INTERNATIONAL ISO

STANDARD 8537

Third edition
2016-03-15

Sterile single-use syringes, with or

without needle, for insulin
Seringues à insuline, stériles, non réutilisables, avec ou sans aiguille

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ISO 8537:2016
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d58fdfc6eebb/iso-8537-2016

Reference number
ISO 8537:2016(E)

© ISO 2016
ISO 8537:2016(E)


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ISO 8537:2016
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d58fdfc6eebb/iso-8537-2016

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 ISO 8537:2016(E)


Contents Page

Foreword...........................................................................................................................................................................................................................................v
Introduction................................................................................................................................................................................................................................. vi
1 Scope.................................................................................................................................................................................................................................. 1
2 Normative references....................................................................................................................................................................................... 1
3 Terms and definitions...................................................................................................................................................................................... 2
4 Types of syringes................................................................................................................................................................................................... 5
5 Requirements........................................................................................................................................................................................................... 5
5.1 General requirements........................................................................................................................................................................ 5
5.2 Material selection.................................................................................................................................................................................. 6
5.3 Colour coding............................................................................................................................................................................................ 6
5.4 Extraneous matter................................................................................................................................................................................ 7
5.4.1 General...................................................................................................................................................................................... 7
5.4.2 Limits for acidity or alkalinity............................................................................................................................... 7
5.4.3 Limits for extractable metals................................................................................................................................. 7
5.5 Lubrication.................................................................................................................................................................................................. 7
5.5.1 Lubrication of syringes................................................................................................................................................ 7
5.5.2 Lubrication of needle tube....................................................................................................................................... 8
5.6 Dimensions.................................................................................................................................................................................................. 8
5.6.1 Barrel and plunger stopper..................................................................................................................................... 8
5.6.2 iTeh STANDARD PREVIEW
Finger grips........................................................................................................................................................................... 8
5.7 Plunger/plunger stopper................................................................................................................................................................ 8
5.7.1
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General...................................................................................................................................................................................... 8
5.7.2 Fit of plunger stopper in barrel............................................................................................................................ 8
5.8 ISO 8537:2016
Nozzle.............................................................................................................................................................................................................. 8
5.8.1 https://standards.iteh.ai/catalog/standards/sist/9c4c602a-56e4-45fa-b8bb-
Conical fitting....................................................................................................................................................................... 8
5.8.2 Position of nozzle d58fdfc6eebb/iso-8537-2016
on end of barrel.................................................................................................................... 8
5.9 Needle tubing and needles............................................................................................................................................................ 9
5.9.1 Needles for syringe types 3 and 4...................................................................................................................... 9
5.9.2 Needle tubing for syringe types 5, 6, 7 and 8........................................................................................... 9
5.9.3 Bond between hub and needle tube................................................................................................................ 9
5.10 Standard test environmental conditions........................................................................................................................... 9
5.11 Performance of assembled syringe........................................................................................................................................ 9
5.11.1 Dead space............................................................................................................................................................................. 9
5.11.2 Freedom from leakage at needle...................................................................................................................... 10
5.11.3 Freedom from leakage past plunger stopper........................................................................................ 10
6 Packaging................................................................................................................................................................................................................... 10
6.1 Unit packaging and self-contained syringe units.................................................................................................... 10
6.1.1 General................................................................................................................................................................................... 10
6.1.2 Unit packaging providing sterile barrier syringes (types 1, 3, 5 and 7)........................ 10
6.1.3 Self-contained syringes with sterile interiors (types 2, 4, 6 and 8)................................... 10
6.2 Multiple-unit packaging (for syringe types 2, 4, 6 and 8)................................................................................ 11
6.3 User packaging...................................................................................................................................................................................... 11
7 Information supplied by the manufacturer...........................................................................................................................11
7.1 General......................................................................................................................................................................................................... 11
7.2 Syringes....................................................................................................................................................................................................... 11
7.2.1 General................................................................................................................................................................................... 11
7.2.2 Additional marking for self-contained syringes (syringe types 2, 4, 6 and 8).......... 12
7.3 Unit packaging (for syringe types 1, 3, 5 and 7)....................................................................................................... 12
7.4 Multiple unit packs (syringe types 2, 4, 6 and 8).................................................................................................... 12
7.5 User packaging...................................................................................................................................................................................... 13
7.6 Storage container................................................................................................................................................................................ 14
7.7 Transport wrapping......................................................................................................................................................................... 14

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Annex A (normative) Fluid for determination of acidity/alkalinity and extractable metals..................15

