Standard Operating Procedure for Reference Product Selection and Procurement in BA/BE Studies

Department	BA-BE Studies
SOP No.	SOP/BA-BE/011/2025
Supersedes	SOP/BA-BE/011/2022
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 a standard process for identifying, selecting, verifying, and procuring the reference product (RLD – Reference Listed Drug or RMP – Reference Medicinal Product) required for conducting Bioavailability/Bioequivalence (BA/BE) studies.

2. Scope

This SOP applies to the Regulatory Affairs, Procurement, and Quality Assurance departments involved in BE study preparation and submission to regulatory agencies such as USFDA, EMA, CDSCO, TGA, and WHO.

3. Responsibilities

• Regulatory Affairs: Identifies and confirms the appropriate RLD/RMP based on regulatory requirements.
• Procurement Team: Sources and purchases the approved product from authorized suppliers.
• Quality Assurance: Verifies product integrity, batch information, and storage conditions.
• Warehouse/Logistics: Manages receipt, labeling, and storage of the reference product.

4. Accountability

The Head of Regulatory Affairs is accountable for ensuring the selected reference product is compliant with country-specific regulatory guidelines and properly documented for submission.

5. Procedure

5.1 Identification of Reference Product

1. Determine the regulatory submission region (e.g., US, EU, India).
2. Identify the appropriate RLD or RMP using:
   • USFDA Orange Book
   • EMA Community Register
   • Health Canada Drug Product Database
3. Record details in Annexure-1: Reference Product Identification Log.

5.2 Regulatory Confirmation

1. Verify that the selected reference product matches:
   • Strength
   • Dosage form
   • Route of administration
2. Document product-specific guidance and regulatory citations supporting selection.

5.3 Procurement Process

1. Procure from:
   • Country of origin (same region as submission)
   • Authorized distributor or licensed pharmacy
2. Ensure:
   • Minimum 2 batches of same expiry or with different expiry for bridging
   • Batch certificate or invoice with batch number, expiry, and country of origin
3. Log procurement details in Annexure-2: Reference Product Receipt Record.

5.4 Verification and Documentation

1. Quality Assurance to verify:
   • Packaging integrity
   • Labeling (language and batch info)
   • Temperature control (if applicable)
2. Retain original packaging and documentation for regulatory audits.

5.5 Storage and Labeling

1. Store reference product in a designated area under labeled “Reference Only” category.
2. Use FEFO (First Expiry First Out) principles for dispensing.
3. Ensure separate labeling from test products.

5.6 Retention Samples

1. Retain sufficient quantity from each reference batch for:
   • Retesting
   • Audit
   • Future regulatory queries
2. Document retention samples in Annexure-3: Retention Sample Log.

6. Abbreviations

• RLD: Reference Listed Drug
• RMP: Reference Medicinal Product
• BE: Bioequivalence
• CDSCO: Central Drugs Standard Control Organization
• QA: Quality Assurance
• FEFO: First Expiry First Out

7. Documents

1. Reference Product Identification Log – Annexure-1
2. Reference Product Receipt Record – Annexure-2
3. Retention Sample Log – Annexure-3

8. References

• USFDA Orange Book Database
• EMA Guideline on the Investigation of Bioequivalence
• WHO Prequalification Guidelines for BE Studies
• Schedule Y, Drugs and Cosmetics Rules, India

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 Product Identification Log

Product Name	RLD/RMP	Country	Strength	Reference Source
ABC 100 mg Tablet	RLD	USA	100 mg	USFDA Orange Book

Annexure-2: Reference Product Receipt Record

Date	Batch No.	Expiry Date	Supplier	Storage Condition	Received By
10/04/2025	RLD1123	03/2026	XYZ Pharmacy (USA)	25°C	Rajesh Kumar

Annexure-3: Retention Sample Log

Batch No.	Quantity Retained	Storage Location	Label Status	QA Verified By
RLD1123	50 tablets	Ref Sample Locker	YES	Sunita Reddy

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
12/01/2022	1.0	Initial Release	New SOP	QA Head
17/04/2025	2.0	Updated procurement flow, added Annexures	Regulatory Alignment	QA Head