EN ISO 11608-1:2015

SLOVENSKI STANDARD
01-marec-2015
1DGRPHãþD
SIST EN ISO 11608-1:2012
Peresa za injiciranje za uporabo v medicini - Zahteve in preskusne metode - 1. del:
Peresa za injiciranje (ISO 11608-1:2014)
Needle-based injection systems for medical use - Requirements and test methods - Part
1: Needle-based injection systems (ISO 11608-1:2014)
Kanülenbasierte Injektionssysteme zur medizinischen Verwendung - Anforderungen und
Prüfverfahren - Teil 1: Kanülenbasierte Injektionssysteme (ISO 11608-1:2014)
Systèmes d'injection à aiguille pour usage médical - Exigences et méthodes d'essai -
Partie 1: Systèmes d'injection à aiguille (ISO 11608-1:2014)
Ta slovenski standard je istoveten z: EN ISO 11608-1:2015
ICS:
11.040.25 Injekcijske brizge, igle in Syringes, needles an
katetri catheters
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EUROPEAN STANDARD
EN ISO 11608-1
NORME EUROPÉENNE
EUROPÄISCHE NORM
January 2015
ICS 11.040.25 Supersedes EN ISO 11608-1:2012
English Version
Needle-based injection systems for medical use - Requirements
and test methods - Part 1: Needle-based injection systems (ISO
11608-1:2014)
Systèmes d'injection à aiguille pour usage médical - Kanülenbasierte Injektionssysteme zur medizinischen
Exigences et méthodes d'essai - Partie 1: Systèmes Verwendung - Anforderungen und Prüfverfahren - Teil 1:
d'injection à aiguille (ISO 11608-1:2014) Kanülenbasierte Injektionssysteme (ISO 11608-1:2014)
This European Standard was approved by CEN on 11 October 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
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11608-1:2015 E
worldwide for CEN national Members.

Contents Page
Foreword .3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC .4
Foreword
This document (EN ISO 11608-1:2015) has been prepared by Technical Committee ISO/TC 84 “Devices for
administration of medicinal products and catheters” in collaboration with Technical Committee CEN/TC 205
“Non-active medical devices” 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 July 2015, and conflicting national standards shall be withdrawn at the
latest by July 2015.
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 ISO 11608-1:2012.
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.
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.
Endorsement notice
The text of ISO 11608-1:2014 has been approved by CEN as EN ISO 11608-1:2015 without any modification.
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC
This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide one means of conforming to Essential Requirements of
the New Approach Directive 93/42/EEC, 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 normative clauses of
this standard confers, within the limits of the scope of this standard, a presumption of conformity with the
relevant Essential Requirements of that Directive and associated EFTA regulations.
WARNING: Other requirements and other EU Directives may be applicable to the products falling within the
scope of this standard.
INTERNATIONAL ISO
STANDARD 11608-1
Third edition
2014-12-15
Needle-based injection systems for
medical use — Requirements and
test methods —
Part 1:
Needle-based injection systems
Systèmes d’injection à aiguille pour usage médical — Exigences et
méthodes d’essai —
Partie 1: Systèmes d’injection à aiguille
Reference number
ISO 11608-1:2014(E)
©
ISO 2014
ISO 11608-1:2014(E)
© ISO 2014
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
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Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
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Published in Switzerland
ii © ISO 2014 – All rights reserved

