EN 13503-7:2001

SLOVENSKI STANDARD
01-maj-2002
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Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations (ISO 11979-
7:2001, modified)
Ophthalmische Implantate - Intraokularlinsen - Teil 7: Klinische Prüfungen (ISO 11979-
7:2001, modifiziert)
Implants ophtalmiques - Lentilles intraoculaires - Partie 7: Investigations cliniques (ISO
11979-7:2001, modifié)
Ta slovenski standard je istoveten z: EN 13503-7:2001
ICS:
11.040.70 Oftalmološka oprema Ophthalmic equipment
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EUROPEAN STANDARD
EN 13503-7
NORME EUROPÉENNE
EUROPÄISCHE NORM
December 2001
ICS 11.040.70
English version
Ophthalmic implants - Intraocular lenses - Part 7: Clinical
investigations (ISO 11979-7:2001, modified)
Implants ophtalmiques - Lentilles intraoculaires - Partie 7: Ophthalmische Implantate - Intraokularlinsen - Teil 7:
Investigations cliniques (ISO 11979-7:2001, modifié) Klinische Prüfungen (ISO 11979-7:2001, modifiziert)
This European Standard was approved by CEN on 11 November 2001.
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 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 Management Centre has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece,
Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2001 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN 13503-7:2001 E
worldwide for CEN national Members.

Contents
page
Foreword .3
Introduction .5
1 Scope .5
2 Normative references.5
3 Terms and definitions.6
4 General requirements.6
5 Methodology.7
5.1 General.7
5.2 Requirements before commencement of the clinical investigation.7
5.3 Clinical investigation plan.7
5.4 Role of sponsor .8
5.5 Role of monitor.8
5.6 Role of clinical investigator.8
6 Presentation of results.8
Annex A (normative) Selected definitions .9
Annex B (informative)  Examples of modifications of a parent IOL model.10
Annex C (informative) Elements of an IOL clinical protocol .15
Annex D (informative) Post-operative adverse event and visual acuity rates associated with historical IOL
control populations .23
Bibliography .29
Annex ZA (informative) A-Deviations .28
Bibliography .29
Foreword
This European Standard has been prepared by 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 June 2002, and conflicting national standards shall be withdrawn at the latest by
June 2002.
European Standard EN 13503-7 was developed by CEN/TC 170, Ophthalmic optics, in cooperation with
ISO/TC 172/SC 7, Ophthalmic optics and instruments, and is published in several 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
It always was and still is the intention of the Technical Committees CEN/TC 170 and ISO/TC 172/SC 7 to prepare
identical ISO and CEN Standards on intraocular lenses. However, during the preparation of part 7 of the above
intraocular lenses standards series, problems were encountered with normative references to the existing
ISO 14155 and EN 540 horizontal standards on clinical investigation of medical devices, those being similar but not
identical.
ISO and CEN principles concerning normative references made it impossible to continue the preparation of
identical European and International Standards on the clinical investigation of intraocular lenses. As a result, two
different standards series, ISO 11979 and EN 13503 had to be prepared.
It is the intention of CEN/TC 170 and ISO/TC 172/SC 7 to revise these standards with the goal to end up with
identical ones as soon as identical ISO and CEN horizontal standards become available.
EN 13503 is the modified ISO 11979. The main difference between both series of standards is that ISO 11979 is
based on the reference to ISO 14155 Clinical investigation of medical devices while EN 13503 is based on the
reference to EN 540 Clinical investigation of medical devices for human subjects.
Compared with ISO 11979-7 the present EN 13503-7 does not contain an informative annex detailing modifications
of IOL parent models.
Modifications of ISO 11979 are indicated as follows:

text which has been deleted is striked out;

