ISO 11979-5:1999

Ophthalmic implants — Intraocular lenses — Part 5: Biocompatibility

Implants ophtalmiques — Lentilles intraoculaires — Partie 5: Biocompatibilité

General Information

• Status: Withdrawn
• Publication Date: 10-Nov-1999
• Withdrawal Date: 10-Nov-1999
• ICS: 11.040.70 - Ophthalmic equipment
• Technical Committee: ISO/TC 172/SC 7 - Ophthalmic optics and instruments
• Drafting Committee: ISO/TC 172/SC 7 - Ophthalmic optics and instruments
• Current Stage: 9599 - Withdrawal of International Standard
• Completion Date: 09-Jun-2006

Relations

• Revised: ISO 11979-5:2006 - Ophthalmic implants — Intraocular lenses — Part 5: Biocompatibility
• Effective Date: 15-Apr-2008
• Consolidates: ISO 2577:1975 - Plastics — Thermosetting moulding materials — Determination of shrinkage of compression moulded test specimens in the form of bars
• Effective Date: 06-Jun-2022

Standards Content (Sample)

INTERNATIONAL ISO
STANDARD 11979-5
First edition
1999-11-15
Ophthalmic implants — Intraocular
lenses —
Part 5:
Biocompatibility
Implants ophtalmiques — Lentilles intraoculaires —
Partie 5: Biocompatibilité
A Reference number
ISO 11979-5:1999(E)

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ISO 11979-5:1999(E)
Contents
1 Scope .1
2 Normative references .1
3 Terms and definitions .1
4 General requirements applying to the biological evaluation of intraocular lenses .2
5 Physicochemical tests .2
5.1 General.2
5.2 Test for extractables and hydrolytic stability .2
5.3 Degradation tests.3
Annex A (normative) Test for extractables and hydrolytic stability .4
Annex B (normative) Test of photostability.7
Annex C (normative) Nd-YAG laser exposure test .9
Annex D (normative) Ocular implantation test.10
Annex E (informative) Selected definitions .13
Bibliography.14
©  ISO 1999
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronic
or mechanical, including photocopying and microfilm, without permission in writing from the publisher.
International Organization for Standardization
Case postale 56 • CH-1211 Genève 20 • Switzerland
Internet [e-mail]
Printed in Switzerland
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© ISO ISO 11979-5:1999(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.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 3.
Draft International Standards adopted by the technical committees are circulated to the member bodies for voting.
Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote.
International Standard ISO 11979-5 was developed by Technical Committee ISO/TC 172, Optics and optical
instruments, Subcommittee SC 7, Ophthalmic optics and instruments.
ISO 11979 consists of the following parts, under the general title Ophthalmic implants — Intraocular lenses:
 Part 1: Vocabulary
 Part 2: Optical properties and test methods
 Part 3: Mechanical properties and test methods
 Part 4: Labelling and information
 Part 5: Biocompatibility
 Part 6: Shelf-life and transport stability
 Part 7: Clinical investigations
 Part 8: Fundamental requirements
Annexes A to D form a normative part of this part of ISO 11979. Annex E is for information only.
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ISO 11979-5:1999(E) © ISO
Introduction
ISO 10993-1 indicates the fundamental principles governing the biological evaluation of medical devices, the
definition of categories based on the nature and duration of contact with the body, and selection of appropriate
tests. Other parts of ISO 10993 present biological test methods, tests for ethylene oxide residues, tests for
degradation and principles for sample preparation.
NOTE It always was and still is the intention of the Technical Committees ISO/TC 172/SC 7 and CEN/TC 170 to prepare
identical ISO and CEN (European Committee for Standardization) standards on intraocular lenses. However, during the
preparation of part 7 of this series, problems were encountered with normative references to the existing ISO 14155 and
EN 540 horizontal standards on clinical investigation of medical devices, which are similar but not identical.
ISO and CEN principles concerning normative references made it impossible to continue the preparation of identical
International and European Standards on the clinical investigation of intraocular lenses. As a result, two different standards
series have had to be prepared. It is the intention of ISO/TC 172/SC 7 and CEN/TC 170 to revise these standards with the goal
to end up with identical ones as soon as identical ISO and CEN horizontal standards on clinical investigations become
available.
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INTERNATIONAL STANDARD  © ISO ISO 11979-5:1999(E)
Ophthalmic implants — Intraocular lenses —
Part 5:
Biocompatibility
1 Scope
This part of ISO 11979 specifies particular requirements for the the biological evaluation of intraocular lenses (IOLs)
which are in addition to the requirements outlined in the relevant parts of ISO 10993. It also gives guidance on
conducting an ocular implantation test.
2 Normative references
The following normative documents contain provisions which, through reference in this text, constitute provisions of
this part of ISO 11979. For dated references, subsequent amendments to, or revisions of, any of these publications
do not apply. However, parties to agreements based on this part of ISO 11979 are encouraged to investigate the
possibility of applying the most recent editions of the normative documents indicated below. For undated
references, the latest edition of the normative document referred to applies. Members of ISO and IEC maintain
registers of currently valid International Standards.
ISO 10993-1:1997, Biological evaluation of medical devices — Part 1: Evaluation and testing.
ISO 10993-6:1994, Biological evaluation of medical devices — Part 6: Tests for local effects after implantation.