ISO 11608-1:2014(E)
Contents Page
Foreword .v
Introduction .vii
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Symbols and abbreviated terms . 3
5 Requirements . 4
5.1 General . 4
5.2 System designations . 5
5.3 Risk analysis requirements . 5
5.4 Uncertainty of measurement and conformance with specifications. 5
5.5 General design requirements . 5
6 Reagent and apparatus . 7
6.1 General . 7
6.2 Test liquid . 7
6.3 Balance . 7
6.4 Test surface for free-fall testing . 7
7 Determination of dose accuracy. 7
7.1 General . 7
7.2 Dosing regions . 8
7.3 Dose settings . 9
7.3.1 Multi-dose containers (system designations A and C) . 9
7.3.2 Single-dose containers (system designations B and D) . 9
7.4 Assessment . 9
7.4.1 General. 9
7.4.2 Determination of dose accuracy limits .10
7.4.3 Determination of last-dose error and last-dose accuracy limits (system
designations A and C) .11
7.4.4 Calculation of dose delivery efficiency (system designations B1 and
D1, user-filled) .11
7.4.5 Calculation of tolerance intervals .12
8 Preparation and operation of NISs .12
9 Test matrix .13
10 Test descriptions .16
10.1 General .16
10.2 Cool, standard and warm atmosphere testing .16
10.2.1 Pre-conditioning .16
10.2.2 Testing .16
10.3 Last-dose testing (system designations A and C only) .17
10.3.1 General.17
10.3.2 Pre-conditioning .17
10.3.3 Testing .17
10.4 Life-cycle testing (systems designations A and B only) — Pre-conditioning .17
10.5 Free-fall testing .17
10.6 Dry-heat and cold-storage testing — Pre-conditioning.19
10.7 Damp-heat testing (system designations A and B only) — Pre-conditioning .19
10.8 Cyclical testing (system designations A and B only) — Pre-conditioning .19
10.9 Vibration testing — Pre-conditioning .20
ISO 11608-1:2014(E)
10.10 Electromagnetic compatibility (EMC) (systems with electronics only) .20
10.10.1 General.20
10.10.2 Exposure to electrostatic discharge — Pre-conditioning .20
10.10.3 Radiated radio-frequency (RF) fields — Pre-conditioning .20
10.10.4 Compliance criteria for electrostatic discharge .20
10.10.5 Radiated radio-frequency (RF) fields .21
11 Inspection .21
11.1 Visual inspection .21
11.2 Container inspection .21
11.3 Dose accuracy acceptance criteria .21
12 Test report .22
13 Information supplied by the manufacturer .22
13.1 General .22
13.2 Marking .22
13.2.1 General.22
13.2.2 Marking on the NIS .23
13.2.3 Marking on the user packaging .23
13.3 Instructions for use .23
Annex A (informative) Dose replicates, accuracy and testing rationale .25
Annex B (normative) One- and two-sided tolerance limit factors, k .29
Bibliography .40
iv © ISO 2014 – All rights reserved

ISO 11608-1:2014(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 on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical Barriers
to Trade (TBT) see the following URL: Foreword - Supplementary information.
The committee responsible for this document is ISO/TC 84, Devices for administration of medicinal
products and intravascular catheters.
This third edition cancels and replaces the second edition (ISO 11608-1:2012), which has been
technically revised.
ISO 11608 consists of the following parts, under the general title Needle-based injection systems for
medical use — Requirements and test methods:
— Part 1: Needle-based injection systems
— Part 2: Needles
— Part 3: Finished containers
— Part 4: Requirements and test methods for electronic and electromechanical pen-injectors
— Part 5: Automated functions
This third edition of ISO 11608-1:2014 incorporates the following corrections:
a) in 4 Y: the term ‘pens’ is changed to ‘NISs’;
b) in 5.5 n): reference to ISO 11608-4 is deleted since 5.5. o) already addresses this;
c) in Table 3: the word “or” is changed to “and” so that it reads “Condition at 70 °C and −40 °C, then
standard DA”;
d) in 10.1, NOTE 1: Explanation is inserted;
e) in 10.5 a) designation B is deleted;
f) in 10.5 b) designation D is deleted;
g) in 10.5 b) 3) iv) the term ‘replacements’ is changed to ‘obvious container failures’;
ISO 11608-1:2014(E)
h) in 10.5 d) 2) iv) the term ‘replacements’ is changed to ‘obvious container failures’;
i) in 10.8 the temperature range is changed from (25 ± 3) °C to (5 ± 3) °C;
j) in 10.10.4 and 10.10.5 “five NISs” is changed to “20 NISs” according to Table 3;
k) in Table 3 – references to 10.10.4 and 10.10.5 are added under column A;
l) in 13.2.3 “unit packaging” has been changed into “user packaging”.
vi © ISO 2014 – All rights reserved

