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 gilt für okulare Endotamponaden (OE), einer Klasse nicht solider chirurgisch invasiver Medizinprodukte, die in der Augenhöhle 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, Kennzeichnung 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
Technical Committee
Current Stage
6060 - National Implementation/Publication (Adopted Project)
Start Date
04-Nov-2021
Due Date
09-Jan-2022
Completion Date
16-Nov-2021

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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.

---------------------- Page: 1 ----------------------
SIST EN ISO 16672:2021
---------------------- Page: 2 ----------------------
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.
---------------------- Page: 3 ----------------------
SIST EN ISO 16672:2021
EN ISO 16672:2021 (E)
Contents Page

European foreword ....................................................................................................................................................... 3

---------------------- Page: 4 ----------------------
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.

---------------------- Page: 5 ----------------------
SIST EN ISO 16672:2021
---------------------- Page: 6 ----------------------
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
---------------------- Page: 7 ----------------------
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
---------------------- Page: 8 ----------------------
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
---------------------- Page: 10 ----------------------
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
---------------------- Page: 11 ----------------------
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

Note 1 to entry: The kinematic viscosity is expressed in square metres per second (m /s).

3.5
ocular endotamponade

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

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
---------------------- Page: 14 ----------------------
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.

---------------------- Page: 1 ----------------------
oSIST prEN ISO 16672:2018
---------------------- Page: 2 ----------------------
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
---------------------- Page: 3 ----------------------
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
---------------------- Page: 4 ----------------------
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

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Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards

bodies (ISO member bodies). The work of preparing International Standards is normally carried out

through ISO technical committees. Each member body interested in a subject for which a technical

committee has been established has the right to be represented on that committee. International

organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.

ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of

electrotechnical standardization.

The procedures used to develop this document and those intended for its further maintenance are

described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the

different types of ISO documents should be noted. This document was drafted in accordance with the

editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/directives).

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of

any patent rights identified during the development of the document will be in the Introduction and/or

on the ISO list of patent declarations received (see www .iso .org/patents).

Any trade name used in this document is information given for the convenience of users and does not

constitute an endorsement.

For an explanation on the 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

Note 1 to entry: The kinematic viscosity is expressed in square metres per second (m /s).

3.5
ocular endotamponade

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

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 range

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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