FDA Seeks to Educate Industry on Device Approval

— WASHINGTON -- The FDA released two draft documents this week that offer background on its approval process and guidance on planning clinical trials.



The agency's Center for Devices and Radiological Health (CDRH) has come under criticism, especially from the device industry, for not being clear enough on what is expected from device makers during the approval process, and for taking too much time to make a decision.

Industry has also chided the agency for having poorly trained device reviewers.

The first guidance documents explains the agency's approval process for diagnostic and therapeutic devices, specifically:

  • How the agency weighs the benefits and risks of a device
  • How the agency assess the seriousness of a disease or condition
  • How many people would use the device if approved
  • The availability of other devices approved to treat the same condition

Reviewers look to pinpoint the type of benefit provided by the device; the probability of the patient experiencing any benefit; the magnitude of that benefit; and how long the benefit is expected to last, according to the guidance.

In terms of device safety, the agency takes into account serious adverse events that result in permanent bodily damage or require surgery and those that aren't considered "serious."

Collecting biological specimens, such as blood for use with a diagnostic device, and the probability of a diagnostic device delivering a false-negative result would also be factored in to the "risk" side of the equation, the agency explained.

The guidance also includes a proposed worksheet that FDA reviewers can use as a pro/con list to tally whether the benefits of a particular device outweigh its risks. After receiving comments, the agency may incorporate the worksheet as a part of its official premarket approval (PMA) review of devices.

The FDA provided a number of real-world examples in which a risk/benefit analyses resulted in a decision.

For instance, ultrasound techniques have been developed to destroy kidney stones, cysts, and fibroid tumors without the need for surgery. These techniques are less effective than surgery but carry far fewer risks. If ultrasound-based treatment techniques fail, then surgery is still an option. Such non-invasive techniques won FDA approval because of their lower level of risk even though they may not be as effective as more invasive treatments.

In another case, a permanent, implantable birth control device was shown in a company's clinical trial to be highly effective at preventing pregnancy. But in several cases, physicians had difficultly correctly placing the device, and in a few other cases, follow-up x-rays showed the devices had cracked. Given those risks, the FDA did not approve that device, in part because there are other safe and effective birth control devices on the market.

"As medical devices grow increasingly complex, many factors impact our benefit-risk determinations, especially for PMA devices," said Jeffery Shuren, MD, director of CDRH. "This guidance aims to provide more clarity to manufacturers about what factors we consider when making an approval decision."

The chief trade group for device makers, the Advanced Medical Technology Association (AdvaMed), said it was still reviewing the draft documents.

"We will be particularly interested in whether these documents increase the predictability and efficiency of the review process, and whether proposed regulatory requirements are appropriate given the risk/benefit profile of a specific device," Janet Trunzo, AdvaMed's executive vice president of technology and regulatory affairs wrote in an email.

In the second draft document, the FDA laid out its expectations for clinical trials for medical devices. The agency stated that it looks for a study to provide reasonable assurance that the device is safe and effective.

The agency also stressed how important communication between industry and FDA reviewers is and suggested that device companies submit their pivotal clinical study design protocol through a pre-submission process.

"Early collaboration with FDA is important to ensure the study design is appropriate to address the pertinent scientific questions and support a potential premarket submission in the future," the guidance stated.

The documents also directs device makers to justify why a particular study design is best suited to test their device. Device makers also are advised to avoid introducing bias into a study design and to collect the most pertinent data.

"Designing studies to collect the right data is more important than designing studies to simply collect more data," the guidance stated.

Both draft documents are open for public comment for 90 days, starting on Aug. 15.