focuses on prioritizing resources on critical data and processes that affect subject safety and data integrity, ensuring efficiency and compliance with ICH GCP, FDA, EMA, CDSCO, and WHO regulatory requirements.

Scope

This SOP applies to sponsors, CROs, Clinical Research Associates (CRAs), data managers, and QA personnel engaged in RBM implementation. It includes centralized, remote, and targeted onsite monitoring activities, documentation of monitoring findings, use of Key Risk Indicators (KRIs) and Quality Tolerance Limits (QTLs), CAPA management, and archiving of monitoring records.

Responsibilities

• Sponsor: Approves RBM plan and provides oversight for execution and compliance.
• Clinical Operations Manager: Ensures RBM execution aligns with protocol and monitoring plan.
• CRA/Monitor: Executes RBM activities, documents findings, and communicates with site staff.
• Central Monitoring Team: Analyzes risk metrics and dashboards to detect data anomalies.
• Data Manager: Provides data-driven insights for KRIs and QTLs.
• QA Officer: Reviews RBM documentation and audits monitoring execution for compliance.

Accountability

The sponsor is accountable for RBM execution and ensuring that documentation supports inspection readiness. CRAs are accountable for site-level monitoring, while central monitoring teams ensure system-wide oversight.

Procedure

1. Risk-Based Monitoring Preparation
Review Monitoring Plan to identify critical processes, endpoints, and KRIs.
Configure monitoring dashboards with real-time data access.
Train CRAs and central monitors in RBM methodology and tool usage.

2. Centralized Monitoring Activities
Review trial-wide data for completeness, consistency, and outliers.
Identify sites with abnormal trends (e.g., high deviation rate, delayed SAE reporting).
Document central review in RBM Central Monitoring Report (Annexure-1).

3. Remote Monitoring Execution
Conduct remote site reviews via EDC access, teleconferences, and document sharing platforms.
Verify informed consent scans, drug accountability records, and data entry timelines.
Capture findings in Remote Monitoring Log (Annexure-2).

4. Targeted Onsite Monitoring
Schedule onsite visits only at high-risk sites based on KRIs and central monitoring findings.
Perform targeted Source Data Verification (SDV) for critical data elements.
Record findings in Onsite Monitoring Report (Annexure-3).

5. KRI and QTL Tracking
Define KRIs such as SAE reporting delays, query resolution time, and consent compliance.
Monitor QTL breaches and escalate when thresholds are exceeded.
Document in KRI/QTL Log (Annexure-4).

6. Documentation of Findings
All monitoring findings must be documented, categorized (critical, major, minor), and tracked.
Ensure documentation is complete, contemporaneous, attributable, and filed in TMF.

7. CAPA Management
Initiate CAPA for critical and repeated findings.
Track CAPA implementation and closure timelines.
Record in CAPA Log (Annexure-5).

8. Reporting and Communication
CRA submits monitoring reports within 7 working days of activity.
Sponsor reviews and approves reports before filing.
Communicate findings to sites promptly with documented follow-up.

9. Archiving
Archive RBM reports, logs, CAPA documentation, and dashboards in TMF.
Retain for at least 15 years or as per regional requirements.

Abbreviations

• SOP: Standard Operating Procedure
• PI: Principal Investigator
• CRA: Clinical Research Associate
• CRO: Clinical Research Organization
• QA: Quality Assurance
• TMF: Trial Master File
• ISF: Investigator Site File
• RBM: Risk-Based Monitoring
• KRI: Key Risk Indicator
• QTL: Quality Tolerance Limit
• SDV: Source Data Verification
• CAPA: Corrective and Preventive Action

Documents

1. RBM Central Monitoring Report (Annexure-1)
2. Remote Monitoring Log (Annexure-2)
3. Onsite Monitoring Report (Annexure-3)
4. KRI/QTL Log (Annexure-4)
5. CAPA Log (Annexure-5)

References

• ICH E6(R2) – Good Clinical Practice
• FDA – Guidance on Risk-Based Monitoring
• EMA – Reflection Paper on RBM
• CDSCO – Clinical Monitoring Guidelines
• WHO – Risk-Based Monitoring Guidance

Version: 1.0

Approval Section

Prepared By	Ravi Kumar, CRA
Checked By	Sunita Reddy, QA Officer
Approved By	Dr. Anil Sharma, Principal Investigator

Annexures

Annexure-1: RBM Central Monitoring Report

Date	KRI Monitored	Sites Flagged	Action Taken	Reviewed By
12/09/2025	SAE Reporting Timeliness	Site 003	Escalated	Central Monitor
14/09/2025	Data Entry Lag	Site 002	Retraining scheduled	QA Officer

Annexure-2: Remote Monitoring Log

Date	Site	Findings	Deviation	Corrective Action
15/09/2025	Site 001	Delayed CRF entries	2	Training provided
16/09/2025	Site 002	Consent form upload missing	1	Corrected by PI

Annexure-3: Onsite Monitoring Report

Date	Site	Findings	Critical Issues	Action Taken
17/09/2025	Site 003	Drug accountability incomplete	1	Immediate reconciliation
18/09/2025	Site 004	Protocol deviations noted	2	Site retrained

Annexure-4: KRI/QTL Log

Date	KRI/QTL	Threshold	Result	Action Taken
19/09/2025	Protocol Deviations	QTL = 5%	7%	Triggered CAPA
20/09/2025	Query Resolution Time	KRI = 10 days	12 days	Site follow-up

Annexure-5: CAPA Log

Date	Issue	CAPA	Responsible	Status
21/09/2025	Late SAE reporting	Site retraining + escalation	CRA	Open
22/09/2025	Excessive deviations	Process improvement	PI	Closed

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

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