coverage factor k . 8
5.1.7 Setting process target doses . 8
5.1.8 Analyse process output . 8
5.1.9 Review . . 8
5.2 Performance qualification outputs . 8
5.2.1 General. 8
5.2.2 Experimental design for PQ. 9
5.2.3 Processing categories . 9
5.3 Components of σ .10
process
5.3.1 General.10
5.3.2 Components related to measurement uncertainty .11
5.3.3 Components related to process variability .12
5.3.4 Combining components of uncertainty .13
5.3.5 Reducing σ .13
process
5.4 Establishing process target doses .16
5.4.1 Coverage factors .16
5.4.2 Process factors .17
5.4.3 Choice of target processing parameters .17
5.4.4 Assessing process capability .18
6 Routine monitoring and control .18
6.1 General .18
6.2 Product handling .19
6.2.1 Receipt of product .19
6.2.2 Loading .19
6.2.3 Unloading .19
6.2.4 Storage .20
6.2.5 Shipment .20
6.3 Processing of product .20
6.3.1 General.20
ISO/TS 11137-4:2020(E)
6.3.2 Processing parameters .20
6.3.3 Location of dosimeters .21
6.3.4 Partially filled containers .21
6.3.5 Process interruptions .21
6.3.6 Transitions between densities .22
6.4 Special processing conditions .22
6.4.1 Off-carrier processing .22
6.4.2 Irradiation of product under modified environmental conditions .22
6.5 Process output interpretation .24
6.5.1 General.24
ster max,acc
6.5.2 Using an acceptance range based on D and D .24
mon mon
6.5.3 Using an acceptance range with alert and action levels .24
6.5.4 Using an acceptance range based on process monitoring .25
6.5.5 Investigation of a dose measurement outside of expectation .26
6.6 Collection and analysis of data .27
6.6.1 General.27
6.6.2 Dosimeter data trending .27
6.6.3 Parametric data trending .28
6.6.4 Statistical process control .29
7 Release of product from the irradiation process .30
8 Maintaining process effectiveness .31
8.1 General .31
8.2 Assessment of changes made to the product .31
8.3 Assessment of changes made to the equipment .31
Annex A (informative) Examples of setting process target dose ranges and interpretation of
process output .32
Bibliography .55
iv © ISO 2020 – All rights reserved
ISO/TS 11137-4:2020(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.
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.
A list of all parts in the ISO 11137 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.
ISO/TS 11137-4:2020(E)
Introduction
ISO 11137-1 describes the requirements for the development, validation and routine control of a
radiation sterilization process, and ISO 11137-3 gives guidance on dosimetric requirements in all stages
of this development, validation and control. The purpose of ISO/TS 11137-4 is to provide additional
guidance on the establishment and control of the irradiation process, including setting process target
doses and verifying that the process is in a state of control.
This document addresses the establishment of methods to set process target doses and verify the
process is in a state of control. Dosimetry is used during the validation of a radiation sterilization process
to measure doses, and the interpretation of dosimetry results from operational and performance
qualification studies is critical in establishing a process that will meet the requirements specified for
minimum and maximum dose as outlined in ISO 11137-1, ISO 11137-2 and ISO/TS 13004.
Routine dosimetry is used to monitor that the process is in a state of control and dose specifications
have been met. One purpose of this technical specification is to provide guidance on the application of
a dose measurement as a tool used for monitoring an irradiation process using statistical techniques.
The guidance given is not normative and is not provided as a checklist for auditors. The guidance
provides explanations and methods that are regarded as being suitable means for achieving conformity
with the minimum and maximum dose specifications. Methods other than those given in the guidance
may be used, if they are effective in achieving conformity with the requirements of ISO 11137-1,
ISO 11137-2 and ISO/TS 13004.
vi © ISO 2020 – All rights reserved
TECHNICAL SPECIFICATION ISO/TS 11137-4:2020(E)
Sterilization of health care products — Radiation —
Part 4:
Guidance on process control
1 Scope
This document provides additional guidance to that given in ISO 11137-3 on meeting the requirements
specified in ISO 11137-1, ISO 11137-2 and ISO/TS 13004 for the establishment and control of a radiation
sterilization process using gamma, electron beam, and X-irradiation.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements 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 11137-1:2006, Sterilization of health care products — Radiation — Part 1: Requirements for
development, validation and routine control of a sterilization process for medical devices
ISO 11137-3:2017, Sterilization of health care products — Radiation — Part 3: Guidance on dosimetric
aspects of development, validation and routine control
3 Terms, definitions and symbols
For the purposes of this document, the terms and definitions given in ISO 11137-1, ISO 11137-3 and the
following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at http:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1 General
3.1.1
acceptance range
range within which the statistic under consideration lies with a specified probability when the process
is in a state of control
3.1.2
action level
value from monitoring that necessitates immediate intervention
[SOURCE: ISO 11139:2018, 3.5]
3.1.3
alert level
value from monitoring providing early warning of deviation from specified conditions
Note 1 to entry: An alert level value provides early warning of a potential deviation for a process under control.
