SIST EN ISO 11980:2013

SLOVENSKI STANDARD
SIST EN ISO 11980:2013
01-februar-2013
1DGRPHãþD
SIST EN ISO 11980:2010
2þHVQDRSWLND.RQWDNWQHOHþHLQL]GHONL]DY]GUåHYDQMHNRQWDNWQLKOHþ1DYRGLOR
]DNOLQLþQHUD]LVNDYH,62
Ophthalmic optics - Contact lenses and contact lens care products - Guidance for clinical
investigations (ISO 11980:2012)
Optique ophtalmique - Lentilles de contact et produits d'entretien pour lentilles de contact
- Directives pour les investigations cliniques (ISO 11980:2012)
Ta slovenski standard je istoveten z: EN ISO 11980:2012
ICS:
11.040.70 Oftalmološka oprema Ophthalmic equipment
SIST EN ISO 11980:2013 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 11980:2013

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SIST EN ISO 11980:2013


EUROPEAN STANDARD
EN ISO 11980

NORME EUROPÉENNE

EUROPÄISCHE NORM
November 2012
ICS 11.040.70 Supersedes EN ISO 11980:2009
English Version
Ophthalmic optics - Contact lenses and contact lens care
products - Guidance for clinical investigations (ISO 11980:2012)
Optique ophtalmique - Lentilles de contact et produits Augenoptik - Kontaktlinsen und Kontaktlinsenpflegemittel -
d'entretien pour lentilles de contact - Directives pour les Leitfaden für die klinische Prüfung (ISO 11980:2012)
investigations cliniques (ISO 11980:2012)
This European Standard was approved by CEN on 14 November 2012.

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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United
Kingdom.





EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2012 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11980:2012: E
worldwide for CEN national Members.

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SIST EN ISO 11980:2013
EN ISO 11980:2012 (E)
Contents Page
Foreword .3

2

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SIST EN ISO 11980:2013
EN ISO 11980:2012 (E)
Foreword
This document (EN ISO 11980:2012) 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 May 2013, and conflicting national standards shall be withdrawn at the
latest by May 2013.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 11980:2009.
According to the CEN/CENELEC Internal Regulations, the national standards organisations of the following
countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech
Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece,
Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom.
Endorsement notice
The text of ISO 11980:2012 has been approved by CEN as a EN ISO 11980:2012 without any modification.
3

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SIST EN ISO 11980:2013

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SIST EN ISO 11980:2013
INTERNATIONAL ISO
STANDARD 11980
Third edition
2012-11-15
Ophthalmic optics — Contact lenses and
contact lens care products — Guidance
for clinical investigations
Optique ophtalmique — Lentilles de contact et produits d’entretien pour
lentilles de contact — Directives pour les investigations cliniques
Reference number
ISO 11980:2012(E)
©
ISO 2012

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SIST EN ISO 11980:2013
ISO 11980:2012(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2012
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 either ISO at the address below or ISO’s
member body in the country of the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland
ii © ISO 2012 – All rights reserved

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SIST EN ISO 11980:2013
ISO 11980:2012(E)
Contents Page
Foreword .iv
Introduction . v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Clinical investigational requirements . 1
4.1 General . 1
4.2 Additional requirements . 1
4.3 Other considerations . 4
Annex A (informative) Elements of a clinical investigation . 5
Annex B (informative) Procedures for the evaluation of safety, physiological performance and effect on
ocular tissues .18
Annex C (informative) The evaluation of visual, refractive and lens performance and
subject acceptance .23
Bibliography .26
© ISO 2012 – All rights reserved iii

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SIST EN ISO 11980:2013
ISO 11980:2012(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 2.
The main task of technical committees is to prepare International Standards. 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.
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.
ISO 11980 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 11980:2009), which has undergone minor
revision in order to update the normative reference to ISO 14155 and to revise 4.2.1.1 b) 6) and the fifth row of
Table A.1 (overnight wear).
This corrected version of ISO 11980:2012 incorporates the following correction:
— in Table A.12, the final equation corresponding to the total number of eyes has been inserted.
iv © ISO 2012 – All rights reserved

