EN ISO 16671:2015

SLOVENSKI STANDARD
01-oktober-2015
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SIST EN ISO 16671:2004
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Ophthalmic implants - Irrigating solutions for ophthalmic surgery (ISO 16671:2015)
Ophthalmische Implantate - Spüllösungen für die ophthalmische Chirurgie (ISO
16671:2015)
Implants ophtalmiques - Solutions d'irrigation pour la chirurgie ophtalmique (ISO
16671:2015)
Ta slovenski standard je istoveten z: EN ISO 16671:2015
ICS:
11.040.70 Oftalmološka oprema Ophthalmic equipment
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EUROPEAN STANDARD
EN ISO 16671
NORME EUROPÉENNE
EUROPÄISCHE NORM
August 2015
ICS 11.040.70 Supersedes EN ISO 16671:2003
English Version
Ophthalmic implants - Irrigating solutions for ophthalmic surgery
(ISO 16671:2015)
Implants ophtalmiques - Solutions d'irrigation pour la Ophthalmische Implantate - Spüllösungen für die
chirurgie ophtalmique (ISO 16671:2015) ophthalmische Chirurgie (ISO 16671:2015)
This European Standard was approved by CEN on 7 May 2015.

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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United
Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 16671:2015 E
worldwide for CEN national Members.

Contents Page
European foreword .3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC .5

European foreword
This document (EN ISO 16671:2015) 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 February 2016, and conflicting national standards shall be withdrawn
at the latest by February 2016.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 16671:2003.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive(s).
For relationship with EU Directive(s), see informative Annex ZA, which is an integral part of this document.
The following referenced documents are indispensable for the application of this document. For undated
references, the latest edition of the referenced document (including any amendments) applies. For dated
references, only the edition cited applies. However, for any use of this standard ‘within the meaning of Annex
ZA’, the user should always check that any referenced document has not been superseded and that its
relevant contents can still be considered the generally acknowledged state-of-art.
When an IEC or ISO standard is referred to in the ISO standard text, this shall be understood as a normative
reference to the corresponding EN standard, if available, and otherwise to the dated version of the ISO or IEC
standard, as listed below.
NOTE The way in which these referenced documents are cited in normative requirements determines the extent (in
whole or in part) to which they apply.
Table — Correlation between normative references and dated EN and ISO standards
Normative references Equivalent dated standard
as listed in Clause 2 of the ISO
EN ISO
standard
ISO 10993-1:2009 EN ISO 10993-1:2009 + AC:2010 ISO 10993-1:2009 + Cor 1:2010
ISO 10993-2:2006 EN ISO 10993-2:2006 ISO 10993-2:2006
ISO 11607-1:2006 EN ISO 11607-1:2009 + A1:2014 ISO 11607-1:2006 + Amd 1:2014