Annex B (normative) Test method for air leakage past syringe piston during aspiration and
for separation of rubber stopper and plunger....................................................................................................................16
Annex C (normative) Test method for determination of forces required to operate piston....................18
Annex D (normative) Test method for determination of dead space...............................................................................20
Annex E (normative) Test method for liquid leakage at syringe piston and syringe nozzle/
hub or needle/barrel unions during compression.........................................................................................................21
Annex F (normative) Test method for air leakage past nozzle/hub or needle/barrel unions
during aspiration...............................................................................................................................................................................................23
Annex G (normative) Preparation of extract for test for pyrogenicity and toxicity..........................................24
Annex H (normative) Syringe sizes and graduated scales...........................................................................................................25
Bibliography.............................................................................................................................................................................................................................. 27

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Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical
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Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information.
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The committee responsible for this document is ISO/TC 84, Devices for administration of medicinal
products and catheters.
ISO 8537:2016
This third edition cancels and replaces the second edition (ISO 8537:2007), which has been technically
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revised to include the following changes: d58fdfc6eebb/iso-8537-2016
a) revised the introduction;
b) revised the scope to include various concentrations of insulin, specified plastic materials and
excluded, e.g. single-use syringes made of glass;
c) added some normative references;
d) added new definitions;
e) added new colour codes for higher concentration of insulin;
f) clarified the drawing to illustrate the component of the syringe;
g) included general requirements;
h) revised test methods for syringes;
i) revised the labelling requirement;
j) moved the syringe sizes and graduated scales in Annex H;
k) deleted Annex I.

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Introduction
This International Standard covers insulin syringes primarily intended for human use and provides
performance and testing requirements. It permits broader variation in design so as to not limit
innovation in technology or methods of packaging. Its appearance and layout are consistent with
other TC 84 International Standards, which are designed to be more performance-based than design-
prescriptive.
Manufacturers are expected to follow a risk-based approach and employ usability engineering during
the design, development and manufacture of insulin syringes.
This edition introduces general requirements as design guidelines for manufacturers. This edition
retains a number of limits on requirements, which were originally based on consensus opinion but
subsequently have been confirmed in practice.
This International Standard does not specify materials to be used for the construction and lubrication
of sterile insulin syringes and needles for single use because their selection will depend, to some extent,
upon the manufacturer’s specific syringe design, process of manufacture, and sterilization method.
Insulin syringes and needles are to be manufactured and sterilized in accordance with recognized
national or international codes of good manufacturing practice for medical devices.
This International Standard emphasizes the importance of having individual syringes that are
appropriately graduated and labelled for only one concentration of insulin. Serious problems can
result if a syringe is used with a concentration of insulin that is different from the one for which it was
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designed. Hazards associated with dosing errors with highly concentrated insulin (U300 and U500) are
considered higher than the experience with U40 and U100.
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It is preferred that when more than one insulin concentration is in a market, the new concentration be
provided in a dedicated delivery system that make ISOmiss-dosing
8537:2016 less likely.
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In acknowledgement that insulin in higher d58fdfc6eebb/iso-8537-2016
concentrations in vials are available in some markets, new
formulations are under development and dedicated delivery systems other than syringes are not always
appropriate for all markets, this International Standard introduces new colour codes to differentiate
syringes for the new higher concentrations of insulin.
The sampling plans for inspection selected for this International Standard are intended to verify the
design at a high confidence level. The sampling plans for inspection do not replace the more general
manufacturing quality systems that appear in standards on quality systems, for example, the ISO 9000
series and ISO 13485.
Guidance on transition periods for implementing the requirements of this International Standard is
given in ISO/TR 19244, developed by ISO/TC 84.

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INTERNATIONAL STANDARD ISO 8537:2016(E)

Sterile single-use syringes, with or without needle, for

insulin

1 Scope
This International Standard specifies requirements and test methods for empty, sterile, single-use
syringes, with or without needles, made of plastic materials and intended solely for the injection of
insulin, with which the syringes are filled by the end user. This International Standard covers syringes
intended for single-use only in humans and with insulins of various concentrations.
The insulin syringes specified in this International Standard are intended for use (i.e. insulin injection)
immediately after filling and are not intended to contain insulin for extended periods of time.
This International Standard excludes single-use syringes made of glass, syringes for use with power-
driven syringe pumps, syringes that are pre-filled by the manufacturer, and syringes intended to be
stored after filling (e.g. in a kit intended for filling by a pharmacist).

