Standard Operating Procedure for Risk Assessment of Study Protocol in BA/BE Studies

Department	BA-BE Studies
SOP No.	SOP/BA-BE/029/2025
Supersedes	SOP/BA-BE/029/2022
Page No.	Page 1 of 13
Issue Date	17/04/2025
Effective Date	20/04/2025
Review Date	17/04/2026

1. Purpose

To define the systematic approach for conducting a risk assessment of the study protocol in Bioavailability/Bioequivalence (BA/BE) studies, ensuring potential risks to subject safety, data quality, and regulatory compliance are identified, evaluated, and mitigated.

2. Scope

This SOP applies to all BA/BE clinical study protocols developed, reviewed, or approved within the organization prior to ethics or regulatory submissions and study initiation.

3. Responsibilities

• Clinical Project Manager: Coordinates the risk assessment meeting and ensures protocol availability.
• Medical Monitor: Assesses subject safety risks and mitigation strategies.
• Regulatory Affairs: Identifies compliance and submission-related risks.
• Quality Assurance: Facilitates formal documentation and periodic review of risk mitigation measures.

4. Accountability

The Head of Clinical Research is accountable for ensuring that a formal risk assessment is completed for each study protocol prior to its implementation and that identified risks are addressed appropriately.

5. Procedure

5.1 Initiating Risk Assessment

1. Schedule a risk assessment meeting during the final protocol review phase.
2. Invite cross-functional representatives from Clinical, QA, Regulatory, Pharmacovigilance, and Biostatistics.

5.2 Risk Identification

1. Review the protocol to identify risks related to:
   • Subject selection and eligibility
   • Study design (e.g., crossover complexity, washout)
   • Drug administration and blood sampling logistics
   • Adverse event (AE) reporting and medical oversight
   • Protocol deviations or non-compliance
2. Document identified risks in Annexure-1: Protocol Risk Identification Log.

5.3 Risk Evaluation

1. Each risk is evaluated for:
   • Likelihood (Low/Medium/High)
   • Impact (Minor/Moderate/Critical)
   • Detection (Easy/Moderate/Difficult)
2. Assign Risk Priority Number (RPN) and categorize as Low, Moderate, or High Risk.
3. Record in Annexure-2: Risk Assessment Matrix.

5.4 Risk Mitigation Planning

1. Define mitigation measures such as:
   • Training for study staff
   • Additional subject eligibility checks
   • Enhanced monitoring visits
   • Back-up sampling or logistics planning
2. Document action plan in Annexure-3: Risk Mitigation Tracker.

5.5 Documentation and Review

1. Summarize all activities in a Protocol Risk Assessment Report and include it in the Trial Master File (TMF).
2. Reassess risks post-protocol amendment or during audits as needed.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• RPN: Risk Priority Number
• AE: Adverse Event
• TMF: Trial Master File

7. Documents

1. Protocol Risk Identification Log – Annexure-1
2. Risk Assessment Matrix – Annexure-2
3. Risk Mitigation Tracker – Annexure-3

8. References

• ICH Q9 – Quality Risk Management
• ICH E6(R2) – Good Clinical Practice
• Schedule Y – Drugs and Cosmetics Rules
• USFDA/EMA Risk-Based Monitoring Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Protocol Risk Identification Log

Risk ID	Category	Description	Identified By	Date
R001	Subject Eligibility	Complex inclusion criteria	Dr. Meera Shah	15/04/2025

Annexure-2: Risk Assessment Matrix

Risk ID	Likelihood	Impact	Detection	RPN	Risk Level
R001	Medium	Moderate	Difficult	45	High

Annexure-3: Risk Mitigation Tracker

Risk ID	Mitigation Measure	Owner	Timeline	Status
R001	Eligibility checklist training for CRCs	Rajesh Kumar	20/04/2025	Planned

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
15/01/2022	1.0	Initial SOP	New implementation	QA Head
17/04/2025	2.0	Added risk matrix and mitigation tracker annexures	Alignment with ICH Q9	QA Head