SIST EN ISO 16671:2025
(Main)Ophthalmic implants - Irrigating solutions for ophthalmic surgery (ISO 16671:2025)
Ophthalmic implants - Irrigating solutions for ophthalmic surgery (ISO 16671:2025)
This document defines requirements with regards to safety for the intended performance, design attributes, preclinical and clinical evaluation, sterilization, product packaging, product labelling, and the information supplied by the manufacturer.
This document applies to ophthalmic irrigating solutions (OIS), used during ophthalmic surgery. These solutions do not provide any primary immunological, pharmacological, or metabolic function.
Ophthalmische Implantate - Spüllösungen für die ophthalmische Chirurgie (ISO 16671:2025)
Dieses Dokument legt sicherheitsbezogene Anforderungen an die beabsichtigte Funktion, Konstruktionsmerkmale, präklinische und klinische Bewertungen, Sterilisation, Produktverpackung, Produktkennzeichnung und die Bereitstellung von Informationen durch den Hersteller fest.
Dieses Dokument gilt für ophthalmische Spüllösungen (OIS, en: ophthalmic irrigating solution), die in der ophthalmologischen Chirurgie zum Einsatz kommen. Diese Spüllösungen weisen keine primär immunologische, pharmakologische oder metabolische Funktion auf.
Implants ophtalmiques - Solutions d'irrigation pour la chirurgie ophtalmique (ISO 16671:2025)
Le présent document définit des exigences en matière de sécurité dans les performances prévues, les attributs de conception, les évaluations précliniques et cliniques, la stérilisation, l’emballage des produits, l’étiquetage des produits et les informations données par le fournisseur.
Le présent document s’applique aux solutions d’irrigation ophtalmiques utilisées en chirurgie ophtalmique. Ces solutions n’ont pas de fonction immunologique, pharmacologique ou métabolique primaire.
Očesni vsadki (implantati) - Raztopine za izpiranje za očesno kirurgijo (ISO 16671:2025)
Ta dokument določa zahteve glede varnosti za predvidene lastnosti, atribute načrtovanja, predklinično in klinično vrednotenje, sterilizacijo, pakiranje izdelkov, označevanje izdelkov in informacije, ki jih dobavlja proizvajalec. Ta dokument se uporablja za raztopine za izpiranje za očesno kirurgijo (OIS), ki se uporabljajo med kirurškimi posegi. Te raztopine nimajo nobene primarne imunološke, farmakološke ali metabolične funkcije.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
01-november-2025
Nadomešča:
SIST EN ISO 16671:2015
SIST EN ISO 16671:2015/A1:2018
Očesni vsadki (implantati) - Raztopine za izpiranje za očesno kirurgijo (ISO
16671:2025)
Ophthalmic implants - Irrigating solutions for ophthalmic surgery (ISO 16671:2025)
Ophthalmische Implantate - Spüllösungen für die ophthalmische Chirurgie (ISO
16671:2025)
Implants ophtalmiques - Solutions d'irrigation pour la chirurgie ophtalmique (ISO
16671:2025)
Ta slovenski standard je istoveten z: EN ISO 16671:2025
ICS:
11.040.70 Oftalmološka oprema Ophthalmic equipment
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
EN ISO 16671
EUROPEAN STANDARD
NORME EUROPÉENNE
June 2025
EUROPÄISCHE NORM
ICS 11.040.70 Supersedes EN ISO 16671:2015, EN ISO
16671:2015/A1:2017
English Version
Ophthalmic implants - Irrigating solutions for ophthalmic
surgery (ISO 16671:2025)
Implants ophtalmiques - Solutions d'irrigation pour la Ophthalmische Implantate - Spüllösungen für die
chirurgie ophtalmique (ISO 16671:2025) ophthalmische Chirurgie (ISO 16671:2025)
This European Standard was approved by CEN on 16 June 2025.
CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2025 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 16671:2025 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
European foreword
This document (EN ISO 16671:2025) has been prepared by Technical Committee ISO/TC 172 "Optics
and photonics" in collaboration with Technical Committee CEN/TC 170 “Ophthalmic optics” the
secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by December 2025, and conflicting national standards
shall be withdrawn at the latest by December 2025.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 16671:2015.
