under 21 CFR 312.32 for IND-regulated clinical trials in the United States. It ensures timely identification, evaluation, and reporting of serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) to the FDA in compliance with regulatory timelines.

Scope

This SOP applies to sponsors, investigators, CROs, pharmacovigilance teams, and regulatory affairs personnel responsible for safety monitoring and reporting in U.S. IND trials. It covers expedited reporting, narrative submissions, follow-up reports, database management, and inspection readiness.

Responsibilities

• Sponsor: Ensures compliance with FDA reporting timelines, submits expedited reports, and maintains safety databases.
• Investigator: Reports all SAEs immediately to the sponsor, provides follow-up data, and documents assessments.
• CRO: Supports safety monitoring, reconciliation, and reporting activities.
• Pharmacovigilance Team: Manages safety database, performs case assessments, and prepares regulatory reports.
• Regulatory Affairs: Submits safety reports to FDA via electronic gateway.
• QA: Audits safety reporting workflows and inspection readiness.

Accountability

The Sponsor’s Drug Safety Officer is accountable for IND safety reporting compliance. Investigators remain accountable for subject-level SAE reporting.

Procedure

1. SAE Identification
1.1 Investigators must report SAEs to sponsor within 24 hours of awareness.
1.2 Record in SAE Log (Annexure-1).

2. Sponsor Evaluation
2.1 Assess causality, expectedness, and seriousness of each SAE.
2.2 Record assessment in SAE Assessment Log (Annexure-2).

3. Expedited Reporting to FDA
3.1 Report fatal or life-threatening SUSARs within 7 calendar days.
3.2 Report other SUSARs within 15 calendar days.
3.3 Submit reports via FDA electronic gateway (MedWatch Form 3500A).
3.4 Document in Expedited Reporting Log (Annexure-3).

4. Follow-Up Reports
4.1 Submit additional data or narratives as follow-up within 15 days.
4.2 Record in Follow-Up Reporting Log (Annexure-4).

5. Annual IND Reports
5.1 Submit annual safety report (DSUR/IND Annual Report) summarizing all SAEs.
5.2 Record in Annual Safety Report Log (Annexure-5).

6. Safety Database Management
6.1 Maintain validated safety database with audit trails.
6.2 Perform reconciliation with clinical databases quarterly.
6.3 Record in Database Reconciliation Log (Annexure-6).

7. Inspection Readiness
7.1 Maintain safety records in inspection-ready format.
7.2 Conduct mock inspections documented in Safety Inspection Log (Annexure-7).

Abbreviations

• SOP: Standard Operating Procedure
• SAE: Serious Adverse Event
• SUSAR: Suspected Unexpected Serious Adverse Reaction
• IND: Investigational New Drug
• DSUR: Development Safety Update Report
• CRO: Contract Research Organization
• QA: Quality Assurance
• FDA: Food and Drug Administration
• TMF: Trial Master File
• ISF: Investigator Site File

Documents

1. SAE Log (Annexure-1)
2. SAE Assessment Log (Annexure-2)
3. Expedited Reporting Log (Annexure-3)
4. Follow-Up Reporting Log (Annexure-4)
5. Annual Safety Report Log (Annexure-5)
6. Database Reconciliation Log (Annexure-6)
7. Safety Inspection Log (Annexure-7)

References

• 21 CFR 312.32 – IND Safety Reporting
• FDA – IND Safety Reporting Guidance
• ICH GCP – E2A and E2F Safety Guidelines

Version: 1.0

Approval Section

Prepared By	Ravi Kumar, Pharmacovigilance Specialist
Checked By	Sunita Reddy, QA Officer
Approved By	Dr. Anil Sharma, Head Clinical Operations

Annexures

Annexure-1: SAE Log

Date	Subject ID	SAE	Reported By	Status
01/09/2025	S101	Severe Hypotension	Investigator	Submitted

Annexure-2: SAE Assessment Log

Date	SAE	Assessment	Reviewed By	Status
02/09/2025	Severe Hypotension	Related and Unexpected	Sponsor Safety Officer	Confirmed

Annexure-3: Expedited Reporting Log

Date	SAE	Reported To FDA	Form	Status
03/09/2025	Severe Hypotension	Yes	MedWatch 3500A	Accepted

Annexure-4: Follow-Up Reporting Log

Date	SAE	Follow-Up Report	Submitted By	Status
05/09/2025	Severe Hypotension	Additional Labs	Safety Officer	Filed

Annexure-5: Annual Safety Report Log

Date	Report Type	Submitted To	Reviewed By	Status
10/09/2025	IND Annual Report	FDA	Reg Affairs	Filed

Annexure-6: Database Reconciliation Log

Date	Database	Reconciliation Performed	Reviewed By	Status
12/09/2025	Clinical vs Safety DB	Completed	QA	Matched

Annexure-7: Safety Inspection Log

Date	Agency	Simulation	Performed By	Status
15/09/2025	FDA	Mock Inspection	QA Team	Completed

Revision History

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
26/08/2025	00	Initial version	New SOP creation	Head Clinical Operations

For more SOPs visit: Pharma SOP