ISO 13408-1:2008 + Amd 1:2013 EN ISO 13408-1:2011 + A1:2013 ISO 13408-1:2008 + Amd 1:2013
ISO 14155:2011 EN ISO 14155:2011 + AC:2011 ISO 14155:2011 + Cor 1:2011
ISO 14630:2012 EN ISO 14630:2012 ISO 14630:2012
ISO 14971:2007 EN ISO 14971:2012 ISO 14971:2007
ISO 15223-1:2012 EN ISO 15223-1:2012 ISO 15223-1:2012
ISO 22442-1:2007 EN ISO 22442-1:2007 ISO 22442-1:2007
EN 1041:2008 + A1:2013 EN 1041:2008 + A1:2013 —
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, Former Yugoslav Republic of Macedonia, France, Germany, Greece,
Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom.
Endorsement notice
The text of ISO 16671:2015 has been approved by CEN as EN ISO 16671:2015 without any modification.
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC
This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide a means of conforming to the Essential Requirements of
Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has been
implemented as a national standard in at least one Member State, compliance with the normative clauses of
this standard given in Table ZA.1 confers, within the limits of the scope of this standard, a presumption of
conformity with the corresponding Essential Requirements of that Directive and associated EFTA Regulations.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Directive 93/42/EEC, as amended by 2007/47/EC. This means that
risks have to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’ or ‘removed’,
according to the wording of the corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with essential requirements
1, 2, 5, 6, 7, 8, 9, 11 and 12 of the Directive.
NOTE 3 This Annex ZA is based on normative references according to the table of references in the European
foreword, replacing the references in the core text.
NOTE 4 When an Essential Requirement does not appear in Table ZA.1, it means that it is not addressed by this
European Standard.
Table ZA.1 — Correspondence between this European Standard and Directive 93/42/EEC
Essential Requirements
Clause(s)/subclause(s) of this Qualifying
(ERs) of Directive
European Standard remarks/notes
93/42/EEC
5.4.3 & 5.4.6, 7.2
7 in respect of EO contamination
only.
6.3 7.3
7 7.6
7 8.1
5.2, 5.4.3, 6.2.1 8.2
9, 8.3
10 in respect of exposure to
environmental elements
7 in respect of EO sterilization 8.4
10 13.1
10 13.2
10 13.3 a), b), c), d),
e), f), i), j), k), m)
10 13.4
10 13.6 a), b), e), f), g)
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.
INTERNATIONAL ISO
STANDARD 16671
Second edition
2015-08-01
Ophthalmic implants — Irrigating
solutions for ophthalmic surgery
Implants ophtalmiques — Solutions d’irrigation pour la chirurgie
ophtalmique
Reference number
ISO 16671:2015(E)
©
ISO 2015
ISO 16671:2015(E)
© ISO 2015, Published in Switzerland
All rights reserved. Unless otherwise specified, 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
Ch. de Blandonnet 8 • CP 401
CH-1214 Vernier, Geneva, Switzerland
Tel. +41 22 749 01 11
Fax +41 22 749 09 47
copyright@iso.org
www.iso.org
ii © ISO 2015 – All rights reserved

