ISO/DIS 11608-6

Needle-based injection systems for medical use -- Requirements and test methods

Systèmes d'injection à aiguille pour usage médical -- Exigences et méthodes d'essai

Standards Content (sample)

DRAFT INTERNATIONAL STANDARD
ISO/DIS 11608-6
ISO/TC 84 Secretariat: DS
Voting begins on: Voting terminates on:
2020-02-18 2020-05-12
Needle-based injection systems for medical use —
Requirements and test methods —
Part 6:
On-body delivery systems
ICS: 11.040.25
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
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STANDARD UNTIL PUBLISHED AS SUCH.
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This document is circulated as received from the committee secretariat.
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ISO/DIS 11608-6:2020(E)
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PROVIDE SUPPORTING DOCUMENTATION. ISO 2020
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ISO/DIS 11608-6:2020(E)
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ISO/DIS 11608-6:2020(E)
Contents Page

Foreword ........................................................................................................................................................................................................................................iv

Introduction ..................................................................................................................................................................................................................................v

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 1

4 Requirements .......................................................................................................................................................................................................... 2

4.1 General ........................................................................................................................................................................................................... 2

4.2 Risk assessment ..................................................................................................................................................................................... 3

4.3 Usability engineering ........................................................................................................................................................................ 3

4.4 Uncertainty of measurement and conformity 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 for body-worn OBDS .............................................................................................. 3

4.6.6 Occlusion ................................................................................................................................................................................ 4

4.7 Functional performance requirements and test methods ................................................................................. 4

4.7.1 General...................................................................................................................................................................................... 4

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 to be supplied by the manufacturer ............................................................................................................... 7

Annex A (informative) Test methods for adhesion ................................................................................................................................ 8

Annex B (informative) Dose delivery profiles ............................................................................................................................................. 9

Annex C (informative) In vitro methods in relation to needle/cannula displacement .................................14

Bibliography .............................................................................................................................................................................................................................15

© ISO 2020 – All rights reserved iii
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ISO/DIS 11608-6:2020(E)
Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards

bodies (ISO member bodies). The work of preparing International Standards is normally carried out

through ISO technical committees. Each member body interested in a subject for which a technical

committee has been established has the right to be represented on that committee. International

organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.

ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of

electrotechnical standardization.

The procedures used to develop this document and those intended for its further maintenance are

described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the

different types of ISO documents should be noted. This document was drafted in accordance with the

editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of

any patent rights identified during the development of the document will be in the Introduction and/or

on the ISO list of patent declarations received (see www .iso .org/ patents).

Any trade name used in this document is information given for the convenience of users and does not

constitute an endorsement.

For an explanation on 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 the following

URL: 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 2020 – All rights reserved
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ISO/DIS 11608-6:2020(E)
Introduction

ISO 11608 has traditionally addressed hand-held needle-based injection systems (NISs) which 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 .

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 medicinal product delivery requirements of some

medicinal products may make manual manipulation and stabilization of a hand-held NIS during the

medicinal product delivery process impractical or impossible, and may result in an incomplete dose,

missed dose, or user injury. For example, it may not be appropriate 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 patient

discomfort.

Delivery systems which 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).

Like ISO 11608-1 and ISO 11608-5, this document is developed more as a “horizontal” than “vertical”

one, to accommodate anticipated variation in the designs. Thus, it 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 ISO 11608 are defined as “hand-held” or “on-body” delivery systems (OBDSs).

By 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 back-pack or pocket). In either configuration, the time

or speed employed to deliver a discrete volume would be based upon tolerability or convenience

rather than clinical relevance (e.g. medication efficacy) as would be the case with insulin patch pumps

or traditional infusion pumps (e.g. IEC 60601-2-24:2012 Ed 2.0, ISO 28620:2010) associated with

continuous delivery (e.g. insulin). However, while this document is not intended to directly apply to

these pump products, it does contain requirements and tests methods that can be used to help design

and evaluate them.

This document only addresses the basic safety and effectiveness of the product and manufacturers may,

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

standards on quality systems, e.g. ISO 9001 or ISO 13485.

There can be legal or regulatory requirements that take precedence over the requirements in this

document.

ISO 11608-1 is the umbrella document. All other parts, including this document, are used in conjunction

with ISO 11608-1.

Guidance on transition periods for implementing the requirements of this document is given in

ISO/TR 19244.

1) 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.
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DRAFT INTERNATIONAL STANDARD ISO/DIS 11608-6:2020(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), which

are body-worn or patient-worn 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. To ensure consistency, these requirements will not be repeated in this document, but referenced.

Infusion pumps which are not body or patient worn, or those 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 and may be covered by IEC 60601-2-24 (if electronic) or ISO 28620 (if

non-electronic). However, while this document is not intended to directly apply to these pump products,

it does contain requirements and tests methods that can be used to help design and evaluate them.

2 Normative references

The following documents are referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

undated references, the latest edition of the referenced document (including any amendments) applies.

