ISO/FDIS 11040-8

Prefilled syringes — Part 8: Requirements and test methods for finished prefilled syringes

ISO 11040-8:2016 is applicable to aseptically filled or terminally sterilized finished prefilled syringes (intended for single use only) based on ISO 11040‑4 or ISO 11040‑6, together with ISO 11040‑5, for parenteral injection preparations with focus on quality, functional performance and safety requirements, as well as relevant test methods. Finished prefilled syringes which have undergone an additional preparation step by the user before injection (e.g. diluent syringes that have been emptied for reconstitution and in which the reconstituted drug solution has been aspirated after reconstitution) are excluded from the scope of ISO 11040-8:2016.

Seringues préremplies — Partie 8: Exigences et méthodes d'essai pour les seringues préremplies prêtes à l'emploi

ISO 11040-8:2016 s'applique aux seringues remplies en mode aseptique ou aux seringues préremplies prêtes à l'emploi, stérilisées après conditionnement (destinées exclusivement à un usage unique), basées sur l'ISO 11040‑4 ou l'ISO 11040‑6 complétée par l'ISO 11040‑5 pour les préparations parentérales injectables, en se concentrant particulièrement sur la qualité, les performances fonctionnelles, les exigences de sécurité et les méthodes d'essai appropriées. Les seringues préremplies prêtes à l'emploi auxquelles l'utilisateur a fait subir une étape de préparation supplémentaire avant injection (par exemple, les seringues de diluant qui ont été vidées pour reconstitution et dans lesquelles la solution de médicament reconstituée a été aspirée, après reconstitution) sont exclues du domaine d'application de l'ISO 11040-8:2016.

General Information

• Status: Not Published
• ICS: 11.040.25 - Syringes, needles an catheters
• Technical Committee: ISO/TC 76 - Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use
• Drafting Committee: ISO/TC 76 - Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use
• Current Stage: 5020 - FDIS ballot initiated: 2 months. Proof sent to secretariat
• Start Date: 04-Mar-2026
• Completion Date: 04-Mar-2026

Relations

• Revises: ISO 11040-8:2016 - Prefilled syringes — Part 8: Requirements and test methods for finished prefilled syringes
• Effective Date: 22-Oct-2022

Overview

ISO/FDIS 11040-8 is an international standard developed by ISO focused on the requirements and test methods for finished prefilled syringes. This document is applicable to aseptically filled or terminally sterilized prefilled syringes intended for single use, particularly for parenteral injection preparations. The standard is especially relevant to products based on components from ISO 11040-4, ISO 11040-5, or ISO 11040-6, ensuring comprehensive coverage of quality, safety, and performance aspects.

Prefilled syringes have become increasingly common in clinical and home healthcare settings due to their convenience, reduced risk of contamination, and ease of use. ISO/FDIS 11040-8 provides a harmonized framework for manufacturers, regulators, and healthcare professionals to demonstrate product safety, reliability, and usability. It covers critical elements such as system characterization, functional performance, pharmaceutical quality, and relevant testing methods.

Key Topics

• Scope: Applies to finished prefilled syringes intended for single-use parenteral delivery, excluding those that require further preparation (e.g., reconstitution by users).
• Intended Use & Risk Management: Emphasizes defining intended use, including medical indication, patient population, administration route, user environment, and associated risks.
• System Characterization: Includes critical dimensions, component descriptions (barrel, plunger, closures), and the properties of contents (viscosity, pH, filling volume).
• Performance Requirements: Details functional tests such as break-loose and extrusion forces, flange breakage resistance, needle penetration, leakage resistance, and connectivity with small-bore connectors.
• Usability & Safety: Addresses requirements for usability engineering, including validation of instructions for use and ergonomic features. Also covers sharps injury protection per ISO 23908.
• Documentation: Highlights requirements for thorough product documentation, supporting quality assurance and regulatory compliance.

Applications

ISO/FDIS 11040-8 is vital for:

• Medical Device Manufacturers: Ensuring design, verification, and production of compliant prefilled syringes.
• Pharmaceutical Companies: Establishing product safety and performance for drug-device combination products.
• Healthcare Providers: Selecting syringes that meet stringent quality and safety standards, reducing the risk of use errors and contamination.
• Regulatory Agencies: Providing a universal benchmark when evaluating prefilled syringes for market approval or compliance audits.
• Quality Assurance Professionals: Guiding the implementation of robust testing methods and risk management throughout the product lifecycle.

Practical benefits include assurance of consistent product performance, minimized contamination risks, enhanced user safety (e.g., sharps injury protection), and simplified integration in diverse administration environments, from hospitals to home care.

Related Standards

ISO/FDIS 11040-8 is part of the comprehensive ISO 11040 series, which addresses all aspects of prefilled syringes:

• ISO 11040-4: Glass barrels for injectables and sterilized subassembled syringes
• ISO 11040-5: Plunger stoppers for injectables
• ISO 11040-6: Plastic barrels for injectables
• ISO 11608-1 to ISO 11608-7: Needle-based injection systems for medical use and related test methods
• ISO 7864: Sterile hypodermic needles for single use
• ISO 80369 series: Small-bore connectors in healthcare applications
• ISO 23908: Sharps injury protection features
• IEC 62366-1: Usability engineering for medical devices

Adherence to ISO/FDIS 11040-8, alongside these related standards, promotes harmonization, global trade, and patient safety while supporting innovation in injectable drug delivery systems.

Keywords: ISO 11040-8, prefilled syringes, quality requirements, test methods, parenteral injection, medical device safety, functional performance, pharmaceutical packaging, ISO standards, healthcare compliance.

Standards Content (Sample)

DRAFT
International
Standard
ISO/DIS 11040-8
ISO/TC 76
Prefilled syringes —
Secretariat: DIN
Part 8:
Voting begins on:
Requirements and test methods for 2025-07-10
finished prefilled syringes
Voting terminates on:
2025-10-02
ICS: 11.040.25
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENTS 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
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
This document is circulated as received from the committee secretariat.
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
NATIONAL REGULATIONS.
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.
Reference number
ISO/DIS 11040-8:2025(en)
DRAFT
ISO/DIS 11040-8:2025(en)
International
Standard
ISO/DIS 11040-8
ISO/TC 76
Prefilled syringes —
Secretariat: DIN
Part 8:
Voting begins on:
Requirements and test methods for
finished prefilled syringes
Voting terminates on:
ICS: 11.040.25
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENTS 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
BEING ACCEPTABLE FOR INDUSTRIAL,
© ISO 2025
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
STANDARDS MAY ON OCCASION HAVE TO
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on
This document is circulated as received from the committee secretariat. BE CONSIDERED IN THE LIGHT OF THEIR
the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
or ISO’s member body in the country of the requester.
NATIONAL REGULATIONS.
ISO copyright office
RECIPIENTS OF THIS DRAFT ARE INVITED
CP 401 • Ch. de Blandonnet 8
TO SUBMIT, WITH THEIR COMMENTS,
CH-1214 Vernier, Geneva
NOTIFICATION OF ANY RELEVANT PATENT
Phone: [phone]
RIGHTS OF WHICH THEY ARE AWARE AND TO
PROVIDE SUPPORTING DOCUMENTATION.
Email: [e-mail]
Website: www.iso.org
Published in Switzerland Reference number
ISO/DIS 11040-8:2025(en)
ii
ISO/DIS 11040-8:2025(en)
Contents Page
Foreword .iv
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 User requirements .3
4.1 Definition of intended use .3
4.2 Risk management .3
4.3 Application of usability engineering .3
5 System characterization .3
5.1 Critical dimensions .3
5.2 Description of components and materials .4
5.2.1 General .4
5.2.2 Syringe barrels and front end closures .4
5.2.3 Plunger stoppers/pistons .5
5.2.4 Additional components and/or devices .5
5.3 Description of the contents of the finished prefilled syringe .5
6 Functional performance requirements.6
6.1 General .6
6.2 Break-loose and extrusion forces .6
6.3 Flange breakage resistance .7
6.4 Front end closure pull-off forces and torques .7
6.5 Connectivity with small-bore connectors .7
6.6 Residual volume .7
6.7 Needle penetration force .7
6.8 Needle pull-out force .7
6.9 Sharps injury protection requirements .8
6.10 Liquid leakage resistance .8
6.11 Markings .8
6.12 Administration time with defined constant test force .8
7 Pharmaceutical requirements . 8
7.1 General .8
7.2 Interactions between container closure system and contents (injectable product) .8
7.3 Biological hazards and microbiological requirements .9
7.4 Container closure integrity .9
7.5 Deliverable volume .10
7.6 Particles (visible and sub-visible) .10
8 Documentation . 10
Annex A (normative) Test method for break-loose and extrusion forces of finished prefilled
syringes .11
Annex B (normative) Test method for residual volume of finished prefilled syringes. 14
Annex C (informative) Test methods for liquid leakage resistance of finished prefilled syringes .16
Annex D (informative) Test method for administration time with defined constant test force . 19
Annex E (informative) Unintended plunger stopper movement of finished prefilled syringes .21
Bibliography .24

iii
ISO/DIS 11040-8:2025(en)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out through
ISO technical committees. Each member body interested in a subject for which a technical committee
has been established has the right to be represented on that committee. International organizations,
governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely
with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are described
in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the different types
of ISO documents should be noted. This document was drafted in accordance with the editorial rules of the
ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of any patent
rights identified during the development of the document will be in the Introduction and/or on the ISO list of
patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment,
as well as information about ISO’s adherence to the World Trade Organization (WTO) principles in the
Technical Barriers to Trade (TBT) see the following URL: www.iso.org/iso/foreword.html.
The document was prepared by ISO/TC 76, Transfusion, infusion and injection, and blood processing equipment
for medical and pharmaceutical use.
This second edition cancels and replaces the first edition (ISO 11040-8:2016), which has been technically
revised.
The main changes are as follows:
— The entire document was revised for consistent use of terms and language.
— A basic statistical approach for design verification testing of functional performance requirements was
included in the Clause and in Clause 6.1.
— Single Terms and definitions (Clause 3) were revised, deleted or included.
— The Definition of intended use (Clause 4.1) was revised for clarity.
— Break-loose and extrusion forces (Clause 6.2) was revised, and it was clarified to perform testing with
the finished prefilled syringe as intended for use. The normative Annex A with the respective test method
was introduced.
— The former clause for burst resistance was removed; parts of its contents were included in the revised
clause for Liquid leakage resistance (Clause 6.10).
— Flange break resistance (Clause 6.3) was revised to include specification limits and a test method
reference. It was clarified to perform testing with the finished prefilled syringe, with further instructions.
Front end breakage resistance requirements were deleted.
— Front end closure pull-off forces and torques (Clause 6.4) was revised to clarify test methods and
specification limits.
— Connectivity with small-bore connectors (Clause 6.5) was clarified to perform testing with the finished
prefilled syringe as intended for use.
— Residual Volume (Clause 6.6) was clarified to perform testing with the finished prefilled syringe as
intended for use. The normative Annex B with the respective test method was introduced.

