Standard Operating Procedure for Reviewing Reference Product Literature in BA/BE Studies

Department	BA-BE Studies
SOP No.	SOP/BA-BE/002/2025
Supersedes	SOP/BA-BE/002/2022
Page No.	Page 1 of 12
Issue Date	17/04/2025
Effective Date	20/04/2025
Review Date	17/04/2026

1. Purpose

To define the procedure for identifying, retrieving, and critically reviewing the reference product literature for the purpose of designing scientifically sound and regulatory-compliant bioavailability/bioequivalence (BA/BE) studies.

2. Scope

This SOP is applicable to the regulatory affairs, medical writing, and clinical research teams involved in the planning and design of BA/BE studies for generic and reformulated drug products intended for submission to global regulatory authorities.

3. Responsibilities

• Regulatory Affairs Team: Responsible for sourcing reference product information from regulatory databases.
• Medical Writer: Reviews and summarizes SmPC, FDA labels, and prescribing information for protocol development.
• Clinical Pharmacologist: Assesses pharmacokinetics, safety, and dosing regimen details from the literature.
• Project Manager: Ensures timely collection and distribution of reviewed documents to relevant stakeholders.

4. Accountability

The Regulatory Affairs Head is accountable for ensuring that the reference product literature is up-to-date, relevant, and appropriately documented in the BA/BE study file.

5. Procedure

5.1 Identification of Reference Product

1. Confirm the regulatory target market for the submission (e.g., US, EU, India).
2. Identify the corresponding reference listed drug (RLD) or reference medicinal product (RMP).
3. Verify dosage form, strength, and therapeutic indication from official databases:
   • USFDA Orange Book
   • EMA Community Register
   • CDSCO List of Approved Products

5.2 Collection of Regulatory Product Literature

1. Download relevant documents from regulatory websites:
   • USFDA: Labeling Information, Product Insert
   • EMA: SmPC, Assessment Reports
   • CDSCO: Package Inserts (if available)
2. Ensure that documents are current versions and record the download date.
3. Store all documents in the designated “Reference Product Literature” folder in the eTMF.

5.3 Data Extraction and Review

1. Extract the following details:
   • Dosage regimen
   • Route of administration
   • Indications and contraindications
   • Pharmacokinetics (C_max, T_max, AUC, t_1/2)
   • Food effect recommendations
2. Document extracted data using Annexure-2: Literature Review Summary Template.

5.4 Internal Review and Compilation

1. Submit the draft summary to the Clinical Research and Medical Writing teams.
2. Incorporate feedback into the final document.
3. Attach the summary to the protocol development package and archive in eTMF.

5.5 Literature Update Procedure

1. Set review frequency for long-term projects (minimum once per year).
2. Assign responsibility for periodic verification of label changes or updated SmPCs.
3. Update literature summary with change logs if applicable.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• SmPC: Summary of Product Characteristics
• RLD: Reference Listed Drug
• RMP: Reference Medicinal Product
• eTMF: Electronic Trial Master File
• CDSCO: Central Drugs Standard Control Organization

7. Documents

1. Reference Literature Checklist – Annexure-1
2. Literature Review Summary Template – Annexure-2
3. Change Log for Updated Literature – Annexure-3

8. References

• USFDA Orange Book Database
• EMA Community Register
• ICH M4: Common Technical Document for Registration

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Reference Literature Checklist

Document	Source	Version Date	Verified By
FDA Label	www.fda.gov	15/03/2025	Rajesh Kumar
EMA SmPC	www.ema.europa.eu	18/03/2025	Sunita Reddy

Annexure-2: Literature Review Summary Template

Parameter	Details
Indication	Hypertension
Dosage	50 mg once daily
Cmax	650 ng/mL
Tmax	1.5 hours
Food Effect	Present

Annexure-3: Change Log for Updated Literature

Date	Change Description	Reviewed By
05/04/2025	Updated SmPC with new adverse events section	Neha Patil

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
12/01/2022	1.0	Initial SOP Creation	New Requirement	QA Head
17/04/2025	2.0	Added change log and updated templates	Annual Review	QA Head