Standard Operating Procedure for Designing Clinical Study Protocol for BA/BE Studies

Department	BA-BE Studies
SOP No.	SOP/BA-BE/003/2025
Supersedes	SOP/BA-BE/003/2022
Page No.	Page 1 of 14
Issue Date	17/04/2025
Effective Date	20/04/2025
Review Date	17/04/2026

1. Purpose

To define a structured approach for drafting a scientifically sound and regulatory-compliant clinical study protocol for Bioavailability (BA) and Bioequivalence (BE) studies that ensures safety of participants, integrity of data, and successful regulatory submissions.

2. Scope

This SOP applies to the medical writing, clinical research, pharmacokinetics, biostatistics, and regulatory teams involved in the development and finalization of protocols for BA/BE studies across all therapeutic categories and submission markets.

3. Responsibilities

• Medical Writer: Drafts the protocol document incorporating input from all relevant stakeholders.
• Clinical Pharmacologist: Provides scientific rationale, PK endpoints, and safety considerations.
• Statistician: Defines statistical methods for data analysis.
• Regulatory Affairs: Ensures alignment with regional guidelines and dossier needs.
• QA Team: Verifies GCP and SOP compliance during protocol development.

4. Accountability

The Clinical Research Head is accountable for ensuring the protocol is designed in accordance with applicable ICH GCP guidelines, ethical principles, and local regulatory requirements.

5. Procedure

5.1 Initiation of Protocol Development

1. Initiate protocol development post finalization of:
   • Reference product and dosage
   • Study design (e.g., crossover, fed vs fasted)
   • Product-specific guidance
2. Establish a protocol development team comprising Medical Writer, Pharmacologist, Statistician, and Regulatory Liaison.

5.2 Drafting the Protocol

1. Use the approved protocol template (Annexure-1).
2. Include the following standard sections:
   • Title Page
   • Synopsis
   • Rationale and Background
   • Study Objectives (Primary and Secondary)
   • Study Design
   • Inclusion/Exclusion Criteria
   • Study Procedures
   • PK Sampling Schedule
   • Bioanalytical Method Summary
   • Safety Assessments
   • Statistical Analysis
   • Ethical Considerations
   • Archival and Data Handling

5.3 Integration of Pharmacokinetics and Biostatistics

1. Define PK parameters: C_max, AUC_0-t, AUC_0-∞, T_max, t_1/2.
2. Include the bioequivalence acceptance range: 80.00%–125.00% for log-transformed C_max and AUC.
3. Specify ANOVA model and software to be used.

5.4 Review and Quality Control

1. Conduct internal technical review by all contributors and QA team.
2. Resolve discrepancies and track changes transparently.
3. Document version control history in Annexure-3.

5.5 Approval and Finalization

1. Route the final protocol for electronic signatures by Clinical Head, QA Head, and Regulatory Lead.
2. Lock the version and archive in the eTMF under the “Protocol” folder.
3. Use versioned filename: Protocol_[StudyID]_V2.0_Approved.pdf.

5.6 Translation and Ethics Submission Preparation

1. Coordinate with translation agency if local language version is needed.
2. Ensure consistent terminology between English and translated versions.
3. Compile Ethics Submission Dossier including protocol, ICF, PI CV, and other annexures.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• PK: Pharmacokinetics
• GCP: Good Clinical Practice
• ANOVA: Analysis of Variance
• eTMF: Electronic Trial Master File

7. Documents

1. Protocol Template – Annexure-1
2. Protocol Review Checklist – Annexure-2
3. Protocol Version Control Log – Annexure-3

8. References

• ICH E6 (R2) – Guideline for Good Clinical Practice
• WHO Technical Report Series 937 – BE Guidelines
• USFDA Guidance – Bioequivalence Studies with Pharmacokinetic Endpoints

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 Template (Excerpt)

Section	Content
Title	Comparative Bioavailability Study of Test vs Reference
Design	Randomized, Open-Label, Two-Period Crossover
Objectives	To compare rate and extent of absorption

Annexure-2: Protocol Review Checklist

Review Item	Status	Reviewer	Date
Objectives Clear	Yes	Sunita Reddy	12/04/2025
PK Schedule Adequate	Yes	Rajesh Kumar	13/04/2025

Annexure-3: Protocol Version Control Log

Version	Date	Changes Made	Changed By
1.0	10/02/2022	Initial Draft	Medical Writer
2.0	17/04/2025	Updated per ICH E6 R2 and added bioanalytical summary	Neha Patil

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
10/02/2022	1.0	Initial Protocol Design SOP	New Document	QA Head
17/04/2025	2.0	Added statistical model and ethics preparation section	Regulatory Alignment	QA Head