oSIST prEN ISO 11608-3:2020

Needle-based injection systems for medical use - Requirements and test methods - Part 3: NIS containers and integrated fluid paths (ISO/DIS 11608-3:2020)

Kanülenbasierte Injektionssysteme zur medizinischen Verwendung - Anforderungen und Prüfverfahren - Teil 3: Fertigbehälter (ISO/DIS 11608-3:2020)

Dieses Dokument legt Anforderungen und Prüfverfahren für die Ausführungsverifizierung von Behältern und integrierten Flüssigkeitsbahnen fest, die mit kanülenbasierten Injektionssystemen (en: needle based injection systems, NISs), welche die Festlegungen von ISO 11608 1 (und gegebenenfalls anderer Teile der Normenreihe) erfüllen, zu verwenden sind. Sie ist anwendbar auf Einzeldosis  und Mehrfachdosisbehälter (vom Hersteller [Primärbehälterverschluss] oder durch den Endanwender befüllt [Vorratsbehälter]) und Flüssigkeitsbahnen, die am Ort der Herstellung in das NIS integriert werden.
ANMERKUNG   Vorgefüllte Spritzen (ISO 11040 8) sind in den Anwendungsbereich eingeschlossen, wenn sie zusammen mit einem NIS verwendet werden; siehe auch den Anwendungsbereich von ISO 11608 1:20xx.
Ausgeschlossen vom Anwendungsbereich sind folgende Produkte:
   sterile Subkutankanülen zum Einmalgebrauch;
   sterile Injektionsspritzen zum Einmalgebrauch;
   sterile Spritzen zum Einmalgebrauch, mit oder ohne Kanüle, für Insulin;
   Behälter, die mehrere Male befüllt werden können;
   zum zahnärztlichen Gebrauch vorgesehene Behälter;
   Katheter oder Infusionssets, die vom Benutzer angebracht oder separat zusammengesetzt werden.

Systèmes d'injection à aiguille pour usage médical - Exigences et méthodes d'essai - Partie 3: Conteneurs NIS et chemins de fluide intégrés (ISO/DIS 11608-3:2020)

Peresa za injiciranje za uporabo v medicini - Zahteve in preskusne metode - 3. del: Končna embalaža (ISO/DIS 11608-3:2020)

General Information

• Status: Not Published
• Public Enquiry End Date: 19-Apr-2020
• ICS: 11.040.25 - Syringes, needles an catheters
• Technical Committee: VAZ - Healthcare
• Current Stage: 4020 - Public enquire (PE) (Adopted Project)
• Start Date: 02-Mar-2020
• Due Date: 20-Jul-2020
• Completion Date: 14-Apr-2020
• Ref Project: prEN ISO 11608-3 - Needle-based injection systems for medical use - Requirements and test methods - Part 3: NIS containers and integrated fluid paths (ISO/DIS 11608-3:2020)

RELATIONS

• Revised: SIST EN ISO 11608-3:2013 - Needle-based injection systems for medical use - Requirements and test methods - Part 3: Finished containers (ISO 11608-3:2012)
• Effective Date: 01-Apr-2020

Standards Content (sample)

SLOVENSKI STANDARD
oSIST prEN ISO 11608-3:2020
01-april-2020

Peresa za injiciranje za uporabo v medicini - Zahteve in preskusne metode - 3. del:

Končna embalaža (ISO/DIS 11608-3:2020)

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

3: NIS containers and integrated fluid paths (ISO/DIS 11608-3:2020)

Kanülenbasierte Injektionssysteme zur medizinischen Verwendung - Anforderungen und

Prüfverfahren - Teil 3: Fertigbehälter (ISO/DIS 11608-3:2020)

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

Partie 3: Conteneurs NIS et chemins de fluide intégrés (ISO/DIS 11608-3:2020)
Ta slovenski standard je istoveten z: prEN ISO 11608-3
ICS:
11.040.25 Injekcijske brizge, igle in Syringes, needles an
katetri catheters
oSIST prEN ISO 11608-3:2020 en

