ISO/FDIS 11608-6
(Main)Needle-based injection systems for medical use -- Requirements and test methods
Needle-based injection systems for medical use -- Requirements and test methods
Systèmes d'injection à aiguille pour usage médical -- Exigences et méthodes d'essai
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FINAL
INTERNATIONAL ISO/FDIS
DRAFT
STANDARD 11608-6
ISO/TC 84
Needle-based injection systems for
Secretariat: DS
medical use — Requirements and test
Voting begins on:
2021-07-30 methods —
Voting terminates on:
Part 6:
2021-09-24
On-body delivery systems
RECIPIENTS OF THIS DRAFT ARE INVITED TO
SUBMIT, WITH THEIR COMMENTS, NOTIFICATION
OF ANY RELEVANT PATENT RIGHTS OF WHICH
THEY ARE AWARE AND TO PROVIDE SUPPOR TING
DOCUMENTATION.
IN ADDITION TO THEIR EVALUATION AS
Reference number
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
ISO/FDIS 11608-6:2021(E)
LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
OCCASION HAVE TO BE CONSIDERED IN THE
LIGHT OF THEIR POTENTIAL TO BECOME STAN-
DARDS TO WHICH REFERENCE MAY BE MADE IN
NATIONAL REGULATIONS. ISO 2021
---------------------- Page: 1 ----------------------
ISO/FDIS 11608-6:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2021
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved
---------------------- Page: 2 ----------------------
ISO/FDIS 11608-6:2021(E)
Contents Page
Foreword ........................................................................................................................................................................................................................................iv
Introduction ..................................................................................................................................................................................................................................v
1 Scope ................................................................................................................................................................................................................................. 1
2 Normative references ...................................................................................................................................................................................... 1
3 Terms and definitions ..................................................................................................................................................................................... 1
4 Requirements .......................................................................................................................................................................................................... 3
4.1 General ........................................................................................................................................................................................................... 3
4.2 Risk assessment ..................................................................................................................................................................................... 3
4.3 Usability engineering ........................................................................................................................................................................ 3
4.4 Uncertainty of measurement and conformance with specifications........................................................ 3
4.5 General design requirements ..................................................................................................................................................... 3
4.6 Physical or mechanical requirements and test methods .................................................................................... 3
4.6.1 General...................................................................................................................................................................................... 3
4.6.2 Systems comprising rigid needles .................................................................................................................... 3
4.6.3 Systems comprising a soft cannula(s) ........................................................................................................... 3
4.6.4 Leakage from the OBDS ............................................................................................................................................. 3
4.6.5 Means of attachment .................................................................................................................................................... 4
4.6.6 Occlusion ................................................................................................................................................................................ 4
4.7 Functional performance requirements and test methods ................................................................................. 5
4.7.1 General...................................................................................................................................................................................... 5
4.7.2 Dosing requirements and methods ................................................................................................................. 5
4.7.3 Sharps injury protection ........................................................................................................................................... 6
4.7.4 Automated functions .................................................................................................................................................... 6
4.7.5 Injection depth and needle extension ........................................................................................................... 6
4.8 Biological requirements of the OBDS .................................................................................................................................. 7
4.8.1 Sterility of OBDS ............................................................................................................................................................... 7
4.8.2 Biocompatibility ............................................................................................................................................................... 7
4.9 Medicinal product compatibility ............................................................................................................................................. 7
4.9.1 General...................................................................................................................................................................................... 7
4.9.2 Particulates ........................................................................................................................................................................... 7
4.9.3 Pyrogenicity ......................................................................................................................................................................... 7
4.9.4 Extractable/leachables ............................................................................................................................................... 7
4.10 Electrical safety and software requirements ................................................................................................................ 7
4.10.1 Electrical safety ................................................................................................................................................................. 7
4.10.2 Software................................................................................................................................................................................... 7
5 Inspection .................................................................................................................................................................................................................... 7
6 Information supplied by the manufacturer ............................................................................................................................. 8
Annex A (informative) Test methods for adhesion ................................................................................................................................ 9
Annex B (informative) Dose delivery profiles ..........................................................................................................................................10
Annex C (informative) In vitro methods in relation to needle/cannula displacement .................................16
Bibliography .............................................................................................................................................................................................................................17
© ISO 2021 – All rights reserved iii---------------------- Page: 3 ----------------------
ISO/FDIS 11608-6:2021(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 84, Devices for administration of medicinal
products and catheters.A list of all parts in the ISO 11608 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.iv © ISO 2021 – All rights reserved
---------------------- Page: 4 ----------------------
ISO/FDIS 11608-6:2021(E)
Introduction
The ISO 11608 series has traditionally addressed hand-held needle-based injection systems (NISs)
that are intended for parenteral administration by injection of medicinal products through a needle
to humans. These injections are performed manually, through exertion of force by the user, or
automatically through use of an internal power source through a needle into the patient’s tissue.
