Contact Lens Regulations and Compliance

This article discusses patient compliance with contact lenses and solutions, including the varying roles of all parties involved in the industry.

BY WILLIAM J. GLEASON, O.D.
May 1999

Compliance is a major problem with many areas of health care, and contact lenses are no exception. The U.S. Food and Drug Administration (FDA), product manufacturers, practitioners and patients each play a significant role in establishing compliance with contact lenses and solutions.

Premarket Compliance

The principal objective of the FDA is to provide a reasonable assurance of the safety and efficacy of drugs and devices both before and after they are approved for public marketing. Premarket compliance includes nonclinical and preclinical testing, and controlled clinical investigation.

Nonclinical and preclinical testing -- The FDA does not permit clinical testing until after a device's physical and chemical characteristics (i.e., microbiology and toxicology), are shown to be sufficiently safe for use by human subjects in clinical trials. Microbiological testing must demonstrate that contact lenses and solutions are sterile when delivered by the manufacturer and remain sterile until opened. Shelf-life dating describes the time period in which chemical integrity and sterility is maintained in the unopened package. Once opened, lenses and solution containers are readily subject to external contamination. Microbiological testing must also prove that a solution can maintain a satisfactory degree of preservative or disinfection efficacy after being opened.

Toxicological analysis is also critical because contact lens materials and solutions may be carcinogenic, mutagenic, irritating or sensitizing to ocular tissues and may produce toxic by-products via leaching from the lens or the solution containers. Before lens polymers, additives and solutions can be tested on human subjects, their potential toxic response is evaluated through animal models, bench and laboratory testing. If these tests substantiate sufficient safety, in vivo human studies can begin. Non-human tests include ocular irritation in rabbits, evaluated by the Draize test (slit lamp biomicroscopy and histology), the Agar Diffusion test for cytotoxicity and a systemic toxicity test (Table 1).

Classifications -- The general history and potential risk/benefit factor of a product determine which class it's placed in (Class I - general controls, Class II- special controls or Class III - premarket approval). Class I general controls are insufficient in ensuring the safety and effectiveness of contact lenses and solutions. Paradoxically, polymethylmethacrylate (PMMA) contact lenses were "grandfathered," and are not required to conform to the newer regulations. Even though PMMA lenses have greater potential safety consequences than soft or RGP lenses, the regulation of PMMA lenses in Class I does not require approval.

Class II special controls are used to determine the substantial equivalency of investigational contact lenses or solutions compared with similar, previously approved products. Nonclinical and preclinical testing is performed on lenses and solutions, and if the results are satisfactory, clinical trials begin with randomization techniques, controls of known comparison population or a one-eye-to-one-eye control to demonstrate whether or not performance characteristics of the contact lens or solution performs in relation to comparable, previously approved products. Direct safety and efficacy measures aren't proven. Class II also requires quality assurance testing to demonstrate accurate, consistent device reproduction and to ensure that devices perform according to labeled indications.

Class III also requires appropriate nonclinical and preclinical testing. In addition to a longer clinical testing duration, the extensive controls in Class III also require that a greater number of human eyes be tested. As in Class II, Class III contact lenses are compared with similar, previously approved products to prove substantial equivalency. Class III contact lenses must also demonstrate independent safety and efficacy. Data from Class III device testing is reviewed by FDA personnel and periodically by the Ophthalmic Devices Panel. The Panel is comprised of a group of non-governmental optometric and ophthalmologic experts who act as an objective, independent advisory group to the FDA. The Panel can make recommendations, but only the FDA can make the final decision for approval or rejection. Approval for Class III devices is designated as premarket approval (PMA). Testing data for Class II devices is evaluated without any input from the Ophthalmic Advisory Panel and devices are cleared under a 510(k) premarket notification.

FDA regulations state that submissions for Class III devices should be evaluated and responded to within 6 months and Class II devices within 3 months. When Class II special controls sufficient to assure that the qualities of the device in question and those of similar, preapproved devices are reasonably equivalent, it is in the interest of the public, practitioners and industry to use this quicker, less expensive procedure (Table 2).

Clinical Investigation -- Clinical trials are necessary to obtain safety and efficacy evidence for Class III devices and substantial equivalency evidence for Class II devices. The Investigational Device Exemption (IDE) enforces controlled, clinical trials. The purpose of the IDE is to ensure patients' protection in clinical studies by avoiding undue risks. Patients must be fully informed about the study and its potential risks before they consent to participate. They are given a consent form informing them about the study, along with verbal amplification from the investigator. Both the patient and the investigator must sign the form, which is independently witnessed.

