Revocación. A discreción de la Junta, las credenciales de cualquier ministro Cuadrangular

The application should be in the EC-suggested format, as if the pharmaceutical Directives applied fully. MAL 201 application forms should be used. Expert Reports are always needed for the chemistry and pharmacy parts of the application and might be required for the experimental and biological and the clinical sections, especially in the case of products containing a novel ingredient or an ingredient used in a particular way for the first time.

Contact lens care products have no legal status. The subject of legal status is discussed more fully in Chapter 17. However, the relevant advisory Committee in the UK, the Committee on Dental and Surgical Materials, has indicated that it considers that all contact lens care products should be supplied only through professional outlets (pharmacies, dispensing opticians and optometrists, as well as hospital clinics). This limitation is usually written into product licence applications forms.

10.2.3.2

Chemical and pharmaceutical documentation

The normal data requirements of MAL 2 and the EC requirements apply, with the following amendments or modified emphasis.

(a)

Microbiological studies

Details should be included in the application of the results obtained for antimicrobial preservative efficacy testing by an appropriate method (details of which should be included) and suitable organisms. The test method should be validated, including details of results from recovery experiments using low levels of inocula. In particular the inactivation of preservatives present in the product should be discussed if relevant.

The level of antimicrobial activity expected is related to the intended use of the product—thus, in-eye products and cold disinfection products are expected to show a higher level of activity than, say, a cleaner that is used prior to a rinsing/ disinfection cycle.

Kill curve data should be provided on at least two batches of product over a suitable period (which should be related to the recommended method of use). The level of inoculum used should be sufficient to allow 3 or 4 log orders of reduction in viable count to be followed. Fresh and aged product should be examined. The organisms used should include those recommended in the British 158 SEC. 10.2] CONTACT LENS CARE PRODUCTS

Pharmacopoeia antimicrobial preservative efficacy test, although additional organisms may be included. In some cases it might be appropriate to include Acanthamoeba species or other clinically significant organisms. Adequate data may be required to demonstrate activity of cold disinfectant products against cystic forms of Acanthamoeba species.

(b)

Compatibility studies

Product/container compatibility studies are required for all products. In addition, data are required to demonstrate compatibility of the product with representative examples of the types of lenses with which the product is to be used. Factors such as preservative uptake and release and the physical parameters and properties of the lenses following the normal recommended use procedures for the product should be reported. In the case of physical parameter studies a range of lens prescriptions should be used including high+and high−power lenses. Depending on the claims for use, the product/lens compatibility studies may need to incorporate polymethylmethacrylate (PMMA) lenses, representative types of rigid gas permeable (GP) lenses, and representative high and low water content (i.e <55 per cent and >55 per cent water content) ionic and non-ionic hydrogel lenses, for example.

The compatibility studies should use methods that mimic the recommended usage of the product, or represent a greater challenge.

(c) Container sizes

Products intended for use on more than one occasion should contain sufficient product for use for not more than 28 days unless the container is pressurised or satisfactory additional data to justify a longer use period are supplied. In the case of single-use products the container should not hold an excessive overage and should not be resealable. All containers should have tamper-evident closures. A suitable labelling statement regarding sterility of the product until the seal is broken is often included for products intended to be used on more than one occasion.

10.2.3.3

Experimental and biological studies

For all products coming into contact with the eye, adequate local toxicity data are expected, including sensitisation and ocular irritation tests. Tests should be undertaken on the product to be marketed. The period of testing should be justified but should not be less than four weeks, although longer studies may be appropriate in the case of products containing novel ingredients or novel

combinations of ingredients. The studies should mimic as far as possible recommended clinical usage. Full justification should be provided for the omission of such studies.

Mutagenicity data should be submitted as suggested in the usual guidelines. Provided that the results of these do not indicate mutagenic potential, and provided that the systemic exposure to components in the product is low, it may not be necessary to undertake carcinogenicity studies.

Non-animal test systems may be used where they have been validated and shown to be reliable. Where it is necessary to undertake animal tests, dosage should be over seven days per week, with lenses worn for at least six hours per day in appropriate cases. Where lenses are worn the control eye should be fitted with a lens of the same design and of the same material. Lenses should be examined for changes. Daily examinations should be undertaken, with frequent slit-lamp examinations of the eyes. Terminal histological preparations should be made of the eyes and eye lids. Corneal thickness and the status of the corneal endothelium might be of particular interest. Animals’ organs may need to be preserved in case any clinical findings indicate a need to examine them.

10.2.3.4