text which has been changed or added is underlined.
Cross references to ISO 11979-7 are given where possible.
This Part 7 of EN 13503 contains one normative annex A and three informative annexes C, D and ZA.
According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following
countries are bound to implement this European Standard: Austria, Belgium, Czech Republic, Denmark, Finland,
France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden,
Switzerland and the United Kingdom.
Endorsement notice
The text of the International Standard ISO 11979-7:2001 was approved by CEN as a European Standard with
agreed common modifications as given in the foreword and indicated in the text by strike-out and underlining.
NOTE A-deviations are given in annex ZA (informative).
Introduction
This part of EN 13503 ISO 11979 provides fundamental requirements of a general nature for intraocular lenses. It
refers to other standards applicable to intraocular lenses for specific methods and requirements.
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 this part of EN 13503 ISO 11979, 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.
1 Scope
This part of EN 13503 ISO 11979 specifies particular requirements for clinical investigation protocols for posterior
and anterior chamber monofocal intraocular lenses (IOLs) for the correction of aphakia.
NOTE Any other type of IOL not directly covered by EN 13503 ISO 11979 and any IOL for which the sponsor wishes to
investigate claims in addition to those defined in EN 13503 ISO 11979 may be clinically evaluated by reference to EN 540
ISO 14155.
2 Normative references
This European Standard incorporates by dated or undated reference, provisions from other publications. These
normative references are cited at the appropriate places in the text and the publications are listed hereafter. For
dated references, subsequent amendments to or revisions of any of these publications apply to this European
Standard only when incorporated in it by amendment or revision. For undated references the latest edition of the
publication referred to applies (including amendments).
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.
EN 540:1993, Clinical investigation of medical devices for human subjects.ISO 14155:1996, Clinical investigation of
medical devices.
EN ISO 11979-1:1999, Ophthalmic implants - Intraocular lenses - Part 1: Vocabulary (ISO 11979-1:1999).
EN 13503-3:2000, Ophthalmic implants – Intraocular lenses – Part 3: Mechanical properties and test methods
(ISO 11979-3:1999, modified). ISO 11979-3, Ophthalmic implants - Intraocular lenses - Part 3: Mechanical
properties and test methods
3 Terms and definitions
For the purposes of this part of EN 13503 ISO 11979, the terms and definitions given in EN 540 ISO 14155 and
EN ISO 11979-1 apply, together with the following.
For the conveniance of users of this part of EN 13503 ISO 11979, some definitions from EN ISO 11979-1 are
reprodcued in annex A. Terms relating to the design of IOLs are given in EN 13503-3 ISO 11979-3.
3.1
serious adverse event
in addition to the definition in EN 540, an event which is potentially sight threatening is also considered a serious
adverse event
NOTE 1    The definition for serious adverse event given in the ICH Harmonized Tripartite Guideline for Good Clinical Practices
also applies (see reference [1] in the bibliography).
NOTE 2 Examples of potentially sight-threatening adverse events are included in Tables D.1 and D.2.
4 General requirements
4  Ethical considerations
For clinical investigations of medical devices for human subjects, the requirements of ISO 14155 apply.
5  Requirements
5.1    General requirements
The requirements given in 5.1 to 5.7 of ISO 14155:1996 shall apply.
5.2    Additional requirements
Clause 4 of EN 540:1993 shall apply, together with the following additional requirements.
4.5    Addition (see 5.2.1 of ISO 11979-7:2001):
Addition:
Clinical investigators shall file adverse event reports of all serious adverse events with the sponsor immediately
after learning of their occurrence. Other adverse events shall be reported on the case report forms.
The sponsor and the sponsor's investigators shall evaluate the rates of adverse events and visual acuity (VA) for
the IOLs under clinical investigation on a continuing basis. If poor results at any investigational site are determined
by clinical judgement to be potentially device related, consideration shall be given to termination of further
enrolment in the clinical investigation.
5.2.1   In addition to the requirements given in 5.5 of ISO 14155:1996, the sponsor and the sponsor's investigators
shall evaluate the rates of adverse events and visual acuity (VA) for the IOLs under clinical investigation on a
continuing basis.
NOTE The published national study of cataract surgery in the United Kingdom may provide useful guidance on clinical
performance of IOLs at periods corresponding with the early post-operative case report forms (see references [2] and [3]).
4.6    Addition (see 5.2.2 of ISO 11979-7:2001):
Addition:
The safety and effectiveness of an IOL model shall be established through either:
In addition to the requirements given in 5.6 of ISO 14155:1996, the safety and effectiveness of an IOL
5.2.2
model shall be established through either:

a clinical investigation conducted in accordance with this part of EN 13503 ISO 11979; or