Any feedback and questions on this document should be directed to the users’ national standards
body/national committee. A complete listing of these bodies can be found on the CEN website.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and the
United Kingdom.
Endorsement notice
The text of ISO 16671:2025 has been approved by CEN as EN ISO 16671:2025 without any modification.
International
Standard
ISO 16671
Third edition
Ophthalmic implants — Irrigating
2025-06
solutions for ophthalmic surgery
Implants ophtalmiques — Solutions d'irrigation pour la chirurgie
ophtalmique
Reference number
ISO 16671:2025(en) © ISO 2025
ISO 16671:2025(en)
© ISO 2025
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
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Email: copyright@iso.org
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Published in Switzerland
ii
ISO 16671:2025(en)
Contents Page
Foreword .iv
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Intended performance . 2
5 Design attributes . 2
5.1 General .2
5.2 Chemical description and contaminants .3
5.3 Water used .3
5.4 Characterization of the finished product.3
5.4.1 General .3
5.4.2 pH and buffering capacity .3
5.4.3 Osmolality .4
5.4.4 Spectral transmittance .4
5.4.5 Particulates .4
6 Design evaluation . 5
6.1 General .5
6.2 Evaluation of biological safety .5
6.2.1 General .5
6.2.2 Bacterial endotoxins test .5
6.2.3 Intraocular irritation and inflammation .5
6.3 Clinical evaluation .6
7 Sterilization . 6
8 Product stability . 6
9 Packaging. 7
9.1 Protection from damage during storage and transport.7
9.2 Maintenance of sterility in transit and storage .7
10 Information supplied by the manufacturer . 7
Annex A (informative) Example of a suitable method for pH measurement and buffer capacity
determination . 9
Annex B (normative) Particulate contamination: visible particulates .10
Annex C (normative) Light obscuration test method for particulate contamination: sub-visible
particles . . .11
Annex D (normative) Microscopic test method for particulate contamination: sub-visible
particles . . .13
Annex E (normative) Intraocular irrigation test .18
Annex F (normative) Clinical investigation .20
Annex G (informative) Analyses of OIS clinical data .22
Annex H (informative) Sample size calculation .24
Bibliography .26
iii
ISO 16671:2025(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 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 172, Optics and photonics, Subcommittee
SC 7, Ophthalmic optics and instruments, in collaboration with the European Committee for Standardization
(CEN) Technical Committee CEN/TC 170, Ophthalmic optics, in accordance with the Agreement on technical
cooperation between ISO and CEN (Vienna Agreement).
This third edition cancels and replaces the second edition (ISO 16671:2015), which has been technically
revised. It also incorporates the Amendment ISO 16671:2015/Amd.1:2017.
The main changes are as follows:
— Inclusion of applicable sections from ISO 14630 throughout the document and removal of any reference
to that standard. It was further clarified that ophthalmic irrigation solutions (OIS) are not implants by
their intended use but are likely to share some of the risks related to non-active implants. Therefore, the
following clauses and subclauses have been revised: Clause 4, Clause 5, Clause 7 and 9.1;
— Clarifications of terms 3.1, 3.2, 3.3 and 3.4;
— Revision of 5.1 for a more accurate description of design attributes;
— Revision of Clause 7 to clarify the risks associated with components of OIS sterilized by ethylene oxide (EO);
— Revision of Clause 8 to clarify that the real time shelf-life testing shall be performed and the accelerated
shelf-life testing is optional;
— Revision of Annex E to provide additional clarification regarding the number of test and control eyes
enrolled in the study and that use of medication during the study that could possibly impact the study
results;
— Annex F was changed from informative to normative and clarified that the same intraocular surgical
procedure is performed in the test and control arms and changed the first post-operative intraocular
pressure (IOP) measurement from 6 h ± 2 h to 8 h ± 2 h to capture the effect of irrigation solution on IOP
and align it with ISO 15798:2022, F.2;
iv
ISO 16671:2025(en)
— Inclusion of Annex G;
— The example for patient number calculation is incorporated into Annex H;
— Correction of Formulae H.1 and H.2.
