Now that so many companies are being granted Emergency Use Authorizations (EUAs) for their medical products in response to the coronavirus, how will they (and some existing manufacturers) be expected to report adverse events?

1. Reporting Adverse Events
(AE) Under COVID-19 to FDA
GUIDANCE FOR INDUSTRY: POSTMARKETING ADVERSE EVENT REPORTING FOR MEDICAL
PRODUCTS AND DIETARY SUPPLEMENTS DURING A PANDEMIC - MARCH 24 2020

2. Application of
This Guidance
 “This guidance provides
recommendations to industry regarding
postmarket adverse event reporting for
drugs, biologics, medical devices,
combination products, and dietary
supplements during a pandemic”
 Everything except food
 “widespread use of medical products
indicated for the treatment or
prevention of the pathogen causing
the pandemic may increase”
 Basically, this is their approach for
Enforcement Discretion in AE reporting
FDA anticipates that during
a pandemic, industry and
FDA workforces may be
reduced because of high
employee absenteeism
They anticipate an increase
in AEs related to products in
high use during the
pandemic
Prepared by:

3. Development of
a Continuity of
Operations Plan
 To access general information on
pandemic preparedness planning,
firms should refer to the Health Care
Emergency Preparedness Information
Gateway Web site.
 Pandemic COOP plan should
include:
 Instructions for reporting AEs
 Provide a plan for submission of any
stored reports not submitted in the
regulatory timeframes (late reporting)
FDA requests firms develop
a continuity of operations
plan (COOP)
To ensure that firm’s
operations continue during
all stages of a pandemic
COOP should include
provisions for inability to fulfill
adverse event (AE)
reporting requirements (from
absenteeism)
Prepared by:

4. Information on
Pandemic
Preparedness  They want you to learn about these
Pandemic Preparedness Resources
and structure your rationales and
plans with these in mind
 “Manufacturers should refer to the
Web site frequently for updated
information on pandemics.”
 Ignore this request at your peril,
particularly if you end up with late
reporting (and get to justify)
Department of Health and
Human Services (HHS)
provides a variety of
information about
pandemics, including
general information on
pandemic preparedness
planning
Prepared by:

5. Reporting
Requirements
During a
Pandemic I
 What activities are directly relevant to the
processing and submission of mandatory
AE reports to FDA?
 How would sites based in the United
States and abroad be differentially
affected by a pandemic?
 What are the relative amounts of
resources dedicated to mandatory
adverse event reporting at each site?
Normal adverse event
reporting processes should
be maintained to the
maximum extent possible
Reporting should follow
each firm’s usual standard
operating procedures,
following regulatory and
statutory requirements
Prepared by:

6. Delayed
Reporting
Rationale
 Firms that are unable to fulfill normal
adverse event reporting requirements
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
normal 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.
The Rationale for Why
Reporting Timelines Were
Not Met
Translation: Documentation
and justification of these
factors is required.
There is no free lunch!
Prepared by:

7. Delayed
Reporting
Rationale
 Guidance does not apply to adverse
event reporting during a pandemic by
firms that are able to continue reporting
operations
 Requests prioritization of the order of
report submissions
 15-day reports, 30-day reports) should be
submitted before periodic safety reports
Prepared by:

8. Enforcement
Approach During
a Pandemic with
High Employee
Absenteeism
 Guidance does not apply to adverse
event reporting during a pandemic by
firms that are able to continue reporting
operations
 Requests prioritization of the order of
report submissions
 15-day reports, 30-day reports) should be
submitted before periodic safety reports
Any delayed reports should
be submitted within 6 months
of the restoration of adverse
event reporting processes to
a pre- pandemic state
Prepared by:

9. Enforcement
Approach for
Special Concerns  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)
If there are products and
issues that present special
concerns, the agency
expects compliance with
normal reporting rules
Prepared by:

10. Agency’s Intent
of Reporting
Focus
 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 (no, you’re
not off the hook if they’ve set past
conditions)
Adverse events related to
widespread use of medical
products “indicated for the
treatment or prevention of
the pathogen” causing the
pandemic
Firms should on these types
of reports
Prepared by:

11. Reporting After
the Pandemic
 Firms should follow their plan for the
submission of the stored reports not
submitted in the regulatory timeframes
 Generally expected to submit stored
reports to FDA within 6 months of
restoration of the adverse event reporting
process to the pre-pandemic state
 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
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
Prepared by:

12. Table 1: FDA Approach to
Postmarketing Safety Reporting - 1
Type of Product or Application Type of Report(s) / Statutory or
Regulatory Timeframe(s)
FDA Recommended Reporting
During a Pandemic With High
Employee Absenteeism
Products with special concerns as
specified by FDA (any product or
application type below)
As per regulation(s) and/or
statute(s)relating to the FDA-
specified product
Submit
Prescription drug products marketed
without an approved New Drug
Application (NDA)
15-day Alert report,15-day Alert
report-follow up/15 calendar days
Store if necessary
Approved NDA: all products Periodic adverse drug experience
report5/ Quarterly for3 years from
the date of U.S. approval of the
application(or license) and then
annually thereafter
Store if necessary
Approved ANDA: all products
Approved BLA:all products
Prepared by:

13. Table 1: FDA Approach to
Postmarketing Safety Reporting - 2
Type of Product or Application Type of Report(s) / Statutory or
Regulatory Timeframe(s)
FDA Recommended Reporting
During a Pandemic With High
Employee Absenteeism
Approved NDA, Approved
Abbreviated New Drug Application
(ANDA)
1. labeled indication for pathogen
causing the pandemic
2. approved within prior three years
3. all other products
15-day Alert report,15-day Alert
report – follow up/15 calendar days
AND
Reports to applicant (or licensed
manufacturer) instead of FDA / 5
calendar days
Approved NDA, Approved ANDA
1. Submit
2. Submit
3. Store if necessary
Approved Biologics License
Application (BLA)
1. Pandemic vaccines
2. Biologics (vaccines or nonvaccines)
approved within prior three years
3.Other biologics (vaccines or
nonvaccines)
Approved BLA
1.Submit
2.Submit
3.Submit death outcome reports.
Store if necessary other serious
outcome (non-death)reports
Prepared by:

14. Table 1: FDA Approach to
Postmarketing Safety Reporting - 3
Type of Product or Application Type of Report(s) / Statutory or
Regulatory Timeframe(s)
FDA Recommended Reporting
During a Pandemic With High
Employee Absenteeism
Nonprescription Drugs Marketed
without an Approved Application
Serious adverse event report/15
business days
Store if necessary
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 possible (oral or
written) and 7 days (written)
Submit
Source Plasma Donor fatality report / As soon as
possible (oral)
Submit
Human Cells, Tissue, and Cellular and
Tissue-Based Products (HCT/P)
Adverse reaction report/15 calendar
day
Submit
Prepared by:

15. Table 1: FDA Approach to
Postmarketing Safety Reporting - 4
Type of Product or Application Type of Report(s) / Statutory or
Regulatory Timeframe(s)
FDA Recommended Reporting
During a Pandemic With High
Employee Absenteeism
Medical Device
Manufacturer Medical Device Report
(MDR) to FDA/ 5 work days
Submit
Manufacturer MDR to FDA / 30
calendar days
1. Submit if patient death
2. Store, if necessary, if nonfatal
serious injury or device malfunction
MDR from importer to manufacturer
and FDA / 30 calendar days
1. Submit if patient death
2. Store, if necessary, if nonfatal
serious injury
MDR from user facility to
manufacturer (and/or FDA) / 10work
days
1. Submit if patient death
2. Store, if necessary, if nonfatal
serious injury
Prepared by:

16. 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 Refer to section III.C.2 of this guidance.
5 Includes periodic safety update reports (PSURs) if applicant has a waiver allowing submission of PSURs
in lieu of periodic adverse (drug) experience reports
6 For purposes of section 760 of the Federal Food, Drug, and Cosmetic Act (FD&C Act),nonprescription
drugmeans 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)).
7 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.