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SIST EN ISO 11980:2013
ISO 11980:2012(E)
Introduction
Currently, contact lenses and contact lens care products are regulated in different ways in different countries.
This International Standard has been developed to encourage global harmonization. Widespread adoption
of this International Standard should represent yet another step toward mutual recognition. This International
[1]
Standard can also be used as a basis to fulfil design elements of ISO 9001 .
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SIST EN ISO 11980:2013

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SIST EN ISO 11980:2013
INTERNATIONAL STANDARD ISO 11980:2012(E)
Ophthalmic optics — Contact lenses and contact lens care
products — Guidance for clinical investigations
1 Scope
This International Standard gives guidelines for the clinical investigation (CI) of the safety and performance of
contact lenses and contact lens care products.
NOTE This International Standard attempts to harmonize the recognized regulatory requirements for the conduct of
a CI to meet the marketing and labelling requirements for contact lenses and contact lens care products around the world.
However, national requirements vary greatly. Wherever national practice or regulations dictate some legal requirement,
this requirement takes precedence over this International Standard.
2 Normative references
The following referenced documents are indispensable for the application 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 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14534, Ophthalmic optics — Contact lenses and contact lens care products — Fundamental requirements
ISO 18369-1, Ophthalmic optics — Contact lenses — Part 1: Vocabulary, classification system and
recommendations for labelling specifications
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 14155, ISO 14534 and ISO 18369-1 apply.
4 Clinical investigational requirements
4.1 General
The general requirements for a CI and for a clinical investigation plan (CIP) given in ISO 14155 shall apply, with
additional requirements given below.
4.2 Additional requirements
4.2.1 Study design
4.2.1.1 General
a) The inclusion criteria for subject selection shall relate to the study objectives and should include:
1) subjects with normal eyes who are not using any ocular medications, aged 18 years or over [except
when contact lens investigations have a special indication for use in “children” (for the purposes of
this International Standard, persons less than 18 years of age) such as orthokeratology and paediatric
aphakic lenses];
2) lens powers within the range available for the test lenses;
3) the manifest cylinder less than or equal to 0,75 D (for a study with only spherical power correcting lenses);
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SIST EN ISO 11980:2013
ISO 11980:2012(E)
4) best spectacle corrected visual acuity greater than or equal to 20/25 (less than or equal to LogMAR 0,1).
b) The exclusion criteria for subject selection shall relate to the study objectives and should include, but not
be limited to:
1) anterior segment infection, inflammation or abnormality;
2) any active anterior segment ocular disease that would contraindicate contact lens wear;
3) the use of systemic or ocular medications that would contraindicate contact lens wear;
4) history of herpetic keratitis;
5) history of refractive surgery or irregular cornea (except when the contact lenses under investigation
are indicated for irregular cornea, keratoconus or refractive surgery);
6) slit lamp findings that are more serious than grade 1;
7) corneal vascularization greater than 1 mm of penetration;
8) a pathologically dry eye;
9) participation of the subject in a contact lens or contact lens care product clinical trial within the
previous 30 days.
c) The CIP shall provide a description of the monitoring procedure to ensure consistent quality of data
collection and recording.
d) The CIP shall include a statistical analysis plan. Sample size shall be justified, calculated by a validated
statistical software package.
4.2.1.2 Contact lenses
4.2.1.2.1 General. A CI of contact lenses, including daily wear and extended wear hydrogel, silicone hydrogel,
and rigid gas-permeable contact lenses, shall be designed as one of 4.2.1.2.2 or 4.2.1.2.3.
For CIPs to demonstrate safety and performance, as well as special claims (e.g. comfort), labelling or
additional indications, the following is required: a pre-determined statistical analysis plan (including sample
size calculations) shall be specified in the clinical protocol. Where feasible, the CIP shall define objective
endpoints to help support such claims.
NOTE 1 Inter-subject controls are preferred to intra-subject controls due to the potential dependence between the two
eyes and concerns regarding subject compliance.
NOTE 2 Annex A provides guidance for the design of a CI.
4.2.1.2.2 As a prospective, concurrently controlled study. For investigations evaluating hydrogel, silicone
hydrogel or rigid gas-permeable contact lenses, a prospective, concurrent control study design shall be followed.
Either a bilateral crossover design or a contra-lateral eye (i.e. intra-subject) design or inter-subject controls shall
be utilized. If inter-subject controls are utilized, the ratio of test subjects to control subjects may be either 2:1 or