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
International Standard ISO 16671:2025(en)
Ophthalmic implants — Irrigating solutions for
ophthalmic surgery
1 Scope
This document defines requirements with regards to safety for the intended performance, design attributes,
preclinical and clinical evaluation, sterilization, product packaging, product labelling, and the information
supplied by the manufacturer.
This document applies to ophthalmic irrigating solutions (OIS), used during ophthalmic surgery. These
solutions do not provide any primary immunological, pharmacological, or metabolic function.
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 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 10993-2, Biological evaluation of medical devices — Part 2: Animal welfare requirements
ISO 11135, Sterilization of health-care products — Ethylene oxide — Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials, sterile
barrier systems and packaging systems
ISO 13408-1, Aseptic processing of health care products — Part 1: General requirements
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 15223-1, Medical devices — Symbols to be used with information to be supplied by the manufacturer — Part
1: General requirements
ISO 20417, Medical devices — Information to be supplied by the manufacturer
ISO 22442-1, Medical devices utilizing animal tissues and their derivatives — Part 1: Application of risk
management
ISO 22442-2, Medical devices utilizing animal tissues and their derivatives — Part 2: Controls on sourcing,
collection and handling
ISO 22442-3, Medical devices utilizing animal tissues and their derivatives — Part 3: Validation of the elimination
and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents
European Pharmacopeia (Ph. Eur) 0169, Water for injections
United States Pharmacopeia (USP) <1231>, Water for pharmaceutical purposes
ISO 16671:2025(en)
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
ophthalmic irrigating solution
OIS
aqueous solution that is used to physiologically stabilize the ocular tissue
Note 1 to entry: It does not provide any primary immunological, pharmacological, or metabolic function.
3.2
primary container
container that is in direct contact with the product
3.3
sterile barrier system
minimum package that prevents ingress of microorganisms and allows aseptic presentation of the product
at the point of use
[2]
[SOURCE: ISO11139: 2018, 3.272 ]
Note 1 to entry: For additional details regarding sterile barrier system see ISO 11607-1.
3.4
storage container
part of the packaging intended to protect the device during transport and storage, containing the sterile
barrier system
4 Intended performance
This document describes OIS as non-solid medical devices that are physiologically and functionally
compatible with the ocular tissues and are used to rinse the surface of the eye, stabilize the ocular surface,
and/or manipulate intraocular tissues, spaces, and structures by physiological means.
The manufacturer shall describe and document the functional characteristics of the OIS in terms of its
chemical composition and physical properties, the intended surgical applications, the conditions of use and
effects upon ocular tissues, with particular regard to safety.
The intended performance shall be determined taking into account published standards, published clinical
and scientific literature, validated test results, pre-clinical and clinical evaluation, and clinical investigations.
5 Design attributes
5.1 General
The following subclauses list specific design attributes to be met for the intended performance. Tests
described therein are intended to apply when qualifying materials, but not necessarily apply as a routine
quality assurance/control programme. A risk assessment shall be performed in accordance with ISO 14971.
OIS design attributes shall be documented. Where any of the design attributes are not considered to be
relevant, the reason for such shall be documented and justified.
All testing requirements specified below shall be performed with finished, sterilized product, ready for
release. Any analytical methods utilized shall be validated.
ISO 16671:2025(en)
5.2 Chemical description and contaminants
The manufacturer shall provide a description of each of the component materials in the finished product and
their function within the finished product.
The concentration of each component material in the finished product shall be determined and documented,
and the concentration of each component shall be expressed as weight of material per unit volume of
solution. Since the testing methodology can affect the actual concentration reported, the standard physical
or chemical techniques utilized shall be described and documented. Wherever possible, components shall
comply with stated compendial standards.