ISO 16671:2015(E)
Contents Page
Foreword .iv
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Intended performance . 2
5 Design attributes . 2
5.1 General . 2
5.2 Concentration of the components . 2
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 Chemical and biological contaminants . 3
5.4.4 Osmolality . 4
5.4.5 Spectral transmittance . . 4
5.4.6 Particulates . 4
6 Design evaluation . 5
6.1 General . 5
6.2 Preclinical 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 . 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 (informative) Light obscuration test method for particulate contamination: sub-
visible particles .11
Annex D (informative) Microscopic test method for particulate contamination: sub-
visible particles .13
Annex E (normative) Intraocular irrigation test .18
Annex F (informative) Clinical investigation .19
Bibliography .22
ISO 16671:2015(E)
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
Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 172, Optics and photonics, Subcommittee SC 7,
Ophthalmic optics and instruments.
This second edition cancels and replaces the first edition (ISO 16671:2003), which has been
technically revised.
iv © ISO 2015 – All rights reserved

INTERNATIONAL STANDARD ISO 16671:2015(E)
Ophthalmic implants — Irrigating solutions for
ophthalmic surgery
1 Scope
This International Standard 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 International Standard 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, in whole or in part, are normatively referenced in this document and are
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.
ISO 10993-1:2009, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 10993-2:2006, Biological evaluation of medical devices — Part 2: Animal welfare requirements
ISO 11607-1:2006, Packaging for terminally sterilized medical devices — Part 1: Requirements for
materials, sterile barrier systems and packaging systems
ISO 13408-1:2008 + Amd.1:2013, Aseptic processing of health care products — Part 1: General requirements
ISO 14155:2011, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14630:2012, Non-active surgical implants — General requirements
ISO 14971:2007, 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 22442-1:2007, Medical devices utilizing animal tissues and their derivatives — Part 1: Application of
risk management
EN 1041:2008 + A1:2013, Information supplied by the manufacturer of medical devices
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
delivery system
sealed container in which the product is supplied and any additional components provided to introduce
the product into the eye
ISO 16671:2015(E)
3.2
ophthalmic irrigating solution
OIS
aqueous solution that is physiologically compatible with the intraocular environment and functions
solely by mechanical means
Note 1 to entry: It does not provide any primary immunological, pharmacological, or metabolic function.
3.3
primary container
container providing mechanical and microbiological protection of the content
3.4
sterile barrier system
minimum package that prevents ingress of microorganisms and allows aseptic presentation of the
product at the point of use
[SOURCE: ISO/TS 11139:2006, 2.44]
3.5
storage container
part of the packaging intended to protect the device during transport and storage, containing the
sterile barrier
4 Intended performance
The general requirements for the intended performance of non-active surgical implants specified in
ISO 14630 shall apply.
This International Standard describes non-solid medical devices which are compatible with the ocular
environment, used to rinse the ocular surface or intraocular spaces and structures.
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 general requirements for non-active surgical implants outlined in ISO 14630 shall apply.
All testing requirements specified below shall be performed with finished, sterilized product, ready for
release. Any analytical methods utilized shall be validated.
NOTE Tests described herein are intended to apply when qualifying materials and not necessarily as a
routine quality assurance/control programme.
5.2 Concentration of the components
The identification of potentially hazardous chemical or biological contaminants shall be determined
by a risk analysis. For raw materials of biological origin, these 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 cross-linking agents and antioxidants, that are
2 © ISO 2015 – All rights reserved

ISO 16671:2015(E)
potentially hazardous to the tissues of the eye, or systemically, shall be identified, whenever possible,
and their concentration in the finished products be reported.
Contaminants shall be determined using standard analytical methods when available, and all methods
shall be described. Limits for identified contaminants shall be set and documented. Testing for the
biological effects of these contaminants during evaluation of biological safety may be required if the
risk analysis determines it necessary.
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.
5.3 Water used
The purity of the water used shall be Water for Injections (see Reference [3]).
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 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 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
5.4.3 Chemical and biological contaminants
Potentially hazardous chemical or biological contaminants and impurities shall be determined by a risk
analysis. For raw materials of biological origin, these contaminants can include proteins, nucleic acids or
other biological materials. Contaminants of the finished product that are potentially hazardous either
to the tissues of the eye or systemically, shall be identified, whenever possible, and their concentrations
in the finished product reported.
Contaminants shall be determined using standard analytical methods when available, and all methods
shall be described. Limits for identified contaminants shall be set and included. Testing for the biological
ISO 16671:2015(E)
effects of these contaminants during evaluation of biological safety may be required if the risk analysis
determines it necessary.
5.4.4 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.
5.4.5 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.
5.4.6 Particulates
5.4.6.1 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.
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.
5.4.6.2 Visible particles
The OIS shall be essentially free of visible particles. The method described in Annex B shall be used to
determine this.
5.4.6.3 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.
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.
4 © ISO 2015 – All rights reserved