ISO 11979-1:1999 , Ophthalmic implants — Intraocular lenses — Part 1: Vocabulary.
1)
ISO 11979-2:— , Ophthalmic implants — Intraocular lenses — Part 2: Optical properties and test methods.
ISO 11979-3:1999, Ophthalmic implants — Intraocular lenses — Part 3: Mechanical properties and test methods.
ISO 14971-1:1998, Medical devices — Risk management — Part 1: Application of risk analysis.
3 Terms and definitions
For the purposes of this part of ISO 11979, the terms and definitions given in ISO 11979-1 apply.
NOTE Some definitions from ISO 11979-1 are reproduced for information in annex E.
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ISO 11979-5:1999(E) © ISO
4 General requirements applying to the biological evaluation of intraocular lenses
An evaluation of biological safety shall be undertaken in accordance with the principles and requirements of
ISO 10993-1. The evaluation of the biological safety of the test material shall include an assessment for risk in
accordance with ISO 14971-1. The results of the tests described in clause 5 shall be included in the risk
assessment.
The material shall be either the final product or representative sample material which has undergone the same
processing steps, including sterilization. Where representative sample material is used, the shape and size shall be
justified.
In addition, for each test material the results of the following physicochemical evaluations (see clause 5) shall be
available. All extractions shall be performed using an aqueous solvent and a lipophilic solvent, unless otherwise
stated in the test method:
a) extractables and hydrolytic stability;
b) photostability against ultraviolet/visible (UV/Vis) irradiation; and
c) stability against Nd-YAG laser exposure.
Consideration of the need for an ocular implantation test shall be documented and justified. Where necessary, an
ocular implantation test shall be conducted in line with the general principles in ISO 10993-6, supplemented as
described in annex D.
NOTE As the mass of an intraocular lens is typically only about 20 mg, in general no systemic or chronic toxicity testing is
required.
5 Physicochemical tests
5.1 General
The objectives of this group of tests are:
a) to quantify possible residues from synthesis and additives or impurities from manufacturing;
b) to quantify possible degradation products due to hydrolysis;
c) to quantify leachable chemical components; and
d) to facilitate an analysis of any risks introduced by toxic products which may result from processing, treatment in
use, or ageing of the test material.
5.2 Test for extractables and hydrolytic stability
The material shall be tested for extractables and hydrolytic stability in accordance with annex A, which specifies
several different extraction conditions, including the extraction media, temperature and duration. For all conditions
the following shall be observed.
 The manufacturer shall be required to justify and document the reasons for selecting each solvent.
 The extraction media shall be qualitatively and quantitatively analysed for possible extractable components of
the material, such as process contaminants, residual monomers, additives of any kind, and other extractable
components.
 Before and after extraction, the test material shall be weighed and any change in mass shall be calculated.
The test material underdoing hydrolysis testing shall be examined by light microscopy at 103 and by scanning
electron microscopy (SEM) at 5003 before and after extraction. The test material shall be compared with
nonhydrolysed material and shall exhibit no difference in surface appearance (e.g. bubbles, dendrites, breaks and
fissures).
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© ISO
ISO 11979-5:1999(E)
Optical transmittance curves of the test material in the ultraviolet and visible spectral regions (UV/Vis) shall be
recorded before and after hydrolysis testing. By comparison of the spectra, assurance shall be obtained that no
significant changes in spectral transmittance have occurred due to the testing.
The results shall be evaluated to assess the risk for potentially harmful effects due to extractable components. The
results of the tests described in annex A shall be recorded and included in the assessment for risk in accordance
with ISO 14971-1 as discussed in clause 4.
5.3 Degradation tests
5.3.1 Test for photostability
The test material shall be assessed for photostability in accordance with annex B.
The saline solution surrounding the test material during exposure shall be analysed for migrated components.