The identification and concentration of potentially hazardous chemical or biological contaminants shall be
determined by a risk analysis. For raw materials of biological origin, such impurities can include proteins,
nucleic acids, or other biological materials. Contaminants of the finished product derived from the source
materials or from the manufacturing process, such as antioxidants, and contaminants originating from the
primary container that are potentially hazardous to the tissues of the eye, or systemically, shall be identified,
whenever possible, and their concentration in the finished products shall be reported.
Contaminants shall be determined using standard analytical methods when available, and all methods shall
be described. The limits for the detection of identified contaminants shall be set and documented. Testing
for the biological effects of these contaminants during evaluation of biological safety can be required if the
risk analysis determines it necessary.
5.3 Water used
The purity of the water used shall be water for injection in accordance with USP <1231> and Ph. Eur 0169.
5.4 Characterization of the finished product
5.4.1 General
The manufacturer shall describe and document the physical characteristics that affect the performance of
the OIS safety and efficacy in ophthalmic surgery.
These physical properties should be measured at the conditions expected and relevant at the time of use.
5.4.2 pH and buffering capacity
The pH of the finished product shall be determined and documented with a calibrated pH meter at
25 °C ± 2 °C.
The pH of the product should be close to that of the aqueous humour (pH 7,38) in order to prevent damage
to the corneal endothelial cells. In vitro studies have shown that the pH range tolerated by the endothelium
[6]
narrows as exposure time increases .
A suitable method shall be used to determine buffering capacity. An example of a suitable method is given in
Annex A. The products shall be classified as in Table 1.
Table 1 — Classification according to pH and buffering capacity
Base buffering capacity Acid buffering capacity
Group pH range
mol/l per pH mol/l per pH
Essentially unbuffered <0,000 5 <0,004 6,5 to 8,5
Moderately buffered 0,000 5 to 0,005 0,004 to 0,04 6,7 to 8,2
Buffered >0,005 >0,04 7,2 to 7,6
ISO 16671:2025(en)
5.4.3 Osmolality
The manufacturer shall determine and document the osmolality range of the OIS. Osmolality of the finished
product shall be not less than 200 mosm/kg or greater than 400 mosm/kg. Osmolality shall be determined
using either a vapour pressure osmometer or a cryoscopic osmometer.
5.4.4 Spectral transmittance
The spectral transmittance of the finished product shall be recorded over the range 300 nm to 1 100 nm.
Results shall be presented graphically, plotting % transmission against wavelength.
5.4.5 Particulates
5.4.5.1 General
There is a potential for adverse events to take place as a result of particles of certain sizes and characteristics
in the finished product.
Particulate contamination of OIS consists of extraneous, mobile undissolved particles other than gas
bubbles, unintentionally present in the solutions.
A risk assessment shall evaluate the potential for contamination by, or formation of, particulates in the
product during manufacture as well as the conditions expected during transport and storage, and during
use of the product and the hazards associated with these particulates.
In multi-component products (i.e., where there are two or more separate parts of a product that have to be
mixed prior to use) tests shall be applied to the mixed product.
5.4.5.2 Visible particulates
The OIS shall be essentially free of visible particulates. The method described in Annex B shall be used to
determine this.
5.4.5.3 Sub-visible particles
Either the light obscuration test method given in Annex C or the microscopic test method given in Annex D
shall be used to determine the sub-visible particulate level for OIS with the corresponding limits of each
method as given below. Based on the risk assessment of particles contaminations, further limits can be
necessary.
[7]
The following limits shall apply for the light obscuration test method described in Annex C:
— not more than 50 particles equal to or greater than 10 µm per ml of OIS;
— not more than 5 particles equal to or greater than 25 µm per ml of OIS;
— not more than 2 particles equal to or greater than 50 µm per ml of OIS.
The following limits shall apply for the microscopic test method of Annex D:
— not more than 25 particles equal to or greater than 10 µm per ml of OIS;
— not more than 2,5 particles equal to or greater than 25 µm per ml of OIS;
— not more than 1 particle equal to or greater than 50 µm per ml of OIS.
