ISO/TR 22979:2017
(Main)Ophthalmic implants — Intraocular lenses — Guidance on assessment of the need for clinical investigation of intraocular lens design modifications
Ophthalmic implants — Intraocular lenses — Guidance on assessment of the need for clinical investigation of intraocular lens design modifications
ISO/TR 22979:2017 provides guidance on the application of all parts of the ISO 11979 series of International Standards for intraocular lenses (IOLs).[1?9] It addresses factors to be considered in the risk management process of modifications to anterior and posterior chamber IOLs in accordance with ISO 14971.[11] It also suggests methods of data analysis and interpretation that can be used to determine the need for a clinical investigation and its design.
Implants ophtalmiques — Lentilles intraoculaires — Directives relatives à l'évaluation de la nécessité d'investigation clinique pour les modifications de conception des lentilles intraoculaires
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TECHNICAL ISO/TR
REPORT 22979
Second edition
2017-05
Ophthalmic implants — Intraocular
lenses — Guidance on assessment of
the need for clinical investigation of
intraocular lens design modifications
Implants ophtalmiques — Lentilles intraoculaires — Directives
relatives à l’évaluation de la nécessité d’investigation clinique pour les
modifications de conception des lentilles intraoculaires
Reference number
ISO/TR 22979:2017(E)
©
ISO 2017
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ISO/TR 22979:2017(E)
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ISO/TR 22979:2017(E)
Contents Page
Foreword .iv
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Modifications to parent models . 1
4.1 General . 1
4.2 Modification levels . 2
4.2.1 General. 2
4.2.2 Level A modifications . . 2
4.2.3 Level B modifications . 2
4.2.4 Level C modifications . 2
4.2.5 Clinical investigation with multiple IOL models. 3
5 Considerations for the assignment of modification level . 3
5.1 General . 3
5.2 Risk assessment . 3
5.3 Special considerations . 3
5.3.1 Phakic lenses . 3
5.3.2 Anterior chamber lenses . 3
5.3.3 Posterior chamber lenses intended for implantation in the sulcus . 4
6 Modifications of optical design features . 4
6.1 Optical design changes . 4
6.2 Multifocal lenses (MIOL) . 4
6.3 Toric lenses (TIOL) . 4
6.4 Accommodating lenses (AIOL) . 4
7 Modifications to the mechanical design . 5
7.1 General . 5
7.2 Mechanical analysis . 5
8 Modifications to material . 5
8.1 Interchanging IOL materials . 5
8.2 New materials . 5
Annex A (informative) Examples of modifications to a parent IOL model .6
Annex B (informative) Mechanical data analysis.11
Bibliography .22
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ISO/TR 22979:2017(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
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For an explanation on the voluntary nature of standards, the meaning of ISO specific terms and
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URL: w w w . i s o .org/ iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 172, Optics and photonics, SC 7 Ophthalmic
optics and instruments.
This second edition cancels and replaces the first edition (ISO/TR 22979:2006), which has been
technically revised.
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TECHNICAL REPORT ISO/TR 22979:2017(E)
Ophthalmic implants — Intraocular lenses — Guidance
on assessment of the need for clinical investigation of
intraocular lens design modifications
1 Scope
This document provides guidance on the application of all parts of the ISO 11979 series of International
[1–9]
Standards for intraocular lenses (IOLs). It addresses factors to be considered in the risk management
[11]
process of modifications to anterior and posterior chamber IOLs in accordance with ISO 14971. It
also suggests methods of data analysis and interpretation that can be used to determine the need for a
clinical investigation and its design.
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 11979-1, Ophthalmic implants — Intraocular lenses — Part 1: Vocabulary
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 11979-1 and the following 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 http:// www .iso .org/ obp
NOTE The terms listed are related to Annex B.
3.1
open-loop IOL
IOL model which contains two loops, each loop having one end attached to the body of the IOL and the
other end free
3.2
closed-loop IOL
IOL model, which contains two loops, each loop having both ends attached to the body of the optic
3.3
hybrid open-loop/closed-loop IOL
IOL model which contains two loops, with one loop having one end attached to the body of the IOL and
the other end free, and the other loop having both ends attached to the body of the IOL
4 Modifications to parent models
4.1 General
IOLs, that are modifications of a parent IOL, have different requirements for clinical investigations
depending on the risk associated with the modifications and depending on their location in the eye.
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ISO/TR 22979:2017(E)
This document provides considerations for the risk assessment to determine the clinical investigation
effort that is needed based on the level of modification which is defined in 4.2.
