Guidance for Industry Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During a Pandemic 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 OMB Control No. 0910-0701 Expiration Date 05/31/2021 See additional PRA statement in section IV of this guidance. Guidance for Industry 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/biologics- guidances 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-documents- regulatory-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 Contains Nonbinding Recommendations TABLE OF CONTENTS I. INTRODUCTION ............................................................................................................................ 1 II. BACKGROUND .............................................................................................................................. 2 III. PREPAREDNESS FOR ADVERSE EVENT REPORTING DURING A PANDEMIC ........... 3 A. Information on Pandemic Preparedness ........................................................................................ 3 B. Development of a Continuity of Operations Plan in the Case of a Pandemic ............................ 3 C. FDA Expectations for Adverse Event Reporting During a Pandemic........................................ 3 D. Reporting After the Pandemic ........................................................................................................ 5 IV. PAPERWORK REDUCTION ACT OF 1995 ............................................................................... 5 Table 1. FDA Approach to Postmarketing Safety Reporting During a Pandemic if Processes of Mandatory Adverse Event Reporting Are Not Feasible Because of High Employee Absenteeism........ 7 APPENDIX: CURRENT REQUIREMENTS FOR POSTMARKETING SAFETY REPORTS ....... 9 Contains Nonbinding Recommendations Guidance for Industry 1 Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During a Pandemic This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance. 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 events 3 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 1 This guidance has been prepared by the Office of Surveillance and Epidemiology in the Center for Drug Evaluation and Research (CDER) in cooperation with the Office of Counterterrorism and Emerging Threats (OCET) in the Office of the Commissioner and the Centers for Biologics Evaluation and Research (CBER), Devices and Radiological Health (CDRH), and Food Safety and Applied Nutrition (CFSAN) at the Food and Drug Administration. 2 For requirements related to combination products refer to 21 CFR part 4 (see 78 FR 4307). These are described in the guidance Postmarketing Safety Reporting for Combination Products, accessible at https://www.fda.gov/media/111788/download. In addition to application type-based reporting requirements (see 21 CFR 4.102(b)), Combination Product Applicants are also subject to certain safety reporting requirements associated with the constituent parts of the combination product (see 21 CFR 4.102(c)). FDA recommended reporting during a pandemic with high employee absenteeism for application-type based reporting requirements and those associated with the constituent parts of a combination product are as described in Table 1. 3 For purposes of this guidance, the term adverse event includes adverse experience and adverse reaction. The appendix lists in abbreviated form the current adverse event reporting requirements for drugs, biologics, medical devices, and dietary supplements. Refer to the relevant statutes, regulations, and guidance documents for complete information. 1 Contains Nonbinding Recommendations • 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-19 5. 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-concerning- novel-coronavirus-disease-covid-19-outbreak/. 2 Contains Nonbinding Recommendations 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/technical- resources/17/continuity-of-operations-coop-business-continuity-planning/110. 3 Contains Nonbinding Recommendations • 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 pandemic- related 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. 