ISO 11608-1:2014(E)
Introduction
This part of ISO 11608 covers needle-based injection systems (referred to as NISs) primarily intended
for human use. It provides performance requirements regarding essential aspects so that variations of
design are not unnecessarily restricted.
This part of ISO 11608 should be used in conjunction with the other parts of ISO 11608.
The first edition of this part of ISO 11608 introduced the concept of interchangeability and the labelling
designations “Type A” (i.e. interchangeable) and “non-Type A” for needles and container systems. Since
its promulgation, experience has shown that the complexity of these systems makes it very difficult
to ensure functional compatibility as defined in the different parts of this International Standard,
particularly when products are made by different manufacturers. Based on this experience, it is believed
that the Type A designation does not represent adequate guidance to the user in making decisions on
the compatibility of needles and containers with specific needle-based injector systems. As such, the
labelling designation “Type A” has been removed. The design requirements related to system function
have been maintained as a guide to assist manufacturers during the design phase, supporting the
achievement of cross-platform compatibility. However, these design requirements are an insufficient
replacement for system testing of the components and, where possible, direct communication and/or
quality agreements between system component manufacturers. Therefore, given the patient convenience
benefits associated with cross-platform compatibility, manufacturers of needles, containers and needle-
based injectors shall label their products with the specific system components that have been tested
and demonstrated to be functionally compatible.
The sampling plans for inspection selected for this part of ISO 11608 are intended to verify the design at
a high confidence level. The sampling plans for inspection do not replace the more general manufacturing
quality systems that appear in standards on quality systems, for example the ISO 9000 series and ISO 13485.
Materials to be used for construction are not specified, as their selection will depend on the design, the
intended use and the process of manufacture used by individual manufacturers.
There are other international and national standards and guidance publications and, in some countries,
national regulations that are applicable to medical devices and pharmaceuticals. Their requirements
might supersede or complement this part of ISO 11608. Developers and manufacturers of NISs are
encouraged to investigate and determine whether there are any other requirements relevant to the
safety or marketability of their products.
Manufacturers are expected to follow a risk-based approach during the design, development and
manufacture of the product. Given the specific medicinal product and intended use, this might result in
product-specific requirements and test methods that differ from what is outlined in this part of ISO 11608.
INTERNATIONAL STANDARD ISO 11608-1:2014(E)
Needle-based injection systems for medical use —
Requirements and test methods —
Part 1:
Needle-based injection systems
1 Scope
This part of ISO 11608 specifies requirements and test methods for needle-based injection systems
(NISs) intended to be used with needles and with replaceable or non-replaceable containers. Containers
covered in this part of ISO 11608 include single- and multi-dose syringe-based and cartridge-based
systems, filled either by the manufacturer or by the end-user.
Additional guidance for NISs equipped with electronic or electromechanical components and NISs
equipped with automated functions is given in ISO 11608-4 and ISO 11608-5 respectively.
Needle-free injectors, and requirements relating to methods or equipment associated with end-user
filling of containers, are outside the scope of this part of ISO 11608.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 11608 (all parts), Needle-based injection systems for medical use — Requirements and test methods
ISO 13485:2003, Medical devices — Quality management systems — Requirements for regulatory purposes
ISO 14253-1, Geometrical product specifications (GPS) — Inspection by measurement of workpieces and
measuring equipment — Part 1: Decision rules for proving conformity or nonconformity with specifications
ISO 14971, Medical devices — Application of risk management to medical devices
ISO/IEC Guide 98-3, Uncertainty of measurement — Part 3: Guide to the expression of uncertainty in
measurement (GUM:1995)
IEC 60068-2-6:2007, Environmental testing — Part 2-6: Tests — Test Fc: Vibration (sinusoidal)
IEC 60068-2-30:2005, Environmental testing — Part 2-30: Tests — Test Db: Damp heat, cyclic (12 + 12 h cycle)
IEC 60601-1-2:2007, Medical electrical equipment — Part 1-2: General requirements for basic safety and
essential performance — Collateral standard: Electromagnetic compatibility — Requirements and tests
IEC 62366, Medical devices — Application of usability engineering to medical devices
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO 11608-1:2014(E)
3.1
cap
part of the NIS intended to protect the injector and its contents
3.2
container
primary packaging that contains the medicinal product for injection (either single-compartment or
multi-compartment)
3.3
dose delivery efficiency
ratio of expelled dose to fill volume
Note 1 to entry: Dose delivery efficiency is expressed as a percentage.
Note 2 to entry: Delivery efficiency can be used to evaluate dose accuracy for NISs designed to fully empty single-
dose containers filled by the user.
3.4
dialling resolution
smallest possible increment to be selected between dose amounts
3.5
dose accuracy
accuracy with which the NIS delivers a pre-set dose of medicinal product
3.6
“dose delivered” indication
dose number shown in the dose window indicating the amount of medicinal product delivered
Note 1 to entry: This applies to variable multi-dose NISs that allow the setting of a dose greater than the
remaining volume.
Note 2 to entry: If the dose window indicates the amount of medicinal product yet to be delivered, then the “dose
delivered” indication can be determined as the intended dose minus the indication of medicinal product yet to
be delivered.
3.7
manufacturer-filled
container supplied to the user pre-filled by the manufacturer of medicinal products
Note 1 to entry: This medicinal product can be in liquid form or lyophilized with diluent in the same container.
3.8
minimum deliverable dose
minimum dose that is ensured by the manufacturer to be delivered in a single-dose manufacturer-filled
NIS designed to fully empty the container
3.9
NIS
needle-based injection system
injection system intended for parenteral administration by injection of medicinal products using a
needle and a multi-dose or single-dose container
Note 1 to entry: This term may also be referred to as “system” or “injector” in this part of ISO 11608.
3.10
pre-setting
procedure by which individual amounts of medicinal product can be selected for injection by the user
Note 1 to entry: The doses may be pre-set by the manufacturer or the user.
2 © ISO 2014 – All rights reserved

