Expedited PMA On the Way?

Many, including OTW, have been critical of the FDA’s oversight in getting new medical devices to patients. It seems the agency’s dual mission of protecting and promoting public health has been heavy on the protect side and light on the promote side.

The results are that clinical trials move to other parts of the world, capital is invested elsewhere and U.S. patients have to travel outside the country to get cutting edge treatments. Look no further than high profile professional athletes going to Europe for stem cell therapies.

Who can blame the agency? There are no pats on the back when another patient walks without pain, returns to work or saves insurance companies billions because keeping fit reduces expensive chronic conditions.

But when a device fails, the clamor for someone’s head at the agency is deafening. No wonder they are risk averse.

Yet, the agency continues to promise to speed up promoting lifesaving and enhancing devices. We’ve heard from sources familiar with internal discussions at the FDA that agency leaders have told their staffs that they recognize that medical device start-ups have slowed and they have to find ways to lean on the “promote” pedal.

The “Expedited PMA”

The latest effort is the proposed Expedited Access Premarket Approval Application for Unmet Medical Needs for Life Threatening or Irreversibly Debilitating Diseases or Conditions program, also called, “Expedited Access PMA” or “EAP” program.

The proposal was released for comment on April 22, 2014. The EAP seeks to speed up approvals for patients who have no other treatment options and focuses on earlier and more frequent interactions between companies and FDA staff. It calls for the involvement of senior management and a collaboratively developed plan for collecting the scientific and clinical data to support approval.

The idea is similar to the process the agency uses to speed access to innovative drugs that address serious unmet medical needs such as Fast Track and Breakthrough Therapy designations.

Product Development Focus

The FDA says EAP is not a new pathway to market, but rather a collaborative approach to facilitate product development under the agency’s existing regulatory authorities. While other existing device programs have focused on reducing the time for the premarket review, EAP also seeks to reduce the time associated with product development.

As part of the EAP program, FDA looks to provide more “interactive communications” during device development and more interactive review of Investigational Device Exemption (IDE) applications and premarket approval applications (PMA). In addition, FDA states that it “intends to work interactively with the sponsor to create a data development plan specific to the device.”

Morningstar analyst Debbie Wang told Reuters that this is, “yet another aspect of how FDA is trying to work in a more coordinated fashion so they can reduce the number of false starts and situations of reinventing the wheel, and to help put some priority on which therapies are going to affect the most patients with the greatest need.”

Breakthroughs and Unmet Needs

A device can be eligible for the program if it features breakthrough technology with significant benefits over existing products and are intended to treat or diagnose patients with serious conditions whose medical needs are unmet by current technology.

“We expect most devices that enter this program will be in the preclinical trial phase, says Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health.”

Eligibility

To be eligible for participation in the program, the device must meet one of the following challenging conditions:

First, the device must be intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition.

Second, the device must meet at least one of the following criteria for addressing an unmet need:

1. The device represents a “breakthrough technology” that provides a clinically meaningful advantage over existing technology; or
2. No approved alternative treatment or means of diagnosis exists; or
3. The device offers significant, clinically meaningful advantages over existing approved alternatives; or
4. The availability of the device is in the best interest of patients (e.g., addresses an unmet medical need).

Third, the sponsor submits an acceptable draft Data Development Plan that has been approved by FDA.

More Data, Not Less

In addition to the three prong test to qualify for the EAP program, device companies have to be prepared for some hands on collaboration with FDA. Health Data Management interviewed Bradley Merrill Thompson, a D.C.-based attorney, who questioned the value of EAP.

He said the possible speed of the approval—and there are no guarantees of course that it will in fact turn out to be quicker—comes at the cost of FDA looking over your shoulder the entire way. “Thus, while most devices get approved based on data that the manufacturer develops with modest input from FDA, here the agency potentially micromanages the manufacturer all along the way, potentially driving up the cost of the data development.”