4 Contains Nonbinding Recommendations FDA intends to communicate with firms if there are products and issues that present special concerns and for which the agency therefore expects compliance with reporting as required by statute and regulation during the pandemic. Special concerns could include: • product-related safety issues such as (but not limited to) newly emerging safety issues (e.g., an antihypertensive drug associated with liver failure or a non-pandemic-related vaccine associated with anaphylaxis) • product problems with associated adverse events (e.g., nonfatal serious infections associated with a pre-filled syringe that was recalled due to bacterial contamination) As indicated in Table 1, if FDA has specified a product as presenting special concerns, firms must submit required adverse event reports regardless of the more general recommendations in Table 1. Aside from this circumstance, in Table 1, reporting recommendations for drugs and biologics are prioritized by type of product so that reporting can focus on products that are likely to have greater use and may necessitate greater monitoring during a pandemic. Further, 15-day reports have priority over periodic reports. For medical devices, the reporting priority is specified by outcome (i.e., fatal outcome vs. nonfatal outcome). Table 1 also includes reporting recommendations for other products and additional details. D. Reporting After the Pandemic After the pandemic is resolved and a pre-pandemic state has been restored, it is expected that firms will resume fulfilling all reporting requirements on time as well as submit reports that were stored because of pandemic-related high employee absenteeism. Firms should follow their plan for the submission of the stored reports not submitted in the regulatory timeframes. Firms are generally expected to submit stored reports to FDA within 6 months of restoration of the adverse event reporting process to the pre-pandemic state, or after notification by the Agency, any time frame established by FDA. Firms should prioritize the order of submission for stored reports. 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. Firms that cannot meet adverse event reporting requirements at the minimum levels identified in this guidance should consult the appropriate FDA organizational unit responsible for adverse event reporting compliance. IV. PAPERWORK REDUCTION ACT OF 1995 This guidance contains information collection provisions that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The time required to complete this information collection is estimated to average 50 hours per response to prepare an adverse event reporting plan for a COOP and 8 hours per response to notify FDA when reporting as required by statute and regulation is not feasible, to maintain documentation of the pandemic conditions and resultant high absenteeism, and to maintain records to identify what reports have been stored and when the reporting process was restored, including the time to review instructions, search existing data sources, gather the data needed, and complete and review the information collection. Send comments regarding this burden estimate or suggestions for reducing this burden to: 5 Contains Nonbinding Recommendations Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 4480, Silver Spring, MD 20993-0002. This guidance also refers to previously approved collections of information found in FDA’s adverse event reporting requirements in 21 CFR 310.305, 314.80, 314.98, 600.80, 606.170, 640.73, 1271.350, and part 803. These regulations contain collections of information that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520) and are approved under OMB control numbers 0910-0116, 0910-0291, 0910-0230, 0910-0308, 0910-0437, and 0910-0543. In addition, the guidance also refers to adverse event reports for nonprescription human drug products marketed without an approved application and dietary supplements required under sections 760 and 761 of the Act (21 U.S.C. 379aa and 379aa-1), which include collections of information approved under OMB control numbers 0910-0636 and 0910-0635. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. The OMB control number for this information collection is 0910-0701 (expires 05/31/2021). 6 Contains Nonbinding Recommendations Table 1. FDA Approach to Postmarketing Safety Reporting During a Pandemic if Processes of Mandatory Adverse Event Reporting Are Not Feasible Because of High Employee Absenteeism Type of Product or Application Type of Report(s)/Statutory or Regulatory FDA Recommended Reporting During a Timeframe(s)1 Pandemic With High Employee Absenteeism Products with special concerns as specified by FDA As per regulation(s) and/or statute(s) relating to the Submit3 (any product or application type below)2 FDA-specified product Prescription drug products marketed without an 15-day Alert report, 15-day Alert report -follow up / Submit approved New Drug Application (NDA): drugs 15 calendar days compounded or repackaged by outsourcing facilities4 Prescription drug products marketed without an 15-day Alert report, 15-day Alert report -follow up / Store if necessary5 approved New Drug Application (NDA): other 15 calendar days drugs Approved NDA, Approved Abbreviated New