ISO 11608-1:2014(E)
3.11
residual scale
graduated scale which indicates the remainder of medicinal product in the container
3.12
user packaging
what is provided to the user with one or a collection of devices of the same item and from the same
manufacturing batch, including the directions for use
3.13
user-filled
container that is filled or reconstituted (if in lyophilized form) by the user from a separate medicinal
product or diluent container
4 Symbols and abbreviated terms
NIS Needle-based injection system.
V One of the three pre-set doses (expressed as a volume, in millilitres) used in determining the
set
dose accuracy for a given NIS. V is defined as one of the following:
set
a) minimum dose (V = V ) (specified in the instructions for use);
set min
b) maximum dose (V = V ) (specified in the instructions for use);
set max
c) midpoint dose (V = V ), where V is defined as the injector setting closest to
set mid mid
(V +V )/2.
min max
NOTE 1 Recommended doses as specified in the instructions for use may differ from
the pre-set doses used for determining the dose accuracy.
NOTE 2 System designations B1 and D1 define V to be equal to the manufactur-
set
er-filled or user-filled volumes. System designations B2 and D2 define V to be equal to a
set
single pre-set dose representing a portion of the manufacturer-filled or user-filled volumes.
In the case of last-dose accuracy assessments for system designations A and C, V is equal to
set
V , the TP, or dose error (evaluated over a range of doses within a specified percentage of
mid
the TP).
V The volumetric measurement value for a given V , expressed in millilitres.
meas set
G The gravimetric measurement value for a given V , expressed in grams.
meas set
ρ Density, expressed in grams per millilitre.
p Probability content.
Y Number of NISs required for a given test.
R Number of replicates required for a given test. A replicate is a random sequence of V , V ,
min mid
and V . There are six possible replicates.
max
N Number of measurements, V , to be made for each V .
meas set
The sample mean; when based on a random sample, an estimate of the true mean:
x
xV= /n .
∑ meas
ISO 11608-1:2014(E)
s The sample standard deviation; when based on a random sample, an estimate of the true
standard deviation:
12/
 
sV=−()xn/( −1) .
∑ meas
 
k k value, or tolerance limit factor, determined from the confidence level (95 %), probability con-
tent, p, and number of accuracy measurements, n, conducted at each dose setting.
k Actual k value, determined from the following equations:
act
Two-sided
 
