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By Fred Gebhart
The FDA wants to help drug and device developers get their products approved and on the U.S. market faster and earlier.
A series of new programs and guidances appear to be working, at least for devices. In 2011, approval for a full IDE took a median of 442 days. In 2014, that same full IDE approval took a median of 101 days.
The panel addresses questions during the "Getting to New Horizons: FDA Panel Discussion" session. The panel included (from left) Stuart Abelson, MBA, of ORA Inc., Wiley A. Chambers, MD, of the FDA, Kuldev Singh, MD, Malvina B. Eydelman, MD, also of the FDA, and Eugene de Juan, Jr., MD.
“If you have a device in development, come and talk to us early and often,” advised Malvina Eydelman, MD, director of the FDA Division of Ophthalmic Device Evaluation. “We have new tools like the Early Feasibility Study that allow us to hold your hand through the entire process as needed to get a product to market expeditiously.”
Dr. Eydelman outlined FDA’s new process designed to simplify and streamline the approval process during a panel discussion on “Getting to New Horizons.” The agency has new guidances on early feasibility studies that include some first in-human studies as a new guidance that defines MIGS for the first time.
“You have to remember that we have never before had a consensus on what MIGS means,” said Wiley Chambers, MD, supervisory medical officer in the FDA Division of Transplant & Ophthalmology. “MIGS could mean minimally invasive glaucoma surgery or it could mean micro-incisional glaucoma surgery. You can do a very invasive procedure using very small instruments. You can make a very large bleb through a 50-µm hole in the eye.”
Under a guidance issued in February 2014, MIGS is a minimally invasive glaucoma surgery. A MIGS device is “a type of IOP-lowering Device used to lower IOP using an outflow mechanism with either an ab interno or ab externo approach associated with little or no scleral dissection and minimal or no conjunctival manipulation.”
The draft guidance also contains the agency’s first-ever written recommendations on study design and duration, follow-up, clinical endpoints, safety considerations, and more.
Plan on a minimum of 12 months of patient follow-up and be prepared to justify any follow-up period of less than 24 months based on projected risks and benefits.
All patients should undergo a washout period of all IOP-lowering medications before surgery to establish a baseline IOP. If IOP-lowering medications are restarted after surgery, patients need another washout period prior to IOP measurement and other data collection used in effectiveness analyses.
The recommended primary endpoint is the percentage of subjects with a reduction of at least 20% in mean diurnal IOP from baseline. The recommended secondary endpoint is the mean diurnal IOP change from baseline.
Other recommended analyses include percent reduction in mean diurnal IOP changes in the mean, range, and maximum of diurnal IOP measurements with box-plots for mean, range, and maximum of diurnal IOP; fluctuation of IOP measurements over time; changes in numbers of medications used; and an assessment of balance in baseline variables.
The draft guidance is a point from which to begin discussions with the FDA, Dr. Chambers said. It will not put an end to current applications in which similar devices with similar mechanisms of action are proceeding along different pathways.
One device might aim for a 510(K) approval with a 75-patient study. Another, seemingly identical device, might aim for Premarketing Approval with a 550-patient study. What the agency hopes it will do is encourage developers to work with the FDA early and often to determine which pathway and what types of studies are more appropriate for the most expeditious approval possible.
New internal guidelines and response times are helping too. Dr. Eydelman said her office now has specifically charged with expediting information requests. A product developer looking at a first in-human study, for example, can email the FDA and get a quick, complete response on how to proceed, usually in two business days.
“The response will have links to all of the guidances and guidelines and all of the relevant information that will get you to an actual submission,” Dr. Eydelman added. “At that point you can ask product specific questions and come and meet with us. We will be able to provide you with expeditious answers.”
The agency is trying for similar flexibility in drug trials and approvals. FDA is bound by laws to require accurate and well-controlled trials. Everything else is up for discussion.
“We really don’t care what you do in phase I or phase II,” Dr. Chambers said. “We try to give as much leeway as we can to help people obtain enough information to plan their phase III trial. If you do it right, you can start with a phase III trial and get approval.”