IDEs are granted in both significant and nonsignificant risk categories. Nonsignificant risk studies are performed under an abbreviated IDE, which must be approved by an Institutional Review Board (IRB) prior to study implementation. Nonsignificant risk studies include daily wear contact lenses and solutions with "known" components, while significant risk studies are primarliy restricted to extended wear contact lenses. Significant risk study protocols must be reviewed and approved by both an IRB and the FDA before clinical trials begin. IDE progress reports and continued monitoring by the study's sponsor and the FDA are required to ensure safe progress throughout the study. The study protocol may be modified to address safety concerns and the study may be suspended pending any necessary corrections, or even terminated.

Prior studies and the investigational plan are the major components of a proposed study submitted to an IRB or the FDA. Prior studies include nonclinical and preclinical testing and may also include previous clinical testing done on similar products and small feasibility studies done on the investigational product. The investigational plan includes the study's detailed objective, design, conduct and proposed outcome analysis.

An IRB or the FDA first determine if prior reports substantiate sufficient safety for clinical trials. If they do, the investigational plan is evaluated to ensure that all essential elements are included and properly described so that investigators understand what to do, the subjects receive the proper information and instructions and the study's data are properly gathered and analyzed among investigators. The study must be scientifically valid and the investigational procedure must safeguard patients' well-being.

Significant components related to patient protection are the informed consent form, the written and verbal instructions and the management of any significant tissue complications or adverse effects. Adverse effects are any unanticipated conditions that might be sight-threatening (e.g., a corneal ulcer). Significant tissue complications, while less serious, occur more frequently. Slit lamp quantifications of findings are graded as: 0 (none), 1 (trace), 2 (mild), 3 (moderate) and 4 (severe) for epithelial edema, epithelial microcysts, corneal staining, limbal injection, bulbar injection, corneal neovascularization and tarsal conjunctival abnormalities. The grades of each of these are specifically defined in an approved manner. While grades 0 through 2 are often acceptable, grade 3 is usually suspicious and grade 4 is unacceptable. Corneal striae, corneal infiltrates, corneal ulcers and iritis aren't graded, but their occurrence is also unacceptable. A very small incidence of adverse reactions or sufficient incidence of grade 3 or 4 tissue reactions requires that a study be modified, suspended or terminated to protect the subjects.

Postmarket Compliance

Clinical investigations done before market approval involve a small number of patients and an even smaller number of highly qualified practitioners. Studies are extremely organized and monitored in terms of what, when and how the protocol is followed, including patient education and patient responsibilities. Compliance by both the practitioners (investigators) and the patients (subjects) is especially good. Patients are usually given specific types of contact lenses and care products, which are only to be used according to detailed written instructions. Patients or practitioners who violate these instructions can be disqualified from the study.

After the approval of a device, the floodgates of noncompliance can open widely. Devices are much easier to control in a study because of the limited number of patients and practitioners involved. After a device is approved, nearly 30 million contact lens wearers and thousands of eyecare practitioners may use or prescribe various lenses and solutions, often producing chaos in the eyecare arena. Fitting guides are often not followed, lens care systems are combined and patient instructions are poorly delivered or not followed at all. Studies indicate that over 70 percent of patients are noncompliant in one or more aspects of contact lens care (Fig. 1).

FIG. 1: Thimerosal adsorbed and absorbed on a soft contact lens. Patient had been told not to use solutions containing thimerosal.

The FDA -- While practitioners are governed by state laws and licensure, manufacturers are regulated by the FDA. The FDA's approval terms for a given product are described in the approved labeling section that appears on and is inserted in the packaging. With contact lens solutions, the labeling insert usually includes the purposes of the product, chemical descriptions, actions, use indications and contraindications, warnings and precautions, adverse reactions, directions for use, shelf-life and in some solutions, recommended discard dates. Unfortunately, many patients don't read the labeling insert, especially when it's printed on the inside walls of the cardboard packaging, which makes reading difficult, or when the printing on the package is so small that it's illegible. All manufacturers' product advertising must correspond with FDA approved labeling.

The FDA also has a set of Quality System Regulations (QSRs) that product manufacturers must follow. QSRs ensure that the methods and facilities used in manufacturing, packaging, storing and installing devices are safe, effective and in compliance with the Food and Drug and Cosmetic Act. The FDA visits manufacturing sites periodically to assure compliance with the QSRs. Violating QSRs may result in fines, production and shipping stoppage, the seizure of products or the closure of manufacturing facilities until compliance is reinstated.

If more adverse reactions occur than originally expected after the product has been approved and marketed, the FDA can withdraw approval at any time or work toward modifying the indications. For example, at one time, extended wear soft lenses were approved for a maximum of 30 days of continuous wear based on individual studies. However, the combined data for all FDA related soft extended wear studies and other independent studies suggested that 30 days was too long, so the FDA changed the maximum continuous wear guideline to 7 days.