Ux− xL−
() ()
k =min ,
act  
s s
 
 
One-sided
   
xL− Ux−
() ()
K = or k =
   
act act
s s
   
   
k Target k value, found from the look-up table in ISO 16269-6:2014 (Annexes D and E), or
tar
Annex B.
DR Dialling resolution, the minimum dialling increment of the NIS.
α Absolute error, in millilitres, used to define the upper and lower specification limits for a pre-
set dose in absolute terms.
β Relative error, as a percentage, used to define the upper and lower specification limits for a
pre-set dose in relative terms.
TP The transition point volume, in millilitres, at which the upper and lower specification limits
for V change from absolute terms to relative terms (i.e. V where α and β are equal):
set set
TP = (100 ×α)/β
U Upper specification limit for a given V .
set
L Lower specification limit for a given V .
set
RF Radio frequency
5 Requirements
5.1 General
Companies wishing to verify a NIS shall ensure that the system meets the requirements of this part
of ISO 11608. In addition, companies shall ensure that the appropriate components (e.g. needles and
containers) and features (e.g. electromechanical drive systems and automated functions) specified for
use in the system satisfy the relevant parts of ISO 11608.
4 © ISO 2014 – All rights reserved

ISO 11608-1:2014(E)
5.2 System designations
Given the differences in device designs and containers (e.g. multi-dose, single dose with partial
evacuation, and single-dose with full evacuation), the following system designations are provided
to clearly associate the appropriate test and dose accuracy method with the injection system under
consideration. Containers can be either manufacturer-filled or user-filled.
Table 1 shows the various needle-based injector system designations.
Table 1 — System designations
Multi-dose container Single-dose container
A B1
Needle-based injection device with replaceable con- Needle-based injection device with replaceable con-
tainer. tainer.
Each container holds multiple doses, the size of which Each container holds a single dose, whereby the entire
may be fixed or variable (pre-set by the user). deliverable volume is expelled.
B2
Needle-based injection device with replaceable con-
tainer.
Each container holds a single dose, whereby a portion
of the deliverable volume is expelled.
C D1
Needle-based injection device with integrated non-re- Needle-based injection device with integrated non-re-
placeable container. placeable container.
Each container holds multiple doses, the size of which Each container holds a single dose, whereby the entire
may be fixed or variable (pre-set by the user). deliverable volume is expelled.
D2
Needle-based injection device with integrated non-re-
placeable container.
Each container holds a single dose, whereby a portion
of the deliverable volume is expelled.
5.3 Risk analysis requirements
The manufacturer shall conduct risk assessments in accordance with ISO 14971. These risk assessments
shall consider all aspects of the development, manufacture and intended use of the NIS for medical use.
The NIS shall conform to the usability requirements specified in IEC 62366.
5.4 Uncertainty of measurement and conformance with specifications
Measurement uncertainty shall be evaluated and expressed by the laboratory performing the test in
accordance with ISO/IEC Guide 98-3 (GUM).
Conformance with specifications is established in accordance with ISO 14253-1.
5.5 General design requirements
a) The container holder shall allow visibility of the deliverable volume. The manufacturer shall
determine, by risk analysis, if a residual scale is required and how much of the deliverable volume
shall be visible.
b) With the exception of system designations B2 and D2, NISs shall be designed in such a way that they are
able to accurately deliver the entire labelled volume from the container for which they are designed.
ISO 11608-1:2014(E)
c) NISs with system designation B1 where the container is user-filled shall be designed in such a way
that they are capable of delivering the maximum volume needed to fill the container, as specified in
the labelling.
d) When the injection system requires the user to pre-set the dose, the injector shall provide an
indication of the dose that has been set. This information can be displayed in drug-specific units (e.g.
millilitres, milligrams, international units) or in a setting specified by the physician (e.g. number,
letter, percentage) as appropriate for the drug to be delivered. When the dose has been pre-set by
the manufacturer, the dose can be indicated by the device or the system labelling, as appropriate.
e) There shall be an indication of the pre-setting by visual and either tactile and/or audible means.
f) The NIS shall indicate, at least by visual means, that it is ready for injection.
g) The state of the NIS, when ready to deliver a dose, shall be different from its state when the dose has
been delivered. The difference shall be visible.
h) The NIS shall indicate, by visual, audible or tactile means, or any combination of these, that the
injection stroke has been completed.
i) NISs with system designation D2 shall be designed in such a way that it is impossible to deliver the
remaining volume following the actuation and that it is impossible to reactivate the device.
j) Variable multi-dose NISs (system designations A and C) shall be designed so that they:
1) do not allow a larger dose to be pre-set than is left in the container, or
2) do not allow dose delivery if the pre-set amount exceeds the amount of medicinal product left in
the container, or
3) indicate the amount of medicinal product delivered, or
4) indicate the amount of medicinal product not delivered (of the pre-set dose).
k) Fixed multi-dose NISs shall not allow pre-setting of the dose if a volume that is insufficient for the
full fixed dose remains.
l) The NIS shall be designed to function with its specified needles. ISO 11608-2 provides guidance for
needles.
m) The NIS shall be designed to function with its specified containers. ISO 11608-3 provides guidance
for containers.
n) If the NIS has automated functions, the requirements of ISO 11608-5 shall be fulfilled.
o) If the NIS contains electronic or electromechanical components and/or software, the requirements
of ISO 11608-4 shall be fulfilled.
p) To avoid inadvertent disabling of the NIS containing replaceable batteries, it shall not be possible to
remove the batteries unless two independent movements are applied.
q) If designed with small parts that might be swallowed, the NIS labelling shall include warnings
preventing access by children under the age of 3 years.
r) If the NIS contains batteries, it shall be designed to allow the user to determine the state of the
power supply.
s) If the NIS contains software, the software shall be designed based on a life-cycle model in accordance
with IEC 62304. The NIS shall fulfil the applicable requirements of IEC 62304 including connection
to other equipment.
t) The risk analysis shall take into consideration the use of alarms, as appropriate, as described
in IEC 60601-1-11.
6 © ISO 2014 – All rights reserved