iv
ISO/DIS 11040-8:2025(en)
— Needle penetration force (Clause 6.7) and Needle pull-out force (Clause 6.8) were revised to clarify test
methods and specification limits.
— Liquid leakage resistance (Clause 6.10) was combined with parts of the contents of former clause for
burst resistance and revised. The informative Annex C with the respective test methods was introduced.
— A new clause for Administration time with defined constant test force (Clause 6.12) was included. The
informative Annex D with the respective test method was introduced.
— Where applicable, references to pharmacopoeias were included in the subclauses to Pharmaceutical
requirements (Clause 7).
— The informative Annex E for Unintended plunger stopper movement of finished prefilled syringes was
introduced.
A list of all parts in the ISO 11040 series can be found on the ISO website.

v
ISO/DIS 11040-8:2025(en)
Introduction
Historically, injectable (parenteral) liquid pharmaceutical products have been mainly provided in primary
containers (i.e. ampoules and vials) which required the liquid to be transferred into a hypodermic syringe
and combined with the appropriate injection needle before administration. This procedure is not only time-
consuming, but also presents a multitude of possibilities for contamination and use errors.
Over the past decades, the presentation of liquid pharmaceutical products in prefilled syringes for single
use, many with staked needles, has become more prevalent. The simplicity of use that is provided not only
benefits their use in the clinical setting, but also enables these to be used by lay users in a home setting.
The standardization of the requirements for prefilled syringes has been addressed by ISO/TC 76 in two ways:
— the specifications of the components of the prefilled syringe prior to filling are included in the previous
parts of the ISO 11040 series;
— the requirements for the final prefilled syringe, presented to the user as a finished product, are addressed
in this document.
Finished prefilled syringes can require marketing authorization as a medicinal product, in some regions
as a combination product or as a medical device, depending on their contents and the intended use. The
syringe plays a dual role in the finished prefilled syringe — as a container closure system and as a delivery
device. Safety, functional performance and usability need to be considered, also in case of intended use in
combination with pre-attached, co-packaged or cross-referenced additional components and/or devices.
This document addresses the syringe and its contents as a system, with the intent to ensure the successful
application for its intended use. In this context, the minimal configuration of a finished prefilled syringe is
the syringe barrel filled with the intended contents (i.e. the injectable product) and closed with a front end
closure and a plunger stopper (sealing the back end). Additional components (e.g. either attachment of a
needle for single use or assembly of a plunger rod or both) may need to be added by the manufacturer or user
to make it ready for administration by manual injection according to its intended use. Alternatively, such a
finished prefilled syringe may be combined by the manufacturer or user with a device for administration by
a needle-based injection system according to its intended use.
This document includes requirements for the design verification of the finished prefilled syringe’s functional
performance requirements in accordance with its design specifications. The test methods and other aspects
of testing described in this document are intended to verify the design at a confidence level of 95 %. They
are not intended to stipulate acceptance criteria for lot release (e.g. acceptable quality limits, probability
content, probability or other) in the context of manufacturing processes. Testing at component level can
be sufficient for design verification of specific requirements if the influence of processing on the finished
prefilled syringe can be ruled out.
There are other international and national standards and guidance publications and, in some countries,
national regulations that are applicable to medical devices and medicinal products and combinations
thereof. Their requirements might supersede or complement this document. Developers and manufacturers
of finished prefilled syringes are encouraged to investigate and determine whether there are any other
requirements relevant to the safety and functional performance or marketability of their products.

vi
DRAFT International Standard ISO/DIS 11040-8:2025(en)
Prefilled syringes —
Part 8:
Requirements and test methods for finished prefilled
syringes
1 Scope
This document is applicable to aseptically processed or terminally sterilized finished prefilled syringes
(intended for single use only) based on components addressed in ISO 11040-4 or ISO 11040-6, together with
a front end closure and a plunger stopper (sealing the back end), for parenteral preparations with focus on
quality, functional performance and safety requirements, as well as relevant test methods.
Finished prefilled syringes which have undergone an additional preparation step by the user before injection
(e.g. diluent-containing syringes that have been emptied for reconstitution and in which the reconstituted
injectable product has been aspirated after reconstitution) are excluded from the scope of this document.
NOTE 1 This document can also be used as a guidance for other types, designs and/or sizes of finished prefilled
syringes, e.g. dual chamber prefilled syringes.
NOTE 2 For finished prefilled syringes that are used in needle-based injection systems, see also references
[1] [2] [3] [4] [5] [6] [7]
ISO 11608-1:2022 , ISO 11608-2 , ISO 11608-3 , ISO 11608-4 , ISO 11608-5 , ISO 11608-6 , ISO 11608-7 ).
1)
NOTE 3 Attention is drawn to applicable national or regional regulations and pharmacopoeias such as Ph.Eur. ,
2) 3)
USP or JP .
NOTE 4 Finished prefilled syringes for parenteral preparations which are medical devices or which, according to
the principal mode of action of the product (i.e. the means by which the product achieves its principal intended action),
are borderline between medical devices and medicinal products fall within in the scope of this document, even if they
are not always regulated as medicinal products.
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, Sterile hypodermic needles for single use — Requirements and test methods
ISO 7886-1:2017, Sterile hypodermic syringes for single use — Part 1: Syringes for manual use
ISO 11040-4, Prefilled syringes — Part 4: Glass barrels for injectables and sterilized subassembled syringes
ready for filling
ISO 11040-4:2024, 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
1) See http:// www .edqm .eu/ .
2) See http:// www .usp .org/ .
3) See http:// www .pmda .go .jp.

ISO/DIS 11040-8:2025(en)
ISO 11608-1:2022, Needle-based injection systems for medical use — Requirements and test methods — Part 1:
Needle-based injection systems
ISO 23908, Sharps injury protection — Requirements and test methods — Sharps protection features for single-
use hypodermic needles, introducers for catheters and needles used for blood sampling
IEC 62366-1, Medical devices — Part 1: Application of usability engineering to medical devices
ISO 11040-5, Prefilled syringes — Part 5: Plunger stoppers for injectables
ISO 11040-6, Prefilled syringes — Part 6: Plastic barrels for injectables
ISO 23908, Sharps injury protection — Requirements and test methods — Sharps protection features for single-
use hypodermic needles, introducers for catheters and needles used for blood sampling
ISO 80369-1, Small-bore connectors for liquids and gases in healthcare applications — Part 1: General
requirements
ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications — Part 7: Connectors with
6% (Luer) taper for intravascular or hypodermic applications
ISO 80369-20, Small-bore connectors for liquids and gases in healthcare applications — Part 20: Common
test methods
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
finished prefilled syringe
prefilled container closure system for parenteral preparations as marketed, including, e.g. filling with the
intended contents and assembly of additional components, aseptic processing or terminal sterilization as
applicable, and final packaging by the manufacturer (3.2)
3.2
manufacturer
natural or legal person holding the licence (e.g. marketing authorisation or other as applicable) for the
injectable product with responsibility for the design, development, manufacture, packaging, and labelling of
a finished prefilled syringe (3.1), before it is placed on the market or put into service, regardless of whether
these operations are carried out by that person or on that person's behalf by a third party
3.3
needle-based injection system
injection system intended for parenteral administration of medicinal products using a needle or cannula
and a multi-dose or single-dose container
[SOURCE: ISO 11608-1:2022, 3.15]
3.4
user
patient or health care giver (e.g. clinical personnel, doctor, lay person) who handles (e.g. prepares, applies,
disposes of) the finished prefilled syringe (3.1)

ISO/DIS 11040-8:2025(en)
4 User requirements
4.1 Definition of intended use
The manufacturer shall define the intended use of the finished prefilled syringe. Aspects to be considered
shall include the following:
— intended medical indication and criticality of administration, e.g. in emergency situations;
— patient population including their health status and the user profile;
— the route and frequency of administration and the target tissue;
— the use environment, e.g. clinical or home setting;
— additional components and/or devices (see 5.2.4) that are used for application, e.g. plunger rods/piston
rods, finger flange extensions/backstops, sterile hypodermic needles, needleless small bore connectors,
filters, tubing, vial adapters, needle-based injection systems;
— characteristics of the expected environmental conditions during transport, storage and use;
— operating principle if applicable, and interactions between user, environment and the finished prefilled
syringe including additional components and/or devices, if applicable.
4.2 Risk management
Manufacturers shall follow a risk-based approach during the design, development, manufacture and life
[8]
cycle of the finished prefilled syringe like exemplarily described by ISO 14971 . Risk management shall
consider the intended use, interactions between container closure system and contents, and environmental
conditions. This can result in product-specific requirements and test methods that differ from what is
outlined in this document.
If the finished prefilled syringe is intended to be used in combination with pre-attached, co-packaged or
cross-referenced components and/or devices, the manufacturer shall ensure that the whole combination,
including the connectivity with other components and/or devices, is safe, usable and does not impair the
specified functional performance of the single components and/or devices.
[9]
NOTE For risk management of manufacturing processes, see reference .
4.3 Application of usability engineering
The usability of the finished prefilled syringe shall be considered and validated according to a process
conforming to IEC 62366-1.
[10]
NOTE 1 For further information on usability engineering of medical devices, see reference ANSI/AAMI HE75 .
NOTE 2 The instructions for use are part of the user interface to be validated in the usability testing.
5 System characterization
5.1 Critical dimensions
Critical dimensions shall be defined considering the intended use of the finished prefilled syringe. Particular
attention shall be paid to, but not limited to, the following:
— interfaces with users;
— interfaces and connectivity with other components (e.g. needleless small bore connectors or sterile
hypodermic needles);
ISO/DIS 11040-8:2025(en)
— interfaces with other devices (e.g. sharps injury protection features or needle-based injection systems);
— plunger stopper position depending on the intended use (e.g. for manual injection or for use in needle-
based injection systems) (see Figure 1).
Figure 1 shows examples of measuring the plunger stopper position for finished prefilled syringes.
a) Example 1 b) Example 2
Key
1 plunger stopper
l distance from the plunger stopper to the top of the 90° cone (mechanical or optical gauge) at the syringe
barrel front end shoulders
l and l distance from the plunger stopper to the back end of the syringe (distal or proximal edge of the flange)
2 3
Figure 1 — Examples of measuring the plunger stopper position for finished prefilled syringes
5.2 Description of components and materials
5.2.1 General
The selected components and materials shall be suitable for the intended manufacturing processes (e.g.
terminal sterilization process if applicable).
The interfaces with other components and/or devices (e.g. tubing or needle-based injection systems) shall
be considered.
5.2.2 Syringe barrels and front end closures
ISO 11040-4 and ISO 11040-6 shall apply.

