The Food and Drug Administration (“FDA”) released its final guidance on medical device safety on December 14, 2016, titled “Public Notification of Emerging Postmarket Medical Device Signals (Emerging Signals).” The final guidance comes almost a year after FDA issued a similar draft guidance on the topic. As with the draft guidance, industry remains concerned about FDA’s decision to begin issuing warnings about medical devices that may be causing adverse events.
The final guidance describes the factors that the Center for Devices and Radiological Health (“CDRH”) will evaluate when deciding whether to alert the public about new adverse events and risks associated with a medical device, referred to as “emerging signals.” Emerging signals are defined in the final guidance 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 FDA 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.” However, an emerging signal does not include risk-related information that is unconfirmed, unreliable or lacks sufficient strength or proof.
While devices are typically cleared and approved for certain risks under a risk-benefit analysis, the purpose of the final guidance is to capture and notify users of new or changed risks associated with a medical device after the device is on the market. The final guidance applies only to marketed products that meet the statutory definition of “device” and are regulated by CDRH, and applies to all marketed devices regardless of regulatory classification, except for investigational devices.
Signals and Signal Management
At the outset, while a general outline of the signal and signal management process is provided in the final guidance and discussed here, FDA notes that the process will vary depending on the devices involved.
FDA explains that it receives information about device-related signals through a variety of sources such as Medical Device Reports (“MDRs”), clinical trials, and data from postmarket studies. Generally, if CDRH identifies a signal, a CDRH signal management team will collect and analyze further information to determine 1) the likelihood of a causal relationship between the use of the device and the risk and 2) whether the risk affects a single device or manufacturer or multiple products from many manufacturers. CDRH may, as part of this process, interact with device manufacturers and seek information from other stakeholders, such as patients and other regulatory agencies.
As a next step, the CDRH signal management team will determine what regulatory or other actions must be taken to mitigate the identified risks. FDA may choose, among other actions enumerated in the final guidance, to issue public communication, mandate postmarket surveillance studies, and/or request that manufacturers modify the product labeling.
Factors in Determining When FDA Should Issue a Public Notification About an Emerging Signal
In determining whether or not to notify the public about emerging signals, CDRH will consider a variety of factors as described in the final guidance, including:
- The probability of the harmful event taking place;
- The severity, duration, and possible reversibility of the harmful event;
- The magnitude of the benefits provided by the device; and
- Whether vulnerable patient populations may be disproportionately impacted by the harmful event.
The final guidance indicates that CDRH staff will likely pursue public notification when all of the following statements apply:
- The information supports a new causal association, or a new aspect of a known association (e.g., increased rate or severity of event or reduced benefit), between a medical device and one or more adverse events or clinical outcomes;
- The available evidence is of sufficient strength; and
- The information could have important clinical implications for patient management decisions and/or could significantly impact the known benefit-risk profile of the device.
CDRH staff aims to conduct an initial assessment of the need to issue a public notification within 30 days of receiving the emerging signal information. If the decision is made not to issue a public notification, FDA staff intends to conduct an internal reassessment of the decision within 30 days.
The final guidance notes that FDA’s decision to inform the public about an emerging signal is intended to offer patients and providers current information about a device. A public notice, as the final guidance explains, does not mean that 1) FDA has determined that there is a causal relationship between a medical device and an emerging signal, 2) FDA is suggesting patients and providers avoid use of a particular medical device, or 3) the device manufacturer must take specific actions.
Content of Public Notification and Follow-up/Closure
FDA generally anticipates that a public notification will include:
- A description of the device(s) to which the public notification applies;
- A summary of the emerging signal, including the objective evidence on which the decision to issue a public notification is based; and
- Information on the known benefits and risks of the device and its use.
FDA will inform the impacted manufacturers or companies shortly before a public notification is issued, unless time does not permit due to risk of patient harm or it is not feasible. Updates to the public notification, such as the receipt of new information or efforts taken by the manufacturer, will be provided by FDA on its website at least twice per year or as is necessary and appropriate until the signal evaluation is complete and no further regulatory or other action is required.
Industry groups, such as the Medical Device Manufacturers Association (“MDMA”) and Advanced Medical Technology Association (“AdvaMed”), detailed their concerns about the potential negative effects of emerging signals on the reputation of a device and manufacturer in comment letters to the draft guidance. One notable comment letter stated that the impact of an emerging signal on a device and manufacturer is similar to the effect of a recall. In particular, industry concerns are related to a lack of industry involvement during FDA’s evaluation process of potential risks, as well as a lack of clarity on what constitutes a risk and how FDA would evaluate the risks.
While the final guidance is still very similar to the draft guidance, leaving many of these industry concerns unaddressed, FDA does state in the final guidance that it will involve device manufactures along the stages of risk assessment unless time does not permit due to risk of patient harm.
Manufacturers should actively monitor CDRH’s emerging signals related to their devices to ensure that the signals are based on accurate and complete information regarding their devices’ risks, and if this is not the case, manufacturers should update FDA with the correct information. Manufacturers have the opportunity to get ahead of and be involved in potential emerging signals since FDA bases its emerging signals on information from various sources that are manufacturer-submitted such as MDRs – after such manufacturer-generated notices or reports are submitted to FDA, manufacturers can anticipate that an emerging signal may potentially be considered and try to seek involvement with CDRH in the process.
 See Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 321(h).
 Investigational devices falling under FDA’s Investigational Device Exemptions (IDE) regulations (21 C.F.R. § 812) are not covered by the final guidance.
 Public Notification of Emerging Postmarket Medical Device Signals Final Guidance (“Final Guidance”) at pg. 7 (Dec. 14, 2016).
 Final Guidance at pg. 8.