2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
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indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
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ISO 594-11), Conical fittings with a 6 % (Luer) taper for syringes, needles and certain other medical
equipment — Part 1: General requirements ISO 8537:2016
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ISO 3696, Water for analytical laboratory use — Specification and test methods
d58fdfc6eebb/iso-8537-2016
ISO 7864, Sterile hypodermic needles for single use
ISO 9626, Stainless steel needle tubing for the manufacture of medical devices
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 11608–1, Needle-based injection systems for medical use — Requirements and test methods — Part 1:
Needle-based injection systems
ISO 11608–5, Needle-based injection systems for medical use — Requirements and test methods — Part 5:
Automated functions
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 15223-1:2012, Medical devices — Symbols to be used with medical device labels, labelling and
information to be supplied — Part 1: General requirements
ISO 23908, Sharps injury protection — Requirements and test methods — Sharps protection features for
single-use hypodermic needles, introducers for catheter and needles used for blood sampling
ISO/IEC 80369-7, Small bore connectors for liquids and gases in healthcare applications — Part 7:
Connectors with 6 % (Luer) taper for intravascular or hypodermic applications (under development)
IEC 62366-1, Medical devices — Part 1: Application of usability engineering to medical devices

1) To be replaced by ISO 80369–7.

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3 Terms and definitions

For the purposes of this document, the following terms and definitions apply.
NOTE The nomenclature used for some components of syringes intended for single use is shown in Figure 2.

3.1
needle cap
cover intended to protect physically the needle tube prior to use and, for syringes with a fixed needle
tube (type 8), to maintain the sterility of the needle
3.2
plunger stopper
component connected to the leading end of the plunger and seals the open end of the syringe barrel
3.3
plunger cap
cover intended to maintain the sterility of the syringe and to enclose the projecting portion of the
plunger and push button, if present
3.4
fiducial line
leading edge of the plunger stopper (3.2), which is in contact with and perpendicular to the syringe
barrel and aligns with the zero marking on the syringe barrel when the piston is fully inserted
3.5
graduated capacity iTeh STANDARD PREVIEW
volume of water, at a temperature of 18 °C to 28 °C, expelled from the syringe when the fiducial line (3.4)
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on the piston traverses a given scale interval or intervals
3.6 ISO 8537:2016
total graduated capacity https://standards.iteh.ai/catalog/standards/sist/9c4c602a-56e4-45fa-b8bb-
capacity of the syringe at the graduation line farthest from the zero graduation line
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Note 1 to entry: The total graduated capacity may be equal to, or greater than, the nominal capacity.

3.7
piston
assembled component of plunger and plunger stopper (3.2)
3.8
unit packaging
packaging of an individual device, intended to maintain its sterility
3.9
self-contained syringe
syringe with protective end caps intended to maintain the sterility of the interior of the syringe
Note 1 to entry: Protective end caps may be plunger cap (3.3), nozzle cap or needle cap (3.1).

3.10
user packaging
packaging, which contains one or more items of unit packaging, designed to provide labelling
information to the user
3.11
needle length
usable length of needle
Note 1 to entry: Needle length is shown in Figure 1.

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3.12
nozzle cap
sheath intended to protect physically the needle hub prior to use
3.13
plunger delivery
device mechanism which advances the plunger stopper (3.2) to deliver the medicinal product

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Key ISO 8537:2016
1 needle length https://standards.iteh.ai/catalog/standards/sist/9c4c602a-56e4-45fa-b8bb-
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Figure 1 — Needle length

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1
17
16
2

15
3

14

5
13
12

7
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11

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10

Key
1 needle cap 10 plunger cap
2 nozzle cap 11 finger grips
3 nozzle lumen 12 fiducial line
4 nozzle 13 nominal capacity
5 barrel 14 graduation lines
6 plunger stopper 15 zero line
7 seals 16 needle tube
8 plunger 17 hub
9 push-button

Note This figure is only intended to be illustrative of the components of a syringe. The piston might or
might not be of integral construction and might incorporate more than one seal.

Figure 2 — Schematic representation of insulin syringe for single use

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 ISO 8537:2016(E)