ISO/DIS 11040-8:2025(en)
The syringe barrel can include a staked needle. The needle dimensions including inner and outer diameters
(gauge) and exposed needle length shall be consistent with the intended use, considering e.g. route of
administration, use in needle-based injection systems and content properties.
5.2.3 Plunger stoppers/pistons
ISO 11040-5 shall apply.
NOTE 1 The dimensional requirements of ISO 11040-5 are not applicable to barrier-coated plunger stoppers.
NOTE 2 The dimensional requirements of ISO 11040-5 apply to component level. Plunger stopper dimensions are
different in compressed and uncompressed state.
5.2.4 Additional components and/or devices
Additional components and/or devices required for or supporting the intended use can include but are not
limited to the following:
— plunger rods/piston rods;
— add-on finger flanges/backstops;
— sterile hypodermic needles with 6 % Luer conical fitting in accordance with ISO 7864;
— sharps injury protection features (integrated or combined with the finished prefilled syringe prior to
use) in accordance with ISO 23908;
— other devices with small bore connectors with 6 % Luer conical fitting, for example
— filters;
— tubing;
— vial adapters.
Finished prefilled syringes can be used in needle-based injection systems if appropriately qualified. The
interfaces with the relevant components and/or devices shall be considered.
5.3 Description of the contents of the finished prefilled syringe
Critical quality attributes of the contents shall be defined. Those relevant for interactions between container
closure system and contents (injectable product) and/or affecting administration can include but are not
limited to the following:
— viscosity;
— density;
— surface tension;
— pH;
— osmolality;
— filling volume including filling tolerances;
— head space volume and composition.
These quality attributes are temperature dependent and can change over time.

ISO/DIS 11040-8:2025(en)
6 Functional performance requirements
6.1 General
Based on the intended use (see 4.1) the manufacturer shall ensure that the finished prefilled syringe fulfils
the corresponding functional performance requirements until the end of product shelf life. The finished
prefilled syringe shall be tested in stability studies at time points up to the end of product shelf life. The
tests described in clauses 6.2 to 6.12 should be considered but are not necessarily all inclusive.
[11]
NOTE For conducting stability studies, see reference .
The sampling plans for design verification testing should ensure a probability content level, determined to
be appropriate by risk assessment, with a confidence level of 95 %. The confidence level of 95 % means that
there is a 5 % risk of incorrectly concluding that the testing has demonstrated the reliability level based on
the specific units in the testing sample. The reliability level is the reliability goal or target level of reliability
that the product is expected to achieve. The confidence level of 95 % is the minimum confidence level
commonly used. The typical choice of reliability level is 90 %, 95 % or 99 %, which is determined by the level
of risk that can be accepted depending on the intended use of the product.
EXAMPLE If a process has achieved a 95 % confidence and a 99 % reliability, it has demonstrated with a 95 %
confidence that at least 99 % of the units in the population are conforming to the requirements.
A sample size of 30 units is considered statistically significant as it fulfils the following criteria:
— The central limit theorem states that the distribution of sample means is normally distributed or
transformed if the sample size is 30 units or more. This means that the mean value of a sample is close to
the mean value of the population, regardless of the distribution of the data.
— The law of large numbers also states that the more data points a sample contains, the more accurate
are the results. With fewer than 30 data points, it is difficult to draw reliable conclusions as there is not
enough data to reduce variability and bias.
— In addition, a sample size of 30 units can provide a more complete picture of a histogram that reveals the
underlying distribution of the data.
Specification limits for the functional parameters shall be defined based on the intended use. Testing at
component level can be sufficient for design verification of specific requirements if the influence of
processing on the finished prefilled syringe can be ruled out.
6.2 Break-loose and extrusion forces
Break loose and extrusion forces testing shall be conducted with the finished prefilled syringe as intended
for use (e.g. with attached needle or with assembled plunger rod). Finished prefilled syringes intended
for administration by manual injection shall be assembled with the same plunger rod as for application
according to the intended use (i.e. the plunger rod the product is placed on the market with); for those
intended for administration by a needle-based injection system the plunger rod of the used injection system
may be used if applicable, or an appropriate substitute plunger rod (e.g. of the used tensile and compression
testing machine). For the tests, the temperature of the contents shall be as for application according to the
intended use.
It shall be considered that the break-loose and extrusion forces can change over product shelf life depending
on environmental conditions.
The finished prefilled syringe shall be tested according to Annex A for break-loose and extrusion forces
with constant test speed. The test speed shall be defined based on the intended use, considering injection
duration requirements with the impact of different syringe sizes, filling volumes, needle dimensions (in
particular the inner diameter) as well as the content properties.

ISO/DIS 11040-8:2025(en)
6.3 Flange breakage resistance
For flange breakage resistance, ISO 11040-4:2024, 5.4.4, including the stated specification limits as minimum
requirements, applies. The specification limits may be adapted based on the intended use. The test method
ISO 11040-4:2024, C.1 is applicable and is performed with the finished prefilled syringe. For this purpose,
the tip cap or needle shield (or other front end closure) is removed from the finished prefilled syringe, the
plunger stopper is manually depressed (i.e. the syringe emptied) and may remain in the syringe but the
plunger rod is removed to allow the use of the loading pin required by the test method instead.
NOTE For finished prefilled syringes that are used in needle-based injection systems, the stated specification
limits can be adapted to higher values depending on the intended use.
6.4 Front end closure pull-off forces and torques
The following test methods apply:
— ISO 11040-4:2024, G3 Luer lock adaptor collar pull-off force; the specification limits of ISO 11040-4:2024,
6.5.3.5 apply
— ISO 11040-4:2024, G4 Luer lock adaptor collar torque resistance; the specification limits of
ISO 11040-4:2024, 6.5.3.5 apply
— ISO 11040-4:2024, G5 Luer lock rigid tip cap unscrewing torque; according specification limits shall be
defined based on the intended use
— ISO 11040-4:2024, G6 Pull-off force of the tip cap or the needle shield; according specification limits shall
be defined based on the intended use
6.5 Connectivity with small-bore connectors
Additional small-bore connectors to be used in the fluid path of the finished prefilled syringe according
to the intended use shall be tested for connectivity and leakage following ISO 80369-1, ISO 80369-7 and
ISO 80369-20. The finished prefilled syringe with the intended contents shall be tested with the same
additional small-bore connectors as for application according to the intended use (either pre-attached, co-
packaged or cross-referenced).
Additionally, see ISO 11040-4 and ISO 11040-6 for testing Luer connectors/Luer lock adapters.
6.6 Residual volume
The residual volume (dead space) of the finished prefilled syringe shall be tested according to Annex B
with the intended contents and in combination with additional components and/or devices as intended for
use. For the test, the temperature of the contents shall be as for application according to the intended use.
The residual volume can depend on the content properties (e.g. viscosity) and, for example, on the needle
dimensions (in particular the inner diameter). It is determined, for example, to define a potential overfill for
the manufacturing process in order to achieve the correct deliverable volume (see 7.5).
6.7 Needle penetration force
Needle penetration force for finished prefilled syringes with a staked needle shall be tested according to
ISO 11040-4:2024, Annex F. The specification limits for needle penetration force stated in ISO 11040-4:2024,
6.5.2.4, apply as minimum requirements.
NOTE Terminal sterilization using moist heat can affect the, for example, silicone lubrication layer on the needle.
6.8 Needle pull-out force
Needle pull-out force for finished prefilled syringes with a staked needle shall be tested according to
ISO 11040-4:2024, Annex G.1. The specification limits for needle pull-out force stated in ISO 11040-4:2024,
6.5.2.6, apply as minimum requirements.

ISO/DIS 11040-8:2025(en)
6.9 Sharps injury protection requirements
If the finished prefilled syringe has integrated sharps injury protection features (or is combined with a
sharps injury protection device before use), it shall meet the requirements of ISO 23908.
6.10 Liquid leakage resistance
The finished prefilled syringe should be tested in accordance with the procedures described in Annex C for
liquid leakage resistance by applying an axial force to the plunger stopper through the same plunger rod as
for application and under the same conditions according to the intended use, consistent with the maximum
force generated during administration.
The finished prefilled syringe should be tested with the intended front end closure in accordance with the
procedure for liquid leakage at the plunger stopper [Clause C.2].
When used for example in needle-based injection systems, significantly higher forces can act on finished
prefilled syringes compared to manual injection, whereby the increased pressure in the syringe can lead to
bursting under certain circumstances. Thus, the finished prefilled syringe should be tested in accordance
with the procedure for burst resistance [Clause C.3] with an additional, irreversible sealing of the front end
(i.e. replacing the front end closure). Test pressures and acceptance criteria shall be defined according to the
requirements of the needle-based injection system with adding to the test pressure a safety margin of 20 %.
6.11 Markings
All graduation marks or indicator lines (e.g. preprinted directly on the syringe barrel or printed on a label)
shall be verified to be as accurate as appropriate for the intended use.
NOTE If graduation marks or indicator lines are used (e.g. preprinted directly on the syringe barrel or printed on
a label), ISO 7886-1:2017, Table 1, can be considered.
6.12 Administration time with defined constant test force
The administration of the injectable product is determined by the applicable time and required force. The
administration time is of relevance when considering the capabilities of the intended users for manual
injection or the functional force profile of the needle-based injection system. Applying a defined constant
test force (or force profile if applicable) results in different injection speeds and administration times, which
can be used to determine the suitability of the finished prefilled syringe for the intended use. Therefore,
in addition to break-loose and extrusion forces (see 6.2), the finished prefilled syringe may be tested for
characterization purposes in accordance with Annex D for administration time with a defined constant test
force (or force profile if applicable).
7 Pharmaceutical requirements
7.1 General
Pharmaceutical requirements for injectable products are covered by national or regional regulations,
standards such as pharmacopoeias and applicable guidelines. The container closure system shall be suitable
for the intended contents (in terms of protection, safety, compatibility and functional performance),
considering the intended use (e.g. transport, storage, administration). The tests in 7.2 to 7.6 shall be
performed but are not necessarily all inclusive.
7.2 Interactions between container closure system and contents (injectable product)
The contents of the finished prefilled syringe shall meet the specified quality attributes during transport,
storage and use according to the manufacturer’s instructions throughout product shelf life. The impact of

ISO/DIS 11040-8:2025(en)
additional components and/or devices on the container closure system and contents during administration
shall be considered.
The following aspects shall be considered but are not necessarily all inclusive:
— extractables and leachables migrating into the injectable product from components and the materials
they are made of, e.g. glass, plastic, elastomer components (e.g. rubber), lubrication (e.g. free silicone),
as well as from labels, but also residuals from forming, moulding, gluing, sterilization process, assembly
process and the impurities and degradation products thereof;
— compatibility of the injectable product with container closure system components, e.g. loss of either
assay or potency or both, adsorption, degradation, change of stability indicating quality attributes;
— effects of physical forces (e.g. shear or pressure) during administration on the quality of the injectable
product.
NOTE Exemplary pharmacopoeial chapters for extractables and leachables testing are
— USP general chapters <1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems
and <1664> Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems
7.3 Biological hazards and microbiological requirements
Assessment of biological hazards shall be performed for the finished prefilled syringe following, e.g.
[12]
ISO 10993-1 .
The container closure system shall maintain product sterility, achieved either by aseptic processing or by
terminal sterilization, throughout product shelf life including transport and storage.
[13] [14]
NOTE 1 See references ISO 13408-1 for aseptic processing and ISO 17665 for moist heat sterilization
processes.
Sterility testing requirements are specified in applicable pharmacopoeias.
NOTE 2 Exemplary pharmacopoeial chapters for sterility testing are
— Ph.Eur. chapter 2.6.1. Sterility
— USP general chapter <71> Sterility Tests
— JP section 4.05 Sterility Test
Bacterial endotoxin limits are specified in pharmacopoeial requirements.
NOTE 3 Exemplary pharmacopoeial chapter
...

