EN ISO 11980:2009

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.Augenoptik - Kontaktlinsen und Kontaktlinsenpflegemittel - Leitfaden für die klinische Prüfung (ISO 11980:2009)Optique ophtalmique - Lentilles de contact et produits d'entretien pour lentilles de contact - Directives pour les investigations cliniques (ISO 11980:2009)Ophthalmic optics - Contact lenses and contact lens care products - Guidance for clinical investigations (ISO 11980:2009)11.040.70Oftalmološka opremaOphthalmic equipmentICS:Ta slovenski standard je istoveten z:EN ISO 11980:2009SIST EN ISO 11980:2010en01-januar-2010SIST EN ISO 11980:2010SLOVENSKI
STANDARDSIST EN ISO 11980:20001DGRPHãþD

EUROPEAN STANDARD NORME EUROPÉENNE EUROPÄISCHE NORM
EN ISO 11980
October 2009 ICS 11.040.70 Supersedes EN ISO 11980:1997English Version
Ophthalmic optics - Contact lenses and contact lens care products - Guidance for clinical investigations (ISO 11980:2009) Optique ophtalmique - Lentilles de contact et produits d'entretien pour lentilles de contact - Directives pour les investigations cliniques (ISO 11980:2009)
This European Standard was approved by CEN on 10 October 2009.
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 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 Management Centre has the same status as the official versions.
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Reference numberISO 11980:2009(E)© ISO 2009
INTERNATIONAL STANDARD ISO11980Second edition2009-10-15Ophthalmic 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
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ii © ISO 2009 – All rights reserved
ISO 11980:2009(E) © ISO 2009 – All rights reserved iii 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.2 4.2.1 Study design.2 4.2.2 Variables.4 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.24 Bibliography.28
ISO 11980:2009(E) iv © ISO 2009 – All rights reserved 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 second edition cancels and replaces the first edition (ISO 11980:1997), of which it constitutes a technical revision. It also incorporates the Technical Corrigendum ISO 11980:1997/Cor.1:1998. SIST EN ISO 11980:2010

ISO 11980:2009(E) © ISO 2009 – All rights reserved v 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 Standard can also be used as a basis to fulfil design elements of ISO 9001[1].
INTERNATIONAL STANDARD ISO 11980:2009(E) © ISO 2009 – All rights reserved 1 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 14155-1, Clinical investigation of medical devices for human subjects — Part 1: General requirements ISO 14155-2, Clinical investigation of medical devices for human subjects — Part 2: Clinical investigation plans 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 14155-1, ISO 14155-2, 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 14155-2 shall apply, with additional requirements given below. SIST EN ISO 11980:2010

ISO 11980:2009(E) 2 © ISO 2009 – All rights reserved 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); 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 equal to or more serious than trace findings (greater than or equal to 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 SIST EN ISO 11980:2010

ISO 11980:2009(E) © ISO 2009 – All rights reserved 3 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. 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. SIST EN ISO 11980:2010

ISO 11980:2009(E) 4 © ISO 2009 – All rights reserved 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; 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. SIST EN ISO 11980:2010

ISO 11980:2009(E) © ISO 2009 – All rights reserved 5 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) Wearing modality Subject number completed per group at end of trial Duration Material and design 50 3 months Containing new or new ratio material components; significant design changes Daily wear 30 30 days All materials and designs Daily wear orthokeratology 50 3 months or longer
if necessary to reach defined stability All materials and designs Extended wear, up to 7 days 160 12 months All materials and designs Extended wear,
up to 30 days 570 12 months All materials and designs Overnight wear (may include orthokeratology) 300 12 months All materials and designs
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. SIST EN ISO 11980:2010

ISO 11980:2009(E) 6 © ISO 2009 – All rights reserved 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, H0, is that the test rate of endpoint adverse events, pt, minus the control rate of endpoint adverse events, pc, is greater than or equal to the clinically insignificant difference, δ, between the two rates. The alternative hypothesis, Ha, is that the test rate of endpoint adverse events, pt, minus the control rate of endpoint adverse events, pc, is less than a clinically insignificant difference, δ, between the two rates. H0: pt − pc W δ Ha: pt − pc < δ where pt is the proportion in the test population; pc is the proportion in the control population. 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: 211ttcc2()[(1)(1)]ZZppppnβαδ−−+×−+−= 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, pc, and a test rate, pt, of 0,033 (under Ha), a clinically insignificant 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 patients per treatment group is: 22(0,841,64)[0,033(10,033)0,033(10,033)]1580,05n+××−+×−=≈ SIST EN ISO 11980:2010

ISO 11980:2009(E) © ISO 2009 – All rights reserved 7 This equation is only valid when it is assumed for the alternative hypothesis, Ha, that the test rate of adverse events is equal to the control rate, pt = pc. When this is not a valid assumption, the following equation can be used to provide an approximate calculation for the sample size: 211ttcc2tc()[(1)(1)]()ZZppppnppβαδ−−+×−+−=−− 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, pc, of 0,033 and a test rate, pt, of 0,053 (under Ha), a clinically insignificant 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
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