Standard Operating Procedure for Selection of Comparator Drugs for Global Submissions in BA/BE Studies

Department	BA-BE Studies
SOP No.	SOP/BA-BE/013/2025
Supersedes	SOP/BA-BE/013/2022
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 process for selecting appropriate comparator drugs (Reference Listed Drugs or Reference Medicinal Products) for global regulatory submissions, ensuring scientific validity and compliance with local authority expectations.

2. Scope

This SOP applies to Regulatory Affairs, Clinical Operations, and Procurement teams involved in global bioequivalence (BE) studies intended for submission in the United States, European Union, Canada, WHO, Australia, and other international markets.

3. Responsibilities

• Regulatory Affairs: Identifies acceptable comparator products based on regional guidance and confirms alignment with submission strategy.
• Clinical Team: Ensures scientific compatibility for pharmacokinetic and clinical endpoints.
• Procurement Team: Sources comparator drugs through approved distributors in the region of origin.
• Quality Assurance: Reviews comparator authenticity and documentation upon receipt.

4. Accountability

The Head of Regulatory Affairs is accountable for ensuring comparator selection meets regulatory requirements for each target country and that the justification is properly documented.

5. Procedure

5.1 Identify Target Regulatory Market

1. List countries where BE submission is planned.
2. Document each country’s guidance for comparator selection in Annexure-1.

5.2 Determine Acceptable Comparator Source

1. Acceptable sources per region include:
   • US: RLD as listed in the FDA Orange Book
   • EU: RMP authorized via centralized or national procedure (Community Register)
   • Canada: Canadian Reference Product listed in Health Canada Drug Database
   • WHO PQ: Comparator listed in WHO PQ Comparator Product List
2. Record source verification using Annexure-2: Comparator Product Source Confirmation Log.

5.3 Selection Criteria

1. Comparator must match:
   • Same strength and dosage form
   • Same route of administration
   • Marketed in the country of intended submission
2. Same batch used throughout the BE study.

5.4 Justification for Global Use

1. In case of single global study, select comparator product accepted by multiple agencies.
2. Include scientific and regulatory justification in the protocol and submission dossier.
3. If different comparators are used for different regions, clearly document batch usage and regulatory mapping.

5.5 Documentation Requirements

1. Maintain comparator product invoice and Certificate of Analysis (CoA).
2. Ensure product is stored under labeled and controlled conditions with FEFO system.
3. Log comparator data in Annexure-3: Comparator Product Receipt Record.

5.6 Handling of Multiple Comparators

1. If using more than one comparator across regions, ensure:
   • Separate documentation and retention for each
   • Defined bridging strategy (if applicable)
2. Document study assignment in comparator mapping matrix (Annexure-4).

6. Abbreviations

• RLD: Reference Listed Drug
• RMP: Reference Medicinal Product
• BE: Bioequivalence
• WHO PQ: World Health Organization Prequalification
• CoA: Certificate of Analysis

7. Documents

1. Target Market Comparator List – Annexure-1
2. Comparator Product Source Confirmation Log – Annexure-2
3. Comparator Product Receipt Record – Annexure-3
4. Comparator Mapping Matrix – Annexure-4

8. References

• USFDA Orange Book
• EMA Guideline on the Investigation of Bioequivalence
• Health Canada – Guidance for BE Submissions
• WHO PQ – Guidelines for Comparator Product Selection

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Target Market Comparator List

Region	Comparator Name	Reference Source	Accepted By
USA	ABC Tablet 100 mg	Orange Book	USFDA

Annexure-2: Comparator Product Source Confirmation Log

Date	Product	Supplier	Country	Verified By
12/04/2025	ABC 100 mg	GlobalRx Inc.	USA	Rajesh Kumar

Annexure-3: Comparator Product Receipt Record

Batch No.	Received Date	Expiry Date	Storage Condition	Received By
CMP2211	14/04/2025	01/03/2026	25°C	Sunita Reddy

Annexure-4: Comparator Mapping Matrix

Study ID	Comparator Batch	Country	Submission Region	Bridging Required
BE-001	CMP2211	USA	US, Canada	No

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
10/01/2022	1.0	Initial SOP	New Document	QA Head
17/04/2025	2.0	Added WHO comparator criteria and bridging matrix	Regulatory Alignment	QA Head