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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oSIST prEN ISO 11608-3:2020
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oSIST prEN ISO 11608-3:2020
DRAFT INTERNATIONAL STANDARD
ISO/DIS 11608-3
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 3:
NIS containers and integrated fluid paths
ICS: 11.040.25
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
ISO/CEN PARALLEL PROCESSING
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 11608-3:2020(E)
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 SUPPORTING DOCUMENTATION. ISO 2020
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oSIST prEN ISO 11608-3:2020
ISO/DIS 11608-3:2020(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2020

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
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Phone: [phone]
Fax: [phone]
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Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
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oSIST prEN ISO 11608-3:2020
ISO/DIS 11608-3:2020(E)
Contents Page

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

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

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

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

3 Terms and definitions ..................................................................................................................................................................................... 2

4 Requirements .......................................................................................................................................................................................................... 3

4.1 General ........................................................................................................................................................................................................... 3

4.2 Container integrity .............................................................................................................................................................................. 4

4.2.1 Container Closure Integrity (CCI) ..................................................................................................................... 4

4.2.2 Resealability — All multi-dose cartridges or reservoirs with discs .................................... 4

4.2.3 Fragmentation (disc coring) – cartridges or reservoirs with discs...................................... 4

4.3 Cannula requirements (as part of the fluid path) ..................................................................................................... 4

4.3.1 Rigid needles ....................................................................................................................................................................... 4

4.3.2 Soft cannulas ....................................................................................................................................................................... 5

4.4 Fluid line connections ....................................................................................................................................................................... 5

4.5 Medicinal product compatibility ............................................................................................................................................. 5

4.5.1 General...................................................................................................................................................................................... 5

4.5.2 Medicinal product compatibility with reservoir and integrated fluid path

materials ................................................................................................................................................................................. 5

4.5.3 Reservoir and integrated fluid path particulate matter ................................................................. 5

4.5.4 Reservoir and fluid path pyrogenicity ........................................................................................................... 6

4.5.5 Reservoir and integrated fluid path leachables .................................................................................... 6

4.5.6 Sterility of the reservoir and/or integrated fluid path .................................................................... 7

4.6 Medicinal product leakage ............................................................................................................................................................ 7

5 Test methods ............................................................................................................................................................................................................. 8

5.1 Resealability for multi-dose cartridges or reservoirs ........................................................................................... 8

5.2 Fragmentation (disc coring) – cartridges or reservoirs ...................................................................................... 8

5.3 Sub-visible particulates ................................................................................................................................................................... 9

5.4 Visible particulates .............................................................................................................................................................................. 9

6 Information supplied by the manufacturer ............................................................................................................................. 9

6.1 General ........................................................................................................................................................................................................... 9

6.2 Marking on the unit packaging ................................................................................................................................................. 9

Annex A (informative) Pharmaceutical and medicinal product compatibility references

for medicinal product contacting surfaces – Regulations, guidance, standards or

compendia material .......................................................................................................................................................................................10

Annex B (informative) Historical references to ISO 11608-3:2012, Pen-injector cartridges

dimensions and test methods (Clauses 4 and 5) ................................................................................................................14

Annex C (informative) Theoretical support for resealability requirements ...........................................................17

Annex D (informative) Reservoir and integrated fluid path leachables .......................................................................20

Annex E (informative) Medicinal product compatibility ..............................................................................................................22

Annex F (informative) Primary container closure ..............................................................................................................................24

Bibliography .............................................................................................................................................................................................................................26

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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 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.

This third edition cancels and replaces the second edition (ISO 11608-3:2012), which has been

technically revised.
The main changes compared to the previous editions are specified in Annex B.
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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Introduction

This document is applicable to containers (e.g. cartridges, syringes) and their integrated fluid paths

intended for use with Needle-based Injection Systems (NIS) covered by the umbrella standard,

ISO 11608-1. Containers may be provided pre-filled from the manufacturer (i.e. primary container

closure) or empty for filling by the user (i.e. reservoir).

Prior versions focused on multi-dose pen-injector cartridges, important dimensions (e.g. inner

diameter) and related attributes (e.g. disc seal eccentricity, meniscus) deemed critical for pen-injector

form, fit, and function. The prior edition also included a more general discussion of "other containers"

like syringes given their role in single dose NIS with automated functions (commonly referred to as

auto-injectors).

