1.0 OBJECTIVE:
1.1 The purpose of this SOP is to describe the standardized process for the preparation, review, approval, and submission of the Periodic Safety Update Report (PSUR) and Periodic Benefit-Risk Evaluation Report (PBRER) in accordance with the requirements of the World Health Organization (WHO), European Union Good Pharmacovigilance Practices (EU-GVP, Module VII), and applicable national regulatory guidelines.
1.2 This SOP ensures the periodic and systematic evaluation of cumulative safety data, integration of new safety information, and maintenance of an updated benefit-risk profile of the company’s medicinal products.
1.3 The SOP aims to ensure timely preparation and submission of high-quality PSUR/PBRER documents to regulatory authorities and business partners, in compliance with defined timelines and content requirements.
2.0 SCOPE:
2.1 This SOP applies to all medicinal products for which the company acts as the Marketing Authorization Holder (MAH) or holds contractual pharmacovigilance responsibility through the Safety Data Exchange Agreement (SDEA).
2.2 The procedure covers all activities related to preparing PSUR/PBRER documents including planning, data collection, writing, review, QPPV oversight, QA verification, and regulatory submission.
2.3 This SOP applies to the Pharmacovigilance (PV) Department, Regulatory Affairs (RA), Qualified Person for Pharmacovigilance (QPPV), Quality Assurance (QA), and any contracted vendors involved in PSUR/PBRER preparation.
3.0 RESPONSIBILITIES:
3.1. Pharmacovigilance (PV) Department:
3.1.1 Develop PSUR/PBRER preparation calendars and maintain an updated list of regulatory timelines.
3.1.2 Collect, verify, and analyze cumulative safety data including ICSRs, literature cases, aggregate data, and signal trends.
3.1.3 Draft the PSUR/PBRER in accordance with ICH E2C (R2) structure.
3.1.4 Coordinate with internal and external stakeholders to obtain necessary inputs.
3.1.5 Ensure scientific accuracy, consistency, and completeness of the content.
3.1.6 Review the completed PSUR/PBRER ensuring accuracy and regulatory compliance.
3.1.7 Approve the final version prior to submission.
3.1.8 Provide guidance on benefit-risk evaluation and emerging safety concerns.
3.2. Regulatory Affairs (RA):
3.2.1 Monitor country-specific PSUR/PBRER submission requirements.
3.2.2 Submit the approved report to relevant regulatory authorities within defined timelines.
3.2.3 Maintain submission acknowledgements and regulatory correspondence.
3.3. Quality Assurance (QA):
3.3.1 Verify document control compliance.
3.3.2 Ensure retention and archival requirements are met.
4.0 DEFINATIONS:
4.1. PSUR: A Periodic Safety Update Report containing cumulative safety review for products approved for marketing.
4.2. PBRER: A Periodic Benefit-Risk Evaluation Report that provides an integrated analysis of benefits and risks in addition to safety data.
4.3. DLP (Data Lock Point): The cut-off date for inclusion of data in the report.
4.4. MAH: Marketing Authorization Holder responsible for the submission of PSUR/PBRER.
4.5. QPPV: Qualified Person for Pharmacovigilance responsible for oversight and approval of the report.
5.0 PROCEDURE:
5.1. PSUR/PBRER Planning:
5.1.1 The PV Department shall maintain a PSUR/PBRER Master log listing all products, DLP dates, and responsible persons.
5.1.2 Scheduling shall be performed at least six months before the DLP to allow adequate preparation time.
5.1.3 PV shall notify RA, QPPV, and relevant internal teams regarding upcoming report requirements.
5.2. Data Collection and Compilation:
5.2.1 PV shall extract cumulative and interval ICSRs from the safety database for the reporting period.
5.2.2 Literature screening records, signal detection logs, risk-minimization activities, and product quality complaints associated with AE shall be collected.
5.2.3 Regulatory actions, competitor product findings, and safety commitments shall be reviewed and included.
5.2.4 Clinical and non-clinical study updates, if applicable, shall be requested from Clinical or Medical Affairs.
5.3. Preparation of PSUR/PBRER Document:
5.3.1 PV shall draft the report using the ICH E2C (R2) format, which includes:
5.3.1.1 Section 1: Introduction
5.3.1.2 Section 2: Worldwide Marketing Authorization Status
5.3.1.3 Section 3: Actions Taken for Safety Reasons
5.3.1.4 Section 4: Changes to Reference Safety Information
5.3.1.5 Section 5: Estimated Exposure and Use Patterns
5.3.1.6 Section 6: Data from Complete Interval
5.3.1.6.1 ICSRs
5.3.1.6.2 Literature
5.3.1.6.3 Studies
5.3.1.6.4 Other sources
5.3.1.7 Section 7: Summaries of Significant Findings from Safety Data
5.3.1.8 Section 8: Signal and Risk Evaluation
5.3.1.9 Section 9: Benefit–Risk Evaluation
5.3.1.10 Section 10: Conclusions and Actions
5.3.2 PV shall ensure consistency between safety data, signal management activities, and RMP updates.
5.3.3 Any identified discrepancies or missing information shall be followed up and resolved before submission.
5.4. Review and Approval Process:
5.4.1 The draft report shall undergo internal PV review for completeness and scientific consistency.
5.4.2 The revised document shall be forwarded to QPPV for review.
5.4.3 Reviewer comments shall be consolidated and addressed appropriately.
5.4.4 The Head PV shall conduct a final review and formally approve the PSUR/PBRER prior to submission.
5.5. Submission to Regulatory Authorities:
5.5.1 RA shall ensure that the PSUR/PBRER is submitted to each regulatory authority according to the local reporting requirements.
5.5.2 Submission may be electronic, portal-based, or paper-based depending on country-specific rules.
5.5.3 Submission acknowledgements and communication records shall be archived.
5.6. Archival and Record Management:
5.6.1 The approved and submitted versions of PSUR/PBRER, along with all supporting documents, shall be archived securely within the PV system.
5.6.2 All records shall be retained for a minimum of 5 years or as required by local regulations.
5.6.3 PSUR/PBRER regulatory submission communications / copy of Letters shall retained as submission proof.
5.7. Training:
5.7.1 All relevant personnel shall be trained on this SOP before participating in PSUR/PBRER preparation activities.
5.7.2 Training records shall be maintained as per the Training SOP.
5.8. Deviations:
5.8.1 Any deviation from this SOP shall be documented and addressed in accordance with the company’s Deviation and CAPA SOP.
6.0 REFERENCES:
6.1 WHO Technical Report Series (TRS) – PV guidance
6.2 EU Good Pharmacovigilance Practices (GVP)
6.3 Company QMS SOPs (Document Control, Training, Audit, Risk Management, Deviation & CAPA)
7.0 RECORDS:
Sr No. Title Document No.
1 PSUR / PBRER log F/PV008/001 – 00
2 PSUR / PBRER format F/PV008/002 – 00
8.0 REVISION HISTORY.
Amendment Date: Update Summary Version No.
NA New SOP 01