FINAL DRAFT
International
Standard
ISO/TC 76
Prefilled syringes —
Secretariat: DIN
Part 8:
Voting begins on:
2026-03-04
Requirements and test methods for
finished prefilled syringes
Voting terminates on:
2026-04-29
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
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
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.
Reference number
FINAL DRAFT
International
Standard
ISO/TC 76
Prefilled syringes —
Secretariat: DIN
Part 8:
Voting begins on:
Requirements and test methods for
finished prefilled syringes
Voting terminates on:
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.
© ISO 2026
IN ADDITION TO THEIR EVALUATION AS
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO-
LOGICAL, COMMERCIAL AND USER PURPOSES, DRAFT
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on
INTERNATIONAL STANDARDS MAY ON OCCASION HAVE
the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below
TO BE CONSIDERED IN THE LIGHT OF THEIR POTENTIAL
or ISO’s member body in the country of the requester.
TO BECOME STAN DARDS TO WHICH REFERENCE MAY BE
MADE IN NATIONAL REGULATIONS.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland Reference number
ii
Contents Page
Foreword .iv
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 User requirements . 2
4.1 Definition of intended use .2
4.2 Risk management .3
4.3 Application of usability engineering .3
5 System characterization .3
5.1 Critical dimensions .3
5.2 Description of components and materials .4
5.2.1 General .4
5.2.2 Syringe barrels and front end closures .4
5.2.3 Plunger stoppers/pistons (sealing the back end) .5
5.2.4 Additional components and/or devices .5
5.3 Description of the contents of the finished prefilled syringe .5
6 Functional performance requirements. 6
6.1 General .6
6.2 Break-loose and extrusion forces .6
6.3 Flange breakage resistance .7
6.4 Front end closure pull-off forces and torques .7
6.5 Connectivity with small-bore connectors .7
6.6 Residual volume .8
6.7 Needle penetration force .8
6.8 Needle pull-out force .8
6.9 Sharps injury protection requirements .8
6.10 Liquid leakage resistance .8
6.11 Markings .9
6.12 Administration time with defined constant test force .9
6.13 Unintended plunger stopper movement of finished prefilled syringes .9
7 Pharmaceutical requirements .10
7.1 General .10
7.2 Interactions between container closure system and contents (injectable product) .10
7.3 Biological hazards and microbiological requirements .10
7.4 Container closure integrity .11
7.5 Deliverable volume .11
7.6 Particles (visible and sub-visible) .11
8 Test reports .11
Annex A (normative) Test method for break-loose and extrusion forces of finished prefilled
syringes .13
Annex B (informative) Test method for residual volume of finished prefilled syringes .16
Annex C (normative) Test methods for liquid leakage resistance of finished prefilled syringes .18
Annex D (informative) Test method for administration time with defined constant test force .21
Bibliography .23

iii
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).
ISO draws attention to the possibility that the implementation of this document may involve the use of (a)
patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed patent
rights in respect thereof. As of the date of publication of this document, ISO had not received notice of (a)
patent(s) which may be required to implement this document. However, implementers are cautioned that
this may not represent the latest information, which may be obtained from the patent database available at
www.iso.org/patents. ISO shall not be held responsible for identifying any or all such patent rights.
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment,
as well as information about ISO’s adherence to the World Trade Organization (WTO) principles in the
Technical Barriers to Trade (TBT) see the following URL: www.iso.org/iso/foreword.html.
The document was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection, and
blood processing equipment for medical and pharmaceutical use.
This second edition cancels and replaces the first edition (ISO 11040-8:2016), which has been technically
revised.
The main changes are as follows.
— The entire document has been revised for consistent use of terms and language.
— A basic statistical approach for design verification testing of functional performance requirements has
been included in the Clause and in 6.1.
— Single terms and definitions (see Clause 3) have been revised, deleted or included.
— The definition of intended use (see 4.1) has been revised for clarity.
— Break-loose and extrusion forces (see 6.2) has been revised; it has been clarified to perform testing with
the finished prefilled syringe as intended for use. A new Annex A, with the respective test method, has
been introduced.
— The former subclause for burst resistance was removed; parts of its contents have been included in the
revised subclause for liquid leakage resistance (see 6.10).
— Flange breakage resistance (see 6.3) has been revised to include specification limits and a test method
reference. It was clarified to perform testing with the finished prefilled syringe, with further instructions.
Front end breakage resistance requirements have been deleted.
— Front end closure pull-off forces and torques (see 6.4) have been revised to clarify test methods and
specification limits.
— Connectivity with small-bore connectors (see 6.5) was clarified to perform testing with the finished
prefilled syringe as intended for use.

iv
— Residual volume (see 6.6) was clarified to perform testing with the finished prefilled syringe as intended
for use. A new Annex B, with the respective test method, has been introduced.
— Needle penetration force (see 6.7) and needle pull-out force (6.8) were revised to clarify test methods
and specification limits.
— Liquid leakage resistance (see 6.10) was combined with parts of the contents of former subclause for
burst resistance and revised. A new Annex C, with the respective test methods, has been introduced.
— A new subclause for administration time with defined constant test force (see 6.12) has been included. A
new Annex D, with the respective test method, has been introduced.
— A new subclause for unintended plunger stopper movement of finished prefilled syringes (see 6.13) has
been introduced.
— Where applicable, references to pharmacopoeias have been included in the subclauses to pharmaceutical
requirements (see Clause 7).
A list of all parts in the ISO 11040 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.

v
Introduction
Historically, injectable (parenteral) liquid pharmaceutical products have been mainly provided in primary
containers (i.e. ampoules and vials) which required the liquid to be transferred into a hypodermic syringe
and combined with the appropriate injection needle before administration. This procedure is not only time-
consuming, but also presents a multitude of possibilities for contamination and use errors.
Over the past decades, the presentation of liquid pharmaceutical products in prefilled syringes for single
use, many with staked needles, has become more prevalent. The simplicity of use that is provided not only
benefits their use in the clinical setting, but also enables these to be used by lay users in a home setting.
The standardization of the requirements for prefilled syringes has been addressed by ISO/TC 76 in two
ways:
— the specifications of the components of the prefilled syringe prior to filling are included in the previous
parts of the ISO 11040 series;
— the requirements for the final prefilled syringe, presented to the user as a finished product, are addressed
in this document.
Finished prefilled syringes can require marketing authorization as a medicinal product, in some regions as a
combination product or as a medical device, depending on their contents and the intended use. The syringe
plays a dual role in the finished product — as a container closure system and as a delivery device. Safety,
functional performance and usability need to be considered, also in case of intended use in combination
with pre-attached, co-packaged or cross-referenced additional components and/or devices. This document
addresses the syringe and its contents as a system, with the intent to ensure the successful application for
its intended use. In this context, the minimal configuration of a finished prefilled syringe is the syringe
barrel filled with the intended contents (i.e. the injectable product) and closed with a front end closure and a
plunger stopper (sealing the back end). Additional components (e.g. either attachment of a needle for single
use or assembly of a plunger rod or both) may need to be added by the manufacturer or user to make it ready
for administration by manual injection according to its intended use. Alternatively, such a finished prefilled
syringe may be combined by the manufacturer or user with a device for administration by a needle-based
injection system according to its intended use.
This document includes requirements for the design verification of the finished prefilled syringe’s functional
performance requirements in accordance with its design specifications. The test methods and other aspects
of testing described in this document are intended to verify the design at a confidence level of 95 %. They
are not intended to stipulate acceptance criteria for lot release (e.g. acceptable quality limits, probability
content, probability or other) in the context of manufacturing processes. Finished prefilled syringes based
on customised components can still be tested in accordance with this document. Testing at component, sub-
assembly, or in-process level can be sufficient for design verification of specific requirements if the influence
of processing on the finished prefilled syringe can be ruled out.
There are other international and national standards and guidance publications and, in some countries,
national regulations that are applicable to medical devices and medicinal products and combinations
thereof. Their requirements might supersede or complement this document. Developers and manufacturers
of finished prefilled syringes are encouraged to investigate and determine whether there are any other
requirements relevant to the safety and functional performance or marketability of their products.
In this document, the conjunctive “or” is used as an “inclusive or” so a statement is true if any combination of
the conditions is true.
In this document the following verbal forms are used.
— “Shall” indicates requirements.
— “Should” indicates recommendations.
— “May” indicates permissions.
— "Can" indicates possibility or capability.

vi
FINAL DRAFT International Standard ISO/FDIS 11040-8:2026(en)
Prefilled syringes —
Part 8:
Requirements and test methods for finished prefilled
syringes
1 Scope
This document is applicable to aseptically processed or terminally sterilized finished prefilled syringes
(intended for single use only) based on syringe barrel components addressed in ISO 11040-4 or ISO 11040-6,
together with a plunger stopper (sealing the back end) based on components addressed in ISO 11040-5 and
a front end closure for parenteral preparations with focus on quality, functional performance and safety
requirements, as well as relevant test methods.
Finished prefilled syringes which have undergone an additional preparation step by the user before injection
(e.g. diluent-containing syringes that have been emptied for reconstitution and in which the reconstituted
injectable product has been aspirated after reconstitution) are excluded from the scope of this document.
NOTE 1 This document can also be used as a guidance for other types, designs and/or sizes of finished prefilled
syringes, for example dual chamber prefilled syringes.
NOTE 2 For finished prefilled syringes that are used in needle-based injection systems, see also ISO 11608 (all parts)
[1]
.
[2]
NOTE 3 Attention is drawn to applicable national or regional regulations and pharmacopoeias, such as Ph.Eur. ,
[3] [4]
USP or JP .
NOTE 4 Finished prefilled syringes for parenteral preparations which are medical devices or which, according to
the principal mode of action of the product (i.e. the means by which the product achieves its principal intended action),
are borderline between medical devices and medicinal products fall within the scope of this document, even if they
are not always regulated as medicinal products.
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 11040-4, Prefilled syringes — Part 4: Glass barrels for injectables and sterilized subassembled syringes
ready for filling
ISO 11040-4:2024, 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 11040-6:2019, Prefilled syringes — Part 6: Plastic barrels for injectables and sterilized subassembled
syringes ready for filling
ISO 11040-6, Prefilled syringes — Part 6: Plastic barrels for injectables and sterilized subassembled syringes
ready for filling
ISO 23908, Sharps injury protection — Sharps protection mechanisms for single-use needles, introducers for
catheters and needles used for blood testing, monitoring, sampling and medical substance administration —
Requirements and test methods
ISO 80369-1, Small-bore connectors for liquids and gases in healthcare applications — Part 1: General
requirements
ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications — Part 7: Connectors for
intravascular or hypodermic applications
ISO 80369-20, Small-bore connectors for liquids and gases in healthcare applications — Part 20: Common test
methods
IEC 62366-1, Medical devices — Part 1: Application of usability engineering to medical devices
3 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 https:// www .electropedia .org/
3.1
finished prefilled syringe
prefilled container closure system for parenteral preparations as marketed, including, for example,
filling with the intended contents and assembly of additional components, aseptic processing or terminal
sterilization as applicable, and final packaging by the manufacturer (3.2)
3.2
manufacturer
natural or legal person holding the licence (e.g. marketing authorisation or other as applicable) for the
injectable product with responsibility for the design, development, manufacture, packaging and labelling of
a finished prefilled syringe (3.1), before it is placed on the market or put into service, regardless of whether
these operations are carried out by that person or on that person's behalf by a third party
3.3
needle-based injection system
injection system intended for parenteral administration of medicinal products using a needle or cannula
and a multi-dose or single-dose container
[5]
[SOURCE: ISO 11608-1:2022 , 3.15]
3.4
user
patient or health care giver (e.g. clinical personnel, doctor, lay person) who handles (e.g. prepares, applies,
disposes of) the finished prefilled syringe (3.1)
4 User requirements
4.1 Definition of intended use
The manufacturer shall define the intended use of the finished prefilled syringe. Aspects to be considered
shall include the following:
— intended medical indication and criticality of administration, e.g. in emergency situations;
— patient population including their health status and the user profile;

