1.0 OBJECTIVE:
1.1 To describe the standardized procedure for processing Individual Case Safety Reports (ICSR) including triage, data entry, medical terminology coding using Medical Dictionary for Regulatory Activities (MedDRA), and causality assessment.
1.2 To define the process for reporting ICSRs to local and global regulatory authorities within mandated timelines.
1.3 To outline the follow-up procedure to obtain complete and accurate information to support ICSR assessment and regulatory reporting.
1.4 To ensure compliance with World Health Organization (WHO) and European Union Good Pharmacovigilance Practices (EU-GVP) guidelines.
2.0 SCOPE:
2.1 The SOP applies to all ICSRs received from:
2.1.1 Healthcare professionals
2.1.2 Patients/consumers
2.1.3 Distributors, partners
2.1.4 Literature
2.1.5 Clinical/Bioequivalence study partners
2.1.6 Call centers / emails / letters
2.1.7 Product Quality Complaints with AE (PQC + AE)
2.2 Applies to all marketed products for which the company acts as Marketing Authorization Holder (MAH) or PV responsible partner.
3.0 RESPONSIBILITIES:
3.1 Pharmacovigilance (PV) Department:
3.1.1 Perform case triage and seriousness assessment.
3.1.2 Enter validated cases into the safety database.
3.1.3 Perform MedDRA coding and causality assessment.
3.1.4 Submit ICSRs within regulatory timelines.
3.1.5 Initiate and track follow-up requests.
3.1.6 Maintain case audit trail and documentation.
3.2 Regulatory Affairs (RA):
3.2.1 Maintain an updated list of country-specific ICSR reporting timelines.
3.2.2 Support PV in regulatory submissions and reconciliations.
3.3 Quality Assurance (QA):
3.3.1 Ensure compliance with QMS requirements for documentation.
3.3.2 Support audit readiness.
4.0 DEFINATIONS:
4.1 Individual Case Safety Report (ICSR): A structured report that contains complete safety information about an adverse event or reaction experienced by a single identifiable patient.
4.2 Medical Dictionary for Regulatory Activities (MedDRA): An internationally standardized medical terminology used to accurately code and classify adverse events and medical conditions.
4.3 Adverse Event (AE): Any untoward medical occurrence in a patient after using a medicinal product, regardless of whether it is related to the product.
4.4 Adverse Drug Reaction (ADR): A harmful and unintended response to a medicinal product where a causal relationship with the drug is at least reasonably possible.
4.5 Serious Case: An adverse event or reaction that results in death, is life-threatening, requires hospitalization, causes disability, or is medically significant.
4.6 Follow-up: The process of obtaining additional essential information from the reporter to complete or clarify an ICSR.
