Executive Summary

 

Two outbreaks of infectious keratitis associated with Fusarium and Acanthamoeba have led FDA staff to re-assess FDA’s current guidance recommendations for multipurpose contact lens care products.  The purpose of this meeting is to seek panel input on modifications to the existing guidance that the FDA should consider in an effort to maximize patient safety.

 

In the following, we include a brief history of the outbreaks, followed by the preclinical tests, clinical tests and labeling that we are re-evaluating, and finally our questions for the Panel.

 

Outbreak History:

 

In April of 2006, 180 cases of suspected fungal keratitis resulting from Fusarium infection were reported in 36 states and US territories. Corneal transplant was required in approximately 30 cases.  Many affected patients recalled using a specific contact lens care product in the month prior to their symptoms. Fusarium was not recovered from any unopened contact lens care products, lenses, or contact lens storage cases provided by patients. Nevertheless, within two months of recalling this product, the fusarium outbreak ended.  

 

According to the Centers for Disease Control (CDC), in May 2006, the Illinois Department of Public Health (IDPH) informed CDC about a possible increase in Acanthamoeba keratitis (AK) at an ophthalmology center in Illinois during the preceding 3 years.  In January 2007, CDC initiated a retrospective survey of 22 ophthalmology centers nationwide to assess whether cases were increasing throughout the United States. By May 24, 2007, a total of 138 patients with onset of symptoms on or after January 1, 2005, and positive Acanthamoeba cultures from corneal specimens had been reported to CDC by public health authorities and ophthalmologists from 35 states and Puerto Rico.  Though the contact lens care product that was strongly associated with the AK outbreak was removed from the market, AK cases persist.  CDC noted the increase in cases begun in 2004 and continued to the present.

 

The Panel will hear an update regarding those outbreaks from FDA and CDC.  Attachment A provides materials describing the outbreaks. 

 

FDA’s Re-assessment of Test Methods:

 

The test methods we will be discussing are described in our daily wear contact lens and care guidances that are in Attachment G.  Please refer to the following sections and pages listed below.

 

Daily Wear Contact Lens Guidance

Manufacturing/Chem --- Appendix B soft (hydrophilic) Lens Groupings ……. Page 25

                                    --- Appendix D Preservative Uptake/Release Test ……. Page 27

 

 

 

Contact Lens Care Products Guidance

VI. Recommended Test Methods ………………………………………………  Page 80

A.    Chemistry …………………………………………………………… Page 82

B.     Microbiology ………………………………………………………... Page 89

C.     Toxicology ………………………………………………………….  Page 112

D.    Clinical ……………………………………………………………...  Page 119

E.  Shelf-Life Protocol ………………………………………………….  Page 160

           

A.  Preclinical Test Methods:

In the Fusarium outbreak event, the recalled lens care product had performed well in the current pre-clinical test against that organism.  In the Acanthamoeba event, the product was not tested against that organism since it is not part of the current panel of organisms. The FDA presentations will discuss the synergistic interactions of chemical formulation, microbiological testing, and issues of biocompatibility that we are looking into in order to mitigate these types of events in the future in the contact lens wearing population. The presentations also include specific areas FDA has identified for discussion such as revised preclinical test methodology.  A scientist from CDC will discuss the laboratory testing of Acanthamoeba.

 

Specifically, the chemistry presentation will include a discussion of preclinical test methods and strategies to characterize new and unpredictable interactions resulting from new, complex formulations of lens care products. These interactions include film formation, decreases in preservative effectiveness, and sequestering effects.   In Attachment B, there are several pertinent peer reviewed literature articles that discuss the chemistry concerns of contact lens care products.

 

Likewise, current disinfection and preservative effectiveness methods present certain limitations that are integral to the microbiology discussion. The microbiology presentation will discuss our current panel of test organisms and the effect of preservative uptake by conventional and silicone hydrogel lenses on disinfection effectiveness.  It will also discuss updating performance criteria and directions for use to optimize product performance by consumers.  Attachment C provides current literature relative to these topics.  Additionally, this presentation will also include preliminary information on efforts to develop a new international standard for contact lens care product testing.   In addition we will present a revised method that evaluates the biocidal efficacy of contact lens disinfection solutions in the presence of a contact lens in a lens case.  