— the target route and/or site and frequency of administration;
— the use environment, e.g. clinical or home setting;
— additional components and/or devices (see 5.2.4) that are used for application, e.g. plunger rods/piston
rods, finger flange extensions/backstops, sterile hypodermic needles, needleless small-bore connectors,
filters, tubing, vial adapters, needle-based injection systems;
— characteristics of the expected environmental conditions during transport, storage and use;
— operating principle if applicable, and interactions between the user, the environment and the finished
prefilled syringe including additional components and/or devices, if applicable.
4.2 Risk management
Manufacturers shall follow a risk-based approach during the design, development, manufacture and life
[6]
cycle of the finished prefilled syringe like exemplarily described by ISO 14971 . Risk management shall
consider the intended use, interactions between container closure system and contents, and environmental
conditions. This can result in product-specific requirements and test methods that differ from what is
outlined in this document.
If the finished prefilled syringe is intended to be used in combination with pre-attached, co-packaged or
cross-referenced components and/or devices, the manufacturer shall ensure that the whole combination,
including the connectivity with other components and/or devices, is safe, usable and does not impair the
specified functional performance of the single components and/or devices.
[7]
NOTE For risk management of manufacturing processes, see ICH Q9 Quality Risk Management .
4.3 Application of usability engineering
The usability of the finished prefilled syringe shall be considered and validated according to a process
conforming to IEC 62366-1.
[8]
NOTE 1 For further information on usability engineering of medical devices, see ANSI/AAMI HE75 .
NOTE 2 The instructions for use are part of the user interface to be validated in the usability testing.
5 System characterization
5.1 Critical dimensions
Critical dimensions shall be defined considering the intended use of the finished prefilled syringe. Particular
attention shall be paid to, but not limited to, the following:
— interfaces with users;
— interfaces and connectivity with other components (e.g. needleless small-bore connectors or sterile
hypodermic needles);
— interfaces with other devices (e.g. sharps injury protection features or needle-based injection systems);
— the plunger stopper position depending on the intended use [e.g. for manual injection or for use in needle-
based injection systems] (see Figure 1).
Figure 1 shows examples of measuring the plunger stopper position for finished prefilled syringes.

a) Example 1 b) Example 2
Key
1 plunger stopper
l distance from the plunger stopper to the top of the 90° cone (mechanical or optical gauge) at the syringe
barrel front end shoulders
l and l distance from the plunger stopper to the back end of the syringe (proximal or distal edge of the flange)
2 3
Figure 1 — Examples of measuring the plunger stopper position for finished prefilled syringes
5.2 Description of components and materials
5.2.1 General
The selected components and materials shall be suitable for the intended use and the intended manufacturing
processes (e.g. component sterilization and/or terminal sterilization process if applicable).
The interfaces with other components and/or devices (e.g. tubing or needle-based injection systems) shall
be considered.
5.2.2 Syringe barrels and front end closures
ISO 11040-4 and ISO 11040-6 shall apply.
The syringe barrel can include a staked needle. The needle dimensions including inner and outer diameters
(gauge) and exposed needle length shall be consistent with the intended use, considering, for example, route
of administration, use in needle-based injection systems and content properties.

5.2.3 Plunger stoppers/pistons (sealing the back end)
ISO 11040-5 shall apply.
[9]
NOTE The dimensional requirements of ISO 11040-5 apply to component level. Plunger stopper dimensions are
different in compressed and uncompressed state.
5.2.4 Additional components and/or devices
Additional components and/or devices required for or supporting the intended use can include but are not
limited to the following:
— plunger rods/piston rods;
— add-on finger flanges/backstops;
[10]
— sterile hypodermic needles with 6 % Luer conical fitting in accordance with ISO 7864 ;
— sharps injury protection features (integrated or combined with the finished prefilled syringe prior to
[11]
use) in accordance with ISO 23908 ;
— other devices with small-bore connectors with 6 % Luer conical fitting, for example:
— filters;
— valves;
— needle-less Luer-activated devices;
— tubing;
— vial adapters.
Finished prefilled syringes can be used in needle-based injection systems if appropriately qualified.
The interfaces with the relevant components and/or devices shall be considered.
5.3 Description of the contents of the finished prefilled syringe
Quality attributes of the contents critical to the functional performance of the finished prefilled syringe
shall be defined. Those relevant for interactions between container closure system and contents (injectable
product) and/or affecting administration can include but are not limited to the following:
— viscosity;
— density;
— surface tension;
— pH;
— osmolality;
— filling volume including filling tolerances;
— head space volume and composition.
These quality attributes are temperature dependent and can change over time.

6 Functional performance requirements
6.1 General
Based on the intended use (see 4.1) the manufacturer shall ensure that the finished prefilled syringe
fulfils the corresponding functional performance requirements until the end of product shelf life. The
manufacturer shall establish and document, through a risk-based assessment, which functional performance
requirements of the finished prefilled syringe shall be tested in stability studies at time points up to the
end of product shelf life. For requirements where no performance degradation is expected over time, initial
design verification testing may be sufficient if justified. The tests described in subclauses 6.2 to 6.12 should
be considered but are not necessarily all inclusive.
[12]
NOTE For conducting stability studies, see Reference .
The sampling plans for design verification testing should ensure a probability content level, determined to
be appropriate by risk assessment, with a confidence level of 95 %. The confidence level of 95 % means that
there is a 5 % risk of incorrectly concluding that the testing has demonstrated the reliability level based on
the specific units in the testing sample. The reliability level is the reliability goal or target level of reliability
that the product is expected to achieve. The confidence level of 95 % is the minimum confidence level
commonly used. The typical choice of reliability level is 90 %, 95 %, 97,5 % or 99 %, which is determined by
the level of risk that can be accepted depending on the intended use of the product. The sample size should
be selected based on the required confidence and reliability levels.
EXAMPLE If a process has achieved a 95 % confidence and a 99 % reliability, it has demonstrated with a 95 %
confidence that at least 99 % of the units in the population are conforming to the requirements.
A sample size of 30 units is considered statistically significant as it fulfils the following criteria.
— The central limit theorem states that the distribution of sample means is normally distributed or
transformed if the sample size is 30 units or more. This means that the mean value of a sample is close to
the mean value of the population, regardless of the distribution of the data.
— The law of large numbers also states that the more data points a sample contains, the more accurate
are the results. With fewer than 30 data points, it is difficult to draw reliable conclusions as there is not
enough data to reduce variability and bias.
— In addition, a sample size of 30 units can provide a more complete picture of a histogram that reveals the
underlying distribution of the data.
Specification limits for the functional parameters shall be defined based on the intended use. Testing at
component, sub-assembly, or in-process level can be sufficient and data maybe leveraged for design
verification of specific requirements if the influence of processing on the finished prefilled syringe can be
ruled out. Furthermore, for certain functional tests, the use of a representative surrogate fluid instead of
the final injectable product is permissible, provided its selection is justified by a risk-based assessment
demonstrating that it represents a worst-case condition for the attribute being tested.
6.2 Break-loose and extrusion forces
Break loose and extrusion forces testing shall be conducted with the finished prefilled syringe as intended
for use (e.g. with attached needle or with assembled plunger rod). Finished prefilled syringes intended
for administration by manual injection shall be assembled with the same plunger rod as for application
according to the intended use (i.e. the plunger rod the product is placed on the market with); for those
intended for administration by a needle-based injection system the plunger rod of the used injection system
may be used if applicable, or an appropriate substitute plunger rod (e.g. of the used tensile and compression
testing machine). For the tests, the temperature of the contents shall be as for application according to the
intended use.
It shall be considered that the break-loose and extrusion forces can change over product shelf life depending
on environmental conditions.
The finished prefilled syringe shall be tested according to Annex A for break-loose and extrusion forces
with constant test speed. The test speed shall be defined based on the intended use, considering injection
duration requirements with the impact of different syringe sizes, filling volumes, needle dimensions (in
particular the inner diameter) as well as the content properties.
6.3 Flange breakage resistance
Flange breakage resistance of finished prefilled syringes shall be tested. The specification limits stated in
ISO 11040-4:2024, 5.4.4 shall apply as minimum requirements for both finished prefilled syringes with glass
barrels (in accordance with ISO 11040-4) or with plastic barrels (in accordance with ISO 11040-6). The
specification limits may be adapted based on the intended use.
NOTE 1 For finished prefilled syringes that are used in needle-based injection systems, the stated specification
limits can be adapted to higher values depending on the intended use.
The test method ISO 11040-4:2024, C.1 is applicable to finished prefilled syringes with glass barrels and
is performed with the finished prefilled syringe. Accordingly, the test method ISO 11040-6:2019, C.1 is
applicable to finished prefilled syringes with plastic barrels and is performed with the finished prefilled
syringe.
[13]
NOTE 2 The failure mode for plastic barrels (in accordance with ISO 11040-6 ) can be different than breakage,
for example deformation.
For testing purposes, the tip cap or needle shield (or other front end closure) is removed from the finished
prefilled syringe, the plunger stopper is manually depressed (i.e. the syringe emptied) and may remain in
the syringe but the plunger rod is removed to allow the use of the loading pin required by the test method
instead. The removal of add-on finger flanges/backstops for testing flange breakage resistance is permissible
if required to perform the test method.
6.4 Front end closure pull-off forces and torques
The following test methods shall apply:
— ISO 11040-4:2024, G3 Luer lock adaptor collar pull-off force; the specification limits of ISO 11040-4:2024,
6.5.3.5 apply;
— ISO 11040-4:2024, G4 Luer lock adaptor collar torque resistance; the specification limits of
ISO 11040-4:2024, 6.5.3.5 apply;
— ISO 11040-4:2024, G5 Luer lock rigid tip cap unscrewing torque; according specification limits shall be
defined based on the intended use;
— ISO 11040-4:2024, G6 Pull-off force of the tip cap or the needle shield; according specification limits shall
be defined based on the intended use.
6.5 Connectivity with small-bore connectors
Additional small-bore connectors to be used in the fluid path of the finished prefilled syringe according
to the intended use shall be tested for connectivity and leakage fgollowing ISO 80369-1, ISO 80369-7 and
ISO 80369-20. The finished prefilled syringe with the intended contents shall be tested with the same
additional small-bore connectors as for application according to the intended use (either pre-attached, co-
packaged or cross-referenced). When the finished prefilled syringe is intended for use with a specific pre-
attached, co-packaged, or cross-referenced small-bore connector, testing shall focus on the integrity and
functional performance of the combined system for its intended use (e.g. secure attachment, absence of
leakage during administration). It is recognized that direct application of all test methods in accordance with
ISO 80369-20 may not be feasible with the intended small-bore connector; in such case, the manufacturer
shall perform and document a risk-based assessment to define appropriate functional testing, for example
with a reference small-bore connector.

