SIST EN ISO 16672:2021
(Main)Ophthalmic implants - Ocular endotamponades (ISO 16672:2020)
Ophthalmic implants - Ocular endotamponades (ISO 16672:2020)
This document applies to ocular endotamponades (OE), a group of non-solid surgically invasive medical
devices introduced into the vitreous cavity of the eye to flatten and position a detached retina onto the
retinal pigment epithelium (RPE), or to tamponade the retina.
With regard to the safety and efficacy of OE, this document specifies requirements for their intended
performance, design attributes, pre-clinical and clinical evaluation, sterilization, product packaging,
product labelling and the information supplied by the manufacturer.
Ophthalmische Implantate - Okulare Endotamponaden (ISO 16672:2020)
Dieses Dokument ist anwendbar für okulare Endotamponaden (OE), eine Klasse nicht-solider chirurgisch invasiver Medizinprodukte, die in dem Glaskörperraum zur Glättung und zum Anlegen einer abgelösten Retina an das retinale Pigmentepithel (RPE) oder als Retinatamponade verwendet werden.
Mit Bezug auf die Sicherheit und Effektivität von OE legt dieses Dokument Anforderungen für die beabsichtigte Funktion, Konstruktionsmerkmale, präklinische und klinische Bewertung, Sterilisation, Verpackung, Kenn¬zeichnung und die Bereitstellung von Informationen durch den Hersteller fest.
Implants ophtalmiques - Produits de tamponnement endoculaires (ISO 16672:2020)
Le présent document s'applique aux produits de tamponnement endoculaires, un groupe de dispositifs médicaux invasifs non solides de type chirurgical introduits dans la cavité vitréenne de l'œil pour mettre à plat et repositionner une rétine décollée sur l'épithélium pigmentaire rétinien (EPR), ou pour tamponner la rétine.
Tout en tenant compte de la sécurité et de l'efficacité des produits de tamponnement endoculaires, le présent document définit les exigences relatives à leurs performances attendues, à leurs données de conception, à une évaluation préclinique et clinique, à la stérilisation, au conditionnement du produit, à son étiquetage et aux informations fournies par le fabricant.
Očesni vsadki (implantati) - Sredstva za notranjo očesno tamponado (ISO 16672:2020)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 16672:2021
01-december-2021
Nadomešča:
SIST EN ISO 16672:2015
Očesni vsadki (implantati) - Sredstva za notranjo očesno tamponado (ISO
16672:2020)
Ophthalmic implants - Ocular endotamponades (ISO 16672:2020)
Ophthalmische Implantate - Okulare Endotamponaden (ISO 16672:2020)
Implants ophtalmiques - Produits de tamponnement endoculaires (ISO 16672:2020)
Ta slovenski standard je istoveten z: EN ISO 16672:2021
ICS:
11.040.70 Oftalmološka oprema Ophthalmic equipment
SIST EN ISO 16672:2021 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 16672:2021
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SIST EN ISO 16672:2021
EN ISO 16672
EUROPEAN STANDARD
NORME EUROPÉENNE
October 2021
EUROPÄISCHE NORM
ICS 11.040.70 Supersedes EN ISO 16672:2015
English Version
Ophthalmic implants - Ocular endotamponades (ISO
16672:2020)
Implants ophtalmiques - Produits de tamponnement Ophthalmische Implantate - Okulare Endotamponaden
endoculaires (ISO 16672:2020) (ISO 16672:2020)
This European Standard was approved by CEN on 19 November 2019.
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, Turkey 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
© 2021 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 16672:2021 E
worldwide for CEN national Members.
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SIST EN ISO 16672:2021
EN ISO 16672:2021 (E)
Contents Page
European foreword . 3
2
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SIST EN ISO 16672:2021
EN ISO 16672:2021 (E)
European foreword
This document (EN ISO 16672:2021) 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 April 2022, and conflicting national standards shall be
withdrawn at the latest by April 2022.
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 16672:2015.
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, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 16672:2020 has been approved by CEN as EN ISO 16672:2021 without any modification.