a comparison of the model characteristics that establish the model as a minor modification of a parent model
for which the safety and effectiveness has been established through clinical investigation in accordance with
this part of EN 13503 ISO 11979.
NOTE     Annex B provides guidance in determining if a modification is minor by providing examples of modifications that
have historically been considered minor.
For the IOL intended for correction of aphakia in a general adult population, a clinical investigation shall either be
developed using the protocol elements provided in annex C or a sponsor shall develop an equivalent protocol that
shall have a similar statistical power to detect differences in adverse event and visual acuity rates between the test
population and a concurrent control population. Subjects implanted with a parent IOL that has met the require-
ments of all parts of EN 13503 and EN ISO 11979 may be used as a control population.
In the case of IOLs designed for either chamber, a separate clinical investigation shall be performed to assess the
clinical performance of the IOL in each chamber.
5.2.3  In addition to the requirements given in 5.7 of ISO 14155:1996, all subjects in a clinical investigation shall
be monitored for the duration of the investigation. The clinical investigation shall be considered completed when all
subjects that have been enrolled in the investigation, including those whose IOL was removed or replaced, have
reached the final reporting period.
5 6 Methodology
5.1 General
The requirements given in 5.1 of EN 540:1993 shall apply.
6.1 Documentation
The requirements given in 6.1 of ISO 14155: 1996 shall apply.
5.2 Requirements before commencement of the clinical investigation
The requirements given in 5.2 of EN 540:1993 shall apply.
6.2 Access to information
The requirements given in 6.2 of ISO 14155:1996 shall apply.
6.3 Additional health care
The requirements given in 6.3 of ISO 14155: 1996 shall apply.
5.3 6.4 Clinical investigation plan
5.3.1 6.4.1 General requirements
The requirements given in 5.3 of EN 540:1993 6.4 of ISO 14155:1996 shall apply.
5.3.2 6.4.2 Additional requirements
The following additional requirements shall apply.
The investigational lens shall only be implanted in a single eye of each subject.
5.3.5 Addition (see 5.2.3 of ISO 11979-7:2000):
All subjects in a clinical investigation shall be monitored for the duration of the investigation. The clinical investiga-
tion shall be considered completed when all subjects that have been enrolled in the investigation have completed
the final reporting period of the investigation.
5.3.6 Addition:
The data from all subjects shall be reported including the data from subjects whose IOL was removed or replaced.
The investigational lens shall only be implanted in a single eye of each subject.
5.3.7 Addition:
The clinical performance of the IOL in terms of visual acuity and adverse event rates shall be evaluated.
5.3.11 Addition:
At least the minimum sample size required by the study shall be included in the clinical investigation for each
reporting period. The sponsor shall ensure a sufficient number of subjects in the clinical investigation so that the
minimum number required by the investigation at each reporting period is reached. Each subject has to be
monitored for the duration of the investigation. The investigation is not completed until the last subject has reached
the final reporting period.
NOTE Examples of pre-operative, operative and post-operative case report forms are included in annex C.
5.4 6.5 Role of sponsor
The requirements given in 5.4 of EN 540:1993 6.5 of ISO 14155:1996 shall apply.
5.5 6.6 Role of monitor
The requirements given in 5.5 of EN 540:1993 6.6 of ISO 14155:1996 shall apply.
5.6 6.7 Role of clinical investigator
6.7.1    General requirements
The requirements given in 5.6 of EN 540:1993 6.7 of ISO 14155:1996 shall apply.
6.7.2    Additional requirements
The following additional requirements shall apply.
Clinical investigators shall file adverse event reports of serious adverse events with the sponsor immediately after
learning of their occurrence. Other adverse events shall be reported on the case report forms.
6 7 Presentation of results
The results shall be presented as specified in clause 6 of EN 540:1993 clause 7 of ISO 14155:1996.
Annex A
(normative)
Selected definitions
To facilitate the understanding of this part of EN 13503 ISO 11979, selected definitions are reproduced in this
annex. In the case of discrepancy, the definitions of EN ISO 11979-1 take precedence over those given here.
A.1
best-case subject
subject with no pre-operative pathology
A.2
cumulative adverse events
total number of adverse events which have occurred at any time up to a specified time point post-operatively
A.3
intraocular lens model
identification by which the features of an intraocular lens, including those of its body and its loops, and the
material(s) used in its construction, have been fully specified
NOTE 1 Examples of body features are body diameter, optic diameter, optic shape factor; examples of loop features are
configuration, calibre, angulation.
NOTE 2 Any significant change in the specification of the materials (including their formulation or synthesis procedures)
results in it being considered a new model.
A.4
level A modification of a parent intraocular lens model
modifications of a parent model which are considered minor and are not expected to result in any safety hazards or
loss in effectiveness when compared to the parent model
A.5
level B modification of a parent intraocular lens model
