Many important steps are required to take a product from its initial concept to market, including design, building, packaging, testing, and sales. In medicine, an increasingly complex yet critical part of the process is the FDA’s approval or clearance of the drug or device.
Major lapses in safety prompted the passage of the 1906 Pure Food and Drugs Act. One such disaster involved a mascara called Lash Lure, the use of which caused blindness. Public awareness of tragedies such as the deformation of limbs by the use of thalidomide in the 1960s led to tighter regulations. Today, the FDA regulates roughly $1 trillion of commerce (approximately 25% of the US gross domestic product).1 The agency’s budget is nearly $4 billion, of which about one-half is provided by companies seeking approval/clearance.1 The FDA is a law enforcement arm of government. The agency’s operations and rules are not easy to understand or inexpensive to comply with, but it is essential to work with the FDA to make safe and effective products available to patients. This article serves as an introduction to that process.
WHAT IS THE IDEA?
What sort of product is it? The FDA regulates drugs, devices, diagnostic instruments, biologics, cosmetics, and food.
All new active chemical agents are drugs, and there is a clearly delineated path to demonstrating their safety and efficacy. Generally, when the drug (even an established, well-known agent) is combined with a device or a new formulation, it requires new testing. Not all drug-device combinations are true combined products; some are determined to be primarily a drug (eg, a drug-eluting punctal plug) or primarily a device (eg, a drug-coated cardiac vessel stent).
The 510(k) Process
A new device may bear similarities to a product made available before 1976. If so, the manufacturer can submit a Substantially Equivalent 510(k) application. The pathway to FDA clearance is shorter for these products than for a device not in this category.
Of course, the agency reserves the right to overrule these guidelines. For example, daily wear contact lenses are 510(k) devices. When one of these products is to be sold for extended wear (ie, overnight or longer), however, the FDA has decided that the associated risks are higher and that more extensive testing and controls are needed to support this use and claim. Extended-wear contact lenses require premarket approval, even though it is the manufacturer’s claim—not the device—that is different.
A femtosecond laser can be a 510(k) device. Although lasers were not available prior to 1976, keratomes to cut the cornea were. It was demonstrated to the FDA that a femtosecond laser cuts the cornea in a way that is “substantially equivalent” to how a keratome does.
IOLs are designed to remain in a patient’s eye for the rest of his or her life. These implants are all classified as high-risk (Class III) devices and require a premarket approval regulatory path.
Occasionally, an implant is for use under special conditions identified by the FDA as requiring more limited testing, thus allowing a 510(k) pathway. Glaucoma shunts for use after a failed trabeculectomy are an example.
Rarely (once in ophthalmology), a Humanitarian Device Exemption can be applied to a product. After the device’s 5-year clinical trial in 30 patients, the FDA cleared Second Sight’s Argus II ocular prosthesis for use in blind patients with retinitis pigmentosa. The reasons behind the decision were an absence of other such devices and a demonstration of reasonable safety, as judged by a panel of experts and interested persons. Generally speaking, clinical data on at least 300 patients is required for implants to allow a reasonable assessment of their safety at the 1% incidence level.
The process of obtaining FDA approval or clearance of a product can be complex. The determination of a device’s level of risk (Class I-III) can be helped by the FDA or by a regulatory consultation. The field of ophthalmology will benefit from the recent addition of highly experienced people as consultants and as the heads of the regulatory division on the drug and device arms of the FDA. Those interested in bringing new ideas to market should give them a call.
Eugene de Juan Jr, MD, is founder and vicechairman of ForSight Labs in Menlo Park, California. Dr. de Juan may be reached at firstname.lastname@example.org.
- Food and Drug Administration. Wikipedia website. http://en.wikipedia.org/wiki/FDA. Accessed January 22, 2014.