Although practitioners are not directly governed by the FDA, prescribing or recommending devices in any way that differs from original FDA guidelines can lead to legal problems. Should an adverse reaction occur with subsequent malpractice litigation, practitioners might find it difficult to substantiate the validity of their professional judgement. In today's healthcare world of insurance companies and third-party payers, practitioners are more likely to be found culpable when their patients don't comply and suffer adverse reactions. In our litigious society, this "misprescribing" can lead to lawsuits, loss of panel membership and loss of patient access.

Improved Contact Lenses and Solutions -- Noncompliance is a major cause of contact lens problems, but it involves more than just patients. Contact lens materials and solutions are foreign elements to the ocular surface, that is they do not completely comply with its physiological needs. For example, a lens can act as both a patch and a bandage. The effects of either can produce infectious or inflammatory complications. As a patch, the lens reduces the amount of oxygen available to the cornea as well as the dissipation of carbon dioxide from the cornea. As a bandage, the lens interferes with the flow of precorneal fluid, inhibiting the removal of waste materials, and the lens may become contaminated with particulates, microorganisms and chemical materials.

Contact lens manufacturers are working diligently to produce materials that have greater oxygen transmission in order to reduce the effects of the patch and to enhance physiological compliance. Early RGPs and soft contact lenses had a transmissibility (Dk/L) of less than 10, but today some produce a Dk/L of over 100! The bandage effects have been reduced by the more frequent replacement of soft lenses with disposables or planned replacement modalities and by the development of less toxic solutions. Disposables and planned replacement modalities account for about 80 percent of new or refit soft lens wearers and almost 65 percent of all established soft contact lens wearers.

In addition to developing less toxic solutions, manufacturers have created multipurpose solutions (MPSs), which often combine rinsing, cleaning and disinfecting functions. These solutions simplify lens care and may increase compliance because they reduce or eliminate the need for many separate products. Some practitioners believe that these solutions are less efficacious than separate solutions. This may be so, assuming that patients use the separate solutions correctly, but many of them don't, making multipurpose solutions more equivalent in efficacy to separate solutions. Today, over 80 percent of soft chemical lens disinfection sales and about 90 percent of care kits consist of multipurpose contact lens solutions.

Marketing Considerations -- Not only have contact lens materials, modality uses and solutions changed dramatically in the past decade, but so have other factors relating to patient compliance. The amount of money spent on direct consumer advertising by manufacturers has increased significantly in the past few years. Manufacturers currently spend over $50 million dollars a year on radio, TV, magazine and mail advertisements (about a 10 times increase from the past decade), while solution manufacturers spend over $20 million dollars a year, as compared to about one million dollars only two years ago. Free trial contact lenses cost manufacturers about $80 million dollars a year, or 8 percent of their market sales, and free care kits cost them tens of millions of dollars annually. Although the positive aspect of this increased advertising spending is more patient awareness, it may also lead to more confusion and less compliance with practitioners' recommendations for specific products.

Patients often find themselves confused by the large array of products on drug store and mass merchandise discount store shelves. They may believe that brand X is the same as brand Y and purchase the least expensive. This decision would be acceptable if the chemistries of the solutions were identical or at least notably compatible with their eyes, lenses and other care products, but this is often not the case, especially with private label RGP solutions.

Private label sales were only 3 percent of the total soft lens solution market in 1995, but today they comprise about 15 percent, while over 50 percent of salines used are private label. Mass merchandisers account for about 50 percent of all solution sales and drug stores for about 25 percent.

Contact lens mail-order distributors spend over 3 million dollars in direct consumer advertising a year and they provide about 12 percent of all soft contact lenses and 22 percent of disposable and planned replacement lenses. Some mail-order distributors supply care kits containing solutions that may not be the brand the practitioner has recommended for a particular patient. An increasing number of patients are choosing mail order primarily because the cost is often less than with practitioners, and secondarily because of convenience. A problem with this is that patients may try to solve their problems with lens replacements, when they actually may require professional evaluation.

Despite direct advertising attempts, mail-order products and contact lens and solution purchases at drug and mass merchandisers, over 80 percent of contact lens wearers visit their practitioner about once a year for check-ups and an additional one to two times annually for replacement lenses. Such visits provide practitioners with an excellent opportunity to update and review contact lens compliance factors with patients.

Reasons for Noncompliance -- The general reasons for lens noncompliance vary. Many patients complain that keeping up-to-date with their lenses and products is too much work and that they're too tired or lazy to comply. For others, using the various solutions as recommended is too costly, often leading to shortcuts such as reusing or "topping off" disinfection and storage solutions (Fig. 2). The increase in advertisements, available products, private labels and mail orders contributes to noncompliance by supplying a potentially overwhelming number of choices to patients.