NOTE The light obscuration test method of Annex C is based on light blockage. Amorphous, semi-liquid or otherwise
morphologically indistinct materials contribute to light obscuration and therefore contribute to the particle count. In
the microscopic test method of Annex D, amorphous, semi-liquid or otherwise morphologically indistinct materials
appear as stain or discolouration on the surface of the membrane filter, and are not counted as particles. To compensate
for this difference, the limits for the microscopic test method are one half those for the light obscuration method.
ISO 16671:2025(en)
6 Design evaluation
6.1 General
The OIS shall be evaluated to demonstrate that the intended performance is achieved.
6.2 Evaluation of biological safety
6.2.1 General
The procedure for evaluation of biological safety of an OIS shall commence with an assessment of risk,
performed and documented in accordance with ISO 14971. The results of the risk analysis shall determine
the tests required to evaluate the biological safety of the OIS.
For OIS containing material of animal origin the risk analysis and management requirements outlined in
ISO 22442-1, ISO 22442-2, and ISO 22442-3 shall apply.
During the risk assessment, the manufacturer should take into account the interaction with other ophthalmic
products.
For all OIS the requirements for evaluation of biological safety specified in ISO 10993-1 shall apply.
NOTE 1 Based upon the typical clinical applications, OIS are categorized as “Implant devices, tissue/bone”. The
tests for this and other categories of devices identified in ISO 10993-1, are for guidance only. They do not represent
maximum or minimum test requirements.
NOTE 2 It is allowed to combine biocompatibility tests, thereby reducing the number of animals required for testing.
Multiple tests can be conducted simultaneously in a single animal provided that the test animal is not subjected to
undue pain or distress.
In addition to the biocompatibility tests identified in ISO 10993-1 and by the risk analysis, all of the following
tests shall be considered in the selection of tests to evaluate the biological safety of an OIS.
6.2.2 Bacterial endotoxins test
The OIS shall be evaluated for the presence of bacterial endotoxins using the Limulus Amoebocyte Lysate
(LAL) test, in accordance with applicable pharmacopoeias or an equivalent validated test procedure. Any
product that exceeds a bacterial endotoxin limit of 0,2 endotoxin units (EU) per ml fails the test.
NOTE The manufacturer is recommended to set the release limit lower than 0,2 EU/ml taking in account the
detection limit and the high sensitivity of the eye to endotoxin.
6.2.3 Intraocular irritation and inflammation
The potential for intraocular irritation, inflammation, increase in IOP, and other local events shall be
assessed. If the risk assessment indicates that tests for evaluation of local events are necessary, then
suitable additional testing shall be conducted in a relevant animal model in accordance with Annex E. The
choice of animal species shall be justified and documented. The animal welfare requirements as described
in ISO 10993-2 shall apply.
The animal testing shall mirror the intended clinical use as closely as possible.
The study design shall assess the intraoperative and postoperative ocular irritation and inflammation of
the ophthalmic surgery, with comparative use of the OIS under evaluation and a control OIS that has already
been proven to be non-irritating and non-inflammatory in clinical use for five years. The volume of OIS used
shall simulate the intended use, accounting for ocular volume differences between the human eye and that
of the animal model.
The post-surgical irritation and inflammation shall be monitored and graded in accordance with Annex E.
Based upon the risk management plan, appropriate evaluation at appropriate times can include corneal
pachymetry and slit lamp biomicroscopy. All adverse effects shall be documented.
ISO 16671:2025(en)
The OIS shall show ocular irritation and inflammation results less than or equal to the control OIS, or it shall
be excluded from clinical use.
6.3 Clinical evaluation
A clinical evaluation (e.g. assessment and analysis of available device information) shall be performed as
part of risk assessment. If the risk assessment identifies the need for a clinical investigation, Annex F shall
be performed. Some suggested analyses comparing the clinical performance of the new OIS to the control
OIS are described in Annex G. A method to determine the number of subjects is provided in Annex H. In
addition, the general requirements concerning clinical investigations of medical devices for human subjects
specified in ISO 14155 shall apply.
7 Sterilization
Whenever possible, the product shall be terminally sterilized in its final container.