3
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SIST EN ISO 16672:2021
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SIST EN ISO 16672:2021
INTERNATIONAL ISO
STANDARD 16672
Third edition
2020-06
Ophthalmic implants — Ocular
endotamponades
Implants ophtalmiques — Produits de tamponnement endoculaires
Reference number
ISO 16672:2020(E)
©
ISO 2020
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SIST EN ISO 16672:2021
ISO 16672:2020(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2020
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved
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SIST EN ISO 16672:2021
ISO 16672:2020(E)
Contents Page
Foreword .iv
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Intended performance . 3
5 Design attributes . 3
5.1 General . 3
5.2 Chemical description and contaminants . 3
5.3 Density . 4
5.4 Gaseous expansion . 4
5.5 Interfacial tension . 4
5.6 Kinematic viscosity . 4
5.7 Dynamic viscosity . 4
5.8 Molecular mass distribution . 4
5.9 Particulates. 5
5.10 Refractive index . 5
5.11 Spectral transmittance . 5
5.12 Surface tension . 5
5.13 Vapour pressure . 5
6 Design evaluation . 5
6.1 General . 5
6.2 Evaluation of biological safety . 6
6.2.1 General. 6
6.2.2 Bacterial endotoxins test . 6
6.2.3 Intraocular implantation test . 6
6.2.4 Ethylene oxide . 6
6.3 Clinical investigation . 7
7 Sterilization . 7
8 Product stability . 7
9 Integrity and performance of the delivery system . 7
10 Packaging . 8
10.1 Protection from damage during storage and transport. 8
10.2 Maintenance of sterility in transit . 8
11 Information supplied by the manufacturer . 8
Annex A (normative) Intraocular implantation test .10
Annex B (informative) Clinical investigation .11
Annex C (informative) Method for quantifying incompletely fluorinated contaminants in
perfluorocarbon liquids .14
Bibliography .16
© ISO 2020 – All rights reserved iii
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SIST EN ISO 16672:2021
ISO 16672:2020(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 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.
This third edition cancels and replaces the second edition (ISO 16672:2015), which has been technically
revised.
The main changes compared to the previous edition are as follows:
a) the following terms and their definitions have been included: "secondary packaging", surgical
invasive medical product" and "minimum utilization pressure";
b) the subclause on chemical description and contaminants has been substantially revised;
c) the bacterial endotoxin limit has been revised from 0,5 to 0,2 Endotoxin Units per ml;
d) the total level of EO in the product has been revised: it shall not exceed 1,25 µg/dose for EO and
5,0 µg/dose for ethylene chlorohydrin (ECH);
e) minimum utilization pressure has been included in the list of information supplied by the
manufacturer;
f) B.2.2 giving the clinical variables in a clinical investigation has been revised;
g) Annex C "Method for quantifying incompletely fluorinated contaminants in perfluorocarbon
liquids" has been added.
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.
iv © ISO 2020 – All rights reserved
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SIST EN ISO 16672:2021
INTERNATIONAL STANDARD ISO 16672:2020(E)
Ophthalmic implants — Ocular endotamponades
1 Scope
This document applies to ocular endotamponades (OE), a group of non-solid surgically invasive medical
devices introduced into the vitreous cavity of the eye to flatten and position a detached retina onto the
retinal pigment epithelium (RPE), or to tamponade the retina.
With regard to the safety and efficacy of OE, this document specifies requirements for their intended
performance, design attributes, pre-clinical and clinical evaluation, sterilization, product packaging,
product labelling and the information supplied by the manufacturer.
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 10993-6, Biological evaluation of medical devices — Part 6: Tests for local effects after implantation
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 14630, Non-active surgical implants — General requirements
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 15223-1, Medical devices — Symbols to be used with medical device labels, labelling and information to
be supplied — Part 1: General requirements
EN 1041+A1, Information supplied by the manufacturer with medical devices
OECD Guidelines for the Testing of Chemicals, Section 1: Physical-Chemical properties, Test No. 104:
Vapour Pressure
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
© ISO 2020 – All rights reserved 1
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SIST EN ISO 16672:2021
ISO 16672:2020(E)
3.1
delivery system
sealed container in which the product is supplied including any additional component provided to
introduce the product into the eye
3.2
dynamic viscosity
quotient of shear stress and shear velocity
Note 1 to entry: The dynamic viscosity is expressed in pascal seconds (Pa⋅s).