No significant change shall be detected between the UV/Vis spectra of the test material before and after the exposure.
For anterior chamber IOLs, it shall in addition be shown that no significant change in mechanical properties of the
irradiated test material has occurred, compared with non-irradiated test material.
NOTE The loops of implanted anterior chamber IOLs are exposed to radiation, hence the rationale for requiring
mechanical testing after irradiation.
5.3.2 Nd-YAG laser exposure test
The effect of Nd-YAG laser exposure shall be tested in accordance with annex C.
The physiological saline surrounding the IOLs shall be analysed for released additives and, also, shall show no
cytotoxicity.
The results of the tests described in annexes B and C shall be recorded and included in the assessment for risk as
described in clause 4.
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ISO 11979-5:1999(E) © ISO
Annex A
(normative)
Test for extractables and hydrolytic stability
A.1  Purpose
The purpose of these tests is to quantify extractable additives and other leachables, as well as possible degradation
products due to hydrolysis.
A.2  General remarks
The selected analytical methods should be justified in terms of being well established and of sufficient sensitivity to
detect significant concentrations.
A.3  Test for extractables
A.3.1  Test materials
Use a total of 180 IOLs, if sterile finished IOLs are chosen as the test material.
If representative sample material is chosen, cut it into pieces to give about the same ratio of mass to surface area
as would be obtained with finished IOLs.
A.3.2  Control materials
Use untreated sterile finished IOLs or representative sample material as control material.
Use solvent blanks that have undergone the same procedures as described in A.3.4, for comparison with extracts of
test material.
A.3.3  Apparatus
A.3.3.1  Glass vials, of hydrolytic class I according to EP and USP.
A.3.3.2  Laboratory glassware.
A.3.3.3  Syringes.
A.3.3.4  Analytical balance.
A.3.3.5  Shaker.
A.3.3.6  Incubator.
A.3.3.7  Centrifuge.
A.3.3.8  High pressure liquid chromatograph (HPLC).
A.3.3.9  Gas chromatograph (GC).
.
A.3.3.10 UV/Visible spectrophotometer
NOTE This list is advisory. Other suitable means may be used.
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© ISO
ISO 11979-5:1999(E)
A.3.4  Test procedure
A.3.4.1  Extraction
Extract the test material at 37 °C ± 2 °C for 72 h ± 1 h using two different extraction media, one aqueous and one
lipophilic solvent, selected with relevance to the test material.
Divide the test material into two equal parts for incubation in the two extraction media. Determine the mass of each
part.
Incubate the test material in glass vials with a sufficient volume of medium to achieve a ratio of 10 g of test material
per 100 ml of medium. Use at least two vials for each medium. If necessary, use more vials and agitate to ensure
that all surfaces of the test material are available for extraction during the entire period of extraction.
A.3.4.2  Analysis of extracts
Carry out analysis of the extract of each vial separately.
Remove the vials from the incubator and allow to equilibrate at room temperature for 2 h ± 15 min. Then shake the
vials and centrifuge at room temperature. Collect the clear supernatant with a syringe and transfer to a second vial
for qualitative and quantitative analyses for leachable substances such as UV-absorbers, additives, and
degradation products.
Carry out corresponding qualitative and quantitative analyses on solvent blanks that have undergone the same
incubation procedures.
Compare the results of the qualitative and quantitative analyses of the extracts of the test material to those of the
solvent blank, and interpret the findings in the context of possible material changes.
A.3.4.3  Analysis of the test material
After extraction, rinse the test material and allow to dry. Determine the total mass and calculate and record the
change in mass in each medium.
Take at random five pieces of test material from each extraction condition and determine their spectral
transmittance as described in ISO 11979-2. Compare transmittance spectra of treated test material with spectra of
control material, and record any changes.
A.4  Test for hydrolytic stability
A.4.1  Test material
Use a total of 180 IOLs, if sterile finished IOLs are chosen as the test material.
If representative sample material is chosen, cut it into pieces to give about the same mass to surface area ratio as
would be obtained with
...