1:1. The control lens shall be a currently marketed contact lens in use for the same modality. Randomization
and masking (subject, investigator and evaluator) shall be employed where possible to minimize the potential
for bias. Subjects shall be divided evenly between study investigators.
4.2.1.2.3 As an uncontrolled study. Here, results are compared to a historical control. Alternative
investigational study designs, such as historical controls, shall be utilized when a sponsor has a clinical database
on a marketed contact lens to use as a comparator. If any historical control is used, the control group shall be
defined and adequately characterized for comparison to the test group. Compatibility of test and control groups
shall be demonstrated by comparison of the selection criteria, demographics, refractive characteristics, contact
lens wearing history and CIPs used.
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SIST EN ISO 11980:2013
ISO 11980:2012(E)
4.2.1.3 Contact lens care products
For investigations evaluating contact lens care products, a prospective concurrent control study design shall be
followed. It is recommended that the ratio of test to control subjects be either 2:1 or 1:1. The control care product
shall be a currently marketed contact lens care product. Randomization and masking (subject, investigator and
evaluator) shall be employed where possible to minimize the potential for bias. Subjects shall be divided evenly
between study investigators. Alternative investigational study designs, such as use of historical controls, may be
utilized when a manufacturer has a clinical database on a marketed care product to use for comparison. If any
historical control is used, the control group should be defined and adequately characterized for comparison to
the test group. Compatibility of test and control groups should be demonstrated by comparison of the selection
criteria and CIPs used.
For CIPs to demonstrate safety and performance, as well as special claims (e.g. comfort), labelling or additional
indications, the following is required for the care products: a pre-determined statistical analysis plan (including
sample size calculations) shall be specified in the clinical protocol. Where feasible, the protocol should define
objective endpoints to help support such claims.
NOTE 1 Inter-subject controls are preferred to intra-subject controls due to the potential dependence between the two
eyes and concerns regarding subject compliance.
In a contact lens care product investigation, a daily wear schedule shall be followed for most products in order
to maximize the subject’s exposure to those products. However, a study of a lens or a periodic cleaner, used
at weekly intervals, may provide more valuable clinical data concerning efficacy when extended wear subjects
are enrolled than a similar investigation with daily wear subjects.
When a daily wear schedule is used and safety is a primary objective, one post-dispensing visit should be done
1 h to 2 h after lens insertion in order to permit observation of corneal and conjunctival staining caused by an
immediate toxicity reaction.
A contact lens care product with a cleaning indication shall have an objective measure of lens cleanliness on
at least one lens collected from each subject at the end of the clinical study.
If the manufacturer of a contact lens care product wishes to recommend its use with a specific type of lens in
the labelling, the compatibility with the lens type should be confirmed pre-clinically and during the clinical trial.
If the CI has not collected any data on use with a particular type of lens material (such as silicone hydrogel
lenses), the product label should clearly state this fact.
NOTE 2 Annex A provides guidance for the design of a CI.
4.2.2 Variables
4.2.2.1 Contact lenses
The following variables should be considered during the CI for contact lenses, in addition to the variables
listed in 4.2.2.2:
a) visual performance;
b) refractive performance;
c) keratometric measurements;
d) lens centration;
e) lens movement;
f) lens surface wettability;
g) lens surface deposits;
h) subject acceptance of comfort;
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SIST EN ISO 11980:2013
ISO 11980:2012(E)
i) subject acceptance of vision;
j) subject acceptance of handling.
Additional variables can be studied in the CI to support specific claims.
NOTE Annex C provides guidance on classifications for each of these variables.
4.2.2.2 Contact lens care products
The following variables should be assessed during the CI for contact lens care products:
a) corneal oedema;
b) corneal infiltrates;
c) endothelial irregularity;
d) corneal vascularization;
e) corneal staining;
f) conjunctival observations;
g) palpebral conjunctival observations;
h) corneal ulcers;
i) corneal opacification;
j) hyphema;
k) hypopyon;
l) iritis;
m) corneal scarring.
Additional variables can be studied in the CI to support specific claims.
NOTE Annex B provides guidance on classifications for some of these variables.
4.3 Other considerations
Serious ophthalmic adverse events and all adverse device effects shall be reported using a special case report
form and forwarded to the sponsor as required. All other ophthalmic adverse events shall be reported using the
standard visit case report forms and shall be collected during monitoring.
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SIST EN ISO 11980:2013
ISO 11980:2012(E)
Annex A
(informative)