FIGS. 2A & B: Rubbing and rinsing of contact lenses is very important but is often curtailed by patients because of the related time and expense to do it properly.

However, noncompliance isn't always the patient's fault. Sometimes the initial education of the patient is not done correctly. Over time, patients forget instructions, especially if they aren't reinforced periodically by their practitioner.

The common areas of patient noncompliance with contact lens care are: use of incorrect solutions, incorrect use of appropriate solutions, infrequent use of solutions, not cleaning or disinfecting lenses immediately upon removal, using an improper regimen procedure, not adequately following procedures and using solutions beyond their expiration or "in use" date.

Common areas of patient noncompliance are: wearing lenses beyond their healthy life (Fig. 3), wearing lenses for too long on a daily or extended wear basis, wearing lenses when they shouldn't, not visiting a practitioner when problems begin and not having a reasonably up-to-date pair of eyeglasses so that they can function visually and not wear their lenses excessively or when there are problems. A recent patient survey indicated that lens patients only wear their lenses about 75 percent of the time and about 85 percent continue to use eyeglasses occasionally. It also indicated that disposable lens wearers are least likely to continue to use eyeglasses.

FIG. 3: A coated RGP contact lens.

Patient Education -- For successful contact lens use and compliance, patients must be properly educated. Because patients may become fatigued or have trouble with eye irritation, short educational sessions are preferred.

Psychological factors are extremely important in contact lens care. There are four basic ways to help patients acquire a positive mental mindset toward contact lenses. First, help relieve or resolve the patient's anxieties about contact lens wear. Second, help maintain patient motivation for correct contact lens use. Third, help make the patient aware of the need for responsible lens use. Fourth, help patients fulfill their responsibilities by teaching them how to handle, care for and wear their contact lenses. It is estimated that about 75 percent of lens wearers don't receive full explanations and demonstrations with their original care system orientation. Practitioners' recommendations of storage and disinfection system brands are only followed by about 60 percent of their patients, with planned replacement wearers most likely to switch solution brands.

A key to successful contact lens wear is proper maintenance to ensure that lenses are kept free of deposits and microorganisms (Fig. 4). The easier and less expensive the maintenance is, the more likely patients will comply. Digital cleaning and rinsing is an extremely important step but is often not done or only partially done.

FIG. 4: A schematic representation of deposits on a contact lens.

To improve patient compliance, practitioners must educate patients properly about contact lens use and care by consistently reinforcing a combination of written, oral, visual and demonstration modalities. Practitioners should briefly outline any procedures to the patient and explain each part of the procedure in detail. Because instruction is more effective when information is communicated through more than one sensory mechanism, the practitioner should explain and demonstrate all procedures. The patient should then immediately repeat the procedure so the practitioner can correct any errors. Because instructions should be reviewed, literature should also be given to the patient for reference (Fig. 5).

FIG. 5: Frequent cleaning and replacing of cases is often ignored by patients.

When the patient seems to have grasped the pertinent information, give them the appropriate lenses and products to begin wear. Also provide written instructions for them to take home, making sure to include a summary of what has been discussed, along with your telephone number in case they need further assistance. A card can be made for individual patients, indicating that they are a contact lens wearer, wear a given brand of lenses and use a given care system. Patients can use this card for reference and also carry it to inform others that they wear contact lenses, which may need to be verified for driving purposes or removed if there's an accident. The major components of contact lens care education are illustrated in Table 3.

As patients adapt to contact contact lenses, they may experience certain normal, temporary changes in appearance, vision or comfort. Normal symptoms are low-grade and improve as adaptation progresses, while symptoms that remain the same, become worse or are severe are abnormal, often requiring patients to consult their practitioner. Practitioners are responsible for explaining these differences in more detail to their patients. It's also the practitioner's responsibility to tell their patients that the number, type, and severity of symptoms varies among individuals and also between the two eyes of the same individual. Finally, the practitioner should inform the patient that perseverance is important for contact lens adaptation. However, if abnormal symptoms are experienced, patients should remove their lenses and consult their practitioner. This advice applies to both new and seasoned contact lens wearers.

"An ounce of prevention is worth a pound of cure" is an old but true adage. Helping to develop good habits initially is much more effective than trying to detect and rectify bad ones later. Being aware of the general and specific reasons for patient non-compliance helps provide guidance to practitioners so that they can address this pro facto. The FDA must safeguard the public by assuring appropriate pre-market and post market compliance oversight. This process can only be effective if practitioners educate and periodically reinforce to their patients on what to do and what not to do.

Dr. Gleason is the founder and president of Foresight Regulatory Strategies, Inc., which provides clinical and regulatory services to ophthalmic medical device companies. He has been on the faculty of the New England College of Optometry and was Chief of Contact Lens Services at the Beth Israel Hospital, Boston, MA.