[10]
ISO 13485 provides requirements for the design and development of medical devices, which are
applicable to intraocular lenses including modifications of existing models. The risk assessment and
design evaluation are part of the risk management in the design control process in accordance with
ISO 14971, and can be used as input for the clinical evaluation. ISO 14971 describes sources for data
and information for estimating risks. To determine and evaluate the hazards associated with the
modification of IOL models, the manufacturer can additionally use the following sources:
a) clinical data;
b) literature study of equivalent features of similar IOL models. The literature can be general published
and unpublished reports, proprietary evaluations and post-market surveillance reports;
c) physical model-eyes, laboratory bench testing or numerical/computational models, which have
been verified and validated for evaluation of optical and mechanical behaviour;
[12]
d) usability and human factor engineering data resulting from the application of IEC 62366-1 or
[13]
ANSI/AAMI HE75 such as the use of error risk analysis, formative and summative evaluation
results, including studies to evaluate surgical manipulation and delivery of the IOL in the eye.
Modifications to the delivery system are subject to the design control process in accordance with
ISO 13485 and factors that pertain to the interaction of IOL and delivery system, as described in
ISO 11979-3, and user interaction during surgery are to be considered in a risk assessment.
4.2 Modification levels
4.2.1 General
Design modifications to parent model IOLs are classified as Level A, B or C. The classification depends
on the safety and performance risks that are identified. Examples of risks associated with design
modifications are provided in Annex A.
4.2.2 Level A modifications
Level A modifications of a parent model are those for which all safety and performance questions can
be adequately addressed without clinical investigation. The modified model is essentially equivalent
to the parent model(s). All risks resulting from risk assessment to the modification are adequately
addressed by existing clinical evidence. The residual risk will have to be outweighed by the benefits.
4.2.3 Level B modifications
Level B modifications of a parent model are those that raise safety and/or performance risks that can
be adequately addressed with a limited clinical investigation of a justified number of subjects followed
up for a justified period.
NOTE Typically 100 subjects followed up for 4 months to 6 months. The statistical precision of a 100-subject
investigation to detect differences from the safety and performance end points (SPE) ratings is provided in
ISO 11979-7.
4.2.4 Level C modifications
Level C modifications are modifications that raise safety and/or performance risks that can only be
addressed with a full clinical investigation as defined in ISO 11979-7 and ISO 11979-10.
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ISO/TR 22979:2017(E)
4.2.5 Clinical investigation with multiple IOL models
More than one IOL model can be studied in the same investigation and with the same study end points
if supported by a risk assessment and provided these models are Level A modifications of one another.
If the intent is that data from the various models are to be pooled, a justification from the manufacturer
is required per study end point to demonstrate that the design differences between models will
affect neither investigation outcomes nor investigation execution nor interfere with the application of
statistically sound test design techniques such as randomization and masking.
5 Considerations for the assignment of modification level
5.1 General
The process of assignment of a modification level is illustrated in Figure A.1. A risk assessment of
the model modifications is performed, especially considering any safety and performance changes
due to the differential design aspects compared with the parent models. Multiple parent models can
be considered in the evaluation given the premise that the modifications are related to these parent
model(s).
The assigned modification level depends on the additional potential hazards or hazardous situations,
their probability of occurrence and the probability that they will lead to harm, as well as the severity of
the harm(s) compared with that of the parent model. For additional guidance, see ISO 14971.
Overall, the risk assessment would weigh the risk/performance impact and benefit to determine
modification Level A, B or C. Examples of potential Level A modifications to parent models are provided
in Annex A. A plurality of modifications may change the level assignment. If there is insufficient
data to assess the risk of plurality of modifications, as compared with parent IOLs, a suitable clinical
investigation should be performed.
5.2 Risk assessment
In the risk assessment, the hazards and hazardous situations that are related to the modification(s)
relative to the parent model will be considered. By assigning modification Level A, B or C, the clinical
performance relative to the parent model is addressed. Table A.5 includes examples of potential
hazards and harms that may be associated with the modification and that can be included in the risk
assessment. Table A.5 also includes references to test methods described in the ISO 11979 series, which
can be considered to assess the potential risks. The risk assessment addresses all changes made to the
product and includes changes of labelling, packaging and package inserts.
5.3 Special considerations
5.3.1 Phakic lenses
Phakic lenses require additional considerations in the risk assessment to determine the modification
level because of the proximity of other tissue compared with aphakic anterior and posterior chamber
lenses. The clinical requirements are outlined in ISO 11979-10.