NOTE Although technically a device using a soft cannula is not “needle-based”, the cannula is placed by a
needle and can be included in this classification.The user typically places the hand-held NIS at the injection site and holds the NIS in place until the
injection has completed. The intended use and delivery requirements of some medicinal products can
make manual manipulation and stabilization of a hand-held NIS during the medicinal product delivery
process impractical or impossible, and can result in an incomplete dose, missed dose, or user injury.
For example, it might not be appropriate, practical or possible for users to hold a NIS in place for an
extended period of time required by the volume or viscosity of the medicinal product or required to
preclude patient discomfort.Delivery systems that are affixed to the body of the user eliminate some of the risks associated with
delivery of medicinal product through a traditional NIS. This document provides a consistent method
for evaluating the unique requirements and risks associated with these systems, herein referred to as
"on-body delivery systems" (OBDS).Similarly to ISO 11608-1 and ISO 11608-5, this document will tend to specify the results of the design
effort instead of the physical and construction requirements used as the basis for OBDS design, so that
innovation in achieving the intended purposes is not unnecessarily restricted.NISs governed by the ISO 11608 series are defined as “hand-held” or “on-body” delivery systems (OBDSs).
When hand-held, patients control and stabilize the NIS at the injection site during administration of a
discrete volume. Delivery times for this type of NIS would, therefore, be limited to avoid instability and
the potential for injection site trauma. For NISs with larger delivery volumes or physical properties
requiring a longer time to deliver, OBDS might be more practical. The OBDS would likely exist as either
“body-worn” (directly anchored to the body, e.g. using adhesive) or “patient-worn” (indirectly anchored,
e.g. catheter attached to OBDS contained in a backpack or pocket).In either configuration, the time or speed employed to deliver a discrete volume would be based upon
patient tolerability or patient convenience rather than clinical relevance (e.g. medication efficacy) as
would be the case with insulin patch pumps or traditional infusion pumps associated with continuous
delivery (e.g. insulin).This document only addresses the basic safety and performance of the product and manufacturers can
through risk assessments, identify additional requirements due to the unique nature of their specific
system or application.The sampling plans for inspection selected for this document and outlined in ISO 11608-1 are intended
to verify the design, at a high confidence level. The sampling plan does not replace the more general
manufacturing quality systems, including lot release, which appear in International Standards on
quality systems, e.g. ISO 9001 or ISO 13485.Guidance on transition periods for implementing the requirements of this document is given in
ISO/TR 19244.© ISO 2021 – All rights reserved v
---------------------- Page: 5 ----------------------
FINAL DRAFT INTERNATIONAL STANDARD ISO/FDIS 11608-6:2021(E)
Needle-based injection systems for medical use —
Requirements and test methods —
Part 6:
On-body delivery systems
1 Scope
This document specifies requirements and test methods for On-Body Delivery Systems (OBDS) needle-
based injection systems (NISs) for single patient use, intended for subcutaneous, intramuscular
or intradermal delivery of a discrete volume (bolus) of medicinal product, through needles or soft
cannulas, incorporating pre-filled or user-filled, replaceable or non-replaceable containers.
NOTE 1 Although technically a device using a soft cannula is not “needle-based”, the soft cannula is placed by a
needle and can be included in this classification.NOTE 2 Some requirements and methods are already established and included in other parts of the
ISO 11608 series.Infusion pumps that are designed for continuous delivery at a specific rate required to achieve and/
or maintain a desired plasma medicinal product concentration are excluded from this document.
However, while this document is not intended to directly apply to these pump products, it does contain
requirements and test methods that can be used to help design and evaluate them.NOTE 3 They are covered by IEC 60601-2-24 (if electronic) or ISO 28620 (if non-electronic).