3.3
interfacial tension
tension against liquids
Note 1 to entry: The interfacial tension is expressed in newton per metre (N/m).
3.4
kinematic viscosity
quotient of dynamic viscosity (3.2) and gravity
2
Note 1 to entry: The kinematic viscosity is expressed in square metres per second (m /s).
3.5
ocular endotamponade
OE
non-solid surgically invasive medical device (3.11) introduced into the vitreous cavity of the eye to flatten
and position a detached retina onto the retinal pigment epithelium (RPE), or to tamponade the retina
3.6
primary container
container providing mechanical and microbiological protection of the content
3.7
sterile barrier
minimum package that prevents ingress of microorganisms and allows aseptic presentation of the
product at the point of use
3.8
storage container
part of the packaging intended to protect the device during transport and storage, containing the sterile
barrier (3.7)
3.9
secondary packaging
container external to and providing protection and support for the primary container (3.6)
3.10
surface tension
tension against air
Note 1 to entry: Surface tension is expressed in newton per metre (N/m).
3.11
surgically invasive medical device
invasive device which penetrates inside the body through the surface with the aid or in the context of a
surgical operation
2 © ISO 2020 – All rights reserved
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SIST EN ISO 16672:2021
ISO 16672:2020(E)
3.12
vapour pressure
pressure exerted by the vapour of a liquid OE when in equilibrium with the liquid OE
Note 1 to entry: Vapour pressure is expressed in pascal (Pa) at (35 ± 2) °C.
3.13
minimum utilization pressure
limiting value of the pressure below which the gas or gases mixture shall no longer be withdrawn from
the container for its intended use
4 Intended performance
The general requirements for the intended performance of non-active surgical implants specified in
ISO 14630 shall apply.
This document describes surgically invasive medical devices that are compatible with the internal
ocular environment and, through a primary mechanical action, are used to reposition and/or tamponade
a detached retina. They are used either intra-operatively and removed at the end of surgery, as in the
case of perfluorocarbon liquids, or are designed to remain in the vitreous cavity until removal at a later
date as in the case of silicone oils, or they are completely absorbed as in the case of gaseous OE.
The manufacturer shall describe and document the functional characteristics of the OE in terms of its
chemical composition and physical properties, the intended surgical applications, the conditions of
use and the maximum duration of contact with, and effects upon ocular tissues, with particular regard
to safety.
All available published standards and published scientific and clinical literature, validated test results,
clinical investigations, and pre-clinical and clinical evaluations shall be considered in determining the
intended device.
5 Design attributes
5.1 General
The general requirements for non-active surgical implants specified in ISO 14630 shall apply.
All testing requirements specified below shall be performed with finished and 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 Chemical description and contaminants
The manufacturer shall provide a description of each of the components in the finished product, and
their respective quality specifications and concentrations.
If the component material is derived from biological sources, the organism from which it is obtained
shall be stated along with its source.
Whenever possible, for all polymers, the backbone, any side groups and end-groups shall be identified.
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 by-products, residual monomers, cross-linking agents, catalysts, products derived from
© ISO 2020 – All rights reserved 3
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SIST EN ISO 16672:2021
ISO 16672:2020(E)
auto-oxidation processes or from containers transport and packaging that are potentially hazardous
either systemically or to the tissues of the eye, shall be identified and quantified, whenever possible,
and their concentration in the finished product reported. Limits for identified contaminants shall be
set, justified and documented. Testing of the biological effects of these contaminants during evaluation
of biological safety may be required if the risk analysis determines it necessary. Chemical changes
during transport and storage shall be considered. Any contaminant being identified to cause, directly
or by being the source for other contaminants, considerable harm to the patient, the user or any third
party shall be reduced to a level that the health risk associated with the contaminant is considered
acceptable.
