The FDA has recently proposed changes to its guidance document for lens care approval and lens material classification. This has provoked a great deal of discussion about solution testing revisions, such as the addition of Acanthamoeba to protocol testing. Will more stringent endpoints with additional testing impact safety without placing a heavy emphasis on human factors testing?
Human Factors Validation
Because the FDA is risk averse and 510(k) submissions do not always typify the real world, human factors validation testing helps satisfy FDA concerns for safety. Looking for risky behavior—in particular, evaluating environmental and situational factors that affect care product performance—seems crucial to help assure safe lens wear. And, we don’t have to look too far to see the value in this.
In the past decade, we have seen two solution recalls that highlight the importance of not only evaluating safety measures, but also scrutinizing hygiene practices and patient behaviors. The voluntarily recalled solutions had a low margin for safety when placed under stress, but the recalls were prudent, because better solutions were available at the time.
It is important to note that the solutions recalled were not “unsafe.” When used properly, the products were effective for many thousands of patients and did not yield a significant number of adverse events. But the need for ongoing surveillance cannot be reiterated enough; the problems in the solutions described above likely could have been identified earlier if additional measures were in place.
The FDA Guidelines
From 1982 to 1990, the FDA modified its guidelines for contact lens care products at least six times. A short time later the agency issued guidance documents, “Pre-Market Notification 510(k) Guidance Document for Contact Lens Care Products,” for soft lenses.1 Another important milestone, the International Organization for Standardization (ISO), was developed between 1990 and 2003.
However, by most standards, not much has been modified over the past decade. Current testing protocols do not include using a lens or case for the microbial testing regimen. In addition, the library of isolates tested under the current guidance is outdated. For example, the current American Type Culture Collection strain of Fusarium does not form a robust biofilm and may not adequately predict disinfection efficacy in the lens storage case today. It seems prudent to select clinical isolates based on virulence, and to manage the testing in such a way as to maintain a wild-type capacity for disease.
Real World Disinfection
In 2009, the FDA consortium on lens care addressed the topic of disinfection. At that meeting, proposals for testing under “real world” conditions—specifically for examining both lenses and their cases—were suggested. In addition, Acanthamoeba testing requirements were heartily debated. The conversation addressed several points:
- The necessity for protozoan testing and the most effective methods to do so.
- “Uptake and release” of preservative studies to evaluate the impact on disinfection efficacy.
- Establishing the simulated care scenario using lenses and cases.
- Human factors studies looking at risky behavior (e.g., not rubbing and rinsing, topping off solution, behaviors that promote evaporation, etc.).
Testing under “real world” and extreme climatic conditions seems reasonable. The testing protocol should be structured to be sufficiently sensitive to capture user-related problems.2,3 High priority tasks or user scenarios, including environmental and situational factors that affect performance, also must be part of the protocol. Most importantly, monitoring usage during the clinical trial, as well as post-marketing surveillance, is a key component in assessing any user-generated issues.3
Unfortunately, there hasn’t been a similar consensus on best testing methods for Acanthamoeba; challenges include size, strain(s) to be tested, culturing techniques for growth, cyst stage production (easier to kill when they lose characteristics with passes in sub-cultures), how to measure survivors, protocol for testing solution efficacy in the presence of a lens and case, and whether to measure encystment.3,4 Remember that cysts, although part of the life cycle, don’t cause infection. Trophozoites, however, do.
Mind you, the testing process has served us well and is not entirely broken. But clearly, an overhaul and upgrade is needed. Regulatory mandates that include more stringent endpoints and added testing for protozoa may not, however, be the complete answer. While many experts are uncertain that such testing will significantly impact the rate of rare, non-bacterial infections, the fact that the public has an extremely low tolerance for rare infections makes any preemptive steps that we can take a necessity. We encourage the FDA to place a continued emphasis on human factors testing and analyze the behaviors that can lead to problems in contact lens wear. Appropriate analysis with adequate product labeling and surveillance should be protective.
In addition, human factors testing can be the “safety net” we need to enhance the margin of protection and assure effective lens wear. With these enhanced steps, we’ll not only learn what’s happening in the lens case, but also perhaps we will find out what’s going on in our patients’ heads!
1. Anger CB. Personal communication. 2010 May 2.
2. Clayton-Jeter H. Looking good: safe use and care of contact lenses. FDA. 2010 May.
3. Human factors validation testing. Human Factors MD. Available at: www.humanfactorsmd.com/validation-testing. Accessed January 2013.
4. Willcox M. Acanthamoeba testing for multipurpose disinfecting solutions. Silicone Hydrogels website. 2009 Feb. Available at: www.siliconehydrogels.org/editorials/feb_09.asp. Accessed February 2013.