2 Normative referencesThe 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 11608-1:2021, Needle-based injection systems for medical use - Requirements and test methods - Part 1:
Needle-based injection systemsISO 11608-3:2021, Needle-based injection systems for medical use - Requirements and test methods -
Part 3: NIS containers and fluid pathsISO 11608-4, Needle-based injection systems for medical use - Requirements and test methods - Part 4:
Needle-based injection systems containing electronicsISO 11608-5, Needle-based injection systems for medical use - Requirements and test methods - Part 5:
Automated functions3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp— IEC Electropedia: available at http:// www .electropedia .org/
© ISO 2021 – All rights reserved 1
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ISO/FDIS 11608-6:2021(E)
3.1
body-worn on-body delivery system
body-worn OBDS
on-body delivery system (3.7) that is directly adhered to the skin
3.2
dose accuracy
measure of the total volume of medicinal product delivered to the patient
3.3
dose delivery time
measure of the total time over which the total dose volume is delivered
3.4
dose delivery profile
plot of the volumetric output of the on-body delivery system (3.7) against unit time throughout the
duration of the delivery3.5
leakage
escape of medicinal product from the on-body delivery system (3.7) other than from the patient end of
the fluid path during delivery3.6
needle extension
axial distance from the patient end of the needle or soft cannula tip to the nearest part of the on-body
delivery system body (3.8)Note 1 to entry: See ISO 11608-5:2021, Figures C.1 to C.7 for 90-degree insertion and less than 90-degree
insertion.3.7
on-body delivery system
OBDS
delivery system, which is affixed to the body of the user that actively delivers medicinal product, and
includes the medicinal product container and components for administration through a needle or soft
cannula3.8
on-body delivery system body
OBDS body
defining the point of contact with the patient adjacent to the injection site
3.9
occlusion
blockage or closing of fluid path of on-body delivery system (3.7) during drug administration that is not
part of the intended use3.10
patient tolerability
level to which pain, discomfort and other effects experienced during use of the on-body delivery system
(3.7) are accepted by patients3.11
patient-worn on-body delivery system
on-body delivery system (3.7) that is attached over or under patient’s clothes, but not directly adhered to
the skinNote 1 to entry: This type of injector is attached to the patient through tubing and a catheter.
2 © ISO 2021 – All rights reserved---------------------- Page: 7 ----------------------
ISO/FDIS 11608-6:2021(E)
4 Requirements
4.1 General
The requirements of ISO 11608-1:2021, 5.1 shall apply.
4.2 Risk assessment
The requirements of ISO 11608-1:2021, 5.3 shall apply.
For OBDS, a Safety Assurance Case (SAC) (for example, developed using recommendations such as those
in AAMI/TIR 38) may be used to fulfil the ISO 14971 requirement for a risk management report.
4.3 Usability engineeringThe requirements of ISO 11608-1:2021, 5.4 shall apply.
4.4 Uncertainty of measurement and conformance with specifications
The requirements of ISO 11608-1:2021, 5.5 shall apply.
4.5 General design requirements
Applicable requirements of ISO 11608-1:2021, 5.6 shall apply.
4.6 Physical or mechanical requirements and test methods
4.6.1 General
Unless otherwise specified, the testing shall be performed at standard atmosphere as specified in
ISO 11608-1. For OBDS, manufacturers shall determine the temperature range of the OBDS and drug
during delivery (which may be impacted by body temperature). In use testing, and testing of drug
compatibility should be completed throughout that temperature range.4.6.2 Systems comprising rigid needles
In addition to the requirements in ISO 11608-3, additional physical and functional evaluations shall be
considered, e.g. flexural fatigue. Risk assessment shall be used to determine appropriate evaluations.
4.6.3 Systems comprising a soft cannula(s)The requirements of ISO 11608-3 shall apply.
4.6.4 Leakage from the OBDS
The OBDS shall be inspected for leakage when tested in accordance with ISO 11608-1 in at least
worst-case environments and orientations representative of the expected use. Any amount of leakage
observed during testing shall be assessed for its ability to impact OBDS performance, fluid path or
medicinal product sterility, or risk to humans or the environment.Any allowable leakage shall be addressed by risk assessment and appropriate information shall be
provided to the user in the instructions for use.If any preconditioning creates the appearance of condensation or any other external evidence of fluid,
the manufacturer shall assess and confirm that this was not medicinal product leakage.
© ISO 2021 – All rights reserved 3---------------------- Page: 8 ----------------------
ISO/FDIS 11608-6:2021(E)
4.6.5 Means of attachment
The developer of the OBDS shall establish performance criteria to ensure that the means of attachment
to the body is adequate to maintain a reliable medicinal product delivery pathway.
