Reader and Industry Forum
FDA Takes Steps Toward Updating Guidance
BY RALPH P. STONE, PHD
The Ophthalmic Devices Panel of the Medical Devices Advisory Committee to the U.S. Food and Drug Administration (FDA) met on May 13, 2014 to discuss approaches to revise and modernize the May 1994 Premarket Notification 510(k) Guidance Document for Daily Wear Contact Lenses and the May 1997 Premarket Notification (510(k)) Guidance Document for Contact Lens Care Products.
Much has happened since the issuance of these guidance documents. Silicone hydrogels represented a revolutionary new direction in contact lens technology. There are now 14 different silicone hydrogel lens materials. This technology combines the hydrophilic character of traditional soft lenses with the basic components of GP rigid lenses.
Also, the Fusarium keratitis outbreak in 2006 and the Acanthamoeba keratitis outbreak in 2007 led to the recall of specific contact lens care products.
The FDA Panel meeting included participation by industry, academia, and professional organizations. It reviewed research carried out by the FDA as well as comments from, and activities being carried out by, the American National Standards Institute (ANSI) Z-80 and the International Organization for Standardization (ISO) (TC172/SC7/WG9).
Lens Material Considerations
For the existing and proposed guidances, updating the materials to be included in testing is a main consideration. The availability of silicone hydrogel materials is a key change, and the FDA has created a new group 5 for the silicone hydrogel hydrophilic contact lenses in addition to the four classes of lenses included in the traditional lens material system. It is generally agreed that we can class the currently available silicone hydrogel materials into five subgroups based on hydrophilic structure and the methods used to modify their surfaces (Table 1).
|5A||Silicone hydrogel containing an ionic hydrophilic monomer|
|5B||High-water (>50%) silicone hydrogel|
|5C||Low-water (<50%) without a surface modification|
|5Cm||Low-water (<50%) with a surface modified in a covalent reaction|
|5Cr||Low-water (<50%) using interpenetrating networks|
In the ANSI and ISO classification systems, subscripts used in Table 1 are available for groups 5A and 5B as well, although currently no materials in these categories are being marketed. The ANSI and ISO draft standards also include concerns that the hydrophobic portion of these polymers is not described.
The panel felt that this was a needed step forward that covered current options. The panel also felt that the FDA should continue to work with ANSI and ISO to assure that appropriate lens materials are evaluated.
Lens Care Considerations
Lens Care Safety It is widely recognized that one of the key issues with contact lenses and their care is patient compliance. With noncompliance at such high levels, the FDA outlined steps to enhance the safety of contact lens wear (Table 2).
|•||Enhance product labeling for practitioners and patients|
|•||Education for practitioners and patients via publications and websites|
|•||Safety alerts for both practitioners and patients|
The FDA approach includes added precautions and warnings for “topping off,” exposure to water, and “discard after opening” dating as well as a recommendation for simplifying the language of care solution directions for use.
Preservative Uptake The FDA previewed its approach to the issue of preservative uptake and its potential effect on disinfection efficacy. It is well known that lenses may uptake and release the preservative/disinfecting compounds, which is measured using ISO standard 11986. FDA proposed a testing scheme that measures both biocide uptake and disinfection efficacy using the ISO standard for disinfection (ISO14729). It was not clear how the FDA would develop and implement an acceptance criteria.
Public comment proposed an alternative procedure that has been worked on under the ANSI and ISO process. This work has progressed to the point that it includes a critical inter-laboratory validation of the procedure. The ISO procedure is currently in the final stages of standard approval. It involves evaluating disinfection efficacy using lenses and cases in addition to the care system.
Any changes requiring significantly enhanced efficacy may also potentially increase the amount of biocides taken up into and released from the lenses. This will require a very careful evaluation of the potential for these higher concentrations to have a toxic effect in the eye.
Disinfection Standards Discussions of the Disinfection Standards were based on work that came out of FDA research. The research on Acanthamoeba demonstrated the importance of the experimental variables of strain, life stage, growth methods, and encystment techniques. A recommendation for Acanthamoeba disinfection efficacy procedure was described but was challenged in public comment. The FDA also described testing of real-world organisms; however, replacing or adding additional organisms for testing will require careful selection of appropriate organisms available.
Also reviewed were key factors for improving our understanding of the testing process (Table 3).
|•||Organic soil as a part of disinfection testing|
|•||Longer soak times as a potential safety measure or risk factor|
|•||The effect of lens uptake on disinfection and storage times|
In an invited presentation, Dr. Jennifer Cope reviewed the Centers for Disease Control and Prevention (CDC) investigations of Acanthamoeba keratitis from 1985 to 2011. Critical to note from this new information was that the increases observed in the 2007 outbreak did not return all the way back to the pre-outbreak levels. Additional investigations initiated in 2011 indicated that hygiene factors in lens care were important, with topping off and storing contact lenses in water leading the risk factors.
There was significant discussion on whether the FDA guidelines should recommend that product testing include various aspects of patient noncompliance. While attempts to improve product efficacy are important, the panel was concerned about how far companies or regulations can go in attempting to deal with issues of noncompliance. The panel recommended that the FDA not incorporate noncompliance into the testing requirements. The panel also encouraged the FDA to continue to work with ISO and ANSI to improve our measures of disinfection efficacy.
The final area covered was the use of water during the care of GP lenses. While the general consensus was to use saline, the availability and volumes required in some regimens make this option difficult. It was pointed out that there is no research indicating that tap water is a risk factor if it is used before disinfection.
More to Come
The FDA will continue to work on aspects of microbiological guidance in a workshop that will take place on Sept. 12, 2014. CLS
Dr. Stone is currently president of R.P. Stone Consulting, Inc. and spent more than 33 years in contact lens and lens care research and development for many of the leading companies in the field before his retirement in 2006. He has been a leader in the development of many of the care systems on the market today. Dr. Stone continues as a member of the American National Standards institute and participates on committee Z-80. He is one of the experts representing the United States at ISO TC 172/SC7/WG-9. He is a consultant or advisor to Alcon and NovaBay Pharmaceuticals.