ISO 11608-1 , Needle-based injection systems for medical use - Requirements and test methods - Part 1:

Needle-based injection systems

ISO 11608-3 , Needle-based injection systems for medical use - Requirements and test methods - Part 3:

NIS containers and fluid paths

ISO 11608-4 , Needle-based injection systems for medical use - Requirements and test methods - Part 4:

Needle-based injection systems containing electronics

ISO 11608-5 , Needle-based injection systems for medical use - Requirements and test methods - Part 5:

Automated functions
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.

2) To be published (revises ISO 11608-1:2012). Stage at time of publication: ISO/DIS 11608-1:2020.

3) To be published (revises ISO 11608-3:2012). Stage at time of publication: ISO/DIS 11608-3:2020.

4) To be published (revises ISO 11608-4:2006). Stage at time of publication: ISO/DIS 11608-4:2020.

5) To be published (revises ISO 11608-5:2012). Stage at time of publication: ISO/DIS 11608-5:2020.

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ISO/DIS 11608-6:2020(E)

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— IEC Electropedia: available at http:// www .electropedia .org/
— ISO Online browsing platform: available at http:// www .iso .org/ obp
3.1
body-worn OBDS
OBDS (3.5) that is directly adhered to the skin
3.2
dose delivery profile

plot of the volumetric output of the device against unit time throughout the duration of the delivery

Note 1 to entry: See Annex B.
3.3
leakage

escape of medicinal product from the device, other than from the patient end of the fluid path during

delivery
3.4
needle (cannula) extension

axial distance from the patient end of the needle tip to the nearest part of the OBDS body (defining the

point of contact with the patient adjacent to the injection site)

Note 1 to entry: See ISO 11608-5:20##, Figures C.1 to C.7 for 90-degree insertion and less than 90-degree

insertion.
3.5
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 cannula

Note 1 to entry: OBDS allows for “hands-free” drug delivery and does not prevent free patient movement or

ambulation during use.
3.6
occlusion

blockage or closing of fluid path of OBDS (3.5) during drug administration that is not part of the

intended use
3.7
patient tolerability

level to which pain, discomfort and other effects experienced during use of the device are accepted by

patients
3.8
patient worn injector

body-worn device that is attached over or under patient’s clothes, but not directly adhered to the skin

Note 1 to entry: This type of injector is attached to the patient through tubing and a catheter.

4 Requirements
4.1 General
The general requirements specified in ISO 11608-1:20##, 5.1 apply.
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ISO/DIS 11608-6:2020(E)
4.2 Risk assessment
The requirements in ISO 11608-1:20##, 5.3 apply.

NOTE For OBDS, an assurance case (for example, developed using recommendations such as those in AAMI

TIR 38) can be used to fulfil the ISO 14971 requirement for a risk management report.

4.3 Usability engineering
The requirements specified in ISO 11608-1:20##, 5.4 apply.
4.4 Uncertainty of measurement and conformity with specifications
The requirements specified in ISO 11608-1:20##, 5.5 apply.
4.5 General design requirements
Applicable requirements specified in ISO 11608-1:20##, 5.6 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 device 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
The requirements in ISO 11608-3 apply.
4.6.3 Systems comprising a soft cannula(s)
The requirements in ISO 11608-3 apply.
4.6.4 Leakage from the OBDS

The device shall be inspected for leakage when tested in accordance with ISO 11608-1, in environments

and orientations representative of the expected use. Any amount of leakage observed during testing

shall be assessed for its ability to impact device performance, fluid path or medicinal product sterility,

or risk to humans or the environment.

Any leakage shall be addressed by risk assessment and appropriate information shall be provided to

the user.

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.

4.6.5 Means of attachment for body-worn OBDS

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 is adequate to maintain reliable medicinal product

delivery pathway;
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ISO/DIS 11608-6:2020(E)

— 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 test when used as specified in the instructions for use. Where the device

shall be maintained in a specific orientation, visually confirm that the device 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 device under conditions

consistent with the intended use of the product, which may include exposure to typical fluids that may

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 may 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 device 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.

NOTE 1 The factors that affect Medical Adhesive Related Skin Injuries (MARSI) are complex and related to

factors that the device manufacturer can control (adhesive properties, design of patch geometry, suggested

application points, etc.) and factors that the device manufacturer cannot control (patient 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.

NOTE 2 Extended wear may 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, 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 user 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 by an analogue or digital indicator.

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.

6) Medical Adhesives and Patient Safety: State of the Science by McNichol et al. Wound Ostomy Continence and

Nursing, July/August 2013.
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ISO/DIS 11608-6:2020(E)

These additions 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:

— vibration;
— temperature;
— humidity;
— atmospheric pressure;
— light exposure;
— orientation.

Each additional test shall be carried out at conditions that simulate the operation of the OBDS as

described in the instructions for use.

NOTE Primary functions may 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; and
— 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 accuracy

Design verification of the required dose accuracy, determined by risk assessment, shall be performed in

accordance with and shall meet the requirements specified in ISO 11608-1.

The dose accuracy (dose delivered) shall be verified by measuring the total dose delivered. Where the

dose is specified as discontinuous dosing segments, each dose segment shall be measured for dose

accuracy.

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 device) 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.
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 (time the prescribed dose is delivered) shall be verified by measuring the t

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