If the means of attachment uses adhesive, the following apply:— attachment of the OBDS to the adhesive patch and the adhesive to the body are adequate to maintain
reliable medicinal product delivery pathway;— if odour control, MVTR (moisture vapour transmission rate), water resistance or impermeability,
absorbency or conformity have been identified requirement for the OBDS, the adhesive material
should be tested for these properties.Conduct adhesion/attachment tests when used as specified in the instructions for use. Where the OBDS
shall be maintained in a specific orientation, visually confirm that the OBDS maintains the required
orientation during testing. If an adhesive is used, see Annex A, which contains suggested test methods
for verifying the functional performance of an adhesive. It is up to the manufacturer to identify suitable
tests from those suggested or to develop their own test.Testing of adhesion/attachment shall also measure performance of the OBDS under conditions
consistent with the intended use of the product, which may include exposure to typical fluids that can
be encountered during use (e.g. water, personal cleaning products, deodorants, skin lotion, medical
alcohols, perspiration) including the medicinal product, if appropriate. Adhesive tests may be performed
on material that has undergone sterilization or aging if it is anticipated through the risk analysis that
the adhesive property will be adversely affected by such conditioning. Based on risk assessment,
additional evidence might be required to demonstrate the performance and safety of the means of
attachment. This may include use on humans under simulated conditions of actual use (not necessarily
including the actual delivery). This evidence may also need to confirm that the adhesive bond between
the OBDS and the user does not cause unacceptable tissue trauma (as defined by risk assessment) or
create a bond that is too difficult for the user to remove. It is recognized that in some cases, reference to
existing clinical and/or other evidence may be sufficient to demonstrate performance of the means of
attachment.The factors that affect Medical Adhesive Related Skin Injuries (MARSI) are complex and related to
factors that the OBDS manufacturer can control (adhesive properties, design of patch geometry,
suggested application points, etc.) and factors that the OBDS manufacturer cannot control (patient
[74]population, removal technique, etc.). The selection of the adhesive should show due consideration
for the risk of MARSI to the end user balanced against the performance requirements of the OBDS,
applying risk control, where practicable.Extended wear can result in the adhesive developing a stronger bond over time, which could impact the
patient. This should be considered and addressed in the testing.4.6.6 Occlusion
The potential harm to the patient of a partial or complete occlusion resulting in a reduction or cessation
of delivery, or delivery of a fast bolus upon clearance of the occlusion, shall be determined, and the risk
based on the criticality of the medicinal product shall be addressed in the risk assessment. If required,
appropriate control(s) (design and/or indicator, instruction for use etc.) shall be implemented, which
may include a mechanism for the user to determine the ongoing status of the delivery (i.e., a delivery
indicator).NOTE 1 Occlusion might lead to OBDS not meeting its primary function such as dose accuracy or delivery
time. The clearance after occlusion might lead to an instantaneous fast injection that might adversely impact the
patient.NOTE 2 Delivery indication can be done by audible or tactile means or visually by an analogue or digital
indicator.4 © ISO 2021 – All rights reserved
---------------------- Page: 9 ----------------------
ISO/FDIS 11608-6:2021(E)
4.7 Functional performance requirements and test methods
4.7.1 General
In addition to the conditioning specified in ISO 11608-1, manufacturers shall evaluate if simulating
additional conditions to which the OBDS is subjected as worn before and/or during delivery (e.g.
"normal/anticipated conditions" from ISO 11608-1) when testing primary functions is appropriate.
These additional test conditions shall be based on the risk analysis (e.g. due to the potential for extended
dose delivery time and warming of the OBDS while affixed to the body). Potential conditions to consider
include the following:— vibration;
— temperature;
— humidity;
— atmospheric pressure;
— light exposure;
— orientation.
Each additional test shall be carried out at conditions that simulate the operation of the OBDS.
NOTE Primary functions can be able to be assessed during the same testing protocol and on one set of
samples.4.7.2 Dosing requirements and methods
4.7.2.1 General
There are three measurements relevant to the dosing of OBDS:
— dose accuracy;
— dose delivery time;
— dose delivery profile.
At a minimum, dose accuracy is considered a primary function. Risk assessment shall determine
whether dose delivery time is considered a primary function, in accordance with ISO 11608-1.
4.7.2.2 Dose accuracyThe dose accuracy (dose delivered) shall be verified by measuring the total dose delivered. Where
the dose is specified as discontinuous dosing segments, dose accuracy shall be assessed for each dose
segment, including last dose accuracy (for variable dose OBDS) and dose delivery efficiency for user
filled OBDS.If the OBDS is intended to be paused or stopped by the user (i.e., delivery volume during pause = 0),
then the dose accuracy testing at standard atmosphere conditions shall include this state to ensure that
the accuracy of the dose delivered shall not be adversely affected by any planned interruption (pause/
stop feature on OBDS) of the dose. Based on the risk assessment, the manufacturer shall determine if
assessment of the dose accuracy including the pause/stop feature is required after any additional pre-
conditionings besides standard.Dose accuracy testing should be performed under conditions that simulate in vivo tissue back pressure,
if this is determined to be relevant through risk assessment.© ISO 2021 – All rights reserved 5
---------------------- Page: 10 ----------------------
ISO/FDIS 11608-6:2021(E)
4.7.2.3 Dose delivery time
Dose delivery time is a measure of the time over which the total (or each if there are multiple dose
segments) dose is delivered.Design verification of the required dose delivery time, determined by risk assessment, shall be
performed in accordance with ISO 11608-5.The dose delivery time shall be verified by measuring the time over which the total dose is delivered.
Where the dose is specified as discontinuous dosing segments, the time of the delivery of each dose
segment shall be measured.If the OBDS is intended to be paused or stopped by the user (i.e., delivery volume during pause = 0),
then the testing of the dose delivery time at standard atmosphere conditions shall include this state
to ensure that the time over which the dose is delivered is not adversely affected by any planned
interruption (pause/stop feature on OBDS) of the dose. Based on the risk assessment, the manufacturer
shall determine if assessment of the time of the dose delivered including the pause/stop feature is
required after any additional pre-conditionings besides standard.4.7.2.4 Dose
...