 

In concert with the presentations on chemistry and microbiology, the biocompatibility presentation will discuss the preclinical testing strategies used for new multipurpose solutions (MPS). Questions have been raised with respect to the need to test new MPSs with both conventional hydrogel lenses as well as Silicone hydrogel (Si-Hy) lenses even if the MPS is contraindicated in the labeling for Si-Hy Lenses.  In Attachment D, literature is presented regarding the corneal biocompatibility of MPSs, conventional and Si-Hy lenses.  Differences in transient corneal staining have been observed with certain lens types and lens solutions in relation to identifying risk factors for microbial keratitis.  

 

All of these preclinical concerns impact the clinical testing and performance of lens care products and various categories of contact lens materials. These will be addressed in the clinical presentations of this panel meeting.

 

B.  Clinical Issues:

The current paradigm of tests for the four groups of contact lenses does not provide for a separate categorization of silicone hydrogel contact lenses. This has prompted consideration for directly testing additional types of lenses in clinical studies. The clinical presentation will include a brief review of the historical background surrounding the development of the four-lens grouping system that was subsequently incorporated into current FDA guidance for contact lens care products. This presentation will address the clinical performance of silicone hydrogel contact lenses and lens care product interactions as compared to that of traditional hydrogel lenses. In Attachment E of this document, information is provided that describes the four major contact lens groups, their performance characteristics and those of silicone hydrogel lenses as well. In addition to the preclinical and clinical performance issues of various types of lens products with specific categories of contact lenses, the role of the consumer’s care of contact lenses must also be considered. 

 

C.  Contact Lens Care Products Labeling:

Finally, human factors and labeling presentations will discuss the possible behaviors that can lead to problems for contact lens wearers, and analyze these within a framework of how human factors is considered for the use of other medical devices and how these issues can be addressed in proposed labeling. Topics include patient labeling principles, instructions for use and warning examples to address consumer misuse issues. Attachment F presents literature describing consumer behaviors regarding contact lens care and general human factors considerations related to medical device use.   Attachment G presents  a hard copy of the FDA’s Contact Lens Website, the “Guidance on Medical Device Patient Labeling”, the “Guidance Document for Contact Lens Care Products”, and the Guidance Document for Daily Wear Contact Lenses.

 

 

 

 

 

 

 

 

 

 

 

 

 

Bibliography

 

Attachment A - Outbreak History

 

CDC MMWR.  Acanthamoeba Keratitis---Multiple States, 2005-2007.  Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm56d526a1.htm.  Accessed April 21, 2008.

 

Chang D, et al.  Multistate Outbreak of Fusarium Keratitis Associated with Use of a Contact Lens Solution.  JAMA 296(8): 953-963, 2006.

 

Saviola J, Contact Lens Safety and the FDA:  1976 to the Present.  Eye & Contact Lens 33(6): 404-409, 2007.

 

Attachment B - Chemistry

 

B Levy, D Heiler, S Norton, Report on Testing from an Investigation of Fusarium Keratitis in Contact Lens Wearers, Eye & Contact Lens 32(6):256-261, 2006.

 

F Zhang, MA Glasier, H Sheardown, L Jones, The Use of Confocal Microscopy to Determine the Location of Lysozyme Deposits in Silicone Hydrogels and Conventional Hydrogel Contact Lens Materials, Poster ARVO, 2006.

 

PL Rakow, Current Contact Lens Care Systems, Ophthalol Clin N Am 16:415-432, 2003.

 

Attachment C - Microbiology

 

ISO 14729, “Ophthalmic optics – Contact lens care products – Microbiological requirements and test methods for products and regimens for hygienic management of contact lenses.” (2001)

 

Mowrey-McKee, M. and M. George.  Contact Lens Solution Efficacy Against Acanthamoeba castellani. Eye & Contact Lens 33(5):211-215, 2007.