modifications of a parent model which are greater than level A modifications
NOTE Level B modifications may present a safety hazard or loss of effectiveness concerns which result in a new model that
is significantly different from the parent model.
A.6
lost to follow-up
describing a subject for whom the final post-operative case report form is overdue and who cannot be contacted
despite extensive written and telephone follow-ups to determine the final clinical outcome
NOTE This category does not include subjects who have died.
A.7
optic shape factor
term describing the curvatures of the refracting surfaces of the optic (e.g., plano-convex, bi-convex)
A.8
parent intraocular lens model
intraocular lens model that a sponsor has qualified based on a clinical investigation of at least 100 subjects and
which has met the requirements of all parts of ISO 11979
A.9
persistent adverse event
adverse event which is present at the conclusion of a clinical investigation
Annex B
(informative)
Examples of modifications of a parent IOL model
B.1 Design/material modifications of an IOL model
B.1.1 General
Modifications to an IOL that has previously undergone a clinical investigation by the sponsor have different
requirements depending on the magnitude of the modifications. Two levels of modifications have historically been
associated with a parent IOL: Level A and Level B. Examples of Level A and Level B modifications are given in B.2.
B.1.2 Level A
Level A modifications of a parent model in almost all cases do not require a clinical investigation. A case where a
clinical investigation of a Level A modification of a parent model should be performed is if the modified model poses
additional clinical questions which cannot be adequately addressed by preclinical testing, such as potential tissue
damage associated with a modification in implantation technique necessitated by the modified design.
A Level A modification of a parent IOL usually does not itself become a parent IOL for subsequent modifications.
The only case where it may is described below.
If a model is still under clinical investigation, Level A modified versions of that model may be introduced into the
clinical investigation of the model and the data from the original investigational model and the Level A modified
model(s) may be combined, except in the case of those Level A changes that involve material substitutions from
parent models (i.e., modifications described in B.2.2.12).
A Level A modified IOL which was added to the clinical investigation of the investigational model may only itself be
considered a parent IOL at the conclusion of the study if that Level A modified model was investigated in a
minimum of 100 subjects at each case report form, it met the requirements of all parts of ISO 11979, and if the
results of a clinical analysis indicate that there is no significant difference between its clinical performance and the
clinical performance of the other investigational models in the clinical investigation.
B.1.3 Level B
The clinical investigation of new IOLs that are Level B modifications of a parent model should include a minimum of
100 subjects monitored up to case report form 4 (case report forms are defined in Annex C).
The minimum number of case report forms for each visit should be 100. The sponsor should anticipate needing to
enrol 125 subjects to take into account the subjects that are lost or die in the course of the clinical investigation.
The sample size required for the Level B clinical investigation is the minimum number necessary to detect a
clinically significant difference in adverse event and visually acuity rates between the IOL under investigation and
the rates associated with the historical control population. If the sponsor chooses to compare the performance of
their IOL to a concurrently run control population, the sponsor should enrol sufficient subjects such that the ability of
the study to detect changes in visual acuity and adverse event rates are equivalent to the ability associated with the
study which compares the IOL to the historical control population.
The lost to follow-up subjects in the Level B investigation should be less than 10 %. Each investigator should have
a minimum of 20 subjects, and no more than 25 % of the subjects in the investigation. The Level B clinical investi-
gation should be considered completed when all subjects that have been enrolled in the investigation have reached
case report form 4.
A Level B modified IOL may only itself be considered a parent IOL at the conclusion of the study if it was
investigated in a minimum of 100 subjects at each case report form (therefore the model could not have been
combined with Level A modifications of itself in the clinical study), and it met the requirements of all parts of
ISO 11979.
B.2 Examples of IOL modifications
B.2.1 General
Modifications to an IOL that has undergone a clinical investigation can be classified in one of two categories
depending on the level of modification: Level A or Level B. The criteria that are to be used to determine what level
of modification has occurred to the parent model are described below.
The applicability column indicates the type of IOL that the modification is allowed with:
P   designates polymethylmethacrylate (PMMA) posterior chamber IOLs
A   designates PMMA anterior chamber IOLs
SP  designates posterior chamber IOLs made from soft materials that are of a one-piece, plate design (no loops)
SS  designates multi-piece, posterior chamber IOLs with optics made of soft materials and loops made from standard material
(PMMA, polypropylene, or polyimide)