Although further action is not required, increased supervision of the process is recommended.
ISO/TS 11137-4:2020(E)
[SOURCE: ISO 11139:2018, 3.11, modified — Note 1 to entry has been added.]
3.1.4
cycle time
period of time an irradiation container spends in each dwell position in a gamma process, used as a
control parameter for dose
Note 1 to entry: Cycle time can also apply to x-ray and could also include the time required to move between
dwell positions.
[SOURCE: ISO 11139:2018, 3.73, modified — Note 1 to entry has been added.]
3.1.5
influence quantity
quantity that, in a direct measurement, does not affect the quantity that is actually measured, but
affects the relation between the indication and the measurement result
Note 1 to entry: In radiation processing dosimetry, this term includes temperature, relative humidity, time
intervals, light, radiation energy, absorbed-dose rate, and other factors that might affect dosimeter response, as
well as quantities associated with the measurement instrument.
[SOURCE: VIM 2012, 2.52, modified — Note 1 to entry added from ISO/ASTM 52701:2013.]
3.1.6
measurement uncertainty
parameter, associated with the result of a measurement, that characterizes the dispersion of the values
that could reasonably be attributed to the measurand
3.1.7
process control
specific activities to ensure process requirements are achieved
[SOURCE: ISO 11139:2018, 3.209]
3.1.8
process load
volume of material with a specified product loading configuration irradiated as a single entity
Note 1 to entry: The process load consists of one or more irradiation containers.
[SOURCE: ISO/ASTM 52303:2015, 3.1.10]
3.1.9
process target dose
D
target
dose, at a specified monitoring location, which the irradiation process parameters are set to deliver
3.1.10
process variability
measure of factors that result in a random distribution of data around the average that provides
information on how well the process can perform when all special cause variation is removed
3.1.11
Statistical Process Control
SPC
set of techniques for improving the quality of process output by reducing variability through the use of
one or more control charts and a corrective action strategy used to bring the process back into a state
of statistical control
[SOURCE: ASTM E2587-16]
2 © ISO 2020 – All rights reserved
ISO/TS 11137-4:2020(E)
3.1.12
targeting buffer
standard factor or factors used to determine process target doses which has been demonstrated to be
more conservative calculated values of UF and UF during historical routine processing
lower upper
3.2 Symbols
Symbol Meaning
D direct measurement of minimum dose in a given irradiation container
min
D direct measurement of maximum dose in a given irradiation container
max
D direct measurement of dose at the routine monitoring position
mon
D Sterilization dose determined in accordance with
ster
ISO 11137-1:2006, 8.2
D maximum acceptable dose determined in accordance with
max,acc
ISO 11137-1:2006, 8.1
limit
D = D * UF calculated dose at the minimum dose position used for establishing
min ster lower
process parameters that ensures at a specified level of confidence that
D is met or exceeded during routine processing
ster
limit
D = D * UF calculated dose at the maximum dose position used for establishing
max max,acc upper
process parameters that ensures at a specified level of confidence that
D is not exceeded during routine processing
max,acc
min lower limit
UF = 1/(1 ‒ k * σ /100) process factor used to calculate D and D
lower process target min
min
(where σ is expressed as a percentage)
process
max upper limit
UF = 1/(1 + k * σ /100) process factor used to calculate D and D
upper process target max
max
(where σ is expressed as a percentage)
process
R = D / D ratio of minimum to monitor dose determined by dose mapping
min/mon min mon
R = D / D ratio of maximum to monitor dose determined by dose mapping
max/mon max mon
ster
D = D /R dose at the monitoring position that correlates to the sterilization dose
mon ster min/mon
specification
max,acc
D = D /R dose at the monitoring position that correlates to maximum acceptable
mon max,acc max/mon
dose specification
lower limit
D = D / R calculated dose at the routine monitoring position used for establishing
target min min/mon
process parameters that ensures at a specified level of confidence that
D is met or exceeded during routine processing
ster
upper limit
D = D / R calculated dose at the routine monitoring position used for establishing
target max max/mon
process parameters that ensures at a specified level of confidence that
D is not exceeded during routine processing
max,acc
σ component of uncertainty related to the calibration of the dosimetry
cal
system including the uncertainty reported by the calibration laborato-
ry, uncertainty in the mathematical fit of the calibration function, and
uncertainties due to influence quantities, but excluding components due
to the reproducibility of the dosimeter measurement (see σ )
rep
σ component of variability related to the radiation source and convey-
mach
or system
σ component of variability measured during a dose mapping exercise
map
σ standard deviation associated with the irradiation process used for
process
setting process target doses
max
σ — The standard deviation associated with the process
process
maximum dose
min
σ — The standard deviation associated with the process
process
minimum dose
σ component of variability associated with the reproducibility of the
rep
dosimeter measurement
ISO/TS 11137-4:2020(E)
4 Principles applied in validating and controlling an irradiation process
4.1 General
Many dose measurements are made in the validation of an irradiation process as described in
ISO 11137-1 and ISO 11137-3. These measurements are used to establish a relationship between
processing parameters, monitoring dose, and the range of doses to a product, and to characterize the
variability associated with the process itself. These measurements are made with calibrated dosimetry
systems traceable to internationally recognized standards with a known level of uncertainty.