Drug 15-day Alert report, 15-day Alert report -follow up / Approved NDA, Approved ANDA Application (ANDA) 15 calendar days 1. use for the pathogen causing the pandemic or 1. Submit the disease caused by the pathogen6 AND 2. approved within prior three years 2. Submit Reports to applicant (or licensed manufacturer) instead 3. all other products of FDA / 3. Submit death outcome reports. Store if 5 calendar days necessary other serious outcome (non-death) reports. Approved Biologics License Application (BLA) Approved BLA 1. use for the pathogen causing the pandemic or the 1. Submit disease caused by the pathogen6 2. approved within prior three years 2. Submit 3. all other biologics 3. Submit death outcome reports. Store if necessary other serious outcome (non-death) reports. 1 Refer to the appendix for Current Requirements for Postmarketing Safety Reports. 2 FDA will specifically communicate with firms regarding which products present special concerns. Refer to section III.C.2 of this guidance for further discussion of special concern products. 3 As used in this document, “submit” means that the Agency continues to expect compliance with the specific regulatory requirements for submission, including applicable timeframes. 4 Reporting is to be continued because of the potential for increased production of compounded drugs during a pandemic, including the COVID-19 pandemic, by this relatively new industry. 5 Refer to section III.C.2 of this guidance. 6 Whether or not the use is included in the labeling for the drug. 7 Contains Nonbinding Recommendations Type of Product or Application Type of Report(s)/ Statutory or Regulatory FDA Recommended Reporting During a Timeframe(s) Pandemic With High Employee Absenteeism Approved NDA: all products Periodic adverse drug experience report7/ Quarterly for 3 Store if necessary years from the date of U.S. approval of the application (or Approved ANDA: all products license) and then annually thereafter Approved BLA: all products Nonprescription Drugs Marketed without an Approved Serious adverse event report / 15 business days Store if necessary Application8 Dietary Supplement Products Serious adverse event report / 15 business days Store if necessary Blood and Blood Components Blood collection/transfusion fatality report / As soon as Submit possible (oral or written) and 7 days (written) Source Plasma Donor fatality report / As soon as possible (oral) Submit Human Cells. Tissue, and Cellular and Tissue-Based Adverse reaction report / 15 calendar days Submit Products (HCT/P) Medical Device Manufacturer Medical Device Report (MDR) to FDA / 5 Submit work days Manufacturer MDR to FDA / 30 calendar days 1. Submit if patient death 2. Store, if necessary, if nonfatal serious injury or device malfunction9 MDR from importer to manufacturer and FDA / 30 1. Submit if patient death calendar days 2. Store, if necessary, if nonfatal serious injury MDR from user facility to manufacturer (and/or FDA) / 1. Submit if patient death 10 work days 2. Store, if necessary, if nonfatal serious injury 7 Includes periodic safety update reports (PSURs) and periodic benefit-risk evaluation reports (PBRERs) if applicant has a waiver allowing submission of PSURs or PBRERs in lieu of periodic adverse (drug) experience reports. 8 For purposes of section 760 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), nonprescription drug means a drug that is (1) not subject to section 503(b) of the FD&C Act and (2) not subject to approval in an application submitted under section 505 of the FD&C Act. See section 760(a)(2) of the FD&C Act (21 U.S.C. 379aa(a)(2)). 9 The recommendations are also applicable to events reported under the Voluntary Malfunction Summary Reporting (VMSR) Program. See 83 FR 40973 for more details regarding VMSR Program conditions of participation. 8 Contains Nonbinding Recommendations APPENDIX: CURRENT REQUIREMENTS FOR POSTMARKETING SAFETY REPORTS Type of Product or Section of Type of Report(s)/ Timeframe Type of Information Persons with Reporting Type of Application 21 CFR or Responsibility FD&C Act DRUGS AND BIOLOGICS Prescription Drug 310.305 15-day Alert report; 15-day Alert report- Serious and unexpected adverse drug Manufacturers, packers, distributors Products Marketed followup / 15 calendar days experience; New information from follow up of without an Approved 15-day Alert report NDA Reports to manufacturer (or licensed Serious adverse drug experiences Packers and distributors manufacturer) instead of FDA / 5 calendar days Approved NDA 314.80, 314.98, 15-day Alert report; 15-day Alert report- Serious and unexpected adverse drug Applicants (§§ 314.80, 314.98), licensed (prescription and and 600.80, followup / 15 