SN  designates multi-piece, posterior chamber IOLs with optics made of soft materials and loops made from non-standard
materials
A modified model may have various combinations of the modifications listed below as long as all of the required
criteria are met (e.g., the modified model may have a larger optic, with a slightly modified loop configuration and a
larger overall diameter than the parent model). Modification B.2.2.12 differs from the other modifications in that it
involves material/design substitutions of parent models only.
B.2.2 Level A modifications (see B.2.1 for P, A etc.)
B.2.2.1     Mirror-image version of a model
Applicability is P/A/SP/SS/SN
B.2.2.2     Change in overall diameter
Applicability in the case of the addition of a size specific to patients with a certain anterior chamber width range is
A.
B.2.2.3     Changes in loop features
Applicability in the case of changes such as the addition of notches, or the addition of small loops or rounded ends
to loops is P/A/SS/SN.
B.2.2.4     Change in loop angulation
Applicability in the case of a change from planar to a design with the body angulated posterior to loops resulting in
an increase in the sagitta value up to a maximum of 1,6 mm for the 20 D version of the model is P/SS/SN.
B.2.2.5     Change in loop configuration, in loop thickness or width (calibre)
B.2.2.5.1   General
Applicability is P/SS/SN.
To determine if these changes result in modified lenses, which are Level A modifications of the parent lenses, an
analysis of the change in mechanical properties that has occurred as a result of the modification is required.
The sponsor should be aware that loop modifications of a model that have satisfied the requirements of this part of
ISO 11979 should not be considered Level A modifications (even if the results of the required mechanical testing
qualify them as such) if the modified model poses additional clinical questions that cannot be adequately
addressed by preclinical testing (such as potential tissue damage associated with a modification in implantation
technique necessitated by the new design).
Two methods of comparing the mechanical properties of a parent model and a modified model are given in this part
of ISO 11979 and are described below. A sponsor may use either method. If the sponsor finds that a model is not a
Level A with one of the methods, he should determine whether it might be a Level A by the other method before
beginning a clinical evaluation of that modified model.
NOTE     A discussion of the methods and data analysis to be used for the testing listed below is contained in ISO 11979-3.
B.2.2.5.2   Comparison to a single parent model
Applicability: P/SS/SN
For comparisons between a modified model and an investigational model which is currently undergoing a clinical
investigation, the sponsor should demonstrate that the mechanical properties of the modified lens are not
significantly different from the mechanical properties of the investigational model under study.
For comparisons between a modified model and a single parent model, the sponsor should demonstrate that the
mechanical properties of the modified lens are not significantly different from the mechanical properties of the
parent model.
NOTE     A detailed description with examples showing how to apply this method is given in ISO 11979-3.
B.2.2.5.3   Comparison to multiple parent models
Applicability: P/SS/SN
For comparisons between a modified model and multiple parent models, the sponsor should demonstrate that the
mechanical properties of the modified lens are not significantly different from the range of characteristics defined by
the parent models.
NOTE     A detailed description with examples showing how to apply this method is given in ISO 11979-3.
B.2.2.6     Change in the dioptric power range
Applicability: P/A/SP/SS/SN
There is no limit to the power range that the sponsor makes available for these types of IOLs, provided each power
within the range that a sponsor makes available for a model meets the minimum optical quality level required in
ISO 11979-2.
Sponsors should be advised that for certain combinations of optic shape factor and material, certain powers may
not meet that level because of the affects of spherical aberrations. In such cases, the powers made available have
to be restricted to those meeting the requirements of ISO 11979-2.
B.2.2.7     Change in optic or body size and addition of tabs to the periphery of the optic
Applicability: P/SP/SS/SN
Changes in body circumference design or optic size are allowed if the length is not less than 5,0 mm along any
meridian (e.g., going from a circular to an ovoid body), and not greater than 7,5 mm along any meridian.
B.2.2.8     Additions, deletions, or moving of positioning holes
Applicability: P/A/SP/SS/SN
Positioning holes, or any other obstruction that interferes with the performance of the optic, should be placed no
less than 2,25 mm from the centre of the optic to minimize the possibility of glare or other visual disturbances that
may result from these structures.
B.2.2.9     Addition of a ridge to the posterior surface of the body
Applicability: P
Addition of a ridge to the posterior body is permissible, if the ridge design has been qualified by being a part of a
model that has been the subject of a clinical investigation and has satisfied the requirements of this part of
ISO 11979, and if the edge of the ridge is not any closer than 2,25 mm to the centre of the optic.
B.2.2.10    Multiple designs in a single clinical investigation
Applicability: P/SS/SN
A single material may be investigated with more than one design, if all of the designs in the clinical investigation