The following list, although not exhaustive, provides some information on likely contaminants of
common endotamponade materials: Materials of biological origin may contain proteins, nucleic acids,
or other biological materials as contaminants. Perfluorocarbon liquids may contain oxygen containing
compounds and incompletely fluorinated contaminants, including HF. Specifically incompletely
fluorinated contaminants, including HF, are likely to occur and they bear a high risk for the patient
already at the ppm level. Therefore, the concentration of incompletely fluorinated contaminants,
including HF, shall be as low as possible. Different methods can be used for which the specific limits
need to be specified based on the risk analysis. In Annex C a method is described for which a level of
10 ppm has been published, to assure material safety in regard of the aforementioned impurities.
Silicone oils may contain catalysts, heavy metals, residual monomers and short chain oligomers and
polymers as a result from their synthesis.
For any liquid OE, control over synthesis of the tamponade material according to applicable standards
and monographs and analytically controlled purification procedures according to applicable standards
or monographs are minimum requirements.
5.3 Density
3
The density of liquid forms of OE shall be specified in kilograms per cubic metre (kg/m ).
5.4 Gaseous expansion
For gaseous forms of OE the intraocular gaseous expansion at (35 ± 2) °C and its dependence on
atmospheric pressure shall be expressed.
5.5 Interfacial tension
Where applicable, the interfacial tension against water shall be determined and expressed in newton
per metre (N/m) at (35 ± 2) °C.
5.6 Kinematic viscosity
Where applicable, the kinematic viscosity at (35 ± 2) °C shall be determined and expressed in
2
millimetres squared per second (mm /s).
5.7 Dynamic viscosity
For viscous or viscoelastic OE, the dynamic viscosity shall be determined at (35 ± 2) °C in the frequency
−1 −1
range between 0,01 s and 100 s and expressed in millipascal second (mPa⋅s).
5.8 Molecular mass distribution
If the OE is a polymer, the average molecular mass, the range of molecular mass distribution and the
polydispersity shall be reported.
4 © ISO 2020 – All rights reserved
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SIST EN ISO 16672:2021
ISO 16672:2020(E)
The manufacturer shall conduct and report such additional tests as necessary to provide an adequate
description of the molecular mass distribution of the components in the finished product. Whenever
possible, standard methods shall be named and used.
5.9 Particulates
A risk assessment shall evaluate the potential for the formation of and contamination by particulates
in the product throughout the life of the product including manufacture, transport and storage under
specified conditions, and during use. The potential for associated hazards shall be described.
The manufacturer shall characterize and set limits for the types, range of sizes and levels of particles
present in the finished product. Limits according to USP <789> are deemed acceptable. Alternatively,
the manufacturer shall investigate the level of particles in the clinical study. For each type of particle
present, a limit which has been validated in a clinical study shall be set and an adequate justification for
the limit shall be documented.
5.10 Refractive index
Where applicable, the refractive index between OE and air shall be measured with a refractometer at
(35 ± 2) °C and (546 ± 10) nm or (589 ± 10) nm wavelength.
5.11 Spectral transmittance
The spectral transmittance of the OE shall be measured by transmission spectrophotometry over the
range 300 nm to 1 100 nm. Results shall be presented graphically, plotting percentage transmission
against wavelength.
5.12 Surface tension
Where applicable, the surface tension shall be determined and expressed in newton per metre (N/m) at
(35 ± 2) °C.
5.13 Vapour pressure
If the vapour pressure exceeds 100 Pa, the vapour pressure shall be determined and expressed in pascal
(Pa) at (35 ± 2) °C (OECD Test No. 104: Vapour Pressure).
6 Design evaluation
6.1 General
The OE shall be evaluated for safety by performing a risk assessment in accordance with ISO 14971. The
results of the risk assessment shall determine the tests required to evaluate the safety of the OE.