 

K. Warburton, J. Noble-Wang, B. Henry, S. Holliday, M. Smith, J. Hutter and J. Saviola. Absorption of Alexidine by Contact Lenses and Lens Cases and its Effect on Disinfection Efficacy against Fusarium solani.  Poster presented at annual American Society for Microbiology Meeting by K. Warburton. (May 2007).

 

Shih, K. et al. The Microbiological Benefit of Cleaning and Rinsing Contact Lenses. International Contact Lens Clinic. 12(4), 1985.

 

Visvesvara G,  Moura H, and Schuster FL.  Pathogenic and opportunistic free-living amoebae:  Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri and Sappinia diploidea.  FEMS Immumol Med Microbiol 50 (2007) 1-26.

 

 

 

 

Attachment D - Biocompatibility

 

Imayasu et al.  Effects of multipurpose solutions on corneal epithelial tight junctions.  Eye & Contact Lens 34 (1), 50 – 55, 2008.

 

Mowrey-McKee et al.  Comparative cytotoxicity potential of soft contact lens care regimens.  The CLAO Journal 28 (3), 160 – 164, 2002.

 

Papas et al.  Complications associated with care product use during silicone daily wear of hydrogel contact lens.  Eye & Contact Lens 33(6), 392 – 393, 2007.

 

Attachment E - Clinical

 

American Optometric Association. Doctors of Optometry support AMO’s voluntary solution recall, urge contact lens wearers to discontinue use. Available at:  http://www.aoa.org/x8194.xml. Accessed May 1, 2008.

 

American Academy of Optometry.  AAO Best Practices: Acanthamoeba keratitis alert. June 07, 2007. Available at: http://www.aaopt.org/news/index.asp?record_id=269. Accessed May 1, 2008.

 

American Academy of Ophthalmology.  American Academy of Ophthalmology offers contact lens wearers advice on protecting their eyes against infection.  Available at: http://www.aao.org/newsroom/release/20070530.cfm.   Accessed May 1, 2008. 

 

Andrasko, Gary.  Corneal staining grid. Available at: http://staininggrid.com/. Accessed May 1, 2008.

 

Bausch & Lomb Corporation. Truth about corrneal staining. Available at: http://www.truthaboutstaininggrid.com. Accessed May 1, 2008.

 

Butcko V, McMahon T, et al.  Microbial keratitis and the role of rub and rinsing. Eye Contact Lens 33(6): 421-423, 2007.

 

Hutter J. FDA Group V: Is a single grouping sufficient to describe silicone hydrogel performance. Available at: http://www.siliconehydrogels.org/editorials/nov_07.asp. Accessed May 1, 2008.

 

Jones L, MacDougall N, et al. Asymptomatic corneal staining associated with the use of balafilcon silicone-hydrogel contact lenses disinfected with a PHMB-preserved care regimen. Optom Vis Sci. 79(12): 753-761, 2002.

 

 

 

 

Attachment F - Human Factors

 

De Oliveira PR, Temporini-Nastari ER, Ruiz Alves M, Kara-Jose N. Self-evaluation of contact lens wearing and care by college students and health care workers. Eye Contact Lens. 2003 July;29(3):164-7.

 

Donshik PC, Ehlers WH, Anderson LD, Suchecki JK.  Strategies to better engage, educate, and empower patient compliance and safe lens wear: compliance: what we know, what we do not know, and what we need to know.  Eye Contact Lens. 2007 Nov;33(6 Pt 2): 430-3; discussion 434.

 

Kaye R, North R, Peterson M. UPCARE: an analysis, description, and educational tool for medical device use problems. Available at:

https://www.medsun.net/participants/Uploads/kaye_2491.pdf. 2003. Accessed November 2005.

 

Attachment G – Documents

 

US FDA/CDRH. Contact Lenses. Available at: www.fda.gov/cdrh/contactlenses. Accessed May 1, 2008.

 

US FDA/CDRH. Guidance on Medical Device Patient Labeling; Final Guidance for Industry and FDA. (April 2001).

 

US FDA/CDRH. Premarket Notification (510(k)) Guidance Document for Daily Wear Contact Lenses. (May 1994).

 

US FDA/CDRH. Premarket Notification (510(k)) Guidance Document for Contact Lens Care Products. (May 1997).