Chapter 5

Management of Safety Information and ICSR Workflows

ICSR Validity — The 4 Minimum Criteria

1

Identifiable Reporter

An identifiable person who reported the event

2

Identifiable Patient

An identifiable patient (initials, age, gender, etc.)

3

Suspect Drug

At least one suspected medicinal product

4

Adverse Event

At least one suspected adverse reaction

All four criteria must be present for a valid ICSR — "Day 0" is logged at receipt

ICSR Workflow — Start to Finish

1

Receipt & Triage

Case received and checked for 4 validity criteria, seriousness, and expectedness. Day 0 regulatory clock starts.

Day 0Validity checkSeriousness
2

Data Entry & Coding

Medical events coded to MedDRA, drug products coded to WHODrug. Clinical narratives written to tell the story of the event.

MedDRAWHODrugNarrative
3

Quality Review (QC)

Secondary check to ensure data entered matches the source documents provided by the reporter. Catches transcription errors.

Source verificationData integrity
4

Medical Review

Physician reviews the case to provide a medical assessment of causality and clinical plausibility. WHO-UMC or Naranjo assessment applied.

CausalityPhysician sign-off
5

Regulatory Dispatch

Case formatted into an E2B(R3) XML file and transmitted to health authorities (FDA FAERS, EMA EudraVigilance).

E2B(R3)XML15-day deadline

US Safety Reporting Requirements

15 Calendar Days Expedited (IND)

Suspected, unexpected, serious, and fatal/life-threatening adverse experiences from clinical trials

IND Safety Reports: Any finding that suggests a significant risk to trial subjects, including important safety findings from animal studies or in vitro testing.

15 Calendar Days Expedited (Post-Market)

Serious and unexpected adverse drug experiences from spontaneous reports or literature

15-Day Alert Reports: Must be filed via MedWatch or electronically through the FDA ESG (Electronic Submissions Gateway).

Periodic PBRER / PSUR

Periodic Benefit-Risk Evaluation Report — comprehensive aggregate analysis at defined intervals

Submitted at intervals determined by the ICH E2C(R2) standard. Includes cumulative analysis of the drug's benefit-risk profile.

Annual IND Annual Report

Summary of all adverse experiences and safety information accumulated during the year

Includes a narrative summary of findings, line listings, and any changes to the Investigator's Brochure.

E2B(R3) Electronic Transmission Structure

Batch Wrapper
Identifies the sender organization and the batch of cases being transmitted. Contains routing and authentication information.
Message Header
Technical metadata about the transmission — timestamps, message identifiers, format version (HL7 model).
Core Data Elements
The clinical content of each individual case safety report, organized into standardized sections.
D

Patient

Demographics, medical history, weight, height

E

Reaction / Event

MedDRA-coded events, onset, duration, outcome

F

Test Results

Lab data, investigations, relevant findings

G

Drug Information

Suspect & concomitant drugs, dosage, routes

Interoperability Advantage

The E2B(R3) standard ensures that safety data can be transmitted from a pharmaceutical company's database directly into a regulator's database without manual re-entry, reducing data entry errors and enabling faster regulatory decision-making.

Pharmacovigilance Manual — Causality Assessment & Signal Detection · Chapter 5