The scope of the latest revision of ISO 11608 (all parts) has been expanded to include on-body delivery

devices (ISO 11608-6), resulting in additional possibilities for future container types. This expansion

of 11608-3 to include evolving NIS technologies requires a broader discussion of containers, integrated

fluid paths, and test methods.

Given the expansion in scope of this document, test methods and dimensions specific to traditional pen-

injector “Type A” cartridges have been removed and, for historical reference, that information has been

preserved in informative Annex B.

There are other international and national standards, guidance materials and, in some countries,

national regulations that are applicable to medical devices and pharmaceuticals; their requirements

might supersede or complement this document. Developers and manufacturers of NIS are encouraged

to investigate and determine if there are any other requirements relevant to the safety of their products.

ISO 11608-1 is the umbrella document of the ISO 11608 series. All other parts, including this document,

are to be used in conjunction with ISO 11608-1.

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

ISO/TR 19244.
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oSIST prEN ISO 11608-3:2020
DRAFT INTERNATIONAL STANDARD ISO/DIS 11608-3:2020(E)
Needle-based injection systems for medical use —
Requirements and test methods —
Part 3:
NIS containers and integrated fluid paths
1 Scope

This document specifies requirements and test methods for design verification of containers and

integrated fluid paths to be used with Needle-Based Injection Systems (NIS) that fulfil the requirements

of ISO 11608-1 (and other subparts as appropriate). It is applicable to single and multi-dose containers

(either filled by the manufacturer [primary container closure] or by the end-user [reservoir]) and fluid

paths that are integrated with the NIS at the point of manufacture.

NOTE Prefilled syringes (ISO 11040-8) are included in the scope when used with a NIS; see also scope of

ISO 11608-1:20xx.
Products excluded from scope are:
— sterile hypodermic needles for single use;
— sterile hypodermic syringes for single use;
— sterile single-use syringes, with or without needle, for insulin;
— containers that can be refilled multiple times;
— containers intended for dental use;

— catheters or infusion sets that are attached or assembled separately by the user.

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 7864:2016, Sterile hypodermic needles for single use — Requirements and test methods

ISO 8872, Aluminium caps for transfusion, infusion and injection bottles — General requirements and

test methods

ISO 9626:2016, Stainless steel needle tubing for the manufacture of medical devices — Requirements and

test methods

ISO 10555-1:2013, Intravascular catheters — Sterile and single-use catheters — Part 1: General

requirements

ISO 10555-5:2013, Intravascular catheters — Sterile and single-use catheters — Part 5: Over-needle

peripheral catheters

ISO 10993-11, Biological evaluation of medical devices — Part 11: Tests for systemic toxicity

1) To be published (revises ISO 10555-1:2013). Stage at time of publication ISO/PWI 10555-1:2019.

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ISO 10993-17, Biological evaluation of medical devices — Part 17: Establishment of allowable limits for

leachable substances

ISO 11040-4, Prefilled syringes — Part 4: Glass barrels for injectables and sterilized subassembled syringes

ready for filling
ISO 11040-5, Prefilled syringes — Part 5: Plunger stoppers for injectables

ISO 11040-6, Prefilled syringes — Part 6: Plastic barrels for injectables and sterilized subassembled

syringes ready for filling

ISO 11040-8, Prefilled syringes — Part 8: Requirements and test methods for finished prefilled syringes

ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials,

sterile barrier systems and packaging systems

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

Needle-based injection systems

ISO 13926-1, Pen systems — Part 1: Glass cylinders for pen-injectors for medical use

ISO 13926-2, Pen systems — Part 2: Plunger stoppers for pen-injectors for medical use

ISO 13926-3, Pen systems — Part 3: Seals for pen-injectors for medical use
ISO 21881:2019, Sterile packaged ready for filling glass cartridges

ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications — Part 7: Connectors

for intravascular or hypodermic applications
3 Terms and definitions

For the purposes of this document, the terms and definitions given in ISO 11608-1 and the following apply.

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 https:// www .iso .org/ obp
3.1
cartridge

container for the medicinal product which is closed on one end with a cartridge cap (3.2) and disc (3.5),

and on the other end with a plunger stopper (3.8)
3.2
cartridge cap
component which attaches the disc (3.5) to the cartridge (3.1)
3.3
container closure integrity
CCI

adequacy of Primary Container Closure (PCC) to maintain a sterile barrier against potential

contaminants until first intentional user interaction
Note 1 to entry: See definition for PCC in ISO 11608-1:20##.