It is a requirement to monitor that the validated radiation sterilization process is in a state of control.
ISO 11137-1:2006, 10.6 requires the use of dosimeters in routine monitoring and control and provides
guidance on the additional review of monitoring of process parameters when determining that product
has been processed according to specification.
The combination of dose measurements, monitoring of the associated processing parameters used to
achieve those doses, and procedural controls are critical in establishing a process and determining
whether or not it is in a state of control.
4.2 Use of the dose measurement at the monitoring location
4.2.1 General
Analysis of measurements from routine monitoring dosimeters is used to determine whether or not
process specifications have been met. There are two methods of analysis that can be considered:
1) interpretation of dose measurements as a direct or indirect measure of dose delivered to
product; and
2) interpretation of dose measurements to monitor that a process is in a state of control.
In all cases, a validated process provides an expectation of the monitored dose based on derived process
target doses and associated processing parameters. The interpretation of the monitoring dose should
be documented in the process specification.
The ability to detect changes in the process is limited by the intrinsic variability of dose at the routine
monitoring location i.e. the variability measured when the process is in control. If σ of the monitoring
rep
dosimetry system is large or dosimeter placement imprecise, this variability might be significantly
higher than the true variability of the process. In such circumstances, significant changes in the process
could go undetected, because they are masked by the high intrinsic variability at the monitoring
location. Steps should be taken to minimise variability arising from the monitoring dosimetry system
and dosimeter placement. See 6.5.4 and Annex A, Example 3.
4.2.2 D as an indirect measurement of dose to product
mon
In an indirect measurement, the maximum and minimum doses to product are calculated from the
monitoring dose measurement. The calculated doses have uncertainties associated with the dose at
the monitoring location as well as the uncertainty associated with the dose at maximum or minimum
locations and associated ratios, plus any other applicable components of uncertainty. A combination
of these components can be used to determine the maximum and minimum targets for the routine
monitoring dose. See 6.5.2, 6.5.3 and Annex A, Examples 1, 2 and 5.
4.2.3 D as a process monitor
mon
It is acceptable to monitor a process where the maximum or minimum dose to product are not measured
routinely (directly or indirectly), but rather where a range of monitoring doses are established that
indicate that the process meets specification. In this situation, the variability associated with the
measurement of minimum and maximum doses from PQ, combined with other relevant components
of uncertainty can be used in determining maximum and minimum targets for the routine monitoring
4 © ISO 2020 – All rights reserved
ISO/TS 11137-4:2020(E)
dose. The variability of dose at the monitoring location is then used to determine the acceptable range
of doses that indicate that the process is in a state of control and meets process specifications. Because
the routine monitoring dosimeter is not used to measure minimum or maximum dose to product,
the uncertainty associated with the relationship between the monitored dose and the maximum and
minimum doses within a process load has no relevance in determining process target doses and process
conformance.
4.2.4 D or D as a direct measurement of dose to product
min max
When routine dose is measured at the minimum and/or maximum dose location in the process load,
then the dosimeter measurement provides a direct measurement of dose to product. It can also be used
as an indicator that the process is in control. In such case, the benefits of both 4.2.2 and 4.2.3 might be
achieved. See Annex A, Example 2.
There are circumstances where a limited amount of data is available to predict the outcome of a process.
An example of this is an off-carrier process which is based on a single dose map (see 6.4.1). In these
cases, enough dosimeters need to be placed on products to provide a direct measurement of minimum
and maximum dose.
4.3 Monitoring of critical process parameters
An important consideration in process control is the ability to detect if a processing parameter is
changing in a manner that can affect the output of the process. The ability to monitor and/or control
process parameters critical to the process output is, therefore, an important factor in ensuring the
state of control of the irradiation process.
There are three main classes of processing parameters to be considered: parameters that relate to
the radiation field, parameters that relate to the exposure time of the product to the radiation field,
and parameters that relate to product influence. Table 1 provides an overview of the effect of critical
process parameters and how they could be monitored.
