National foreword

This British Standard is the UK implementation of ISO 11040‑4:2024. It supersedes BS ISO 11040‑4:2015+A1:2020, which is withdrawn.

The UK participation in its preparation was entrusted to Technical Committee CH/212, IVDs.

A list of organizations represented on this committee can be obtained on request to its committee manager.

Contractual and legal considerations

This publication has been prepared in good faith, however no representation, warranty, assurance or undertaking (express or implied) is or will be made, and no responsibility or liability is or will be accepted by BSI in relation to the adequacy, accuracy, completeness or reasonableness of this publication. All and any such responsibility and liability is expressly disclaimed to the full extent permitted by the law.

This publication is provided as is, and is to be used at the recipient’s own risk.

The recipient is advised to consider seeking professional guidance with respect to its use of this publication.

This publication is not intended to constitute a contract. Users are responsible for its correct application.

Compliance with a British Standard cannot confer immunity from legal obligations.

This British Standard was published under the authority of the Standards Policy and Strategy Committee on 30 June 2024.

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 document 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 of the voluntary nature of standards, the meaning of ISO specific terms and expressions related to conformity assessment, as well as information about ISO's adherence to the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see www.iso.org/iso/foreword.html.

This document was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use.

This fourth edition cancels and replaces the third edition (ISO 11040‑4:2015), which has been technically revised.

The main changes are as follows:

Clause 3 has been updated;
update on general requirements have been added on quality systems, testing and documentation;
additional requirements to specific components of sterilized subassembled syringes ready for filling have been revised;
requirements on syringes barrels have been revised by:
- addition of specification for finger flange breakage resistance,
- addition of specification for cone breakage resistance,
- addition of requirements specifically for staked needle syringes,
- addition of performance requirements for non-lubricated syringes.
figures in Annex A have been updated;
information of former Annex B has been implemented in 5.1; new Annex B shows information of typical components of a finished prefilled syringe;
general update of annexes.

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.

Introduction

In the past, ampoules and injection vials were mainly used for (parenteral) injectable products. However, for the injection of the products contained in those ampoules and vials, a hypodermic syringe combined with the appropriate injection needle is also needed. This means the injectable product must be transferred by the user into the hypodermic syringe before its final use. This procedure is not only time-consuming, but also presents a great number of possibilities for contamination.

To ensure safe use of an injectable product, prefilled syringes for single use are on the market for many years. Without a doubt, such prefilled syringes permit immediate injection of the product contained after relatively simple handling. These syringes can also be used in injectors with automated functions where further and particular requirements apply.

Based on the diameter of the prefilled syringes, appropriate components, such as plunger stoppers, tip caps, needle shields, and other syringe closure systems can also be standardized. In conjunction with the right sealing components, they offer a system for (parenteral) injectable use. The producers of filling machines can use this document to standardize the equipment of the machines.

In the beginning of prefilled syringe processing by the pharmaceutical industry, syringes made of tubing glass were delivered to the pharmaceutical companies in the form of so called non-sterile “bulkware” only. The process steps washing, drying, inner surface lubrication, sealing the syringe with a syringe closure system, sterilization, as well as filling and closing, were then performed in the pharmaceutical companies. Processing of “bulkware” is still performed this way. Sterilized subassembled syringes have partially replaced non-sterile “bulkware”.

In the case of sterilized subassembled syringes ready for filling, responsibility for the aforementioned process steps relevant to the injectable product lies with the manufacturer of the primary packaging material. Following the assembly of the needle shield on syringes with a staked needle or tip caps for the Luer slip version, the subassembled syringes are placed into so called nests. The nests, in turn, are placed into a plastic tub. The syringes in the nest are protected against contamination by means of an insert liner and the tub itself is sealed by a sealing lid (which is currently and, so far, primarily achieved using a gas permeable material). Thus, the tub properly sealed with the sealing lid represents the “sterile barrier system”. The sealed tub is then wrapped into a sealable bag and, thus, ready for sterilization, which is currently and, so far, primarily performed using ethylene oxide.

In this form, the sterilized subassembled syringes ready for filling are delivered to the pharmaceutical companies in a sterile condition, where they are processed on suitable machines.

1 Scope

This document specifies materials, dimensions, quality, and performance requirements, as well as relevant test methods.

This document also specifies components that are part of the sterilized subassembled syringe ready for filling.

This document is applicable to

tubing-glass barrels (single-chamber design) for injection preparations, and
sterilized subassembled syringes ready for filling.

Glass barrels and sterilized subassembled syringes ready for filling in accordance with this document are intended for single use only.

Components to complete the subassembled syringe, such as plunger stopper and plunger rod, are outside the scope of this document.

NOTE National or regional regulations such as Ph.Eur., USP, or JP can apply.

2 Normative references

3 Terms and definitions

4 General requirements

4.1 Quality systems

4.2 Testing

4.3 Documentation

5 Syringe barrel

5.1 Design including dimensions

5.2 Functional testing of Luer connection

5.3 Material

5.4 Performance requirements

6 Sterilized subassembled syringes ready for filling

6.1 General

6.2 Sterility

6.3 Pyrogenicity/endotoxins

6.4 Particulate matter

6.5 Additional requirements to specific components of sterilized subassembled syringes ready for filling

6.6 Syringe closure system tightness

7 Packaging

8 Labelling

Bibliography

BS ISO 11040-4:2024

Prefilled syringes - Glass barrels for injectables and sterilized subassembled syringes ready for filling

Current

Published:

30 Jun 2024