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

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3.4
fragmentation

formation of elastomeric particles which are generated when the disc is pierced by a needle, spike or

other access device for filling or delivery
Note 1 to entry: Disc coring is one mechanism to generate fragments
[SOURCE: ISO 8871-5:2016, 3.2 - modified]
3.5
disc

component of a container (typically a cartridge (3.1)), which seals the end of the container through

which the medicinal product is accessed
Note 1 to entry: E.g. disc septum or elastomeric closure.
3.6
fluid path

pathway the medicinal product follows from the container or reservoir to the targeted delivery site

3.7
medicinal product compatibility
impact of the device on the quality of the medicinal product

Note 1 to entry: Impact of medicinal product on device is covered in ISO 11608-1.

3.8
plunger stopper

component that seals one end of the container and interfaces with the delivery device

3.9
sterility assurance level
SAL
probability of a single viable microorganism occurring after sterilization
Note 1 to entry: It is expressed as the negative exponent to the base 10.
[SOURCE: ISO 11139:2018, 3.275 - modified]
3.10
sterile barrier system
system of components that provide a barrier to microbial ingress
4 Requirements
4.1 General

These requirements apply to containers or integrated fluid paths intended to be used with a NIS. When

test methods and specifications are noted, they are included to assist manufacturers and suppliers in

supporting compliance with design specification of the NIS in accordance with the applicable parts of

ISO 11608.
Specific requirements for NIS primary container closure system components are:

a) glass syringes (including integrated needles) shall comply with applicable clauses of ISO 11040-4

and ISO 11040-8;

b) plastic syringes (including integrated needles) shall comply with applicable clauses of ISO 11040-6

and ISO 11040-8;
c) syringe plunger stoppers shall comply with applicable clauses of ISO 11040-5;
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d) glass cartridges shall comply with applicable clauses of ISO 13926-1 and ISO 21881;

e) cartridge plunger stoppers shall comply with applicable clauses of ISO 13926-2;

f) cartridge discs shall comply with applicable clauses of ISO 13926-3;
g) cartridge caps shall comply with applicable clauses of ISO 8872;

h) all reservoirs provided empty to the user shall be free of droplets of fluid (lubrication) on the

outside or inside surfaces when viewed under normal or corrected-to-normal vision.

4.2 Container integrity
4.2.1 Container Closure Integrity (CCI)

Container closure integrity shall be ensured until first intentional user interaction which breaks CCI.

If the NIS is manufacturer-assembled with a Primary Container Closure (PCC) to form a single integral

unit, the manufacturing processes, including assembly, shall be shown to not adversely impact container

closure integrity, in accordance with applicable pharmacopeia.
4.2.2 Resealability — All multi-dose cartridges or reservoirs with discs

For all cartridges or reservoirs with discs intended for multiple penetrations, after having been

penetrated in accordance with the test method specified in 5.1, the penetrated discs of 20 cartridges or

reservoirs shall not leak from the penetration site when the cartridge is pressurized.

The resealable disc of the cartridge or reservoir shall be punctured 1,0 times the maximum number of

penetrations expected during its intended use.
4.2.3 Fragmentation (disc coring) – cartridges or reservoirs with discs

Cartridges or reservoirs that are accessed through an elastomeric disc (barrier) with a needle, spike

or other access device for delivery shall not exceed six elastomeric disc fragments in the visible range

(>150 µm in diameter) per 100 punctures in accordance with the method described in 5.2, collected

from both coring (ejected from the needle) and fragmentation (collected from the liquid in the container

or reservoir).

For multi-dose cartridges or reservoirs, each disc (barrier) shall be punctured 1.0 times the maximum

number of penetrations expected during its intended use.

Risk assessment shall assess the impact of fragments on the function of the NIS to determine if

additional mitigations or lowering the limit of allowed fragments are required.

NOTE The impact of any fragments on the function of the NIS can be assessed through dose accuracy testing.