Additional considerations are required for the use of needle-less Luer-activated devices. Although, for
example, the threaded part of such a device is covered by ISO 80369-7, the internal design and function are
not covered by this document. Connectivity and functionality need to be verified in order to prevent cone
breakage or cone blockage.
[14] [13]
Additionally, see ISO 11040-4 and ISO 11040-6 for testing Luer connectors/Luer lock adapters.
6.6 Residual volume
The residual volume (dead space) of the finished prefilled syringe should be tested according to Annex B
with the intended contents and in combination with additional components and/or devices as intended for
use. For the test, the temperature of the contents shall be as for application according to the intended use.
The residual volume can depend on the content properties (e.g. viscosity) and, for example, on the needle
dimensions (in particular the inner diameter). It is determined, for example, to define a potential overfill for
the manufacturing process in order to achieve the correct deliverable volume (see 7.5).
6.7 Needle penetration force
Needle penetration force for finished prefilled syringes with glass barrels and a staked needle shall be
tested according to ISO 11040-4:2024, Annex F; for those with plastic barrels and a staked needle it shall be
tested according to ISO 11040-6:2019, Annex F. The specification limits for needle penetration force stated
in ISO 11040-4:2024, 6.5.2.4 shall apply for both finished prefilled syringes with glass barrels (in accordance
with ISO 11040-4) and finished prefilled syringes with plastic barrels (in accordance with ISO 11040-6).
NOTE Terminal sterilization using moist heat can affect the, for example, silicone lubrication layer on the needle.
6.8 Needle pull-out force
Needle pull-out force for finished prefilled syringes with glass barrels and a staked needle shall be
tested according to ISO 11040-4:2024, G.1; for those with plastic barrels and a staked needle it shall be
tested according to ISO 11040-6:2019, G.1. The specification limits for needle pull-out force stated in
ISO 11040-4:2024, 6.5.2.6 shall apply as minimum requirements for both finished prefilled syringes with
glass barrels (in accordance with ISO 11040-4) and finished prefilled syringes with plastic barrels (in
accordance with ISO 11040-6).
6.9 Sharps injury protection requirements
If the finished prefilled syringe has integrated sharps injury protection features (or is combined with a
sharps injury protection device before use), it shall meet the requirements of ISO 23908.
6.10 Liquid leakage resistance
The finished prefilled syringe shall be tested in accordance with the procedures described in Annex C for
liquid leakage resistance by applying an axial force to the plunger stopper through the same plunger rod as
for application and under the same conditions according to the intended use, consistent with the maximum
force generated during administration.
The finished prefilled syringe shall be tested with the intended front end closure in accordance with the
procedure for liquid leakage at the plunger stopper (see Clause C.2).
When used, for example, in needle-based injection systems, significantly higher forces can act on finished
prefilled syringes compared to manual injection, whereby the increased pressure in the syringe can lead
to bursting under certain circumstances. Thus, the finished prefilled syringe shall be tested in accordance
with the procedure for burst resistance (see Clause C.3) with an additional, irreversible sealing of the front
end (i.e. replacing the front end closure). Test pressures and acceptance criteria shall be defined according
to the requirements of the needle-based injection system with adding to the test pressure a safety margin of
20 %.
6.11 Markings
All graduation marks or indicator lines (e.g. preprinted directly on the syringe barrel or printed on a label)
shall be verified to be as accurate as appropriate for the intended use.
NOTE If graduation marks or indicator lines are used (e.g. preprinted directly on the syringe barrel or printed on
[15]
a label), ISO 7886-1:2017 , Table 1, can be considered.
6.12 Administration time with defined constant test force
The administration of the injectable product is determined by the applicable time and/or required force.
The administration time is of relevance when considering the capabilities of the intended users for manual
injection or the functional force profile of the needle-based injection system. Applying a defined constant
test force (or force prof
...

ISO/DISFDIS 11040-8
ISO/TC 76
Secretariat: DIN
Date: 2026-01-2102-18
Prefilled syringes —
Part 8:
Requirements and test methods for finished prefilled syringes
DISFDIS stage
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ISO/DISFDIS 11040-8:2026(en)
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
E-mail: [e-mail]
Website: www.iso.org
Published in Switzerland
ii
ISO/DISFDIS 11040-8:2026(en)
Contents
Foreword . iv
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 User requirements . 3
4.1 Definition of intended use . 3
4.2 Risk management . 3
4.3 Application of usability engineering . 3
5 System characterization . 4
5.1 Critical dimensions . 4
5.2 Description of components and materials . 5
5.3 Description of the contents of the finished prefilled syringe . 6
6 Functional performance requirements . 6
6.1 General . 6
6.2 Break-loose and extrusion forces . 7
6.3 Flange breakage resistance . 7
6.4 Front end closure pull-off forces and torques . 8
6.5 Connectivity with small-bore connectors . 8
6.6 Residual volume . 8
6.7 Needle penetration force . 8
6.8 Needle pull-out force . 9
6.9 Sharps injury protection requirements . 9
6.10 Liquid leakage resistance . 9
6.11 Markings . 9
6.12 Administration time with defined constant test force . 9
6.13 Unintended plunger stopper movement of finished prefilled syringes . 9
7 Pharmaceutical requirements . 10
7.1 General . 10
7.2 Interactions between container closure system and contents (injectable product) . 11
7.3 Biological hazards and microbiological requirements . 11
7.4 Container closure integrity . 12
7.5 Deliverable volume . 12
7.6 Particles (visible and sub-visible) . 12
8 Test reports . 12
Annex A (normative) Test method for break-loose and extrusion forces of finished prefilled
syringes . 14
Annex B (informative) Test method for residual volume of finished prefilled syringes . 17
Annex C (normative) Test methods for liquid leakage resistance of finished prefilled syringes . 20
Annex D (informative) Test method for administration time with defined constant test force . 23
Bibliography . 26

