FDA adverse event reporting for medical products and dietary supplements during a pandemic

https://www.fda.gov/hi/media-base/72498/download

Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During a Pandemic

Additional copies are available from: Office of Counterterrorism and Emerging Threats (HF-29) Office of the Commissioner (Tel) 301-796-8510 and/or Office of Communication, Division of Drug Information Center for Drug Evaluation and Research (Tel) 301-796-3400; (Fax) 301-847-8714

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm and/or Office of Communication, Outreach and Development (HFM-40) Center for Biologics Evaluation and Research (Tel) 800-835-4709 or 301-827-1800

https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologicsguidances and/or Office of Policy Guidance and Policy Development Center for Devices and Radiological Health Food and Drug Administration 10903 New Hampshire Ave., Bldg. 66, Room 5431 Silver Spring, MD 20993-0002 Email: CDRH-Guidance@fda.hhs.gov

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments /default.htm and/or Office of Food Defense, Communication and Emergency Response (HFS-005) Center for Food Safety and Applied Nutrition (Tel) 240-276-9300

https://www.fda.gov/food/guidance-regulation-food-and-dietary-supplements/guidance-documentsregulatory-information-topic-food-and-dietary-supplements U.S. Department of Health and Human Services Food and Drug Administration Office of Counterterrorism and Emerging Threats (OCET) Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Center for Devices and Radiological Health (CDRH) Center for Food Safety and Applied Nutrition (CFSAN) May 2020 Safety

I. INTRODUCTION This guidance provides recommendations to industry regarding postmarketing adverse event reporting for drugs, biologics, medical devices, combination products,2 and dietary supplements during a pandemic. FDA anticipates that during a pandemic, industry and FDA workforces may be reduced because of high employee absenteeism while reporting of adverse events3 related to widespread use of medical products indicated for the treatment or prevention of the pathogen causing the pandemic may increase. The extent of these possible changes is unknown. This guidance discusses FDA’s intended approach to enforcement of adverse event reporting requirements for medical products and dietary supplements during a pandemic. FDA believes this approach will make it possible for firms with reporting responsibilities to focus their limited resources on the following types of reports: • reports related to medical products indicated for the treatment or prevention of the pathogen causing the pandemic