EO shall not be used to sterilize the OIS. The OIS itself, being an aqueous solution, cannot be sterilized by EO.
Terminal sterilization of the primary container with EO shall not be used, unless justified. EO can diffuse
into the OIS if the packaging containing it is sterilized with EO and will react with water to form derivatives
(e.g., ethylene glycol, ethylene chlorohydrin). Any detectable level of EO or degradation product in OIS can
result in endothelial cell damage in patients.
For packaging components (e.g., primary container) sterilized using EO, the requirements of ISO 11135 shall
apply. The potential for EO leaching into OIS and resulting in degradation products in the OIS at baseline and
shelf life shall be taken into account in the risk analysis.
NOTE 1 The manufacturer is recommended to set the release limit as low as possible because of the high sensitivity
of the eye to EO.
For OIS that are not terminally sterilized, but aseptically processed, ISO 13408-1 shall apply. The process
−3
shall be demonstrated to comply with a contamination rate limit of 10 by a validated media fill study.
NOTE 2 ISO 13408-1 specifies the general requirements for, and offers guidance on, processes, programmes, and
procedures for the validation and control of aseptically processed healthcare products. ISO 13408-1 particularly
applies, but is not limited to, the processing of aqueous solutions, and is thus relevant to the preparation of OIS.
8 Product stability
The manufacturer shall define and state the shelf-life of the product. Real-time shelf-life testing shall be
performed to demonstrate that the essential characteristics for safe and effective performance of the
finished product remain within product specifications over the labelled shelf life under expected conditions
of transport and storage. The parameters that shall be followed during shelf-life studies are the pH,
osmolality, particulate levels, colour and clarity, sterility, plus any other factors identified by risk analysis as
crucial to safe use of the product. Accelerated shelf-life testing can be performed but shall be always verified
by real time study and the real time study results shall always take precedence over accelerated shelf-life
studies.
[8]
NOTE 1 ASTM F1980 provides additional guidance on accelerated aging testing.
The established shelf-life of the OIS shall be re-validated if a risk assessment identifies any change in
manufacture that can affect the stability of the product.
NOTE 2 Changes in the composition of the product, source materials, material suppliers, manufacturing conditions,
including the sterilization process, package design or package materials, can affect the shelf-life of the product.
ISO 16671:2025(en)
9 Packaging
9.1 Protection from damage during storage and transport
The packaging requirements for medical devices outlined in ISO 11607-1 shall apply.
9.2 Maintenance of sterility in transit and storage
OIS shall be packaged with validated packaging process in such a way that they remain sterile during
transport and storage. The sterile packaging requirements outlined in ISO 11607-1 shall apply.
10 Information supplied by the manufacturer
The general requirements for information provided by the manufacturer of medical devices specified in
ISO 20417 shall apply together with the following particular requirements. Whenever possible, symbols
should be used. When symbols are used, the requirements of ISO 15223-1 shall apply.
The labelling shall contain information on whether the OIS is buffered and if so, shall contain information on
the buffer type and capacity.
If the product is vulnerable to damage by exposure to environmental elements, there shall be clear warning
signs on the shipping container.
The batch number and expiration date shall be provided on a self-adhesive label to be used for patient
records.
A package insert shall be included within the storage container, provided in such a way that it can be
removed and read without damaging the sterile barrier system.
The minimum information required on the storage container, package insert, sterile barrier system and
primary container is listed in Table 2.
Table 2 — Information supplied by the manufacturer
Sterile barri-
Storage Package Primary
Information er system (if
container insert container
present)
a
Name of the manufacturer or authorized representative × × × ×
Address of the manufacturer or authorized representative × ×
a
Trade name of product × × × ×
Brief description of the chemical composition of the product
× ×
and the volume supplied
Conditions for storage × ×
Indications for use ×
Contra-indications for use ×
Warnings, precautions and known interactions with other
×
ocular products
Instructions for use (including the date of issue) ×
Spectral transmittance ×
Statement that the contents are for single use only × × × ×
Statement “Sterile” and the method(s) of sterilization of the
a
× × × ×
product and primary container
Statement “Do not use if sterile barrier system is breached” × × ×
a
The name of the manufacturer or authorized representative, trade name of product, batch number, expiration date and
sterility statement need to be provided on the sterile barrier system only if it is not transparent and the required information
cannot be read directly from the primary container without breaching the seal.