calendar days experience; New information from follow up of manufacturers (§ 600.80), nonprescription respectively 15-day Alert report manufacturers, packers, and distributors drugs), (§§ 314.80, 314.98, and 600.80) and Approved ANDA joint manufacturers, shared (prescription and manufacturers, or any other participant nonprescription involved in divided manufacturing drugs), and (§ 600.80) Approved BLA Reports to applicant (or licensed Serious adverse drug experiences (biologics) manufacturer) instead of FDA / 5 Manufacturers, packers, and distributors calendar days (§§ 314.80, 314.98,and 600.80) and joint manufacturers, shared manufacturers, or any participant involved in divided manufacturing (§ 600.80) Periodic adverse drug experience report / • Individual case safety reports for each adverse Quarterly for 3 years from the date of drug experience not submitted to FDA as a 15- Applicants (§§ 314.80, 314.98) or U.S. approval of the application/issuance day Alert report, excluding reports from licensed manufacturers (§ 600.80) of license and annually thereafter unless postmarketing studies, reports in the scientific otherwise required by FDA literature, and foreign marketing experience • Summary portion: includes narrative summary and analysis of adverse drug experiences that occurred during the reporting interval including 15-day Alert reports previously submitted to FDA, an index of individual case safety reports included in the report, and history of actions taken since the last Periodic report. 9 Contains Nonbinding Recommendations Type of Product or Section of Type of Report(s)/ Timeframe Type of Information Persons with Reporting Type of Application 21 CFR or Responsibility FD&C Act DRUGS AND BIOLOGICS (cont’d) Nonprescription Drugs FD&C Act Serious adverse event report, new Serious adverse events Manufacturers, packers, or distributors Marketed without an Subchapter H medical information (followup) report / Approved Application Sec.760 15 business days DIETARY SUPPLEMENTS Dietary Supplements FD&C Act Serious adverse event report, new Serious adverse events Manufacturers, packers, or distributors Subchapter H medical information (followup) report / Sec.761 15 business days BLOOD AND BLOOD COMPONENTS, INCLUDING SOURCE PLASMA Blood and Blood 606.170 Blood collection/transfusion fatality Fatalities associated with complications of Blood collecting facility or transfusing Components report / notification as soon as possible blood collection or transfusion facility (by telephone, fax, e-mail or express mail) and written report of investigation within 7 days Source Plasma 640.73 Donor fatality report / as soon as Fatalities associated with Source Plasma Source Plasma establishments possible (by telephone) collection 10 Contains Nonbinding Recommendations HUMAN CELLS, TISSUE, AND CELLULAR AND TISSUE-BASED PRODUCTS Type of Product or Section of Type of Report(s)/ Timeframe Type of Information Persons with Reporting Type of Application 21 CFR or Responsibility FD&C Act Human Cells, Tissue, 1271.350(a) Adverse reaction report / 15 calendar Communicable disease associated with HCT/P Establishments that make the HCT/P and Cellular and Tissue- days if fatal, life-threatening, results in permanent available for distribution Based Products (HCT/P) impairment of body function or permanent damage to body structure or necessitates medical or surgical intervention MEDICAL DEVICES Medical Devices 803.50 Medical device reporting (MDR) to Device may have caused/contributed to death or Manufacturers FDA / 30 calendar days serious injury, or device malfunctioned and would be likely to cause/contribute to death or serious injury if malfunction recurs 803.53 MDR to FDA / 5 work days MDR reportable event necessitates remedial Manufacturers action to prevent unreasonable risk of substantial harm to public health, or report requested by FDA 803.56 Supplemental (followup) reports / within Followup information received on a previously Manufacturers 30 calendar days submitted 5-day or 30-day MDR 803.40 MDR to manufacturer and FDA / Device may have caused/contributed to death or Importers 30 calendar days serious injury 803.40 MDR to manufacturer/ 30 calendar days Device has malfunctioned and would be likely Importers to cause/contribute to death or serious injury if malfunction recurs 803.30 MDR to manufacturer and FDA / Device may have caused/contributed to death User Facilities 10 work days 803.30 MDR to manufacturer (or FDA if Device may have caused/contributed to serious User Facilities manufacturer not known) / 10 work days injury 803.33 Annual Report / yearly by January 1 Summary of previously submitted reports (not User Facilities required if no reports) 11