• other reports indicated in this guidance • reports on products presenting special concerns as specified by FDA This guidance is not intended to discourage adverse event reporting during a pandemic by firms that are able to continue reporting operations. In addition, this guidance does not address monitoring and reporting of adverse events that might be imposed as a condition for medical products authorized for emergency use under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360bbb-3).4 This guidance also does not address monitoring and reporting of adverse events as required by regulations establishing the conditions for investigational use of drugs, biologics, and devices. (See 21 CFR parts 312 and 812.) FDA is revising the final guidance for industry entitled “Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During an Influenza Pandemic" (2012 final guidance) to clarify that the guidance is applicable to any pandemic, not just an influenza pandemic. This action is necessary to address the Coronavirus Disease 2019 (COVID-19) pandemic and to ensure that the Agency’s recommendations in the 2012 final guidance apply to any pandemic, including COVID-195 . Accordingly, this guidance replaces the 2012 final guidance. FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required. II. BACKGROUND FDA plays a critical role in protecting the United States from threats such as emerging infectious diseases, including the COVID-19 pandemic. FDA is committed to providing timely guidance to support response efforts to this pandemic. Pandemic preparedness is a global responsibility. It is expected that widespread human outbreaks of a pandemic, whether overseas or in the United States, will affect industry’s functions. Although overseas outbreaks may not seem to directly affect domestic operations, international medical product and dietary supplement production, availability, and adverse event reporting may be disrupted if a firm’s international sites are affected. Thus, industry should develop plans to ensure continuity of operations during a pandemic (discussed in section III.B). It is important that firms consider the adverse event reporting functions of their U.S. locations and their international locations in the face of a potential pandemic. 4 For information regarding Emergency Use Authorizations (EUAs), please refer to the guidance on Emergency Use Authorization of Medical Products (July 2007), available on the internet at http://www.fda.gov/RegulatoryInformation/Guidances/ucm125127.htm. 5 The Secretary of Health and Human Services Alex M. Azar issued a “Determination that a Public Health Emergency Exists. (Jan. 31, 2020, renewed April 21, 2020), which is available at https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx. The President also issued a Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19) Outbreak (Mar. 13, 2020), available at https://www.whitehouse.gov/presidential-actions/proclamation-declaring-national-emergency-concerningnovel-coronavirus-disease-covid-19-outbreak/. Contains Nonbinding Recommendations 3 III. PREPAREDNESS FOR ADVERSE EVENT REPORTING DURING A PANDEMIC A. Information on Pandemic Preparedness The Department of Health and Human Services (HHS) provides a variety of information about pandemics, including general information on pandemic preparedness planning, e.g. Pandemic Preparedness Resources. 6 Manufacturers should refer to this web page frequently for updated information on pandemics. B. Development of a Continuity of Operations Plan in the Case of a Pandemic To access general information on pandemic preparedness planning, firms should refer to the HealthCare Emergency Preparedness Information Gateway website.7 This site includes resources for developing a continuity of operations plan (COOP) to ensure that a firm’s operations continue during all stages of a pandemic. 8 This guidance is limited to FDA recommendations for reporting adverse events during a period of pandemic. Each firm’s pandemic COOP plan should include instructions for reporting adverse events and provide a plan for the submission of any stored reports not submitted in the regulatory timeframes. C. FDA Expectations for Adverse Event Reporting During a Pandemic 1. Reporting Requirements During a Pandemic During a pandemic, adverse event reporting processes as required by statute and regulation should be maintained to the maximum extent possible. All adverse event data should be handled using each firm’s usual standard operating procedures, and regulatory and statutory requirements for adverse event reporting should be met to the maximum extent possible. Firms should develop and prepare to implement their COOP in the event that they are not able to fulfill all adverse event reporting requirements because of pandemic-related high employee absenteeism. FDA recommends that in planning, firms consider the following types of factors (not all-inclusive): • What activities are directly relevant to the processing and submission of mandatory adverse event reports to FDA? • How would sites based in the United States and abroad be differentially affected by a pandemic? 6 Available at https://www.cdc.gov/coronavirus/2019-ncov/php/pandemic-preparedness-resources.html. 7 Available at https://asprtracie.hhs.gov/. 8 See Continuity of Operations (COOP) /Business Continuity Planning available at https://asprtracie.hhs.gov/technicalresources/17/continuity-of-operations-coop-business-continuity-planning/110. Contains Nonbinding Recommendations 4 • What are the relative amounts of resources dedicated to mandatory adverse event reporting at each site? Firms that are unable to fulfill adverse event reporting requirements during a pandemic should maintain documentation of both of the following conditions: 1. Declaration of a pandemic (e.g., by the World Health Organization), including date of declaration of the pandemic and ending date of the pandemic, and 2. High absenteeism and/or other factors (e.g., an increase in adverse event reporting) that is/are preventing the firm from meeting adverse event reporting requirements

The appropriate FDA organizational units responsible for adverse event reporting compliance should be notified when these conditions exist as soon as practicable, recognizing that notifications may be delayed due to the need to address more urgent safety issues. 2. Enforcement Approach During a Pandemic with High Employee Absenteeism FDA anticipates that during a pandemic, industry and FDA workforces may be reduced because of high employee absenteeism at the same time that reporting of adverse events related to pandemicrelated medical products may increase.

FDA encourages all firms to plan for these circumstances to maintain the highest feasible level of adverse event monitoring and reporting throughout the pandemic period when a firm is experiencing pandemic-related high employee absenteeism. Recognizing that a pandemic may reduce a firm’s capacity to comply with adverse event reporting requirements, however, FDA offers this general guidance to help manufacturers strategize use of their resources. As explained below, FDA does not intend to object if, because of pandemic-related high employee absenteeism, certain required adverse event reports are not submitted to the FDA within the timeframes required by statute and regulation, provided that any delayed reports are submitted within 6 months of the restoration of adverse event reporting processes to their pre-pandemic state (see section III.D for discussion of prioritizing timeframes for submission of stored reports).

Table 1 indicates which reports firms may generally store if necessary because of pandemic related high employee absenteeism, without FDA objection.

Where Table 1 indicates a type of report may be stored if necessary, this means that FDA does not intend to object if firms maintain newly received information regarding the underlying adverse events and do not submit reports in the timeframes mandated by statute or regulation. However, any delayed reports must be submitted after adverse event reporting processes have been restored to the pre-pandemic state. Firms should maintain records to identify what has been stored and when the processes were restored. This guidance does not apply to adverse event reporting during a pandemic by firms that are able to continue reporting operations. Firms that are able to report more than the minimum described in Table 1 but less than that required by the statute and applicable regulations should prioritize the order of report submissions. For example, reports with regulatory timeframes of 30 days or less (e.g., 15-day reports, 30-day reports) should be submitted before periodic safety reports. During a pandemic, all firms are strongly encouraged to submit as many required reports as possible. This will minimize reporting burdens once adverse event reporting processes have been restored to the pre-pandemic state.

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