FDA making changes in approval processes for industry, patients

The laws governing ophthalmic drug and device approvals have changed little in recent years. But the FDA is making significant and far-reaching changes in its approvals process.

On the drug side, sponsors can expect a renewed emphasis on risks and benefits compared to existing products. And on the device side, new final and draft advices are changing the way sponsors and FDA reviewers approach approval decisions.

Two speakers from the FDA offered the latest insider perspectives on the current approval processes during “FDA: Getting to New Horizons” at the 2016 Glaucoma 360 meeting.

Eugene de Juan, Jr., MD, co-moderator, directs a question about the approval process to the FDA's Wiley Chambers, MD (far right). Kuldev Singh, MD, co-moderator, listens. Courtesy of Glaucoma Research Foundation.

Pharmaceutical process

There is no secret to gaining marketing approval for a new glaucoma medication. All sponsors have to do is follow the FDA’s familiar rules. A product must be both safe and effective.

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The problem is determining the balance of safety and efficacy that will sway FDA reviewers. For many medications, higher efficacy is associated with lower safety–and vice versa.

“The last product I saw that had no adverse events had no efficacy,” said Wiley Chambers, MD, supervisory medical officer, Division of Transplant and Ophthalmology Products. “In order to get labeled for a particular indication, you have to pick the indication you wish to be labeled for and conduct ‘adequate and well-controlled trials,’ which are defined in law. And you have to demonstrate the product has the efficacy you think it has.”

Demonstrating efficacy in glaucoma doesn’t have to be difficult, Dr. Chambers continued. The agency has decades of experience with active ingredients, including timolol, latanoprost, travoprost, and bimatoprost. Sponsors are not obliged to compare their product candidates to these agents, but it can be a wise move.

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“These are all products that we have seen in multiple trials,” Dr. Chambers explained. “We know how they behave, we know the safety, we know the efficacy. If you do a comparison to one of those products, you can compare yourself to something we think is efficacious.

“And if you are more efficacious than one of those products, we think you can probably tolerate more adverse events. If you are less efficacious than that product, you should have less adverse events. We didn’t set out to create those comparators, but without them, it becomes difficult to set some kind of bar,” he added.

Shortcuts don’t work when it comes to clinical trials, he continued. The FDA still expects sponsors to conduct at least two phase III clinical trials to demonstrate safety and efficacy, as well as nonclinical studies to evaluate carcinogenicity and other properties that are difficult to study in clinical trials.

Device trial changes

Device trial changes

Device approvals are often compared to a moving target, but approval for minimally invasive glaucoma surgery (MIGS) devices is clearer than before. The agency issued a final guidance on Premarket Studies of Implantable Minimally Invasive Glaucoma Surgical (MIGS) Devices in December 2015. The guidance grew out of a joint FDA-American Glaucoma Society workshop in early 2014.

“There was a lack of definition of devices and patient populations and there were no clear safety targets or endpoints for safety and effectiveness in clinical trials,” said Malvina Eydelman, MD, director of the division of Ophthalmic Device Evaluation. “While we were seeing quite a rapid increase in submissions for MIGS, there was a lack of recognized standards that would clearly delineate safety and efficacy endpoints. We ended up having substantial discussions with each of the individual sponsors.”

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The new guidance delineates key clinical and nonclinical recommendations for MIGS developers. But it does not address one of the hottest topics inside the FDA–patient preferences. Device designers and makers, as well as clinicians, must bring patients into the decision-making process.

“Patient views about the most important benefits and most acceptable risks for MIGS devices may differ considerably from those of health care professionals,” Dr. Eydelman said. “We feel the patient perspective is imperative to incorporate into the next step of MIGS evolution.”

Saying that “patients are the heart of what we do at FDA,” Dr. Eydelman noted that patient preferences have come to inform the development and assessment of medical progress.

The FDA Center for Devices and Radiological Health created a patient preference initiative to develop a systematic approach to assessing, measuring, and incorporating patient preference through the product life cycle, she continued. The agency’s first-ever patient preference draft guidelines were published in May.

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The agency also launched collaborations with Johns Hopkins University School of Medicine to assess patient preferences in glaucoma treatment with a focus on MIGS devices and with Stanford University to develop a patient-reported outcomes measure, assessing quality of life in mild-to-moderate glaucoma patients.

“We believe that the patient perspective should inform medical device development during the total life cycle of the device,” Dr. Eydelman said. “Starting with discovery, patient information is needed. (Patient involvement) will proceed to development of prototype, preclinical, and clinical assessment. Once we look at safety and effectiveness data, patient preference should be part of the benefit-risk assessment.”