ISO 16671:2015(E)
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.
6 Design evaluation
6.1 General
The OIS shall be evaluated to demonstrate that the intended performance is achieved. The requirements
for evaluation of non-active implants outlined in ISO 14630 shall apply.
6.2 Preclinical 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, carried out 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 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 10993-1:2009, Table A.1, are for guidance only.
They do not represent maximum or minimum test requirements.
NOTE 2 It might be possible 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 0,5 Endotoxin Units (EU) per ml fails the test.
6.2.3 Intraocular irritation and inflammation
If the risk assessment indicates that it is necessary to undertake tests for intraocular irritation,
inflammation, intraocular pressure and other local events, such tests shall be conducted in a suitable
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 should 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
ISO 16671:2015(E)
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 bio microscopy. All adverse effects shall be documented.
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
If clinical evaluation and risk assessment identify the need for a clinical investigation, Annex F shall be
considered. 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. The requirements
for sterilization of non-active surgical implants outlined in ISO 14630 shall apply.
Ethylene oxide shall not be used to sterilize the OIS solution and, unless justified, not to sterilize the
primary container either. In case of justification and use for the latter, ethylene oxide and related
contaminants can diffuse into the solution, for which the following limits shall then apply:
— ethylene oxide: less than 20 µg/ml
— ethylene chlorohydrin: less than 100 µg/ml
NOTE 1 It has been found that the requirements determining acceptable limits for ethylene oxide residuals
specified in ISO 10993-7 are inadequate for devices in contact with highly sensitive tissues, such as those of the
eye. For this case AAMI TIR No. 19 provides additional guidance to the application of ISO 10993-7.
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. Future parts of that International Standard will address specialized processes, such as
filtration and lyophilisation.
8 Product stability
The manufacturer shall define and state the shelf-life of the product. Real time or accelerated shelf-life
testing shall be performed to demonstrate that the finished product remains within specifications for
a period of the labelled shelf-life under expected conditions of transport and storage. Real time testing
shall reflect normal storage temperature and temperature fluctuations and the relative humidity shall
be controlled within 60 % ± 20 %. In accelerated testing the temperature shall not exceed 45 °C and the
relative humidity shall be at least 40 %. The parameters that shall be followed during shelf-life studies
are the pH, osmolality, particulate levels, colour and clarity, plus any other factors identified by risk
analysis as crucial to safe use of the product.
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 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.
6 © ISO 2015 – All rights reserved

ISO 16671:2015(E)
9 Packaging
9.1 Protection from damage during storage and transport
The packaging requirements for medical devices outlined in ISO 11607-1 and ISO 14630 shall apply.
9.2 Maintenance of sterility in transit
OIS shall be packaged 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 EN 1041:2008 + A1:2013 shall apply together with the following particular requirements. Symbols
may be used instead of text, where appropriate. 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 give 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 may be provided on a self-adhesive label.
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.
The minimum information required on the storage container, package insert, sterile barrier and
primary container is listed in Table 2.
Whenever possible, symbols according to ISO 15223-1 should be used.
Table 2 — Information supplied by the manufacturer
Sterile bar-
Storage Package Primary
Information rier (if
container insert container
present)
a
Name of the manufacturer or authorized representative × × × ×
Address of the manufacturer or authorized representa-
× ×
tive
a
Trade name of product × × × ×
Brief description of the chemical composition of the prod-
× ×
uct and the volume supplied
Conditions for storage × ×
Indications for use ×
Contra-indications for use ×
Warnings, precautions and known interactions with
×
other ocular products
Statement that the contents are for single use only × × × ×
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 only if it is not transparent and the required information
cannot be read directly from the primary container without breaching the seal.
ISO 16671:2015(E)
Table 2 (continued)
Sterile bar-
Storage Package Primary
Information rier (if
container insert container
present)
Statement “Sterile” and the method(s) of sterilization of
a
× × × ×
the product and primary container
Statement “Do not use if sterile barrier is breached” × × ×
a
Expiration date × × ×
Information on whether the OIS is buffered and if so
×
information 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 only if it is not transparent and the required information
cannot be read directly from the primary container without breaching the seal.
8 © ISO 2015 – All rights reserved

ISO 16671:2015(E)
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 10-ml burette, capable of accurately delivering titrant in 0,1 ml increments.
A.2.2 Stirring plate.
A.2.3 Stirring bar.
A.2.4 Sodium hydroxide, 0,005 N volumetric standard.
A.2.5 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
s 1
the 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
2 t
NaOH volumetric 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 16671:2015(E)
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 a mat black panel, of appropriate size, held in a vertical position.
B.2.2 a non-glare white panel, of appropriate size, held in a vertical position next to the black panel.
B.2.3 an 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.
10 © ISO 2015 – All rights reserved

ISO 16671:2015(E)
Annex C
(informative)
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 cou
...