5.3.2 Anterior chamber lenses
Additional hazards may arise from the potential direct IOL-tissue interaction, static or dynamic, which
needs to be evaluated including the risk of rotation, displacement, aqueous flow and corneal damage.
The clearance analysis described in ISO 11979-3 can be used to assess the clearance to the cornea.
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ISO/TR 22979:2017(E)
5.3.3 Posterior chamber lenses intended for implantation in the sulcus
Posterior chamber lenses implanted in the sulcus have more potential interaction with surrounding
tissue than lenses implanted in the capsular bag. Examples of potential tissue interaction effects are
pigment dispersion and changes to the ciliary body.
6 Modifications of optical design features
6.1 Optical design changes
Optical bench testing of imaging quality, as defined in ISO 11979-2, is performed and analysed to
compare the modified IOL model and parent IOL model(s).
Interchanging optics or combining two or more optical design concepts (spherical, aspheric, monofocal,
toric, multifocal and/or accommodative optics) may be considered Level A modifications if the optical
designs have been evaluated in parent IOL models. The risk assessment is conducted to evaluate any
new risk when interchanging optical designs and includes the following:
a) the potentially increased misalignment of the IOL optic (i.e. tilt, decentration and rotation) due to
the parent IOL body and haptic designs. The analysis includes comparison of clinical study reports
of centration and mechanical differences in IOL design;
b) evaluation of the potential for changes in the predictability and stability of post-operative refraction
and, if applicable, changes in the stability and magnitude of the accommodative amplitude at the
point of stabilization;
c) when combining two or more approved optical concepts, all clauses applicable to these concepts
and their interaction are considered.
Examples of Level A and B modifications are listed in Annex A.
6.2 Multifocal lenses (MIOL)
When the modification of the multifocal parent design is a change of the fundamental technology
creating the multiple dioptric powers, e.g. diffraction versus refraction, this modification is potentially
a Level B or Level C modification depending on the risk assessment. A change to a multifocal design
that can be verified and compared with a parent multifocal may be considered a Level A modification
if it does not increase the risk profile. However, if the modification increases the risk profile, for
example adding risks of visual disturbances, the change is potentially a Level B or Level C modification.
If the material of the modified model IOL is different from the material of the multifocal parent IOL
with respect to optical material characteristics, in particular refractive index and dispersion, this is
potentially a Level B or Level C modification.
6.3 Toric lenses (TIOL)
Refer to ISO 11979-7 and ISO 11979-10 for evaluation of modifications of the mechanical design
platform, in particular with respect to rotational stability. Changes in mechanical design affecting the
axial and rotational stability are potentially Level B or Level C modifications.
6.4 Accommodating lenses (AIOL)
Any change in optic design (single and multi-optic lenses) or haptic design is reviewed for potential
impact on the accommodative power of the IOL and optical performance, as defined in ISO 11979-2
and ISO 11979-7, of the IOL at far power configuration and configurations associated with the designed
range of accommodation in 0,5 D increments. The risks associated with interaction with surrounding
tissue due to the accommodative action need to be evaluated to classify the modification level of a
model change. Any characteristic of the parent lens optics and material that may have an impact on the
accommodative performance of the approved AIOL is considered in the risk assessment.
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ISO/TR 22979:2017(E)
7 Modifications to the mechanical design
7.1 General
Evaluation of modifications of the mechanical design considers the impact of the modification on the
mechanical interaction with ocular tissue, consequences for the surgical handling, interaction with
delivery systems, refractive outcomes, visual outcomes including visual disturbances and any potential
biological response. Examples of modifications to the mechanical design and the biological response are:
a) changes in the vault height, sagitta, axial displacement under compression may affect the refraction
stability and axial position of the IOL;
b) changes in the compression force and contact angle may damage the capsular bag and the zonular
fibres with the effect of tilt and decentration, and may change the shape of the capsular bag with
the consequences of capsular striae and optical disturbances and posterior capsule opacification.
Any modification to the mechanical design of anterior chamber IOLs is considered a Level B modification.
7.2 Mechanical analysis
The data from the compression force, compression force decay and angle of contact, tested in accordance
with ISO 11979-3, is used to assess the difference in mechanical behaviour between the modified IOL
model and potential parent IOL model(s). The methods for assessment of the differences in compression
force (decay) and angle of contact between a modified IOL model and one or more parent IOL models are
described in Annex B. These methods can be used to determine whether a modified posterior chamber
IOL is a Level A modification of one or more parent IOL models included in the analysis.