Elements of a clinical investigation
A.1 General
The following are elements of a CIP which can assist in collecting data for the purpose of determining the
safety and performance of contact lenses and contact lens care products.
A.2 Study size and duration
A.2.1 Contact lens investigations
Table A.1 — Guide to the subject numbers (completed subjects) suggested for contact lens
clinical investigations (informative)
Subject number
Wearing modality completed per group Duration Material and design
at end of trial
Containing new or new ratio material
50 3 months
components; significant design changes
Daily wear
30 30 days All materials and designs
3 months or longer
Daily wear
50 if necessary to reach All materials and designs
orthokeratology
defined stability
Extended wear,
160 12 months All materials and designs
up to 7 days
Extended wear,
570 12 months All materials and designs
up to 30 days
Overnight wear
100 pre-market/
(may include 6 months All materials and designs
200 post-market
orthokeratology)
A.2.2 Contact lens care product investigations
A.2.2.1 Contact lens care products, including saline solutions, daily cleaners, periodic cleaners, disinfecting
solutions, neutralizers, “in-eye” solutions, conditioning solutions, and multipurpose solutions that have any new
active ingredient, or any active ingredient outside the concentration range used in a comparable marketed
product, should undergo a 3 month clinical study.
A.2.2.2 Products for use with soft (hydrophilic) lenses: sample size (completed) should be 30 subjects in the
test solution and 15 subjects in the control solution (a currently marketed solution for the same indication) for
each appropriate representative category such as:
— Group I;
— Group IV;
— A separate group for each silicone hydrogel lens. If more than one lens is made by a given manufacturer,
and they all have the same general chemistry, it is sufficient to use only the lens of highest water content.
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SIST EN ISO 11980:2013
ISO 11980:2012(E)
A.2.2.3 Products for use with rigid lenses: sample size (completed) should be 15 or 30 subjects using the test
solution and 15 subjects using the control solution (a currently marketed solution for the same indication) for
each appropriate material group.
A.2.2.4 For a contact lens solution that does not contain any new active ingredients (as described in A.2.2.1),
but contains any active ingredient lower than the concentration range used in a comparable marketed product,
a 1 month clinical study should be conducted. In this case, the sample size should be about half of that
recommended in A.2.2.2 and A.2.2.3, using the same general distribution of subjects.
A.2.3 Statistical considerations for extended wear evaluations
A.2.3.1 General
Primary safety analysis: the key safety endpoint should be the frequency of serious and significant adverse events.
The null hypothesis, H , is that the test rate of endpoint adverse events, p , minus the control rate of endpoint
0 t
adverse events, p , is greater than or equal to the clinically insignificant difference, δ, between the two rates.
c
The alternative hypothesis, H , is that the test rate of endpoint adverse events, p , minus the control rate of
a t
endpoint adverse events, p , is less than a clinically insignificant difference, δ, between the two rates.
c
H : p − p ≥ δ
0 t c
H : p − p < δ
a t c
where
p is the proportion in the test population;
t
p is the proportion in the control population.
c
When using a 1:1 ratio of patient allocation between treatment and control, the minimum number, n, of completed
patients necessary for each treatment group is determined by:
2
()ZZ+×[(pp11−+)(pp− )]
11−−βα tt cc
n =
2
δ
where
α
is the significance level (also known as the type 1 error rate);
1 − β is the power of the test;
Z
is the standard normal quantile.
The following is an example of the calculation that makes assumptions found to be reasonable for clinical