have been previously qualified by being associated with parent models. Therefore, the only variable being
investigated is the new material. The only restriction is that the mechanical properties of the parent design should
not be significantly altered (i.e., not greater than those allowed as a Level A modification) by being manufactured
from the new material.
B.2.2.11    Multiple materials in a single clinical investigation
Applicability (see note to C.2.1): P/SS/SN
A single design may be investigated with more than one loop, body, or single-piece material if all of the materials in
the clinical investigation have been previously qualified by being associated with parent models. Therefore, the only
variable being investigated is the new design. The only restriction is that if more than one material is used for the
loops, all of the models should be Level A modifications of each other in terms of mechanical properties (see
B.2.1.5).
B.2.2.12    Interchanging IOL materials and designs
Applicability: P/SS/SN
Materials and designs from parent models may be interchanged if the use of the material with the new (for that
material) design does not result in any significant change in the mechanical properties of the original parent design.
B.2.3 Level B modifications
B.2.3.1     Change in overall diameter
Applicability: P/SS/SN
Change in overall diameter that results in a lens modification that displays mechanical behavior that does not meet
the requirements for a minor modification in B.2.1.5 when compared to a single parent model or when compared to
the range of acceptable mechanical behavior of parent models.
B.2.3.2     Change in loop configuration
Applicability: P/SS/SN
Change in loop configuration that results in a lens modification that displays mechanical behavior that does not
meet the requirements in B.2.1.5 when compared to a single parent model or when compared to the range of
acceptable mechanical behavior of parent models. If the change in loop configuration of the modified lens (e.g., a
single piece disc lens) appears to have the potential to cause different or greatly increased safety concerns as
compared to the parent model(s), the new model should undergo the 300 subject clinical investigation required for
new models.
B.2.3.3     Change in loop material or calibre
Applicability: P/SS/SN
Change in loop material (to another material that has been qualified by being part of a parent model) or calibre that
results in a lens modification that does not meet the requirements in B.2.2.5 when compared to a single parent
model or when compared to the range of acceptable mechanical behavior of parent models.
B.2.3.4     Change to new loop material for sponsor
Applicability: P/SS/SN
Change in loop material to a material that is new to the sponsor, but is a material whose long-term safety as a loop
material can be supported by the ophthalmic literature. The articles must provide the identity of the material used,
and the sponsor must be using the identical material.
B.2.3.5     Change in body material
Applicability: P/SS/SN
Change in body material to a material that is new to the sponsor, but is a material whose long-term safety as an
body material can be supported by the ophthalmic literature. The articles must provide the identity of the material
used, and the sponsor must be using the identical material.
B.2.3.6     Change in body or optic diameter
Applicability: P/SS/SN
Change in body or optic diameter outside of the range from 5,0 mm to 7,5 mm. The sponsor should be aware that
the evaluations of models that incorporate optics less than 5,0 mm in diameter should include clinical testing to
evaluate the effects of glare on the subject's visual acuity that may result from the small optic.
B.2.3.7     Initial addition of a model with a ridge
Applicability: P
Initial addition of a model with a ridge on the posterior surface of the body.
Annex C
(informative)
Elements of an IOL clinical protocol
C.1 IOL clinical protocol elements
C.1.1 General
The following are important elements of a clinical protocol which will assist the sponsor in collecting sufficient,
relevant and appropriate data to determine the safety and effectiveness of IOLs which are within the scope of this
part of EN 13503 ISO 11979. These elements were derived from the historical data on the long clinical experience
associated with these types of IOLs.
C.1.2 Control population
The clinical results of a historical control population are provided in annex D. The clinical performance of the IOL
under investigation may either be compared to these data or to the results of a concurrently run control population
using an appropriate control.
C.1.3 Number of subjects
The clinical investigation should include a minimum of 300 subjects when the performance of the IOL will be
compared to the performance of the historical control population. The comparison of the performance of the IOL to
an appropriate, concurrently studied control population should require the sponsor to enrol sufficient subjects such
that the ability of the study to detect changes in visual acuity and adverse event rates is equivalent to the ability
associated with the 300 subject study which compares the IOL performance to the performance of the historical
control population. The sponsor should be aware that any additional claims beyond the safety and effectiveness of
the IOL will require the sponsor to calculate an appropriate sample size in all cases.
To take into account the subjects that are lost during the course of the clinical investigation, the sponsor should
anticipate needing to enrol about:

