SPECIAL ANNIVERSARY SECTION
Contact Lenses: A Regulatory Perspective
BY WILLIAM J. GLEASON, OD
Before the release of soft contact lenses in the early 1970s, the United States Food and Drug Administration had little to do with regulating the contact lens industry.
Prior to the development of device regulations, the FDA approved and regulated the polymacon (B&L Soflens) material as a drug, including the requirement of additional labeling information printed with the advertising. While these restrictions were quickly relaxed, it did provide an indication of the oversight this new industry would be under.
In 1976, the first medical device regulations placed contact lenses and their various care systems into the most restrictive Class III designation. This classification was far less restrictive than the drug classification, but there was confusion at the time regarding what information would demonstrate the safety and efficacy of the product. Nevertheless an independent panel recommended that the agency keep contact lenses classified as Class III-Premarket Approval (PMA). This action kept contact lenses under the highest form of premarket scrutiny prior to approval.
After several iterations of guidance, FDA Device Center's Ophthalmic Division issued its broadest document pertaining to testing requirements in 1986 (20 years ago), providing the industry with a well-defined path to follow and minimum requirements expected in a product approval application. While many disagreed at the time with the burden this put on small manufacturers, at least there were rules to follow.
The mid- to late-1970s saw the emergence of GP materials and two different industries both under the same set of regulations. Unfortunately, the original guidance document applied mostly to soft lens development, and some of the regulations were unnecessary for the new GP materials.
Incorporating Lens Care
The initial FDA Guidance documents focused on lens materials. The FDA incorporated contact lens care systems into these guidances as accessories to the regulated device, contact lenses. If history has taught us anything it's that care systems and accessory solutions including in-eye drops are as much a part of the success or failure of the material as is the safety and efficacy of the device.
On the soft lens side the industry soon realized that a daily cleaner was a necessary part of the care system along with the nightly disinfection in the converted bottle warmer. Because soft lenses were expensive in the early days, they required an aggressive cleaner to extend their life expectancy, resulting in the introduction of enzyme cleaners.
Regulators had not envisioned complications following the use of salt tablets to make normal saline or the irritation and toxicity that would result from prepackaged preserved saline. While never officially removed from the market, the FDA's request to manufacturers to discontinue distribution of salt tablets and the potential legal consequences from consumers eventually resulted in their disappearance from the market.
The introduction of various packaged saline solutions using previously familiar preservatives also resulted in a number of complications. Thimerosal and chlorhexidine acetate resulted in numerous irritations and levels of toxicity giving rise to a number of new contact lens complications, all of which were discovered in clinical practice once the products had received approval. In addition, it also became apparent that not all formulations were compatible with all new materials introduced to the market. Lens care manufacturers now needed to demonstrate compatibility with multiple lenses or at least with a class of materials. From this came the segregation of hydrophilic materials into four classes depending on their water content and surface charge as calculated from their chemical formulation.
On the GP side of the industry, three main competitors were turning out new materials annually in an attempt to reach the perfect combination of oxygen permeability (pure silicone) while maintaining the optical clarity, durability and surface characteristics of PMMA material. These new materials required new manufacturing techniques, special handling and protection from certain lipids and creams once in the hands of patients. This resulted in the development of new cleaners and conditioners and the use of soft lens enzymatic cleaners for GP lenses. All of these new materials and alternate indications for solutions required review and approval and frequently a change in thinking by the FDA.
Indications for Use
In addition to approving materials and solutions that were safe and effective, the FDA also had to address indications for use. The biggest approval was the use of soft contact lenses for extended wear. It became a challenge to see which would wear out first the lens or the eye. In several unfortunate cases it was the eye. In 1989 in cooperation with the FDA, manufacturers reduced extended wear labeling from 30 days to seven days. The incidence of corneal ulcers in contact lens use prompted the agency to issue a new guidance document in April 1989 outlining the various steps necessary to receive extended wear approval for up to seven days.
In 1992, the United States Congress passed the Safe Medical Device Act, the first revision of the Medical Devices Amendments of 1976. Included in this legislation was the requirement for FDA to reclassify daily wear use of contact lenses to Class II. The FDA issued this guidance in 1994 followed by the solutions guidance in 1997. Both gave updated information on the material and clinical testing necessary to prove a new material was "substantially equivalent" (SE).
While not all statisticians will agree, justifying SE required less testing than justifying safety and efficacy as long as manufacturers could find a previously approved product as a comparison. One outcome of the new regulations is that the FDA has approved several new products by smaller manufacturers who most likely would not have had the resources to approve a product under the previous Class III designation.
New fluorosilicone hydrogel materials began to emerge at the turn of the century, and once again the FDA faced the challenge of approving a lens for greater than seven days extended wear. CIBA Vision was the first in line with its Night & Day, followed quickly by B&L's Purevision contact lens. Menicon Z, a fluorosilicone GP material, also received approval for the same indication.
Along with the initial approvals, the FDA attached a stipulation that the materials must undergo post-market surveillance in a population sufficiently large to assure the agency there were no additional safety concerns. This is consistent with drug approvals and other significant risk devices.
While materials have been pushing the envelope for extended wear, solutions have been doing the same in the form of multipurpose solutions. While current solutions meet the requirements established many years ago for compatibility, microbial challenge and cleaning efficacy tests, they may no longer be appropriate or compatible for newer materials. It appears we can no longer classify materials by their water content and calculated surface charge. The various surface treatments and polymers impregnated into the new material matrix may have antiquated this approach.
Into the Future
The FDA is currently facing the challenge of maintaining product approvals, guidance documents and standards of the past while developing new approaches as solution/material complications and interactions come to light. Rare adverse complications have surfaced in the past and will certainly challenge the agency and industry in the future. The guidance documents and standards will need to be living documents that the FDA can modify as new information becomes available. In the end, the agency's job is not to approve products but to protect the general public.
Dr. Gleason is the founder of Foresight Regulatory Strategies, Inc. He has more than 25 years of experience in basic research and management of clinical trials for medical devices.