Closing the ‘approval gap’ for ophthalmic devices

The FDA’s recent initiatives have been industry friendly.

By Jerry Helzner, Senior Editor

For years, ophthalmologists critical of the US Food and Drug Administration (FDA) have been outspoken in their complaint that the agency is slow to approve new ophthalmic devices that use advanced technology to deliver improved patient outcomes, especially when compared to European regulatory authorities. A 2010 industry-sponsored study and presentation titled “FDA Impact on US Medical Technology Innovation” and conducted by Stanford University Professor Josh Makower, MD, estimates the time lag in US approvals compared to Europe runs from two years to as many as six years.

But while the FDA does not accept all the conclusions of industry-sponsored studies, it does acknowledge a time lag exists in US medical device approvals. What’s more, the FDA doesn’t think its slower, more deliberate process that requires time-tested proof of both safety and efficacy is such a bad thing.

In fact, Malvina B. Eydelman, MD, director of the FDA Division of Ophthalmic and ENT Devices, has called the agency’s process “the gold standard” for demanding that an ophthalmic device demonstrate both safety and effectiveness.

“I am aware of many instances where ophthalmic devices have made it to European markets prior to getting to the US market and have been removed due to safety issues while still being investigated in the United States,” Dr. Eydelman has stated.

Both the Calhoun (left) and Synchrony advanced IOLs are approved in Europe but not in the United States.

NEW FDA INITIATIVES

Be that as it may, the FDA has been hearing the message of its industry critics that the time it takes to review device applications has actually increased significantly since 2007. It has also heard the dire warnings from some of these critics who foresee the lion’s share of medical device innovation moving overseas.

One organization that represents the medical device industry, AdvaMed, estimates that FDA device review times have increased 45% to 75% since 2007, depending on whether the device is simply an enhancement of existing technology or a totally new concept requiring a more extensive review.

In an attempt to reverse that negative trend, the agency last year embarked on a multi-faceted program to help the medical device industry navigate the approval process in a more informed and speedier manner. The program already includes a new public-private partnership called the Medical Device Innovation Consortium to develop a set of best practices for product development and commercialization, new guidelines to help industry conduct more effective clinical trials, and a ground-breaking initiative designed to use the fees industry pay for FDA services to reduce the agency’s review times for device applications.

A ‘regulatory toolkit’

Moreover, in response to questions from Ophthalmology Management, the FDA said it is now finalizing “draft guidance” for manufacturers on early feasibility studies (including first-in-human) that supports device development and the earlier initiation of human clinical studies. One major advantage of the feasibility study initiative, the FDA says, is to allow continuous close contact between developers and clinical investigators as a device moves along the development path.

“This guidance will provide the regulatory toolkit for sponsors and regulators to think in new ways about device development and the evidence appropriate to move from the bench to clinical evaluation,” the FDA said.

The FDA says it recognizes the efficacy and safety of many medical devices can only be proven in human trials and that, in these cases, it advocates for “early clinical use of a device in a limited number of subjects.”

NOT ALL COMPLAIN

Interestingly, some of the nation’s most prolific innovators do not fault the FDA for taking more time than international regulatory authorities to rule on the suitability of commercializing a device.

Daniel Schwartz, MD, of the University of California San Francisco (UCSF), is point person for an ophthalmic innovation team that enlists the expertise of the faculties of UCSF and California Institute of Technology (Caltech). One of the major innovations that has come out of the UCSF/Caltech group is the Calhoun Light-Adjustable-Lens (Calhoun Vision), an IOL that can actually be adjusted once it is in the eye.

Already approved in several European countries and being used successfully in patients, the Calhoun lens is still years away from approval in the United States. Yet Dr. Schwartz understands the FDA’s deliberate pace.

“I’m not surprised it is taking so long to obtain FDA approval for the Calhoun lens,” Dr. Schwartz says. “It’s a breakthrough technology that requires thorough evaluation. We are currently in phase 3 US trials to treat sphere and cylinder.”

Crosslinking procedure shows saturation of the cornea with riboflavin.

Steven Silverstein, MD, FACS, of Kansas City, Mo., has also been involved in the innovation process. He, too, takes a balanced view. “Though frustrating for all of us to read of the technologies and pharmaceuticals available to our colleagues overseas, the FDA, the fierce overseer of safety and efficacy in the United States, is itself under significant scrutiny,” he notes.

“One look back at the class action lawsuits centered on non-selective systemic NSAIDS is a sobering reminder of the consequences that are periodically witnessed when the results of well-structured clinical trials do not pan out when a given product is placed into widespread use,” Dr. Silverstein adds. “We have seen this in ophthalmology as well, for example, with the LTK [laser thermal keratoplasty] treatment for hyperopia and the Holmium laser.”

Doctors offer solutions

Dr. Silverstein says he “strongly agrees that our system is too bogged down with perhaps overly protective regulations” that require proof of product superiority rather than non-inferiority. He says the FDA has in the past been too slow to react when companies either request approval following a successful, lengthy clinical trial, or in fast tracking efficacious, overtly successful and safe technologies.

After a long and arduous process, the Implantable Miniature Telescope (IMT) from Vision-Care Technologies was approved by the FDA in 2010.

“Perhaps, as a starting point, we can come to a consensus with the FDA for speeding up the approval process, not by lowering its standards for safety and efficacy, but rather in significantly increasing the budget for manpower and resources that would permit a much smoother and efficient road to more quickly bringing new, patient-benefiting treatment modalities to market,” Dr. Silverstein says.

Alan Aker, MD, of Boca Raton, Fla., in a guest editorial in Ophthalmology Management last year, was highly critical of the FDA approval process for ophthalmic devices.

“The United States, the traditional leader in new technology in most fields of endeavor, has now become the land of the Have-Nots,” he wrote. “We look longingly at those who have — namely, our European colleagues with unfettered access to a whole array of products to enhance the vision of their patients. The Old World gets all the newest products these days.”

In his editorial, Dr. Aker proposed a modification of the FDA approval process, questioning why ophthalmic products currently safely and routinely used in Europe should not also be approved in the United States.

PESSIMISTIC PREDICTION

“The losers at present are US surgeons and our patients,” Dr. Aker concluded. “But companies that develop and manufacture ophthalmic technology also suffer. Because of the almost prohibitive costs needed to sustain an FDA approval process, many technologies will take years to make it to our shores, if they make it at all. Some companies are forced to make the hard-nosed business decision to simply opt out of the US market, after they sized up the return on investment and found it wanting. ‘Why bother?’ they ask. Why, indeed.” OM