Standard Operating Procedure for Contingency Planning for Subject Withdrawal in BA/BE Studies

Department	BA-BE Studies
SOP No.	SOP/BA-BE/140/2025
Supersedes	SOP/BA-BE/140/2022
Page No.	Page 1 of 9
Issue Date	17/04/2025
Effective Date	20/04/2025
Review Date	17/04/2026

1. Purpose

To define a systematic approach for handling subject withdrawals during BA/BE clinical trials, including documentation, notification, replacement strategies, and regulatory compliance to ensure study continuity and integrity.

2. Scope

This SOP applies to all clinical trials conducted at the site under the BA/BE program, covering both voluntary and investigator-mandated subject withdrawals at any stage of the study.

3. Responsibilities

• Principal Investigator (PI): Makes final decision on subject withdrawal, oversees documentation, and notifies sponsor/regulatory authorities.
• Study Coordinator: Assists in documentation, tracks subject disposition, and maintains logs.
• Medical Officer: Conducts safety assessments and records medical justifications, if applicable.
• QA Officer: Ensures protocol compliance and verifies withdrawal records during audits.

4. Accountability

The Principal Investigator is accountable for ensuring that subject withdrawals are handled ethically, documented properly, and evaluated for impact on study validity.

5. Procedure

5.1 Reasons for Subject Withdrawal

1. Subjects may withdraw from the study for the following reasons:
   • Voluntary withdrawal (personal reasons, discomfort, etc.)
   • Medical reasons (e.g., adverse events, abnormal lab results)
   • Non-compliance with study procedures
   • Protocol deviations
   • Investigator’s discretion for subject safety

5.2 Initial Assessment and Reporting

1. Immediately upon a subject expressing intent to withdraw, the Study Coordinator must notify the Medical Officer and PI.
2. Conduct a medical evaluation to assess safety or adverse events leading to withdrawal.
3. Document the event in Annexure-1: Subject Withdrawal Form, including:
   • Subject ID
   • Date and study period
   • Reason for withdrawal
   • Medical findings, if any
   • Investigator and subject signatures
4. Update the Subject Disposition Log accordingly.

5.3 Follow-Up and Safety Monitoring

1. Offer voluntary follow-up visit to withdrawn subjects to assess health status.
2. Record outcomes of the follow-up in Annexure-2: Post-Withdrawal Safety Report, if applicable.
3. If adverse event is related to IMP, initiate SAE reporting per SOP/BA-BE/68/2025.

5.4 Replacement of Withdrawn Subjects

1. Check protocol-specific replacement criteria:
   • Pre-dose withdrawals: Replace with reserve subjects, if enrolled.
   • Post-dose withdrawals: Generally not replaced unless protocol allows.
2. Activate standby subjects if identified prior to dosing.
3. Update randomization records and ensure blinding is maintained, if applicable.
4. Record new subject inclusion in Annexure-3: Replacement Subject Log.

5.5 Notification to Sponsor and Ethics Committee

1. Send written notification to the sponsor within 24 hours for all withdrawals.
2. If withdrawal is related to safety or protocol deviation, notify IEC/IRB as per their SOPs.
3. Maintain copies of all communications in the Trial Master File (TMF).

5.6 Final Documentation and Archival

1. Update eCRF or paper CRF with withdrawal status and date.
2. Ensure all associated logs (dispensing, lab samples, consent) are reconciled and closed.
3. Archive withdrawal forms in subject file for minimum 5 years or as per regulatory requirement.

6. Abbreviations

• BA/BE: Bioavailability / Bioequivalence
• PI: Principal Investigator
• IMP: Investigational Medicinal Product
• SAE: Serious Adverse Event
• IEC: Institutional Ethics Committee
• TMF: Trial Master File

7. Documents

1. Subject Withdrawal Form – Annexure-1
2. Post-Withdrawal Safety Report – Annexure-2
3. Replacement Subject Log – Annexure-3

8. References

• ICH E6(R2) – Good Clinical Practice
• Schedule Y – Drugs and Cosmetics Rules, India
• CDSCO Bioavailability/Bioequivalence 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: Subject Withdrawal Form

Subject ID	Date	Study Period	Reason	Investigator Signature
SUB123	17/04/2025	P1	Personal reason	Dr. Meena Joshi

Annexure-2: Post-Withdrawal Safety Report

Subject ID	Follow-Up Date	Symptoms	Treatment	Outcome
SUB123	20/04/2025	None	NA	Recovered

Annexure-3: Replacement Subject Log

Withdrawn ID	Replaced By	Period	Date	Remarks
SUB123	SUB129	P1	17/04/2025	Used reserve subject

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial SOP release	New procedure	QA Head
17/04/2025	2.0	Expanded procedure for follow-up and annexures	Regulatory alignment	QA Head