The risk assessment shall take into consideration the following:
a) the type of product and the location and duration of intraocular contact;
b) potential interactions of the OE with other materials and energy sources, e.g. laser likely to be used
in ophthalmic surgery;
c) for intraocular gases, any impurity profile changes as the gas is withdrawn
...
SLOVENSKI STANDARD
oSIST prEN ISO 16672:2018
01-november-2018
2þHVQLYVDGNL LPSODQWDWL 6UHGVWYD]DQRWUDQMRRþHVQRWDPSRQDGR ,62',6
Ophthalmic implants - Ocular endotamponades (ISO/DIS 16672:2018)
Ophthalmische Implantate - Okulare Endotamponaden (ISO/DIS 16672:2018)
Implants ophtalmiques -- Produits de tamponnement endoculaires (ISO/DIS 16672:2018)
Ta slovenski standard je istoveten z: prEN ISO 16672
ICS:
11.040.70 Oftalmološka oprema Ophthalmic equipment
oSIST prEN ISO 16672:2018 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 16672:2018
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oSIST prEN ISO 16672:2018
DRAFT INTERNATIONAL STANDARD
ISO/DIS 16672
ISO/TC 172/SC 7 Secretariat: DIN
Voting begins on: Voting terminates on:
2018-07-30 2018-10-22
Ophthalmic implants — Ocular endotamponades
Implants ophtalmiques — Produits de tamponnement endoculaires
ICS: 11.040.70
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
ISO/CEN PARALLEL PROCESSING
BEING ACCEPTABLE FOR INDUSTRIAL,
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
STANDARDS MAY ON OCCASION HAVE TO
BE CONSIDERED IN THE LIGHT OF THEIR
POTENTIAL TO BECOME STANDARDS TO
WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 16672:2018(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
©
PROVIDE SUPPORTING DOCUMENTATION. ISO 2018
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oSIST prEN ISO 16672:2018
ISO/DIS 16672:2018(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2018
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2018 – All rights reserved
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oSIST prEN ISO 16672:2018
ISO/DIS 16672:2018(E)
Contents Page
Foreword .iv
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Intended performance . 3
5 Design attributes . 3
5.1 General . 3
5.2 Chemical description and contaminants . 3
5.3 Density . 4
5.4 Gaseous expansion . 4
5.5 Interfacial tension . 4
5.6 Kinematic viscosity . 4
5.7 Dynamic viscosity . 4
5.8 Molecular mass distribution . 5
5.9 Particulates. 5
5.10 Refractive index . 5
5.11 Spectral transmittance . 5
5.12 Surface tension . 5
5.13 Vapour pressure . 5
6 Design evaluation . 5
6.1 General . 5
6.2 Evaluation of biological safety . 6
6.2.1 General. 6
6.2.2 Bacterial endotoxins test . 6
6.2.3 Intraocular implantation test . 6
6.2.4 Ethylene oxide . 6
6.2.5 Perfluorocarbon liquids (PFCL) cytotoxicity testing . 7
6.3 Clinical investigation . 7
7 Sterilization . 7
8 Product stability . 7
9 Integrity and performance of the delivery system . 8
10 Packaging . 8
10.1 Protection from damage during storage and transport. 8
10.2 Maintenance of sterility in transit . 8
11 Information supplied by the manufacturer . 8
Annex A (normative) Intraocular implantation test .10
Annex B (informative) Clinical investigation .11
Annex C (informative) Method for quantifying incompletely fluorinated contaminants in
perfluorocarbon liquids .14
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC [OJ L 169] aimed to be covered .16
Bibliography .18
© ISO 2018 – All rights reserved iii
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oSIST prEN ISO 16672:2018
ISO/DIS 16672:2018(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 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 the following
URL: 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.
This third edition cancels and replaces the second edition (ISO 16672:2015), which has been technically
revised.
