A new final guidance document published by the US Food and Drug Administration (FDA) recommends to sponsors methods of conducting clinical research in support of investigational medical device products intended to treat retinal diseases and their associated impairments.
The release of the guidance, Investigational Device Exemption (IDE) Guidance for Retinal Prostheses, comes just weeks after FDA's Center for Devices and Radiological Health (CDRH) approved Second Sight Medical Product's Argus II Retinal Prosthesis System, dubbed by some to be the "world's first bionic eye."
That device was approved by FDA as a humanitarian use device (HUD), and is indicated to treat advanced retinitis pigmentosa (RP), a rare genetic eye condition marked by progressive damage done to light-sensitive cells that help people to see in low-light conditions and more fully in general. The condition often leads to total blindness.
The prosthesis works by turning the signal from an attached video camera-mounted on a pair of eyeglasses-into a signal, which is then transmitted to the implanted retinal prosthesis. While the device is unable to replicate sight perfectly, it allows patients to regain enough sight to accomplish simple but otherwise unattainable tasks.
Scope of Guidance
But for every trail-blazing product, there are others wishing to follow in its wake. The Argus was perhaps unique in that it had a massive amount of government support--$100 million from the Department of Energy, the National institutes of Health (NIH) and the National Science Foundation (NSF). Other companies aren't always so well-capitalized, and rely heavily on seeking out the regulatory path of least resistance.
That's where FDA's final guidance comes in. Regulators said it is intended to assist sponsor with a future 510(k) premarket notification, premarket approval (PMA), or humanitarian device exemption (HUD) application going before the agency for a visual prosthetic device.
These devices include "visual prosthetic devices implanted on or beneath the retina, and those on or beneath the outer surface of the globe that use electrical stimulation to provide some level of visual perception for persons suffering from degenerative retinal conditions," FDA explained. Not included: devices that stimulate the optic nerve or higher brain areas.
IDE applications submitted to the agency must include general information about the device-pictorial representations, engineering drawings, schematics, detailed descriptions of cabling and interconnects-but also information more specific to visual prostheses, such as the type of photosensor or video input and processor used with the retinal implants, the resolution and configuration of the sensors, eye-tracking capabilities and how these are connected to the human body or the device.
Pre-clinical testing should focus on the device's biocompatibility, including bacterial endotoxin testing, leachables testing and pyrogen testing. Animal testing is recommended, and should be structured to test the device's effect on the animal eye (acute testing) over short- and long-term periods, with the formal representing near-maximal limit stimulation testing and the latter representing normal use over a period of at least six months.
Testing should also be done to simulate electrode stimulation, assess the durability and lifetime of the device's numerous parts and coatings, determine how the software and electronic hardware used on the device operate in various conditions, assess the product's compatibility with magnetic resonance imaging and other forms of radiation, and the functions of its packaging.
The guidance also describes the numerous clinical considerations associated with testing the device on human subjects. Chief among FDA's concerns seems to be safety, as the Argus device had a high number of serious adverse events, including "erosion of the conjunctiva (the clear covering of the eyeball), dehiscence (splitting open of a wound along the surgical suture), retinal detachment, inflammation, and hypotony (low intraocular pressure)."
Sponsors are advised to report all unanticipated adverse device effects, and to set primary safety endpoints in trials to ensure that patients are not adversely impacted if the device is not well-tolerated.
As per efficacy, FDA's guidance outlines a number of "assessments of visual function" that it recommends be used to evaluated a retinal prosthesis: use of letter charts, full-field grating acuity using forced-choice paradigms and fixed-time intervals or presentation, spatial mapping, form vision assessments, orientation and mobility tests (real-world performance), activities of daily living, and patient-reported outcomes.
FDA also noted in the guidance that the field is still remarkably young, and that its guidance may become outdated shortly.
"Given the limited history with devices in this field, additional information may become available at a later date that suggests alternative test methods or functional assessments that may be more appropriate to assess the safety and effectiveness of retinal prostheses."
"For this reason, we strongly suggest the sponsors of such devices submit a Pre-Submission to facilitate discussion of clinical trial designs, pre-clinical test protocols, and proposed indications for use for any specific retinal prosthesis," FDA concluded.