4 Types of syringes
The type of syringe shall be designated as follows.
— Type 1; syringe having a 6 % (Luer) male conical fitting, supplied with no needle and packaged in
unit packaging.
— Type 2; syringe having a 6 % (Luer) male conical fitting, supplied with no needle and fitted with
protective end caps and packaged.
— Type 3; syringe having a 6 % (Luer) male conical fitting, and supplied with a detached or detachable
needle and packaged in a unit packaging.
— Type 4; syringe having a 6 % (Luer) male conical fitting and supplied with a detachable needle and
fitted with protective end caps and packaged.
— Type 5; syringe having a fitting other than a 6 % (Luer) taper, supplied with a needle not intended
to be detached and packaged in a unit packaging.
— Type 6; syringe having a fitting other than a 6 % (Luer) taper, supplied with a needle not intended
to be detached and fitted with protective caps and packaged.
— Type 7; syringe with fixed needle tube and packaged in a unit packaging.
— Type 8; syringe with fixed needle tube and fitted with protective end caps and packaged.
NOTE This International Standard provides designations for eight types of syringes to encompass different
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product configurations, but the number of types in use in a particular country is likely to be fewer than eight.
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5 Requirements
ISO 8537:2016
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5.1 General requirements d58fdfc6eebb/iso-8537-2016
The general requirements listed below are considered to be design guidelines for manufacturers.
a) Given the likelihood that multiple insulin concentrations and concentration-specific syringes will
exist in a particular country or locality, the manufacturer shall develop risk mitigation strategies to
minimize the occurrence of “wrong dose” medication errors.
b) The syringe shall indicate, through visual means, the insulin concentration it is intended to contain.
The insulin syringes should also indicate, through non-visual means (e.g. tactile), the insulin
concentration it is intended to contain.
c) Syringes designed to contain a specific concentration of insulin (e.g. U-100) shall be adequately
differentiated visually from other dedicated syringes. This differentiation shall be determined
based on a risk assessment and confirmed through usability validation testing.
d) The syringe and needle should be free from defects affecting safety, serviceability for their intended
use, and appearance.
e) The syringe scale shall be graduated in increments corresponding to units of only one concentration
of insulin. The syringe scale graduation and numbering increments shall be determined through
risk analysis and confirmed through usability validation testing.
NOTE 1 Annex H offers guidance from prior versions of ISO 8537 for graduation and numbering
increments on U-40 and U-100 syringes.

f) The nominal capacity of the syringe shall be designated in millilitres (ml).

g) The tolerances on the graduated capacity shall be in accordance with Table H.1.

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h) Syringes indicated for use with devices or accessories that provide automated functions (e.g.
needle insertion and retraction) shall comply with applicable requirements of ISO 11608-1 and
ISO 11608-5.
i) Syringes with integrated or add-on sharps protection shall comply with ISO 23908.
j) Syringes with Luer attachment features shall comply with ISO 80369-7.
k) The length of the barrel shall be sufficient to allow the expulsion of any air bubbles without
affecting the syringe’s nominal capacity.
NOTE 2 Compliance with this requirement may be demonstrated, for example, by meeting the
requirements in 5.6.1.

l) The syringe’s finger grips shall be of adequate size, shape and strength for the intended purpose.
The design specifications for the finger grips shall be determined through risk analysis and
confirmed through usability validation testing.
m) The materials used in the syringe shall be tested and qualified according to ISO 10993-1.
n) The self-contained syringes with sterile interiors and syringes provided in its unit packaging shall
have been subjected to a validated sterilization process.
NOTE 3 For testing these properties, the manufacturer may use an extract, as specified in Annex G.

5.2 Material selection

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With regard to material selection,
—
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materials used for fabrication of the syringe barrel shall be of sufficient clarity to enable dosages to
be read and for air bubbles to be seen without difficulty,
ISO 8537:2016and
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— materials used for fabrication of syringes and needles (including lubricant) and packaging shall
not, in their final form after sterilization d58fdfc6eebb/iso-8537-2016
and under conditions of intended use, adversely affect the
efficacy, safety and acceptability of insulin preparations. The fabrication materials shall also not be
affected, either physically or chemically, by insulin preparations.

5.3 Colour coding

Colour coding of syringes intended for dedicated use with specific insulin concentrations is as follows.
— The barrel of the insulin syringe shall be clear, with graduation markings of a colour that contrasts
clearly with the syringe.
— The colour used to indicate the insulin concentration shall appear on at least one component of the
syringe (e.g. needle cap, plunger cap, plunger, a portion of the barrel that does not interfere with
visibility of the graduation lines).
— For insulin syringes with fixed needles, the colour of the needle cap shall be the colour designated
for the insulin concentration.
— The colour coding used on the syringes shall be repeated and explained on the user packaging and,
if applicable, on the unit packaging.
NOTE 1 The presence of colour coding on a syringe or package does not absolve the user of the
responsibility to check the marked insulin concentration of the syringe.

— No additional colours, other than black and white, shall be used on the syringe barrel.
NOTE 2 In acknowledgement that established syringes on the market use red to indicate the U40 insulin
strength on the barrel, these syringes are exempted.

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