FINAL
INTERNATIONAL ISO/FDIS
DRAFT
STANDARD 11608-6
ISO/TC 84
Needle-based injection systems for
Secretariat: DS
medical use — Requirements and test
Voting begins on:
2021-10-06 methods —
Voting terminates on:
Part 6:
2021-12-01
On-body delivery systems
RECIPIENTS OF THIS DRAFT ARE INVITED TO
SUBMIT, WITH THEIR COMMENTS, NOTIFICATION
OF ANY RELEVANT PATENT RIGHTS OF WHICH
THEY ARE AWARE AND TO PROVIDE SUPPOR TING
DOCUMENTATION.
IN ADDITION TO THEIR EVALUATION AS
Reference number
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
ISO/FDIS 11608-6:2021(E)
LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
OCCASION HAVE TO BE CONSIDERED IN THE
LIGHT OF THEIR POTENTIAL TO BECOME STAN-
DARDS TO WHICH REFERENCE MAY BE MADE IN
NATIONAL REGULATIONS. © ISO 2021
---------------------- Page: 1 ----------------------
ISO/FDIS 11608-6:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2021
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
© ISO 2021 – All rights reserved
---------------------- Page: 2 ----------------------
ISO/FDIS 11608-6:2021(E)
Contents Page
Foreword ........................................................................................................................................................................................................................................iv
Introduction .................................................................................................................................................................................................................................v
1 Scope ................................................................................................................................................................................................................................. 1
2 Normative references ..................................................................................................................................................................................... 1
3 Terms and definitions .................................................................................................................................................................................... 1
4 Requirements .......................................................................................................................................................................................................... 3
4.1 General ........................................................................................................................................................................................................... 3
4.2 Risk assessment ..................................................................................................................................................................................... 3
4.3 Usability engineering ........................................................................................................................................... ............................. 3
4.4 Uncertainty of measurement and conformance with specifications ..................................................... 3
4.5 General design requirements .................................................................................................................................................... 3
4.6 Physical or mechanical requirements and test methods .................................................................................. 3
4.6.1 General ........................................................................................................................................................................................ 3
4.6.2 Systems comprising rigid needles ...................................................................................................................... 3
4.6.3 Systems comprising a soft cannula(s) ............................................................................................................. 3
4.6.4 Leakage from the OBDS ........................................................................................................................................... ..... 3
4.6.5 Means of attachment....................................................................................................................................................... 4
4.6.6 Occlusion ................................................................................................................................................................................... 4
4.7 Functional performance requirements and test methods .............................................................................. 5
4.7.1 General ........................................................................................................................................................................................ 5
4.7.2 Dosing requirements and methods ................................................................................................................... 5
4.7.3 Sharps injury protection ............................................................................................................................................. 6
4.7.4 Automated functions ...................................................................................................................................................... 6
4.7.5 Injection depth and needle extension ............................................................................................................. 6
4.8 Biological requirements of the OBDS ................................................................................................................................. 7
4.8.1 Sterility of OBDS ................................................................................................................................................................. 7
4.8.2 Biocompatibility ................................................................................................................................................................. 7
4.9 Medicinal product compatibility ............................................................................................................................................ 7
4.9.1 General ........................................................................................................................................................................................ 7
4.9.2 Particulates ............................................................................................................................................................................. 7
4.9.3 Pyrogenicity ........................................................................................................................................................................... 7
4.9.4 Extractable/leachables ................................................................................................................................................. 7
4.10 Electrical safety and software requirements ............................................................................................................. 7
4.10.1 Electrical safety .................................................................................................................................................................. 7
4.10.2 Software ..................................................................................................................................................................................... 7
5 Inspection .................................................................................................................................................................................................................... 7
6 Information supplied by the manufacturer ............................................................................................................................ 8
Annex A (informative) Test methods for adhesion ............................................................................................................................... 9
Annex B (informative) Dose delivery profiles ........................................................................................................................................10
Annex C (informative) In vitro methods in relation to needle/cannula displacement ...............................16
Bibliography .............................................................................................................................................................................................................................17
iii© ISO 2021 – All rights reserved
---------------------- Page: 3 ----------------------
ISO/FDIS 11608-6:2021(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 84, Devices for administration of medicinal
products and catheters.A list of all parts in the ISO 11608 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 2021 – All rights reserved
---------------------- Page: 4 ----------------------
ISO/FDIS 11608-6:2021(E)
Introduction
The ISO 11608 series has traditionally addressed hand-held needle-based injection systems (NISs)
that are intended for parenteral administration by injection of medicinal products through a needle
to humans. These injections are performed manually, through exertion of force by the user, or
automatically through use of an internal power source through a needle into the patient’s tissue.