8 Modifications to material
8.1 Interchanging IOL materials
Interchanging IOL materials may be considered Level A modifications if the materials and designs have
each been evaluated in a parent IOL. The risk assessment is conducted to evaluate any new risk when
interchanging IOL materials in particular when interchanging material from one-piece, three-piece or
plate lens design.
8.2 New materials
If the material of the modified IOL model is different from the material of the parent IOL model(s), a
clinical investigation is considered depending on the risk assessment. If the change in material is a
change in polymeric structure, and there is no experience for use of this polymer in the eye, typically a
full clinical investigation is performed.
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ISO/TR 22979:2017(E)
Annex A
(informative)
Examples of modifications to a parent IOL model
A.1 General
Modifications to an IOL that has undergone a clinical investigation can be classified in one of three
categories depending on the level of modification: Level A, Level B or Level C. This annex provides
typical examples of potential Level A and B modifications with additional criteria where applicable.
The examples in this annex do not apply to phakic IOLs or iris fixation lenses.
The applicability column indicates the type of IOL that the modification is applicable to:
a) P designates non-plate posterior chamber IOLs, for in the capsular bag implantation;
b) A designates anterior chamber IOLs;
c) S designates IOLs for sulcus implantation;
d) PL designates posterior chamber IOLs made from flexible materials that are of a one-piece plate
design.
A.2 Potential Level A modification examples
Examples of potential Level A modifications are listed in Tables A.1 and A.2. If the risk assessment
brings forward new risks or results in increased risks from individual or multiple changes over the
parent models(s), the classification of modification level should be reconsidered.
Table A.1 — Change in optic design
Modification Applicability
Change in dioptric power range
P/A/PL/S
Whereby any power of the IOL model is in the range that the manufacturer
makes available.
Change of dioptric power increments
Inclusion or deletion of power steps inside the range of the power steps of the
P/A/PL/S
parent model e.g. the current power steps are 5,0 D, 6,0 D, 7,0 D, etc., are modified
to 5,0 D, 5,5 D, 6,0 D, 6,5 D, 7,0 D, etc.
Change in cylinder power range (TIOL)
P/A/PL/S
Where any cylinder power ≥1,0 D of the IOL model is within the range of
manufacturer’s available cylinder power range.
Change in addition power (MIOL)
Whereby any addition power of the IOL is within the range of manufacturer’s
P/A/PL/S
available addition powers, that the manufacturer makes available for parent
models with identical optical principles to accomplish the multifocality and the
same optical specifications.
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Table A.1 (continued)
Modification Applicability
Change to axis indicator marks of TIOL
P/A/PL/S
Provided that the markings remain compatible with a vision evaluation system.
Change in spherical aberration level
P/A/PL/S
Whereby the spherical aberration remains within the range of that the
manufacturer makes available.
The application of a multifocal optic design of one parent model to the optic
of another parent model
P/A/PL/S
Whereby optical design, optical specifications, material and technology to
accomplish the multifocality of the IOL are identical to the parent model(s).
Table A.2 — Change in mechanical design
Mechanical
Modification Applicability
data analysis
Changes in haptic features
P/S No
Changes such as the addition of notches or the addition of eyelets or rounded
ends to loops.
Change in overall diameter
P/S Yes
Changes within the previously clinically investigated overall diameter range.
Change in haptic thickness or width P/S Yes
Change in haptic configuration (shape) P/S Yes
Change in optic or body size
Changes in body circumference design or optic size if the length is not less than
P/S No
5,0 mm along any meridian (e.g. going from circular to an ovoid body) and not
greater then 7,5 mm along any meridian.
Change of clear optic
P/S No
Any obstruction that interferes with the performance of the optic, provided
that the clear optic diameter is greater than 4,25 mm.
A.3 Potential Level B modification examples
Examples of potential Level B modifications are listed in Tables A.3 and A.4. If the risk assessment
brings forward new risks, the classification of modification level should be reconsidered.
Table A.3 — Change in optic design
Modification Applicability
Change in addition power outside the range of addition power made
available by the manufacturer through the MIOL parent lenses
P/A/PL/S
Whereby any addition power of the IOL follows the identical optical
principles as the parent model(s) to accomplish the multifocality and the
same optical specifications as the parent model(s).
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Table A.4 — Change in mechanical design
Mechanical
Modification Applicability
data analysis
Change in haptic configuration
Including change in overall diameter, haptic thickness or width, when not
meeting the Level A criteria mechanically.
P Yes
If the change in haptic configuration of the modified lens appears to have the
potential to cause different or greatly increased safety concerns as compared
with the parent model(s), it is considered to be a Level C modification.
Change in haptic configuration
Includ
...
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