“I see these programs rolled out by FDA every few years; indeed, this program is just the formalization of something that the agency started in 2011. Unfortunately, for the vast majority of companies, these initiatives really do not prove to be useful. As I recall, when the pilot program came out in 2011, there was only one company that participated. A couple years later, when they revised the program, they got only a couple more.”

The problem, he says, is that the bar for the EAP program is too high and the vast majority of medical device developers will not qualify.

Thompson also pointed out that a product has to be a breakthrough technology that is above and beyond currently existing therapies. “Frankly, most medical devices represent incremental improvements.” He says most entrepreneurs proudly tout the benefits of their new products, but when the FDA looks at them it characterizes the gains as more modest.

Mark DuVal, a well-known industry attorney, agrees with Thompson. He told us the proposal requires more premarket work for companies, not less as was recommended by Institutes of Medicine. DuVal also said while it’s important for the agency to encourage breakthrough technologies and orphan drugs and devices, most of innovation comes in increments through the 510(k) program. He fears the agency is increasing resources for fewer and smaller niches.

Review Times

The narrative about the FDA is that in recent years, review times dragged out as the agency faced a rising number of new product applications.

So what’s the record?

On March 13, 2014, Margaret Hamburg, M.D., the agency’s commissioner told Congress that since 2010, the FDA has improved its performance in reviewing device applications

Specifically, she said the agency has achieved:

• 27% decrease in the backlog of lower device applications
• 10% decrease in average total review time
• 43% decrease in higher risk devices backlog
• 32% decrease in average total review time

Hamburg said the agency is at the “cutting edge in terms of review and approval of new products, ” compared to the rest of the world. “If you look at drugs approved in recent years, I think about three-quarters of them were approved in the United States first and on devices, apart from the highest risk devices, we are I think at par with comparable other countries in terms of review times. We do ask for more clinical data often on the higher risk devices. But, I think there’s some urban mythology about where we stand in comparison to review times and leadership.

Under the most recent user fee agreement (MDUFA III) with the device industry, the FDA will collect almost $600 million in fees over five years. The agency plans to hire an additional 200 full-time employees over that time to speed up review times. Hamburg added that since October 1, 2013, the agency has already hired 90 of those employees.

After Hamburg’s testimony, Janet Trunzo, senior executive vice president, technology and regulatory affairs of AdvaMed, told us, “AdvaMed is encouraged by the progress FDA has made in meeting its commitments under the new user fee agreement, but we all recognize there is a long way to go. So far, the agency appears to be meeting its MDUFA III decision goals and commitments for substantive interactions with submission sponsors. Initial data from FDA shows marked improvement in total review times for PMAs and modest improvement in total review times for 510(k)s compared to the historic highs seen in 2010.”

A Better Way?

But maybe there are other solutions to speeding up device reviews.

The EAP proposal came out at the same time the Manhattan Institute for Policy Research (MIPR) published a research report entitled “An FDA Report Card: Wide Variance in Performance Found Among Agency’s Drug Review Divisions.”

The MIPR found a wide gap in the approval rates of different drugs. The report notes that “[s]ome review divisions, such as the Center for Drug Evaluation and Research’s (CDER) oncology and antiviral divisions, approved drugs with nearly twice the speed as the next-fastest divisions, and nearly four times as quickly as CDER’s slowest division.” The neurology division took nearly 600 days to approve a drug, and the two fastest units, oncology and anti-viral, took under 200 days.

The authors of the report said their analysis of performance has “revealed large differences among the FDA divisions. High-performing divisions are several-fold better on output measures than low-performing divisions, and they perform better without commensurately greater resources or less complexity of tasks or reduced safety. Inconsistent performance across divisions is thus a strong indication of inefficiency, but also of opportunity. A careful comparison of the performance of the agency’s drug review divisions suggests that agency performance can be dramatically improved at little cost to taxpayers.”

Speak Your Piece

You’ve got 90 days after publication of the draft guidance in the Federal Register to review the proposal and submit comments. The proposal is available here.

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM393978.pdf

Submit electronic comments to http://www.regulations.gov.

Submit comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Identify all comments with the docket number listed in the notice of availability that publishes in the Federal Register.