SIST EN ISO 16672:2021

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

• Status: Published
• Public Enquiry End Date: 04-Nov-2018
• Publication Date: 15-Nov-2021
• ICS: 11.040.70 - Ophthalmic equipment
• Technical Committee: VAZ - Healthcare
• Current Stage: 6060 - National Implementation/Publication (Adopted Project)
• Start Date: 04-Nov-2021
• Due Date: 09-Jan-2022
• Completion Date: 16-Nov-2021
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning medical devices
• Mandate: M/023 - Standardization mandate to CEN/CENELEC concerning the development of European standards relating to medical devices
• Ref Project: EN ISO 16672:2021 - Ophthalmic implants - Ocular endotamponades (ISO 16672:2020)

Relations

• Replaces: SIST EN ISO 16672:2015 - Ophthalmic implants - Ocular endotamponades (ISO 16672:2015)
• Effective Date: 01-Dec-2021

Standards Content (Sample)

SLOVENSKI STANDARD
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
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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.

Contents Page
European foreword . 3

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.

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
ISO 16672:2020(E)
© 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: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii © ISO 2020 – All rights reserved

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 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

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 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
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

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 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
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
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

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 cont
...