390 subjects in the one-year investigation;

500 subjects in the three-year investigation.
The sponsor should further refrain from enrolling significantly larger numbers of subjects than are listed above to
minimize the number of subjects exposed to the risks associated with the implantation of an IOL model which has
not yet been determined to be safe and effective.
To assist in achieving a balance in the number of subjects from each investigator, the sponsor's clinical protocol
should require that each investigator have a minimum of 20 subjects, and no more than 25 % of the subjects in the
investigation.
To minimize the uncertainty in the data, the lost to follow-up subjects in the three-year investigation should be less
than 30 % and the lost to follow-up in one-year investigation should be less than 10 %.
C.1.4 Duration of the clinical investigation
Extensive clinical experience indicates that the following study durations are necessary to make an adequate
assessment of the adverse event rates associated with the following types of IOLs:

one year (case report form 5): for all posterior chamber IOLs;

three years (case report form 7): for all anterior chamber IOLs.
The above is relevant whether the IOLs are surface modified or not by a coating or by chemical treatment designed
to alter the surface chemistry to enhance the biocompatibility of the IOL.
To minimize the risks associated with the clinical investigation of a new IOL, the clinical investigation of a new IOL
model should consist of two phases:

Phase 1: The first phase of the clinical investigation consists of the implantation of the IOL model in no more
than 100 subjects. After at least 50 of those subjects have reached case report form 4, their data are clinically
evaluated by the sponsor and the investigator. If the IOL model's performance in these first 50 subjects is
acceptable, the sponsor may begin the next phase of the investigation.

Phase 2: The second phase of the clinical investigation consists of the implantation of the remainder of the
subjects necessary for the clinical investigation.
C.1.5 Reporting periods
As a minimum, the clinical data for the subjects should include the post-operative case report forms up to case
report form 5 for the one-year clinical investigation. These forms are defined below:

Case Report Form 0: Pre-operative/Operative reporting;

Case Report Form 1: Post-operative reporting 1 or 2 days post-operatively;

Case Report Form 2: Post-operative reporting 7 to 14 days post-operatively;

Case Report Form 3: Post-operative reporting 30 to 60 days post-operatively;

Case Report Form 4: Post-operative reporting 120 to 180 days post-operatively;

Case Report Form 5: Post-operative reporting 330 to 420 days post-operatively.
As a minimum, the three-year clinical investigations should include all the case report forms listed above and both
case report forms defined below:

Case Report Form 6: Post-operative reporting 630 to 780 days post-operatively;

Case Report Form 7: Post-operative reporting 990 to 1140 days post-operatively.
Clinical evaluations during these reporting periods are necessary to capture the data associated with the potential
adverse events of the types of IOLs which are within the scope of EN 13503 ISO 11979.
Unscheduled visits and the procedures to capture adverse events that may occur between case report forms
should be addressed in the clinical investigation plan.
For the one-year and three-year clinical investigations, the minimum number of case report forms for each reporting
period should be 300.
C.2 Additional clinical guidance
C.2.1 General
Additional clinical guidance which will assist the sponsor in designing their IOL clinical investigation protocol and in
analyzing the data from that investigation is provided below.
C.2.2 Standardization of the clinical evaluation
The sponsor should ensure to the extent possible that the criteria used by all investigators for evaluation of adverse
events, and the parameters associated with the visual acuity evaluation (e.g., chart design, light levels, uniformity of
chart illumination, chart reflectivity, minimization of glare, test distance, general methodology) are sufficiently similar
to allow for the combining of data from the investigators.
If the sponsors determine that it is necessary to correlate the optotypes used in their clinical investigation to a
standard optotype, they should use the method described in EN ISO 8597 (see reference [3] in the Bibliography).
C.2.3 Guidance on data analysis
The sponsors should consider evaluating the clinical data in terms of the following to look for trends which may
suggest a problem exists or does not exist with the lens design, which may not be apparent from an overall
analysis of the adverse event and visual acuity (VA) rates:

VA by age;

best-case VA;

VA by adverse event;

VA by pre-operative ocular pathology;

patient-by-patient analysis of reasons why patient failed to achieve 0,5 (6/12; 20/40) VA;

rates of cumulative adverse events by age;

rates of persistent adverse events by age;

rates of other adverse events;

VA by investigator;

adverse event by investigator.
This clinical data evaluati
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