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
- Determine the regulatory submission region (e.g., US, EU, India).
- Identify the appropriate RLD or RMP using:
- USFDA Orange Book
- EMA Community Register
- Health Canada Drug Product Database
- Record details in Annexure-1: Reference Product Identification Log.
5.2 Regulatory Confirmation
- Verify that the selected reference product matches:
- Strength
- Dosage form
- Route of administration
- Document product-specific guidance and regulatory citations supporting selection.
5.3 Procurement Process
- Procure from:
- Country of origin (same region as submission)
- Authorized distributor or licensed pharmacy
- 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
- Log procurement details in Annexure-2: Reference Product Receipt Record.
5.4 Verification and Documentation
- Quality Assurance to verify:
- Packaging integrity
- Labeling (language and batch info)
- Temperature control (if applicable)
- Retain original packaging and documentation for regulatory audits.
5.5 Storage and Labeling
- Store reference product in a designated area under labeled “Reference Only” category.
- Use FEFO (First Expiry First Out) principles for dispensing.
- Ensure separate labeling from test products.
5.6 Retention Samples
- Retain sufficient quantity from each reference batch for:
- Retesting
- Audit
- Future regulatory queries
- 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
- Reference Product Identification Log – Annexure-1
- Reference Product Receipt Record – Annexure-2
- 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 |