NOTE Although technically a device using a soft cannula is not “needle-based”, the cannula is placed by a
needle and can be included in this classification.The user typically places the hand-held NIS at the injection site and holds the NIS in place until the
injection has completed. The intended use and delivery requirements of some medicinal products can
make manual manipulation and stabilization of a hand-held NIS during the medicinal product delivery
process impractical or impossible, and can result in an incomplete dose, missed dose, or user injury.
For example, it might not be appropriate, practical or possible for users to hold a NIS in place for an
extended period of time required by the volume or viscosity of the medicinal product or required to
preclude patient discomfort.Delivery systems that are affixed to the body of the user eliminate some of the risks associated with
delivery of medicinal product through a traditional NIS. This document provides a consistent method
for evaluating the unique requirements and risks associated with these systems, herein referred to as
"on-body delivery systems" (OBDS).Similarly to ISO 11608-1 and ISO 11608-5, this document will tend to specify the results of the design
effort instead of the physical and construction requirements used as the basis for OBDS design, so that
innovation in achieving the intended purposes is not unnecessarily restricted.NISs governed by the ISO 11608 series are defined as “hand-held” or “on-body” delivery systems (OBDSs).
When hand-held, patients control and stabilize the NIS at the injection site during administration of a
discrete volume. Delivery times for this type of NIS would, therefore, be limited to avoid instability and
the potential for injection site trauma. For NISs with larger delivery volumes or physical properties
requiring a longer time to deliver, OBDS might be more practical. The OBDS would likely exist as either
“body-worn” (directly anchored to the body, e.g. using adhesive) or “patient-worn” (indirectly anchored,
e.g. catheter attached to OBDS contained in a backpack or pocket).In either configuration, the time or speed employed to deliver a discrete volume would be based upon
patient tolerability or patient convenience rather than clinical relevance (e.g. medication efficacy) as
would be the case with insulin patch pumps or traditional infusion pumps associated with continuous
delivery (e.g. insulin).This document only addresses the basic safety and performance of the product and manufacturers can
through risk assessments, identify additional requirements due to the unique nature of their specific
system or application.The sampling plans for inspection selected for this document and outlined in ISO 11608-1 are intended
to verify the design, at a high confidence level. The sampling plan does not replace the more general
manufacturing quality systems, including lot release, which appear in International Standards on
quality systems, e.g. ISO 9001 or ISO 13485.© ISO 2021 – All rights reserved
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FINAL DRAFT INTERNATIONAL STANDARD ISO/FDIS 11608-6:2021(E)
Needle-based injection systems for medical use —
Requirements and test methods —
Part 6:
On-body delivery systems
1 Scope
This document specifies requirements and test methods for On-Body Delivery Systems (OBDS) needle-
based injection systems (NISs) for single patient use, intended for subcutaneous, intramuscular
or intradermal delivery of a discrete volume (bolus) of medicinal product, through needles or soft
cannulas, incorporating pre-filled or user-filled, replaceable or non-replaceable containers.
NOTE 1 Although technically a device using a soft cannula is not “needle-based”, the soft cannula is placed by a
needle and can be included in this classification.NOTE 2 Some requirements and methods are already established and included in other parts of the
ISO 11608 series.Infusion pumps that are designed for continuous delivery at a specific rate required to achieve and/
or maintain a desired plasma medicinal product concentration are excluded from this document.
However, while this document is not intended to directly apply to these pump products, it does contain
requirements and test methods that can be used to help design and evaluate them.NOTE 3 They are covered by IEC 60601-2-24 (if electronic) or ISO 28620 (if non-electronic).
2 Normative referencesThe 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 11608-1:2021, Needle-based injection systems for medical use - Requirements and test methods - Part
1: Needle-based injection systemsISO 11608-3:2021, Needle-based injection systems for medical use - Requirements and test methods - Part
3: NIS containers and fluid pathsISO 11608-4, Needle-based injection systems for medical use - Requirements and test methods - Part 4:
Needle-based injection systems containing electronicsISO 11608-5, Needle-based injection systems for medical use - Requirements and test methods - Part 5:
Automated functions3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp— IEC Electropedia: available at http:// www .electropedia .org/
© ISO 2021 – All rights reserved
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ISO/FDIS 11608-6:2021(E)
3.1
body-worn on-body delivery system
body-worn OBDS
on-body delivery system (3.7) that is directly adhered to the skin
3.2
dose accuracy
measure of the total volume of medicinal product delivered to the patient
3.3
dose delivery time
measure of the total time over which the total dose volume is delivered
3.4
dose delivery profile
plot of the volumetric output of the on-body delivery system (3.7) against unit time throughout the
duration of the delivery3.5
leakage
escape of medicinal product from the on-body delivery system (3.7) other than from the patient end of
the fluid path during delivery3.6
needle extension
axial distance from the patient end of the needle or soft cannula tip to the nearest part of the on-body
delivery system body (3.8)Note 1 to entry: See ISO 11608-5:2021, Figures C.1 to C.7 for 90-degree insertion and less than 90-degree
insertion.3.7
on-body delivery system
OBDS
delivery system, which is affixed to the body of the user that actively delivers medicinal product, and
includes the medicinal product container and components for administration through a needle or soft
cannula3.8
on-body delivery system body
OBDS body
defining the point of contact with the patient adjacent to the injection site
3.9
occlusion
blockage or closing of fluid path of on-body delivery system (3.7) during drug administration that is not
part of the intended use3.10
patient tolerability
level to which pain, discomfort and other effects experienced during use of the on-body delivery system
(3.7) are accepted by patients3.11
patient-worn on-body delivery system
on-body delivery system (3.7) that is attached over or under patient’s clothes, but not directly adhered to
the skinNote 1 to entry: This type of injector is attached to the patient through tubing and a catheter.
