FDA Guidance for Industry and FDA Staff Summary of Public Notification of Emerging Postmarket Medical Device Signals (“Emerging Signals”) Effective: December 14, 2016 www.Rx-360.org This summary was prepared by the Rx-360 Monitoring and Reporting Working Group which tracks regulatory, legislative and policy developments relevant to pharmaceutical/medical device supply chain integrity. The summary is not intended to serve as comprehensive and formal interpretation or guidance (and should not replace your own review and analysis of any referenced source documents). If you have questions, please contact Brittany Tobery, Rx-360 Secretariat, at 301.710.9399 or btobery@rx-360.org

I. Introduction and III. Scope Emerging Signal = new information about a marketed medical device: 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 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 Signal ≠ Information that is unconfirmed, unreliable, or lacks sufficient strength of evidence is not an emerging signal. Timely notification about Emerging Signals is intended to: Make the most current performance and benefits/risks information concerning marketed medical devices available to end users to make informed patient management decisions. Help reduce/limit the number of patients exposed to the potential risk while the issue is being further evaluated, and enhanced vigilance on the part of clinicians, risk managers, patients and consumers. Recognition of an adverse event before more serious complications occur. The guidance describes the factors that CDRH intends to consider in deciding whether to notify the public about an emerging signal, and the processes and timelines it should follow in issuing and updating the notification. Guidance does NOT apply to IDEs (21 CFR 812). www.Rx-360.org

II. Background Process includes: FDA recognizes that postmarket use provides useful real-world information on device use and performance Types of information to be looked at: newly recognized type of adverse event associated with a medical device 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 a reduction in benefit to the patient Process includes: Collecting available information from multiple sources Interaction with impacted device company(ies) Review by SME multidisciplinary team Other stakeholder engagement Management oversight

IV. Signal and Signal Management General CDRH signal management process: Information received about device-related signals Examples of Signal sources provided, e.g.: MDRs, MedSun Network reports, mandated postmarket studies data, clinical trials, scientific literature, etc. CDRH signal management team convened and perform: Signal refinement and characterization process: CDRH seeks a to understand the fundamental nature of the observed adverse event/newly identified risk The likelihood of a causal relationship between the device use and the adverse event/risk Conduct a preliminary assessment as to whether the issue is limited (e.g., to one device model or one manufacturer) or has a broader impact Identifies public health and/or regulatory actions to mitigate the identified risk(s)

V. Considerations of Determining When FDA Should Issue a Public Notification About an Emerging Signal CDRH to apply specific factors to improve consistency, transparency, and predictability for vetting signals, for example, e.g., likelihood of the harmful event(s); magnitude (severity), duration, and reversibility of the harmful event(s); magnitude of the benefit; etc. Decision to provide public information does not mean the FDA: Has concluded there is a causal relationship between device use & emerging signal Is advising end users to limit their use of the device Specific actions are expected by the manufacturer at that time CDRH will consider public notification when all conditions apply: 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 Available evidence is of sufficient strength Information could have important clinical implications and/or could significantly impact the known benefit-risk profile of the device. CDRH intend to initiate an assessment of the need for public notification within 30 days of receiving information

VI. Content of Public Notification and Follow-up/Closure Public notification required information: Device description to which the public notification applies Summary of the emerging signal Information on the known benefits/risks of the device and its use FDA will inform the impacted company(ies) shortly before issuing the public notification, unless time does not permit due to the risk of patient harm or it is otherwise not feasible Following issuance of a public notification, the FDA will update when: Provide additional information collected Notify that no additional substantive information or change to benefits/risks has occurred Notify that additional actions by the FDA or manufacturer have taken place FDA has completed its evaluation and determined that additional regulatory or public health actions are not needed Updates to the public notification should be posted to the FDA Website at least 2 times/year

Thank you info@Rx-360.org For More Information www.Rx-360.org