iii
ISO/DISFDIS 11040-8:2026(en)
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).
ISO draws attention to the possibility that the implementation of this document may involve the use of (a)
patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed patent rights
in respect thereof. As of the date of publication of this document, ISO had not received notice of (a) patent(s)
which may be required to implement this document. However, implementers are cautioned that this may not
represent the latest information, which may be obtained from the patent database available at
www.iso.org/patentswww.iso.org/patents. ISO shall not be held responsible for identifying any or all such
patent rights.
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment, as
well as information about ISO’s adherence to the World Trade Organization (WTO) principles in the Technical
Barriers to Trade (TBT) see the following URL: www.iso.org/iso/foreword.html.
The document was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection, and blood
processing equipment for medical and pharmaceutical use.
This second edition cancels and replaces the first edition (ISO 11040-8:2016), which has been technically
revised.
The main changes are as follows.
— The entire document has been revised for consistent use of terms and language.
— A basic statistical approach for design verification testing of functional performance requirements has
been included in the Error! Reference source not found. and in 6.1.
— Single terms and definitions (see 3()) have been revised, deleted or included.
— The definition of intended use (see 4.1()) has been revised for clarity.
— Break-loose and extrusion forces (see 6.2()) has been revised; it has been clarified to perform testing with
the finished prefilled syringe as intended for use. A new Annex A,, with the respective test method, has
been introduced.
— The former subclause for burst resistance was removed; parts of its contents have been included in the
revised subclause for liquid leakage resistance (see 6.10().).
iv
ISO/DISFDIS 11040-8:2026(en)
— Flange breakage resistance (see 6.3()) has been revised to include specification limits and a test method
reference. It was clarified to perform testing with the finished prefilled syringe, with further instructions.
Front end breakage resistance requirements have been deleted.
— Front end closure pull-off forces and torques (see 6.4()) have been revised to clarify test methods and
specification limits.
— Connectivity with small-bore connectors (see 6.5()) was clarified to perform testing with the finished
prefilled syringe as intended for use.
— Residual volume (see 6.6()) was clarified to perform testing with the finished prefilled syringe as intended
for use. A new Annex B,, with the respective test method, has been introduced.
— Needle penetration force (see 6.7()) and needle pull-out force (6.8()) were revised to clarify test methods
and specification limits.
— Liquid leakage resistance (see 6.10()) was combined with parts of the contents of former subclause for
burst resistance and revised. A new Annex C,, with the respective test methods, has been introduced.
— A new subclause for administration time with defined constant test force (see 6.12()) has been included.
A new Annex D,, with the respective test method, has been introduced.
— A new subclause for unintended plunger stopper movement of finished prefilled syringes (see 6.13()) has
been introduced.
— Where applicable, references to pharmacopoeias have been included in the subclauses to pharmaceutical
requirements (see 7().).
A list of all parts in the ISO 11040 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.
v
ISO/DISFDIS 11040-8:2026(en)
Introduction
Historically, injectable (parenteral) liquid pharmaceutical products have been mainly provided in primary
containers (i.e. ampoules and vials) which required the liquid to be transferred into a hypodermic syringe and
combined with the appropriate injection needle before administration. This procedure is not only time-
consuming, but also presents a multitude of possibilities for contamination and use errors.
Over the past decades, the presentation of liquid pharmaceutical products in prefilled syringes for single use,
many with staked needles, has become more prevalent. The simplicity of use that is provided not only benefits
their use in the clinical setting, but also enables these to be used by lay users in a home setting.
The standardization of the requirements for prefilled syringes has been addressed by ISO/TC 76 in two ways:
— the specifications of the components of the prefilled syringe prior to filling are included in the previous
parts of the ISO 11040 series;
— the requirements for the final prefilled syringe, presented to the user as a finished product, are addressed
in this document.
Finished prefilled syringes can require marketing authorization as a medicinal product, in some regions as a
combination product or as a medical device, depending on their contents and the intended use. The syringe
plays a dual role in the finished product — as a container closure system and as a delivery device. Safety,
functional performance and usability need to be considered, also in case of intended use in combination with
pre-attached, co-packaged or cross-referenced additional components and/or devices. This document
addresses the syringe and its contents as a system, with the intent to ensure the successful application for its
intended use. In this context, the minimal configuration of a finished prefilled syringe is the syringe barrel
filled with the intended contents (i.e. the injectable product) and closed with a front end closure and a plunger
stopper (sealing the back end). Additional components (e.g. either attachment of a needle for single use or
assembly of a plunger rod or both) may need to be added by the manufacturer or user to make it ready for
administration by manual injection according to its intended use. Alternatively, such a finished prefilled
syringe may be combined by the manufacturer or user with a device for administration by a needle-based
injection system according to its intended use.
This document includes requirements for the design verification of the finished prefilled syringe’s functional
performance requirements in accordance with its design specifications. The test methods and other aspects
of testing described in this document are intended to verify the design at a confidence level of 95 %. They are
not intended to stipulate acceptance criteria for lot release (e.g. acceptable quality limits, probability content,
probability or other) in the context of manufacturing processes. Finished prefilled syringes based on
customised components can still be tested in accordance with this document. Testing at component, sub-
assembly, or in-process level can be sufficient for design verification of specific requirements if the influence
of processing on the finished prefilled syringe can be ruled out.
There are other international and national standards and guidance publications and, in some countries,
national regulations that are applicable to medical devices and medicinal products and combinations thereof.
Their requirements might supersede or complement this document. Developers and manufacturers of
finished prefilled syringes are encouraged to investigate and determine whether there are any other
requirements relevant to the safety and functional performance or marketability of their products.
In this document, the conjunctive “or” is used as an “inclusive or” so a statement is true if any combination of
the conditions is true.
In this document the following verbal forms are used.
— — “Shall” indicates requirements.
vi
ISO/DISFDIS 11040-8:2026(en)
— — “Should” indicates recommendations.
— — “May” indicates permissions.
— — "Can" indicates possibility or capability.
vii
ISO/DISFDIS 11040-8:2026(en)
Prefilled syringes —
Part 8:
Requirements and test methods for finished prefilled syringes
1 Scope
This document is applicable to aseptically processed or terminally sterilized finished prefilled syringes
(intended for single use only) based on syringe barrel components addressed in ISO 11040-4 or ISO 11040-6,
together with a plunger stopper (sealing the back end) based on components addressed in ISO 11040-5 and a
front end closure for parenteral preparations with focus on quality, functional performance and safety
requirements, as well as relevant test methods.
Finished prefilled syringes which have undergone an additional preparation step by the user before injection
(e.g. diluent-containing syringes that have been emptied for reconstitution and in which the reconstituted
injectable product has been aspirated after reconstitution) are excluded from the scope of this document.
NOTE 1 This document can also be used as a guidance for other types, designs and/or sizes of finished prefilled
syringes, for example dual chamber prefilled syringes.
NOTE 2 For finished prefilled syringes that are used in needle-based injection systems, see also [1].
NOTE 3 Attention is drawn to applicable national or regional regulations and pharmacopoeias, such as Ph.Eur. [2],,
USP [3] or JP [4].
NOTE 4 Finished prefilled syringes for parenteral preparations which are medical devices or which, according to the
principal mode of action of the product (i.e. the means by which the product achieves its principal intended action), are
borderline between medical devices and medicinal products fall within the scope of this document, even if they are not
always regulated as medicinal products.
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, Sterile hypodermic needles for single use — Requirements and test methods
ISO 11040-4, Prefilled syringes — Part 4: Glass barrels for injectables and sterilized subassembled syringes ready
for filling
ISO 11040-4:2024, 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 11040-6:2019, Prefilled syringes — Part 6: Plastic barrels for injectables and sterilized subassembled
syringes ready for filling
ISO 11040-6, Prefilled syringes — Part 6: Plastic barrels for injectables and sterilized subassembled syringes
ready for filling
ISO 11608-1:2022, Needle-based injection systems for medical use — Requirements and test methods — Part 1:
Needle-based injection systems
ISO/DISFDIS 11040-8:2026(en)
ISO 23908, Sharps injury protection — Sharps protection mechanisms for single-use needles, introducers for
catheters and needles used for blood testing, monitoring, sampling and medical substance administration —
Requirements and test methods
ISO 80369-1, Small-bore connectors for liquids and gases in healthcare applications — Part 1: General
requirements
ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications — Part 7: Connectors for
intravascular or hypodermic applications
ISO 80369-20, Small-bore connectors for liquids and gases in healthcare applications — Part 20: Common test
methods
IEC 62366-1, Medical devices — Part 1: Application of usability engineering to medical devices
ISO 80369-1, Small-bore connectors for liquids and gases in healthcare applications — Part 1: General
requirements
ISO 80369-7, Small-bore connectors for liquids and gases in healthcare applications — Part 7: Connectors with
6% (Luer) taper for intravascular or hypodermic applications
ISO 80369-20, Small-bore connectors for liquids and gases in healthcare applications — Part 20: Common test
methods
3 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 https://www.electropedia.org/
3.1
finished prefilled syringe
prefilled container closure system for parenteral preparations as marketed, including, for example, filling with
the intended contents and assembly of additional components, aseptic processing or terminal sterilization as
applicable, and final packaging by the manufacturer (3.2())
3.2
manufacturer
natural or legal person holding the licence (e.g. marketing authorisation or other as applicable) for the
injectable product with responsibility for the design, development, manufacture, packaging and labelling of a
finished prefilled syringe (3.1(),), before it is placed on the market or put into service, regardless of whether
these operations are carried out by that person or on that person's behalf by a third party
3.3
needle-based injection system
injection system intended for parenteral administration of medicinal products using a needle or cannula and
a multi-dose or single-dose container
[SOURCE: [5]ISO 11608-1:2022,, 3.15]
ISO/DISFDIS 11040-8:2026(en)
3.4
user
patient or health care giver (e.g. clinical personnel, doctor, lay person) who handles (e.g. prepares, applies,
disposes of) the finished prefilled syringe (3.1())
4 User requirements
4.1 Definition of intended use
The Error! Reference source not found.manufacturer shall define the intended use of the Error! Reference
source not found.finished prefilled syringe. Aspects to be considered shall include the following:
— intended medical indication and criticality of administration, e.g. in emergency situations;
— patient population including their health status and the user profile;
— the target route and/or site and frequency of administration;
— the use environment, e.g. clinical or home setting;
— additional components and/or devices (see 5.2.4)) that are used for application, e.g. plunger rods/piston
rods, finger flange extensions/backstops, sterile hypodermic needles, needleless small-bore connectors,
filters, tubing, vial adapters, Error! Reference source not found.needle-based injection systems;;
— characteristics of the expected environmental conditions during transport, storage and use;
— operating principle if applicable, and interactions between the Error! Reference source not found.user,,
the environment and the finished prefilled syringe including additional components and/or devices, if
applicable.
4.2 Risk management
Manufacturers shall follow a risk-based approach during the design, development, manufacture and life cycle
of the finished prefilled syringe like exemplarily described by [6]. Risk management shall consider the
intended use, interactions between container closure system and contents, and environmental conditions.
This can result in product-specific requirements and test methods that differ from what is outlined in this
document.
If the finished prefilled syringe is intended to be used in combination with pre-attached, co-packaged or cross-
referenced components and/or devices, the Error! Reference source not found.manufacturer shall ensure
that the whole combination, including the connectivity with other components and/or devices, is safe, usable
and does not impair the specified functional performance of the single components and/or devices.
NOTE For risk management of manufacturing processes, see ICH Q9 Quality Risk Management [7].
4.3 Application of usability engineering
The usability of the finished prefilled syringe shall be considered and validated according to a process
conforming to IEC 62366-1.
NOTE 1 For further information on usability engineering of medical devices, see [8].
NOTE 2 The instructions for use are part of the user interface to be validated in the usability testing.
ISO/DISFDIS 11040-8:2026(en)
5 System characterization
5.1 Critical dimensions
Critical dimensions shall be defined considering the intended use of the finished prefilled syringe. Particular
attention shall be paid to, but not limited to, the following:
— interfaces with users;
— interfaces and connectivity with other components (e.g. needleless small-bore connectors or sterile
hypodermic needles);
— interfaces with other devices (e.g. sharps injury protection features or needle-based injection systems);
— the plunger stopper position depending on the intended use [e.g. for manual injection or for use in needle-
based injection systems] (see 0).).
0 shows examples of measuring the plunger stopper position for finished prefilled syringes.