© ISO 2021 – All rights reserved---------------------- Page: 7 ----------------------
ISO/FDIS 11608-6:2021(E)
4 Requirements
4.1 General
The requirements of ISO 11608-1:2021, 5.1 shall apply.
4.2 Risk assessment
The requirements of ISO 11608-1:2021, 5.3 shall apply.
For OBDS, a Safety Assurance Case (SAC) (for example, developed using recommendations such as those
in AAMI/TIR 38) may be used to fulfil the ISO 14971 requirement for a risk management report.
4.3 Usability engineeringThe requirements of ISO 11608-1:2021, 5.4 shall apply.
4.4 Uncertainty of measurement and conformance with specifications
The requirements of ISO 11608-1:2021, 5.5 shall apply.
4.5 General design requirements
Applicable requirements of ISO 11608-1:2021, 5.6 shall apply.
4.6 Physical or mechanical requirements and test methods
4.6.1 General
Unless otherwise specified, the testing shall be performed at standard atmosphere as specified in
ISO 11608-1. For OBDS, manufacturers shall determine the temperature range of the OBDS and drug
during delivery (which may be impacted by body temperature). In use testing, and testing of drug
compatibility should be completed throughout that temperature range.4.6.2 Systems comprising rigid needles
In addition to the requirements in ISO 11608-3, additional physical and functional evaluations shall be
considered, e.g. flexural fatigue. Risk assessment shall be used to determine appropriate evaluations.
4.6.3 Systems comprising a soft cannula(s)The requirements of ISO 11608-3 shall apply.
4.6.4 Leakage from the OBDS
The OBDS shall be inspected for leakage when tested in accordance with ISO 11608-1 in at least
worst-case environments and orientations representative of the expected use. Any amount of leakage
observed during testing shall be assessed for its ability to impact OBDS performance, fluid path or
medicinal product sterility, or risk to humans or the environment.Any allowable leakage shall be addressed by risk assessment and appropriate information shall be
provided to the user in the instructions for use.If any preconditioning creates the appearance of condensation or any other external evidence of fluid,
the manufacturer shall assess and confirm that this was not medicinal product leakage.
© ISO 2021 – All rights reserved---------------------- Page: 8 ----------------------
ISO/FDIS 11608-6:2021(E)
4.6.5 Means of attachment
The developer of the OBDS shall establish performance criteria to ensure that the means of attachment
to the body is adequate to maintain a reliable medicinal product delivery pathway.