ISO 16671:2025(en)
TTabablele 2 2 ((ccoonnttiinnueuedd))
Sterile barri-
Storage Package Primary
Information er system (if
container insert container
present)
a
Expiration date × × ×
Information on whether the OIS is buffered and if so infor-
×
mation on the buffer type and capacity
Buffering category (see Table 1) ×
a
Batch number preceded by the word “LOT” × × ×
a
The name of the manufacturer or authorized representative, trade name of product, batch number, expiration date and
sterility statement need to be provided on the sterile barrier system only if it is not transparent and the required information
cannot be read directly from the primary container without breaching the seal.
ISO 16671:2025(en)
Annex A
(informative)
Example of a suitable method for pH measurement and buffer
capacity determination
A.1 General
This annex gives an example of a suitable method for pH measurement and buffer capacity determination.
A.2 Equipment and reagents
A.2.1 Calibrated pH meter.
A.2.2 10-ml burette, capable of accurately delivering titrant in 0,1 ml increments.
A.2.3 Stirring plate.
A.2.4 Stirring bar.
A.2.5 Sodium hydroxide, 0,005 N volumetric standard.
A.2.6 Hydrochloric acid, 0,01 N volumetric standard.
A.3 Method
Sodium hydroxide and hydrochloric acid solutions are prepared and standardized using compendia methods
and diluted to the desired concentration prior to use.
To a flask add 25 ml (V ) of sample and with a calibrated glass pH electrode measure the pH (pH ). Using the
s 1
10 ml burette (A.2.1), add sufficient HCl volumetric standard titrant to give a pH change of 1,0 pH unit (pH ).
Record the volume (V ) of titrant added. Repeat with a second aliquot of sample using the NaOH volumetric
t
standard as the titrant.
Calculate the buffer capacity using Formula (A.1):
VN×
t
(A.1)
V ×−()pH pH
s2 1
where N is the normality of the titrant in question.
Report both buffer capacity against acid and buffer capacity against base in units of mol/l per pH.
For solutions with significant buffer capacity, the sample volume may be adjusted to give a suitable volume
of titrant.
ISO 16671:2025(en)
Annex B
(normative)
Particulate contamination: visible particulates
B.1 General
The test is intended to provide a simple procedure for the visual assessment of the OIS as regards visible
particles.
B.2 Apparatus
The apparatus consists of a viewing station comprising:
B.2.1 Mat black panel, of appropriate size, held in a vertical position.
B.2.2 Non-glare white panel, of appropriate size, held in a vertical position next to the black panel.
B.2.3 Adjustable lamp holder, fitted with a suitable light source and a suitable light diffuser.
Any appropriate visible light source is acceptable, provided that the intensity of the illumination at the
viewing point is greater than 2 000 lx. Higher illumination is preferable for containers of coloured glass and
plastic.
B.3 Method
Remove any adherent labels from the container and wash and dry the outside. Gently swirl the container
ensuring that air bubbles are not introduced, and observe and count visible particulates for 5 s in front of
the white panel. Repeat the procedure in front of the black panel. Document the sum of the counts for both
the white and the black panels as the particulate contamination level of the OIS.
ISO 16671:2025(en)
Annex C
(normative)
Light obscuration test method for particulate contamination: sub-
visible particles
C.1 General
This annex describes a light obscuration test method for particulate contamination in the case of sub-visible
particles.
C.2 Apparatus
C.2.1 General
The apparatus is an electronic, liquid-borne particle counting system that uses a light-obscuration sensor
with a suitable sample feeding system. A variety of this type of devices is commercially available. The
operator needs to ensure that the operating parameters of the instrumentation are appropriate to the
required accuracy and precision of the test result. The operator needs to be adequately trained.
C.2.2 Sensor concentra
...
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