Guidance addresses industry concerns about premature public notifications.

On December 14, 2015, the FDA issued a final guidance titled “Public Notification of Emerging Postmarket Medical Device Signals” (Final Guidance). Under the Final Guidance, the FDA’s Center for Devices and Radiological Health (CDRH) established a process for issuing notifications to the public on new and evolving benefit-risk information about medical devices, which it calls “emerging signals.” When the draft version was issued on December 31, 2015, it triggered significant industry concern that FDA would issue public notifications about manufacturers’ devices based on premature and insufficient evidence.

The Final Guidance seeks to address these concerns with several changes to prevent the issuance of emerging signals based on unreliable or unconfirmed information.

WHAT IS AN “EMERGING SIGNAL”?

The Final Guidance defines an emerging signal as

new information about a marketed medical device: (1) that supports a new causal association or a new aspect of a known association between a device and an adverse event or set of adverse events, and (2) for which the Agency has conducted an initial evaluation and determined that the information has the potential to impact patient management decisions and/or the known benefit-risk profile of the device.

Emerging signals could include a newly recognized type of adverse event, an increase in the severity or frequency of a known adverse event, new product-product interactions, device malfunctions or patient injuries potentially related to improper device use or design, or a reduction in benefit to the patient.

This definition reflects significant changes made to the draft description of an emerging signal. FDA historically has communicated important post-market information only after it has analyzed the information, and, in most cases, after having already reached a decision about relevant recommendations and whether it believes further regulatory action is warranted. The 2015 draft version, however, proposed that FDA could issue emerging signal information that “has not yet been fully validated or confirmed.” This caused alarm among the device industry, particularly given that the draft version did not allow device manufacturers an opportunity to interact with the FDA before the issuance of an emerging signal.

In response to these concerns, FDA has incorporated in the Final Guidance several procedural safeguards into the review and management of signals. These include the following:

  • CDRH team will interact with the device manufacturer(s) before issuance of a signal, unless it is not feasible or time does not permit because of the risk of patient harm.
  • CDRH will conduct an initial assessment that will consider several factors, including the likelihood of the harmful event(s); the magnitude, duration, and reversibility of the harmful event(s); the magnitude of the benefit (e.g., any life-sustaining or life-saving benefits, or the degree to which a given condition, symptom, or function is improved); the quality of the data or information; the strength of the evidence of a causal relationship between use of a device and the adverse event; the extent of patient exposure; whether there is a disproportionate impact on vulnerable patient populations; the potential for preventing, identifying, monitoring, or mitigating the risk; and the anticipated time for completion of FDA’s assessment of the available information.
  • An emerging signal will issue only if (1) the information supports a new causal association, or a new aspect of a known association between a medical device and one or more adverse events or clinical outcomes; (2) the available evidence is of sufficient strength; and (3) the information could have important clinical implications for patient management decisions and/or could significantly impact the known benefit/risk profile of the device. Importantly, FDA’s Final Guidance clarifies that “[i]nformation that is unconfirmed, unreliable, or lacks sufficient strength of evidence will not be considered an emerging signal.”

While these changes will require FDA to exercise greater caution in releasing emerging signal notifications, manufacturers should still closely monitor any emerging signals associated with their devices to ensure that the FDA has all the appropriate information on the risk profile of their devices. The release of incomplete information could increase medical device manufacturers’ liability exposure.