ISO 11608-1:2014(E)
u) Adverse effects of the medicinal product contact with the NIS shall be assessed and mitigated
through risk assessment.
v) Biological requirements of the NIS shall be established in accordance with ISO 10993-1.
NOTE It is preferable that the design process incorporate environmentally conscious design (see
IEC 60601–1-9).
w) Where requirements in this part of ISO 11608 provide a test method without acceptance criteria, the
manufacturer shall establish a specification and acceptance criteria appropriate for the intended
use of the device, using a risk-based approach (consistent with ISO 14971 and IEC 62366).
6 Reagent and apparatus
6.1 General
Any suitable test system can be used, when the required accuracy (calibration) and precision (Gauge
R&R) can be obtained. The repeatability and reproducibility (Gauge R&R) of the test apparatus shall
be no greater than 20 % of the allowed tolerance range for any given measurement. For destructive
test measurements, the Gauge R&R shall be no greater than 30 % of the allowed tolerance range. At a
minimum, the Gauge R&R should cover ± 2 standard deviations (thereby covering approximately 95 %
of the variation).
EXAMPLE A measurement system with a measurement specification limit of ± 0,01 ml (range of 0,02 ml)
comes out of the Gauge R&R with a Gauge R&R/tolerance range ratio of 20 %, which means that the Gauge R&R
(4 standard uncertainties) equals 0,02 ml/5 = 0,004 ml. The uncertainty of the measurement is ± 2 standard
deviations (GUM), which equals 0,002 ml.
All doses, V , delivered are recorded gravimetrically, G , (expressed in grams). These recordings are
set meas
converted to volumes, V , by using the density, ρ, (expressed in grams per millilitre) for the test liquid
meas
at environmental conditions. The following equation can be used to convert gravimetric measurements
to volumetric:
V =G /ρ (1)
meas meas
6.2 Test liquid
The test liquid is the original medicinal product intended to be injected by the NIS, or a liquid with
similar physical properties.
6.3 Balance
The balance shall have a resolution of 1 % of the minimum dose delivery.
6.4 Test surface for free-fall testing
The test surface shall be made of smooth, hard, rigid steel of 3 mm t
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