4.3 Cannula requirements (as part of the fluid path)
4.3.1 Rigid needles

If the integrated fluid path contains a rigid needle, the strength of union between the needle at its

connection point to the NIS shall not break when an attachment force given in ISO 7864:2016, Table

2 is applied as tension. The directions of force shall be applied as the needle would encounter during

removal from the injection site.

For tapered needles, the minimum force given in ISO 7864:2016, Table 2 is determined by the outer

diameter at the hub as indicated in ISO 7864:2016, Figure 1.

The performance of the rigid needle part shall fulfil the requirements in ISO 9626:2016, Clause 5 and

ISO 7864:2016, 4.10.4, 4.11, 4.12 and 4.13, or an equivalent and applicable standard for tubing suited to

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medical use but fabricated in materials other than stainless steel, to ensure the rigid needle performs

as intended for the specific design.
4.3.2 Soft cannulas

If the integrated fluid path contains a soft cannula and an introducer needle, the strength of union

between the soft cannula and NIS, or the introducer needle and the NIS, shall meet the requirements

of ISO 10555-5:2013, 4.3.3.4 to ensure the soft cannula and/or introducer needle remains affixed to the

NIS throughout its intended use. The testing shall consider and address the forces and vectors that the

introducer needle and cannula would encounter during removal from the injection site.

In addition, the soft cannula shall meet the requirements of ISO 10555-1:2013, 4.6 to ensure the soft

cannula performs as intended for the specific design. Additional physical and functional evaluations to

be considered may include flexural fatigue, compression force, kink resistance, burst testing, etc. Risk

assessment shall be relied upon to determine appropriate evaluations.
In addition, Annex A of this document may also be of assistance.
4.4 Fluid line connections

If the NIS requires a separate external fluid line to connect the functional core of the NIS to a distant

injection site, any connections along that fluid line shall withstand a static tensile force of not less than

15N for 15 seconds.

If the connection uses a standard luer lock connection, the connector shall comply with ISO 80369-7.

4.5 Medicinal product compatibility
4.5.1 General

All materials of the NIS in direct contact with the medicinal product shall be compatible with the

medicinal product to be delivered with the NIS.

When the NIS is filled by the manufacturer, and the container and/or the integrated fluid path are

designed to protect the medicinal product through shipment and storage, it is considered part of the

primary container closure. The requirements for assessing the adequacy of the PCC is covered by

pharmacopeia and ICH Guidance and are not addressed within this document.

Annex A provides a reference to some relevant regulations, guidance, standards or compendia material

for each topic below.

4.5.2 Medicinal product compatibility with reservoir and integrated fluid path materials

Reservoir and integrated fluid path materials that come into contact with the medicinal product

shall not adversely affect the quality of the medicinal product for the intended time of contact. These

requirements apply to the medicinal product after delivery through the NIS. Annex E provides a

discussion of medicinal product compatibility.
4.5.3 Reservoir and integrated fluid path particulate matter
4.5.3.1 General

The reservoir and/or integrated fluid path shall be assessed for sub-visible and visible particulate matter.

Applicable pharmacopeia establishes limits for the size and number of particulates allowed for

the medicinal product. A portion or subset of the particulate matter limit may be generated by the

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reservoir and/or fluid path during delivery. Manufacturers shall establish particulate matter limits of

the reservoir and/or fluid path based on risk assessment and applicable pharmacopeia.

NOTE 1 It is recommended that the manufacturer and the customer agree upon the test methods to be used

and the allocation of size and number of sub-visible and visible particulate matter permissible for the NIS.

Particulates, which, due to their size, nature and/or quantity interfere with the function of the NIS,

medicinal product compatibility or have a negative impact to patient safety, are not acceptable.

NOTE 2 The impact of any particulates on the function of the NIS can be assessed through dose accuracy

testing.
4.5.3.2 Sub-visible

Unless otherwise justified, limits for the NIS reservoir and/or integrated fluid path shall be:

— Particles ≥10µm: 600 max. per NIS
— Particles ≥25µm: 60 max. per NIS
when tested, for example, in accordance with the method described in 5.3.
NOTE These above listed limits are taken from ISO 11040-4:2015.
4.5.3.3 Visible

Visible particulate matter (>150µm in diameter) for the NIS reservoir and/or integrated fluid path shall

not be present when teste
...