If the means of attachment uses adhesive, the following apply:— attachment of the OBDS to the adhesive patch and the adhesive to the body are adequate to maintain
reliable medicinal product delivery pathway;— if odour control, MVTR (moisture vapour transmission rate), water resistance or impermeability,
absorbency or conformity have been identified requirement for the OBDS, the adhesive material
should be tested for these properties.Conduct adhesion/attachment tests when used as specified in the instructions for use. Where the OBDS
shall be maintained in a specific orientation, visually confirm that the OBDS maintains the required
orientation during testing. If an adhesive is used, see Annex A, which contains suggested test methods
for verifying the functional performance of an adhesive. It is up to the manufacturer to identify suitable
tests from those suggested or to develop their own test.Testing of adhesion/attachment shall also measure performance of the OBDS under conditions
consistent with the intended use of the product, which may include exposure to typical fluids that can
be encountered during use (e.g. water, personal cleaning products, deodorants, skin lotion, medical
alcohols, perspiration) including the medicinal product, if appropriate. Adhesive tests may be performed
on material that has undergone sterilization or aging if it is anticipated through the risk analysis that
the adhesive property will be adversely affected by such conditioning. Based on risk assessment,
additional evidence might be required to demonstrate the performance and safety of the means of
attachment. This may include use on humans under simulated conditions of actual use (not necessarily
including the actual delivery). This evidence may also need to confirm that the adhesive bond between
the OBDS and the user does not cause unacceptable tissue trauma (as defined by risk assessment) or
create a bond that is too difficult for the user to remove. It is recognized that in some cases, reference to
existing clinical and/or other evidence may be sufficient to demonstrate performance of the means of
attachment.The factors that affect Medical Adhesive Related Skin Injuries (MARSI) are complex and related to
factors that the OBDS manufacturer can control (adhesive properties, design of patch geometry,
suggested application points, etc.) and factors that the OBDS manufacturer cannot control (patient
[73]population, removal technique, etc.). The selection of the adhesive should show due consideration
for the risk of MARSI to the end user balanced against the performance requirements of the OBDS,
applying risk control, where practicable.Extended wear can result in the adhesive developing a stronger bond over time, which could impact the
patient. This should be considered and addressed in the testing.4.6.6 Occlusion
The potential harm to the patient of a partial or complete occlusion resulting in a reduction or cessation
of delivery, or delivery of a fast bolus upon clearance of the occlusion, shall be determined, and the risk
based on the criticality of the medicinal product shall be addressed in the risk assessment. If required,
appropriate control(s) (design and/or indicator, instruction for use etc.) shall be implemented, which
may include a mechanism for the user to determine the ongoing status of the delivery (i.e., a delivery
indicator).NOTE 1 Occlusion might lead to OBDS not meeting its primary function such as dose accuracy or delivery
time. The clearance after occlusion might lead to an instantaneous fast injection that might adversely impact the
patient.NOTE 2 Delivery indication can be done by audible or tactile means or visually by an analogue or digital
indicator.© ISO 2021 – All rights reserved
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ISO/FDIS 11608-6:2021(E)
4.7 Functional performance requirements and test methods
4.7.1 General
In addition to the conditioning specified in ISO 11608-1, manufacturers shall evaluate if simulating
additional conditions to which the OBDS is subjected as worn before and/or during delivery (e.g.
"normal/anticipated conditions" from ISO 11608-1) when testing primary functions is appropriate.
These additional test conditions shall be based on the risk analysis (e.g. due to the potential for extended
dose delivery time and warming of the OBDS while affixed to the body). Potential conditions to consider
include the following:— vibration;
— temperature;
— humidity;
— atmospheric pressure;
— light exposure;
— orientation.
Each additional test shall be carried out at conditions that simulate the operation of the OBDS.
NOTE Primary functions can be able to be assessed during the same testing protocol and on one set of
samples.4.7.2 Dosing requirements and methods
4.7.2.1 General
There are three measurements relevant to the dosing of OBDS:
— dose accuracy;
— dose delivery time;
— dose delivery profile.
At a minimum, dose accuracy is considered a primary function. Risk assessment shall determine
whether dose delivery time is considered a primary function, in accordance with ISO 11608-1.
4.7.2.2 Dose accuracyThe dose accuracy (dose delivered) shall be verified by measuring the total dose delivered. Where
the dose is specified as discontinuous dosing segments, dose accuracy shall be assessed for each dose
segment, including last dose accuracy (for variable dose OBDS) and dose delivery efficiency for user
filled OBDS.If the OBDS is intended to be paused or stopped by the user (i.e., delivery volume during pause = 0),
then the dose accuracy testing at standard atmosphere conditions shall include this state to ensure that
the accuracy of the dose delivered shall not be adversely affected by any planned interruption (pause/
stop feature on OBDS) of the dose. Based on the risk assessment, the manufacturer shall determine if
assessment of the dose accuracy including the pause/stop feature is required after any additional pre-
conditionings besides standard.Dose accuracy testing should be performed under conditions that simulate in vivo tissue back pressure,
if this is determined to be relevant through risk assessment.© ISO 2021 – All rights reserved
---------------------- Page: 10 ----------------------
ISO/FDIS 11608-6:2021(E)
4.7.2.3 Dose delivery time
Dose delivery time is a measure of the time over which the total (or each if there are multiple dose
segments) dose is delivered.Design verification of the required dose delivery time, determined by risk assessment, shall be
performed in accordance with ISO 11608-5.The dose delivery time shall be verified by measuring the time over which the total dose is delivered.
Where the dose is specified as discontinuous dosing segments, the time of the delivery of each dose
segment shall be measured.If the OBDS is intended to be paused or stopped by the user (i.e., delivery volume during pause = 0),
then the testing of the dose delivery time at standard atmosphere conditions shall include this state
to ensure that the time over which the dose is delivered is not adversely affected by any planned
interruption (pause/stop feature on OBDS) of the dose. Based on the risk assessment, the manufacturer
shall determine if assessment of the time of the dose delivered including the pause/stop feature is
required after any additional pre-conditionings besides standard.4.7.2.4 Dose delivery profile
[6]
In instances where the dose delivery profile is determined to be clinically relevant , the manu
...
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