5.0 PROCEDURE:
5.1 Case receipt:
5.1.1 PV shall verify minimum required elements:
5.1.1.1 Identifiable patient
5.1.1.2 Identifiable reporter
5.1.1.3 Suspect product
5.1.1.4 AE/ADR description
5.1.2 Assign unique case ID (e.g., AE/YY/NNN).
5.1.3 Perform triage:
5.1.3.1 Serious vs non-serious
5.1.3.2 Expedited reporting required or non-expedited
5.1.4 Enter initial intake information in the ICSR Intake Log.
5.1.5 Cases linked to Product Quality Complaint (PQC)shall be escalated to Quality Assurance (QA).
5.2 Data Entry into Safety Database:
5.2.1 ICSR entry in the safety database shall be created.
5.2.2 Enter the following:
5.2.3.1 Patient demographics
5.2.3.2 Reporter details
5.2.3.3 Suspect/concomitant medications
5.2.3.4 Event details verbatim
5.2.3.5 Treatment outcomes
5.2.3.6 Seriousness
5.2.3.7 Lab tests, investigations
5.2.3.8 Product details (batch, expiry)
5.2.3.9 Mark incomplete fields for follow-up.
5.3 MedDRA Coding:
5.3.1 Code the AE/ADR using latest MedDRA version.
5.3.2 Select appropriate:
5.3.2.1 Lowest Level Term (LLT)
5.3.2.2 Preferred Term (PT)
5.3.2.3 System Organ Class (SOC)
5.3.3 Do not change the reporter’s wording; only code using MedDRA.
5.3.4 Document coding date and coder details.
5.4 Causality Assessment:
5.4.1 Causality shall be performed by trained PV personnel or medical reviewer.
5.4.2 Assessment shall do using standard categories such as:
5.4.2.1 Certain
5.4.2.2 Probable
5.4.2.3 Possible
5.4.2.4 Unlikely
5.4.2.5 Unrelated
5.4.3 Following factors shall Consider during Causality Assessment:
5.4.3.1 Temporal relationship
5.4.3.2 Dechallenge/rechallenge
5.4.3.3 Medical plausibility
5.4.3.4 Concomitant drugs
5.4.3.5 Underlying disease
5.4.4 Document rationale for causality in case file.
5.5 Case validation and Quality Check:
5.5.1 Ensure all minimum criteria should meet.
5.5.2 Ensure seriousness and causality fields are correct.
5.5.3 Review MedDRA terms for consistency.
5.5.4 Confirm reporting timelines applicable to the case.
5.6 ICSR reporting to Regulatory Authority:
5.6.1 Reporting timelines:
5.6.1.1 Serious cases shall be reported within 24–48 hours or as per country requirement.
5.6.1.2 Non-Serious ICSRs shall be submitted within 90 calendar days to the regulatory authority.
5.6.2 Regulatory Affairs (RA) provides updated reporting rules per country.
5.6.3 Following reporting methods shall be used:
5.6.3.1 E2B gateway (if applicable)
5.6.3.2 Email to authority
5.6.3.3 Online submission portal
5.6.3.4 Paper forms (if required)
5.6.4 Following aspects shall verify before reporting the case:
5.6.4.1 Case completeness
5.6.4.2 MedDRA coding accuracy
5.6.4.3 Narrative quality
5.6.4.4 Causality conclusion
5.6.5 ICSR shall be sent to:
5.6.5.1 Regulatory authorities of concerned markets
5.6.5.2 Partners as per SDEA
5.6.5.3 QPPV where required
5.6.6 The following documents shall be available as evidence:
5.6.6.1 Submission date
5.6.6.2 Submission method
5.6.6.3 Acknowledgement receipt
5.6.6.4
5.6.6.5 Any issues during submission
5.7 Follow up request Generation:
5.7.1 Follow-up is required when:
5.7.1.1 Minimum criteria are incomplete
5.7.1.2 Serious case requires additional details
5.7.1.3 Lab results pending
5.7.1.4 Batch details missing
5.7.1.5 Outcome unknown
5.7.2 Use approved follow-up questionnaire or custom questions.
5.7.3 The follow up shall be performed through:
5.7.3.1 Email
5.7.3.2 Phone
5.7.3.3 Letter
5.7.3.4 Distributor communication
5.7.3.5 Healthcare professional outreach
5.7.4 Document every follow-up attempt in the Follow-up Log.
5.7.5 If no response after 3 attempts, close follow-up with justification.
5.8 Following aspects shall consider while updating ICSR after follow-up:
5.8.1 New information shall be entered into the safety database and update MedDRA terms if event evolves.
5.8.2 Update causality if new details affect assessment.
5.8.3 Re-submit updated case to authorities if:
5.8.3.1 Case becomes serious
5.8.3.2 New medically important information is obtained
5.8.3.3 Required by regional regulations
5.9 Finalization and Archiving:
5.9.1 ICSR shall be locked in the safety database after all processing complete.
5.9.2 Intake form, documents, follow-ups, and submission proof shall be archived.
5.9.3 ICSR documents shall Retain for minimum 5 years.
5.10 Training:
5.10.1 All Pharmacovigilance (PV) and Regulatory Affairs (RA) staff must be trained on this SOP.
5.10.2 Refresher training shall be conducted annually
5.11 Deviations:
5.11.1 Any deviation from this SOP must be documented.
5.11.2 CAPA must be initiated for delays in ICSR reporting.
5.12 ICSR Numbering Pattern:
5.12.1 The format includes, ICSR / YY / NNN, Where:
5.12.1.1 ICSR = Indicates an Individual Case Safety Report
5.12.1.2 YY = Last two digits of the year
5.12.1.3 NNN = Sequential running number starting from 001 each year.
5.12.1.4 ICSR/25/001 = 1st ICSR received in year 2025
6.0 REFERENCES:
5.3 WHO Technical Report Series (TRS) – PV guidance
5.4 EU Good Pharmacovigilance Practices (GVP)
5.5 Company QMS SOPs (Document Control, Training, Audit, Risk Management, Deviation & CAPA)
7.0 RECORDS:
Sr No. Title Document No.
1 ICSR Checklist F/PV005/001 – 00
2 ICSR log F/PV005/002 – 00
6 REVISION HISTORY.
Amendment Date: Update Summary Version No.
NA New SOP 01