The main changes compared to the previous edition are as follows:
a) the following terms and their definitions have been included: "secondary packaging", surgical
invasive medical product" and "minimum utilization pressure";
b) the subclause on chemical description and contaminants has been substantially revised;
c) the bacterial endotoxin limit has been revised from 0,5 to 0,2 Endotoxin Units per ml;
d) the total level of EO in the product has been revised: it shall not exceed 1,25 µg/dose for EO and
5,0 µg/dose for ethylene chlorohydrin (ECH);
e) a new subclause on "Perfluorocarbon liquids (PFCL) cytotoxicity testing" has been added;
f) minimum utilization pressure has been included in the list of information supplied by the
manufacturer;
g) subclause B.2.2 giving the clinical variables in a clinical investigation has been revised;
h) Annex C "Method for quantifying incompletely fluorinated contaminants in perfluorocarbon
liquids" has been added.
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oSIST prEN ISO 16672:2018
DRAFT INTERNATIONAL STANDARD ISO/DIS 16672:2018(E)
Ophthalmic implants — Ocular endotamponades
1 Scope
This document applies to ocular endotamponades (OE), a group of non-solid surgically invasive medical
devices introduced into the vitreous cavity of the eye to flatten and position a detached retina onto the
retinal pigment epithelium (RPE), or to tamponade the retina.
With regard to the safety and efficacy of OE, this document specifies requirements for their intended
performance, design attributes, pre-clinical and clinical evaluation, sterilization, product packaging,
product labelling and the information supplied by the manufacturer.
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 10993-6, Biological evaluation of medical devices — Part 6: Tests for local effects after implantation
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 11137-1+Amd.1, Sterilization of health care products — Radiation — Part 1: Requirements for
development, validation and routine control of a sterilization process for medical devices
ISO 11607-1+Amd.1, Packaging for terminally sterilized medical devices — Part 1: Requirements for
materials, sterile barrier systems and packaging systems
ISO 13408-1+Amd.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 14630, Non-active surgical implants — General requirements
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 15223-1, Medical devices — Symbols to be used with medical device labels, labelling and information to
be supplied — Part 1: General requirements
ISO 17665-1, Sterilization of health care products — Moist heat — Part 1: Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 20857, Sterilization of health care products — Dry heat — Requirements for the development,
validation and routine control of a sterilization process for medical devices
EN 1041+A1, Information supplied by the manufacturer with medical devices
OECD Guidelines for the Testing of Chemicals. Section 1: Physical-Chemical properties, Test No. 104:
Vapour Pressure
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3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at http: //www .electropedia .org/
— ISO Online browsing platform: available at https: //www .iso .org/obp
3.1
delivery system
sealed container in which the product is supplied including any additional component provided to
introduce the product into the eye
3.2
dynamic viscosity
quotient of shear stress and shear velocity
Note 1 to entry: The dynamic viscosity is expressed in pascal seconds (Pa⋅s).
3.3
interfacial tension
tension against liquids
Note 1 to entry: The interfacial tension is expressed in newton per metre (N/m).
3.4
kinematic viscosity
quotient of dynamic viscosity and gravity
2
Note 1 to entry: The kinematic viscosity is expressed in square metres per second (m /s).
3.5
ocular endotamponade
OE
non-solid surgically invasive medical devices introduced into the vitreous cavity of the eye to flatten
and position a detached retina onto the RPE, or to tamponade the retina
3.6
primary container
container providing mechanical and microbiological protection of the content
3.7
sterile barrier system
minimum package that prevents ingress of microorganisms and allows aseptic presentation of the
product at the point of use
3.8
storage container
part of the packaging intended to protect the device during transport and storage, containing the
sterile barrier
3.9
secondary packaging
container external to and providing protection and support for the primary container
3.10
surface tension
tension against air
Note 1 to entry: Surface tension is expressed in newton per metre (N/m).
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3.11
surgically invasive medical device
invasive device which penetrates inside the body through the surface the with the aid or in the context
of a surgical operation
3.12
vapour pressure
pressure exerted by the vapour of a liquid OE when in equilibrium with the liquid OE
Note 1 to entry: Vapour pressure is expressed in Pascal (Pa) at (35 ± 2) °C.