Table 1 — Process parameters critical to radiation sterilization
Elec-
Parameter Effect Monitoring Gamma X-ray
tron
Radiation field
Radioisotope decay Over time the radiation Source decay occurs based
intensity is reduced on the half-life of the isotope;
date of irradiation is recorded
Electron energy Energy affects the penetra- Irradiator parameters asso-
tion depth of electrons, scan ciated with input power and
width, and also X-ray conver- beam current are monitored;
sion efficiency indirect measurements using
beam penetration profiles are
made periodically as part of a
quality control check
Beam current A change in beam current Can be monitored indirectly
will lead to a change in the during operation; indirect
radiation intensity and monitors can be calibrated
possibly of the beam energy
Beam scan width For scanned system, width Monitored indirectly by
will affect the size of the feedback of scanning system,
radiation field and a reduction or directly through intercep-
in width will increase the tion of the beam, or through
radiation intensity periodic dosimetric tests
ISO/TS 11137-4:2020(E)
Table 1 (continued)
Elec-
Parameter Effect Monitoring Gamma X-ray
tron
Exposure time
Cycle time Dose is directly proportional Cycle time is set by operator,
to cycle time. An increase in recorded as part of the pro-
cycle time equals an increase cess and associated timers are
in dose. calibrated
Conveyor speed Dose is inversely Feedback from convey-
proportional to speed of or speed monitors; direct
product travelling through measurements made during
an irradiation field periodic tests
Product influence
Loading pattern Changes to loading pattern Defined product loading
including product orientation patterns and procedures to
inside a carton and/or carton ensure products are loaded
loading into an irradiation according to specification
container can affect dose
delivery
Density and Materials surrounding prod- Appropriate scheduling
loading uct during irradiation can of process loads; defined
pattern of affect dose delivered through criteria resulting from OQ
surrounding attenuation or scattering of for materials surrounding
materials radiation product during irradiation are
documented
5 Establishing process target doses
5.1 Inputs and steps in establishing a process target dose
5.1.1 General
The irradiation process is monitored using processing parameters and dosimeter measurements.
lower upper
Three process target doses at the routine monitoring position can be defined; D , D
target target
and D corresponding, respectively, to the lower and upper set limits for the process target dose
target
and the actual process target dose chosen for processing under given conditions.
There are a number of factors used in the determination of a range of process target doses.
The inputs and steps in establishing a process target dose are listed in the following sections and
depicted in Figure 1.
6 © ISO 2020 – All rights reserved
ISO/TS 11137-4:2020(E)
Figure 1 — Inputs and steps in establishing a process target dose
5.1.2 Process validation inputs (installation, operational and performance qualification)
The results of process validation that can be used to provide input into establishing process target
doses include the following:
a) the magnitude of minimum dose to product D for a given loading configuration and set of
min
operating parameters and its relationship to the routine monitoring dose D ;
mon
b) the magnitude of maximum dose to product D for a given loading configuration and set of
max
operating parameters and its relationship to the routine monitoring dose D ;
mon
c) the variability associated with D , D and D , and the uncertainty associated with their
min max mon
ratios (if used);
and if applicable the effects of
d) process interruptions;
e) transitions between different product;
f) partially filled irradiation containers.
The application of process validation data in establishing process target doses is discussed further in 5.2.
5.1.3 Additional inputs
Additional inputs may include components that contribute to the uncertainty of the process which are
not captured during process validation. These might include, but are not limited to σ , and/or targeting
cal
buffers defined by the operator as applicable.
5.1.4 Determine σ
process
The standard deviation to be used in setting process target doses is designated σ and can be
process
derived by quantifying individual components of measurement uncertainty and process variability or
by quantifying a combination of components obtained during qualification exercises and by the use of
historical data for a given irradiator.
ISO/TS 11137-4:2020(E)
max
Separate determinations of σ used to calculate the upper process target dose (σ ) and
process process
min
lower process target dose (σ ) can be used to determine the range of process target doses. The
process
estimation of these inputs is discussed further in 5.3.
5.1.5 Product dose specifications
Product dose specifications determined in accordance with ISO 11137-1 are:
a) the sterilization dose D ;
ster
b) the maximum acceptable dose D .
max,acc
5.1.6 Select coverage factor k
A coverage factor k is selected, representing the level of confidence required or selected for the process
(see 5.4.1).
5.1.7 Setting process target doses
The combination of these inputs is used to calculate a range of process target doses at the routine
monitoring location defined between:
a) the lowest process target dose that will achieve a minimum dose to product equal to or greater
than D at a defined level of confidence;
ster
b) the highest process target dose that will achieve a maximum dose to product equal to or less than
D at a defined level of confidence.
max,acc
The calculation of these targets is discussed in 5.4.
5.1.8 Analyse process output
Analyses of routine dose measurements and monitored processing parameters are used to determine if
the process is operating in a state of control (see 6.5 and 6.6).
5.1.9 Review
Ongoing
...
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