a) Example 1 b) Example 2
Key
1 plunger stopper
l distance from the plunger stopper to the top of the 90° cone (mechanical or optical gauge) at the syringe barrel front end shoulders
l and l distance from the plunger stopper to the back end of the syringe (proximal or distal edge of the flange)
2 3
Figure 1 — Examples of measuring the plunger stopper position for finished prefilled syringes
ISO/DISFDIS 11040-8:2026(en)
5.2 Description of components and materials
5.2.1 General
The selected components and materials shall be suitable for the intended use and the intended manufacturing
processes (e.g. component sterilization and/or terminal sterilization process if applicable).
The interfaces with other components and/or devices (e.g. tubing or needle-based injection systems) shall be
considered.
5.2.2 Syringe barrels and front end closures
ISO 11040-4 and ISO 11040-6 shall apply.
The syringe barrel can include a staked needle. The needle dimensions including inner and outer diameters
(gauge) and exposed needle length shall be consistent with the intended use, considering, for example, route
of administration, use in needle-based injection systems and content properties.
5.2.3 Plunger stoppers/pistons (sealing the back end)
ISO 11040-5 shall apply.
NOTE The dimensional requirements of [9] apply to component level. Plunger stopper dimensions are different in
compressed and uncompressed state.
5.2.4 Additional components and/or devices
Additional components and/or devices required for or supporting the intended use can include but are not
limited to the following:
— plunger rods/piston rods;
— add-on finger flanges/backstops;
— sterile hypodermic needles with 6 % Luer conical fitting in accordance with [10]ISO 7864;;
— sharps injury protection features (integrated or combined with the finished prefilled syringe prior to use)
in accordance with [11]ISO 23908;;
— other devices with small-bore connectors with 6 % Luer conical fitting, for example:
— filters;
— valves;
— needle-less Luer-activated devices;
— tubing;
— vial adapters.
Finished prefilled syringes can be used in needle-based injection systems if appropriately qualified.
The interfaces with the relevant components and/or devices shall be considered.
ISO/DISFDIS 11040-8:2026(en)
5.3 Description of the contents of the finished prefilled syringe
Quality attributes of the contents critical to the functional performance of the finished prefilled syringe shall
be defined. Those relevant for interactions between container closure system and contents (injectable
product) and/or affecting administration can include but are not limited to the following:
— viscosity;
— density;
— surface tension;
— pH;
— osmolality;
— filling volume including filling tolerances;
— head space volume and composition.
These quality attributes are temperature dependent and can change over time.
6 Functional performance requirements
6.1 General
Based on the intended use (see 4.1)) the Error! Reference source not found.manufacturer shall ensure that
the Error! Reference source not found.finished prefilled syringe fulfils the corresponding functional
performance requirements until the end of product shelf life. The manufacturer shall establish and document,
through a risk-based assessment, which functional performance requirements of the finished prefilled syringe
shall be tested in stability studies at time points up to the end of product shelf life. For requirements where no
performance degradation is expected over time, initial design verification testing may be sufficient if justified.
The tests described in subclauses 6.2 to 6.12 should be considered but are not necessarily all inclusive.
NOTE For conducting stability studies, see Reference [12].
The sampling plans for design verification testing should ensure a probability content level, determined to be
appropriate by risk assessment, with a confidence level of 95 %. The confidence level of 95 % means that there
is a 5 % risk of incorrectly concluding that the testing has demonstrated the reliability level based on the
specific units in the testing sample. The reliability level is the reliability goal or target level of reliability that
the product is expected to achieve. The confidence level of 95 % is the minimum confidence level commonly
used. The typical choice of reliability level is 90 %, 95 %, 97.,5 % or 99 %, which is determined by the level of
risk that can be accepted depending on the intended use of the product. The sample size should be selected
based on the required confidence and reliability levels.
EXAMPLE If a process has achieved a 95 % confidence and a 99 % reliability, it has demonstrated with a 95 %
confidence that at least 99 % of the units in the population are conforming to the requirements.
A sample size of 30 units is considered statistically significant as it fulfils the following criteria.
— The central limit theorem states that the distribution of sample means is normally distributed or
transformed if the sample size is 30 units or more. This means that the mean value of a sample is close to
the mean value of the population, regardless of the distribution of the data.
ISO/DISFDIS 11040-8:2026(en)
— The law of large numbers also states that the more data points a sample contains, the more accurate are
the results. With fewer than 30 data points, it is difficult to draw reliable conclusions as there is not enough
data to reduce variability and bias.
— In addition, a sample size of 30 units can provide a more complete picture of a histogram that reveals the
underlying distribution of the data.
Specification limits for the functional parameters shall be defined based on the intended use. Testing at
component, sub-assembly, or in-process level can be sufficient and data maybe leveraged for design
verification of specific requirements if the influence of processing on the finished prefilled syringe can be ruled
out. Furthermore, for certain functional tests, the use of a representative surrogate fluid instead of the final
injectable product is permissible, provided its selection is justified by a risk-based assessment demonstrating
that it represents a worst-case condition for the attribute being tested.
6.2 Break-loose and extrusion forces
Break loose and extrusion forces testing shall be conducted with the finished prefilled syringe as intended for
use (e.g. with attached needle or with assembled plunger rod). Finished prefilled syringes intended for
administration by manual injection shall be assembled with the same plunger rod as for application according
to the intended use (i.e. the plunger rod the product is placed on the market with); for those intended for
administration by a needle-based injection system the plunger rod of the used injection system may be used
if applicable, or an appropriate substitute plunger rod (e.g. of the used tensile and compression testing
machine). For the tests, the temperature of the contents shall be as for application according to the intended
use.
It shall be considered that the break-loose and extrusion forces can change over product shelf life depending
on environmental conditions.
The finished prefilled syringe shall be tested according to Annex A for break-loose and extrusion forces with
constant test speed. The test speed shall be defined based on the intended use, considering injection duration
requirements with the impact of different syringe sizes, filling volumes, needle dimensions (in particular the
inner diameter) as well as the content properties.
6.3 Flange breakage resistance
Flange breakage resistance of finished prefilled syringes shall be tested. The specification limits stated in ISO
11040-4:2024, 5.4.4 shall apply as minimum requirements for both finished prefilled syringes with glass
barrels (in accordance with ISO 11040-4) or with plastic barrels (in accordance with ISO 11040-6). The
specification limits may be adapted based on the intended use.
NOTE 1 For finished prefilled syringes that are used in needle-based injection systems, the stated specification limits
can be adapted to higher values depending on the intended use.
The test method ISO 11040-4:2024, C.1 is applicable to finished prefilled syringes with glass barrels and is
performed with the finished prefilled syringe. Accordingly, the test method ISO 11040-6:2019, C.1 is
applicable to finished prefilled syringes with plastic barrels and is performed with the finished prefilled
syringe.
NOTE 2 The failure mode for plastic barrels (in accordance with [13])) can be different than breakage, for example
deformation.
For testing purposes, the tip cap or needle shield (or other front end closure) is removed from the finished
prefilled syringe, the plunger stopper is manually depressed (i.e. the syringe emptied) and may remain in the
syringe but the plunger rod is removed to allow the use of the loading pin required by the test method instead.
The removal of add-on finger flanges/backstops for testing flange breakage resistance is permissible if
required to perform the test method.
ISO/DISFDIS 11040-8:2026(en)
6.4 Front end closure pull-off forces and torques
The following test methods shall apply:
— ISO 11040-4:2024, G3 Luer lock adaptor collar pull-off force; the specification limits of ISO 11040-4:2024,
6.5.3.5 apply;
— ISO 11040-4:2024, G4 Luer lock adaptor collar torque resistance; the specification limits of ISO 11040-
4:2024, 6.5.3.5 apply;
— ISO 11040-4:2024, G5 Luer lock rigid tip cap unscrewing torque; according specification limits shall be
defined based on the intended use;
— ISO 11040-4:2024, G6 Pull-off force of the tip cap or the needle shield; according specification limits shall
be defined based on the intended use.
6.5 Connectivity with small-bore connectors
Additional small-bore connectors to be used in the fluid path of the finished prefilled syringe according to the
intended use shall be tested for connectivity and leakage followingfgollowing ISO 80369-1, ISO 80369-7 and
ISO 80369-20. The finished prefilled syringe with the intended contents shall be tested with the same
additional small-bore connectors as for application according to the intended use (either pre-attached, co-
packaged or cross-referenced). When the finished prefilled syringe is intended for use with a specific pre-
attached, co-packaged, or cross-referenced small-bore connector, testing shall focus on the integrity and
functional performance of the combined system for its intended use (e.g. secure attachment, absence of
leakage during administration). It is recognized that direct application of all test methods in accordance with
ISO 80369-20 may not be feasible with the intended small-bore connector; in such case, the manufacturer
shall perform and document a risk-based assessment to define appropriate functional testing, for example
with a reference small-bore connector.
Additional considerations are required for the use of needle-less Luer-activated devices. Although, for
example, the threaded part of such a device is covered by ISO 80369-7, the internal design and function are
not covered by this standarddocument. Connectivity and functionality need to be verified in order to prevent
cone breakage or cone blockage.
Additionally, see [14]ISO 11040-4 and [13]ISO 11040-6 for testing Luer connectors/Luer lock adapters.
6.6 Residual volume
The residual volume (dead space) of the finished prefilled syringe should be tested according to Annex B with
the intended contents and in combination with additional components and/or devices as intended for use. For
the test, the temperature of the contents shall be as for application according to the intended use. The residual
volume can depend on the content properties (e.g. viscosity) and, for example, on the needle dimensions (in
particular the inner diameter). It is determined, for example, to define a potential overfill for the
manufacturing process in order to achieve the correct deliverable volume (see 7.5).).
6.7 Needle penetration force
Needle penetration force for finished prefilled syringes with glass barrels and a staked needle shall be tested
according to ISO 11040-4:2024, Annex F; for those with plastic barrels and a staked needle it shall be tested
according to ISO 11040-6:2019, Annex F. The specification limits for needle penetration force stated in ISO
11040-4:2024, 6.5.2.4 shall apply for both finished prefilled syringes with glass barrels (in accordance with
ISO 11040-4) and finished prefilled syringes with plastic barrels (in accordance with ISO 11040-6).
NOTE Terminal sterilization using moist heat can affect the, for example, silicone lubrication layer on the needle.
ISO/DISFDIS 11040-8:2026(en)
6.8 Needle pull-out force
Needle pull-out force for finished prefilled syringes with glass barrels and a staked needle shall be tested
according to ISO 11040-4:2024, G.1; for those with plastic barrels and a staked needle it shall be tested
according to ISO 11040-6:2019, G.1. The specification limits for needle pull-out force stated in ISO 11040-
4:2024, 6.5.2.6 shall apply as minimum requirements for both finished prefilled syringes with glass barrels (in
accordance with ISO 11040-4) and finished prefilled syringes with plastic barrels (in accordance with ISO
11040-6).
6.9 Sharps injury protection requirements
If the finished prefilled syringe has integrated sharps injury protection features (or is combined with a sharps
injury protection device before use), it shall meet the requirements of ISO 23908.
6.10 Liquid leakage resistance
The finished prefilled syringe shall be tested in accordance with the procedures described in Annex C for liquid
leakage resistance by applying an axial force to the plunger stopper through the same plunger rod as for
application and under the same conditions according to the intended use, consistent with the maximum force
generated during administration.
The finished prefilled syringe shall be tested with the intended front end closure in accordance with the
procedure for liquid leakage at the plunger stopper (see C.2[].).
When used, for example, in needle-based injection systems, significantly higher forces can act on finished
prefilled syringes compared to manual injection, whereby the increased pressure in the syringe can lead to
bursting under certain circumstances. Thus, the finished prefilled syringe shall be tested in accordance with
the procedure for burst resistance (see C.3[]) with an additional, irreversible sealing of the front end (i.e.
replacing the front end closure). Test pressures and acceptance criteria shall be defined according to the
requirements of the needle-based injection system with adding to the test pressure a safety margin of 20 %.
6.11 Markings
All graduation marks or indicator lines (e.g. preprinted directly on the syringe barrel or printed on a label)
shall be verified to be as accurate as appropriate for the intended use.
NOTE If graduation marks or indicator lines are used (e.g. preprinted directly on the syringe barrel or printed on a
label), [15],, Table 1, can be considered.
6.12 Administration time with defined constant test force
The administration of the injectable product is determined by the applicable time and/or required force. The
administration time is of relevance when considering the capabilities of the intended users for manual
injection or the functional force profile of the needle-based injection system. Applying a defined constant test
force (or force profile if applicable) results in different injection speeds and administration times, which can
be used to determine the suitability of the finished prefilled syringe for the intended use. Therefore, in addition
to break-loose and extrusion forces (see 6.2),), the finished prefilled syringe may be tested for characterization
purposes in accordance with Annex D for administration time with a defined constant test force (or force
profile if applicable).
6.13 Unintended plunger stopper movement of finished prefilled syringes
The plunger stopper in accordance with ISO 11040-5 is a component of the container closure system and shall
ensure that the contents of the finished prefilled syringe remain enclosed and protected from microbial
contamination. It is designed to move for administration of the injectable product, but unintended movement
can compromise container closure integrity and sterility. Such movement may occur due to air pressure or
ISO/DISFDIS 11040-8:2026(en)
temperature changes, phase transitions, or assembly forces. Risks related to plunger stopper movement shall
be assessed during design and development.
If the plunger stopper moves beyond the length of the sterile barrier zone, defined by the sealing contact areas
at its distal and proximal ends (see 0),), sterility may be lost. To maintain sterility, the movement of the plunger
stopper should not exceed the length of the sterile barrier zone, L . The theoretical length of this zone is
SB
determined by the design features of the respective plunger stopper ribs.

Key
LSB length of the sterile barrier zone
a distal rib on the plunger stopper
b proximal rib on the plunger stopper
Figure 2 — Schematic representation of a theoretical sterile barrier zone provided by the ribs of a
plunger stopper
For finished prefilled syringes with gaseous headspace (“air bubble”) or exposure to pressure changes (e.g.
during transport), the design and assembly
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