3.13
minimum utilization pressure
limiting value of the pressure below which the gas or gases mixture shall no longer be withdrawn from
the container for its intended use
4 Intended performance
The general requirements for the intended performance of non-active surgical implants specified in
ISO 14630 shall apply.
This document describes surgically invasive medical devices that are compatible with the internal
ocular environment and, through a primary mechanical action, are used to reposition and/or tamponade
a detached retina. They are used either intra-operatively and removed at the end of surgery, as in the
case of perfluorocarbon liquids, or are designed to remain in the vitreous cavity until removal at a later
date as in the case of silicone oils, or they are completely absorbed as in the case of gaseous OE.
The manufacturer shall describe and document the functional characteristics of the OE in terms of its
chemical composition and physical properties, the intended surgical applications, the conditions of
use and the maximum duration of contact with, and effects upon ocular tissues, with particular regard
to safety.
All available published standards and published scientific and clinical literature, validated test results,
clinical investigations, and pre-clinical and clinical evaluations shall be considered in determining the
intended device.
5 Design attributes
5.1 General
The general requirements for non-active surgical implants specified in ISO 14630 shall apply.
All testing requirements specified below shall be performed with finished and 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 Chemical description and contaminants
The manufacturer shall provide a description of each of the components in the finished product, and
their respective quality specifications and concentrations.
If the component material is derived from biological sources, the organism from which it is obtained
shall be stated along with its source.
Whenever possible, for all polymers, the backbone, any side groups and end-groups shall be identified.
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The identification of potentially hazardous chemical or biological contaminants shall be determined
by a risk analysis. For raw materials of biological origin, these impurities may include proteins, nucleic
acids, or other biological materials.
The identification of potentially hazardous chemical or biological contaminants shall be determined
by a risk analysis. Contaminants of the finished product derived from the source materials or from
the manufacturing process, such as by-products, residual monomers, cross-linking agents and
antioxidants, that are potentially hazardous either systemically or to the tissues of the eye, shall be
identified and quantified, whenever possible, and their concentration in the finished product reported.
Limits for identified contaminants shall be set and documented. Testing of the biological effects of these
contaminants during evaluation of biological safety may be required if the risk analysis determines it
necessary. Chemical changes during transport and storage shall be considered. Any contaminant being
identified to cause, directly or by being the source for other contaminants, considerable harm to the
patient, the user or any third party must be reduced to a level that the health risk associated with the
contaminant is considered acceptable.
The following list, although not exhaustive, provides some information on likely contaminants of
common endotamponade materials: Materials of biological origin may contain proteins, nucleic acids,
or other biological materials as contaminants. Perfluorocarbon liquids may contain oxygen containing
compounds and incompletely fluorinated contaminants, including HF. Specifically incompletely
fluorinated contaminants, including HF, are likely to occur and they bear a high risk for the patient
already at the ppm level. Therefore, the concentration of incompletely fluorinated contaminants,
including HF, shall not exceed 10 ppm. A suitable method is described in Annex C.
Silicone oils may contain catalysts, heavy metals, residual monomers and short chain oligomers and
polymers as a result from their synthesis.
For any liquid OE, control over synthesis of the tamponade medium according to applicable standards
and monographs and analytically controlled purification procedures according to applicable standards
or monographs are minimum requirements.
5.3 Density
3
The density of liquid forms of OE shall be specified in kilograms per cubic metre (kg/m ).
5.4 Gaseous expansion
For gaseous forms of OE the intraocular gaseous expansion at (35 ± 2) °C and its dependence on
atmospheric pressure shall be expressed.
5.5 Interfacial tension
Where applicable, the interfacial tension against water shall be determined and expressed in newton
per metre (N/m) at (35 ± 2) °C.
5.6 Kinematic viscosity
Where applicable, the kinematic viscosity at (35 ± 2) °C shall be determined and expressed in
2
millimetres squared per second (mm /s).