studies of 7 day extended wear hydrogel or silicone hydrogel contact lenses. With a control rate, p , and a
c
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SIST EN ISO 11980:2013
ISO 11980:2012(E)
test rate, p , of 0,033 (under H ), a clinically insignificant difference, δ, of 0,05, a power, 1 − β, of 0,80, and a
t a
significance level, α, of 0,05, the minimum number of completed patients per treatment group is:
2
(,0841+×,)64 [,0 033×−(,10 033),+×0 033 (,10− 033)]
n = ≈158
2
00, 5
This equation is only valid when it is assumed for the alternative hypothesis, H , that the test rate of adverse
a
events is equal to the control rate, p = p . When this is not a valid assumption, the following equation can be
t c
used to provide an approximate calculation for the sample size:
2
()ZZ+×[(pp11−+)(pp− )]
11−−βα tt cc
n =
2
()pp−−δ
tc
For clinical studies of 30 day extended wear hydrogel contact lenses, it is recommended that a 7 day extended
wear lens (worn for up to 6 nights/7 days) be used as the control. The following is an example of the calculation
that makes assumptions found to be reasonable for many clinical studies of 30 day extended wear hydrogel
contact lenses. With a control rate, p , of 0,033 and a test rate, p , of 0,053 (under H ), a clinically insignificant
c t a
difference, δ, of 0,05, a power, 1 − β, of 0,80, and a significance level, α, of 0,05, the minimum number of
completed subjects per treatment group is:
2
(,0841+×,)64 [,0 053×−(,10 053),+×0 033 (,10− 033)]
n = ≈ 562
2
(,0 053−00, 333−00,)5
Enrolment should be adjusted to compensate for drop-out which is typically 20 % to 25 % in 1 year contact
lens studies. Therefore, for the above example of a clinical study of a 7 day extended wear contact lens, the
recommended sample size would be adjusted to approximately 215 per subject group. For the above example
of a study of a 30 day extended wear lens, the recommended sample size would be approximately 760 per
subject group.
At the conclusion of the study, sensitivity analyses (e.g. multiple imputation analyses) should be conducted to
evaluate the robustness of the study result accounting for missing observations, if there is more than minimal
subject drop-out.
A.2.3.2 Daily wear hydrogel, silicone hydrogel or rigid gas-permeable contact lens evaluations
Sample sizes are designed to give reasonable assurance of obtaining at least one complication, as a function
of the expected complication rate (i.e. 5 % for a 60 subject test group, 10 % with a 30 subject test group),
with a probability of greater than 95 %. Therefore, in a subject group of 30 (completed) subjects exposed to
a short-term duration (90 days) of a test product, an adverse event occurrence in two to three subjects may
cause concern as to the biocompatibility and fundamental safety of the device being tested. Any investigation
resulting in more than one adverse reaction should include adequate justification in order to establish safety
and efficacy.
A.2.3.3 Contact lens care product evaluations
Clinical sample sizes are designed so that there is 95 % confidence that a study has at least one complication
in a material category, if the true complication rate is ≥ 10 %. This implies that a study should have at least
30 (completed) subjects exposed to a short-term duration (90 days) of a test care product, for each material
grouping. Studies should include all material groupings of interest for the product.
Any investigation resulting in more than one adverse reaction should include adequate justification in order to
establish safety and efficacy.
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SIST EN ISO 11980:2013
ISO 11980:2012(E)
A.2.4 Adverse events and adverse device effects
A.2.4.1 General
Adverse events should be differentiated into device related and non-device related. Any corneal infiltrate, ulcer,
neovascularization, etc. shall be presumed to be device related unless the case history clearly indicates some
other origin. All corneal ulcers shall be recorded in the
...