Regulatory Science Symposium: Bringing Drugs and Biologics to Market - Session 4: "Safety Reporting"

Competencies: Adverse Events, Safety Reporting, Regulatory Science, Clinical Research and Regulations, Project Management, Clinical Trials, Regulatory and Quality Sciences, Clinical Trial Quality

Course Syllabus/Topics

1. Remember that rules differ!
   1. Clinical trials and post-approval reporting
2. Safety Reporting for Drugs and Biologics
3. Adverse Event Reporting
   1. During development, the holder of the Investigational New Drug (IND) application is responsible for collecting and reporting safety information
   2. Mandatory for adverse events related to drugs and biologics
   3. After Approval
      1. Mandatory for industry
      2. Voluntary for the public
4. Forms for Safety Reporting
   1. US Requirements: CFR
   2. EU Requirements: CTR
5. Key Terminology: Adverse Events, SARs, and SUSARs
   1. An "adverse event" is any untoward medical occurrence, regardless of causality
   2. A "suspected adverse reaction" (SAR) implies causality
   3. A "suspected, unexpected, serious adverse reaction" (SUSAR) combines causality, unexpectedness, and seriousness
6. Terminology: Serious Adverse Event (SAE)
   1. Considered "serious" if it results in death, is life-threatening, requires hospitalization, causes persistent or significant disability, or results in a congenital anomaly or birth defect
7. IND Safety Information
   1. Sponsor is responsible for collecting all event-related information
   2. SAEs require expedited reports
   3. Within 7 days for fatal or life-threatening events, within15 days for all other serious events
8. US IND Safety Report
   1. Sponsor must conduct an analysis of similar events (ASE)
9. Who determines causality?
   1. Sponsor can overrule what the PI determines for causality
10. When does the clock start?
    1. When anyone representing the company becomes aware of the event
    2. Day 0=the day the clinical trial site notifies the sponsor’s representative
11. How to Submit in the US
    1. Use 3500A MedWatch Form or CIOMS form
    2. File to FDA Centers
    3. File to IND(s)
12. Guidance for Industry and Investigators: Safety Reporting Requirements for INDs and BA/BE Studies
13. FDA is moving towards Individual Case Safety Reports (ICSRs)
    1. Easier to database information
    2. Based on an International Council on Harmonization (ICH) standard
14. Safety Information from other sources
    1. Safety information can come from various sources, including animal studies, clinical studies, epidemiological studies, scientific literature, and information presented at meetings,
    2. AI is increasingly used to comb through scientific literature for safety information
15. How do reports differ for marketed drugs?
    1. Relies on spontaneous reports from consumers and healthcare professionals
    2. Terminology shifts to "adverse drug experiences"
16. Two Types of Post-Marketing Reports
    1. 15-day Alert Reports: for serious and unexpected events
    2. Periodic ADE Reports: Periodic safety update reports (PSURs), quarterly for the first three years and then annually
       1. Formatted according to Periodic Benefits Risk Evaluation Report (PBRER)
17. Active Learning Activity: Decide - Serious AE?
18. Workshop: Scenarios, Using SAE decision tree
19. Adverse Event Reporting: Summary
20. Q&A

Acknowledgements:
Accompanying text created by: Mahita Parasa, Student Worker; Karen Manrique, Program Administrator, SC CTSI (kmanriqu@usc.edu)