5.7 Dynamic viscosity
For viscous or viscoelastic OE, the dynamic viscosity shall be determined at (35 ± 2) °C in the range
−1
between 0,01 and 100 s and expressed in mPa⋅s.
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5.8 Molecular mass distribution
If the OE is a polymer, the average molecular mass, the range of molecular mass distribution and the
polydispersity shall be reported.
The manufacturer shall conduct and report such additional tests as necessary to provide an adequate
description of the molecular mass distribution of the components in the finished product. Whenever
possible, standard methods shall be named and used.
5.9 Particulates
A risk assessment shall evaluate the potential for the formation of and contamination by particulates
in the product throughout the life of the product including manufacture, transport and storage under
specified conditions, and during use. The potential for associated hazards shall be described.
The manufacturer shall characterize and set limits for the types, range of sizes and levels of particles
present in the finished product. Limits according to USP < 789> are deemed acceptable. Alternatively,
the manufacturer shall investigate the level of particles in the clinical study. For each type of particle
present, a limit which has been validated in a clinical study shall be set and an adequate justification for
the limit shall be documented.
5.10 Refractive index
Where applicable, the refractive index between OE and air shall be measured with a refractometer at
(35 ± 2) °C and (546 ± 10) nm, or (589±10) nm wavelength.
5.11 Spectral transmittance
The spectral transmittance of the OE shall be measured by transmission spectrophotometry over the
range 300 nm to 1 100 nm. Results shall be presented graphically, plotting percentage transmission
against wavelength.
5.12 Surface tension
Where applicable, the surface tension shall be determined and expressed in newton per metre (N/m) at
(35 ± 2) °C.
5.13 Vapour pressure
If the vapour pressure exceeds 100 Pa, the vapour pressure shall be determined and expressed in Pascal
(Pa) at (35 ± 2) °C (OECD Test No. 104: Vapour Pressure).
6 Design evaluation
6.1 General
The OE shall be evaluated for safety by performing a risk assessment in accordance with ISO 14971. The
results of the risk assessment shall determine the tests required to evaluate the safety of the OE.
The risk assessment shall take into consideration the following:
a) the type of product and the location and duration of intraocular contact;
b) potential interactions of the OE with other materials and energy sources, e.g. laser likely to be used
in ophthalmic surgery;
c) for intraocular gases, any impurity profile changes as the gas is withdrawn from the tank.
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NOTE Impurity profile changes can occur as the concentration of the chemical species changes due to the
differences in vapour pressure as the tank is depleted.
The OE shall be evaluated to demonstrate that the intended performance is achieved. The requirements
for evaluation of non-active implants specified in ISO 14630 shall apply.
6.2 Evaluation of biological safety
6.2.1 General
The relevant biocompatibility endpoints specified in ISO 10993-1 and identified by the risk analysis
shall be taken into account when selecting the tests to evaluate the biological safety of an OE.
NOTE Based upon the typical clinical applications in the posterior segment, OE are categorized as “Implant
devices, tissue/bone/dentin”. The tests for this and other categories of devices identified in Table A.1 of
ISO 10993-1:2009 are for guidance only; they do not represent maximum or minimum test requirements.
6.2.2 Bacterial endotoxins test
Where applicable, the OE 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. [1, 2, 3] Any product that exceeds a bacterial endotoxin limit of 0,2 Endotoxin
Units (EU) per ml fails the test.
6.2.3 Intraocular implantation test
Tests for intraocular irritation, inflammation, intraocular pressure (IOP) and other local effects of the
OE shall be conducted in a suitable animal model, in accordance with animal welfare requirements
specified in ISO 10993-2 or following any local legislation.
Due to vascularisation differences between the human retina and the rabbit retina an alternate suitable
animal should be considered, especially for non-aqueous substances.
The particular requirements of the intraocular implantation test are specified in Annex A.
The study design shall mirror the intended clinical use as closely as possible.
The study design should assess the intra-operative and postoperative intraocular irritation,
inflammation, and local effects of the ophthalmic surgery with comparative use of the OE under
evaluation and a control OE which is a well-documented OE
...
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