Standard Operating Procedure for Review of SmPC for EU BA/BE Submissions
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/033/2025 |
| Supersedes | SOP/BA-BE/033/2022 |
| Page No. | Page 1 of 12 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To establish a procedure for reviewing the Summary of Product Characteristics (SmPC) for reference medicinal products used in Bioavailability/Bioequivalence (BA/BE) studies intended for regulatory submission in the European Union (EU).
2. Scope
This SOP applies to all BA/BE studies developed for submission under the EU decentralized procedure (DCP), mutual recognition procedure (MRP), or centralized procedure, where SmPCs guide the design, safety monitoring, and regulatory justification.
3. Responsibilities
- Regulatory Affairs: Retrieves and verifies the latest approved SmPCs from the EMA or national competent authorities.
- Medical Writing: Reviews clinical and safety sections for protocol input.
- Clinical Operations: Aligns dosing and administration procedures with SmPC information.
4. Accountability
The Director of Regulatory Affairs is accountable for ensuring the accuracy, relevance, and timely review of the SmPC prior to protocol finalization and submission to EU authorities.
5. Procedure
5.1 Retrieval of SmPC
- Search the European Medicines Agency (EMA) or Heads of Medicines Agencies (HMA) portal for the latest approved SmPC.
- If not available online, request the document from the reference product’s MAH (Marketing Authorization Holder).
5.2 Key Sections for Review
- Focus the review on the following SmPC sections:
- Section 4.1: Therapeutic Indications
- Section 4.2: Posology and Method of Administration
- Section 4.3–4.9: Contraindications, Warnings, Interactions, AE, Overdose
- Section 5.1 and 5.2: Pharmacodynamics and Pharmacokinetics
- Document findings in Annexure-1: EU SmPC Review Summary.
5.3 Application to Protocol Development
- Use SmPC information to:
- Justify selection of dose and route
- Set fasting/fed conditions
- Address safety precautions and exclusion criteria
- Record cross-references in Annexure-2: Protocol Alignment Log.
5.4 Archival and Documentation
- Include the reviewed SmPC version in the Trial Master File (TMF) and Investigator Site File (ISF).
- Retain document with date-stamp and reviewer initials on Annexure-3: SmPC Control Sheet.
6. Abbreviations
- SmPC: Summary of Product Characteristics
- EMA: European Medicines Agency
- MRP: Mutual Recognition Procedure
- DCP: Decentralized Procedure
- MAH: Marketing Authorization Holder
7. Documents
- EU SmPC Review Summary – Annexure-1
- Protocol Alignment Log – Annexure-2
- SmPC Control Sheet – Annexure-3
8. References
- ICH E6(R2) – Good Clinical Practice
- EMA SmPC Guideline (Rev 2)
- EU Clinical Trial Regulation (CTR) 536/2014
- Schedule Y – Drugs and Cosmetics Rules
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: EU SmPC Review Summary
| Product Name | SmPC Version | Sections Reviewed | Reviewer | Date |
|---|---|---|---|---|
| ABC 50 mg | Rev. 03, Jan 2024 | 4.2, 4.8, 5.2 | Sunita Reddy | 15/04/2025 |
Annexure-2: Protocol Alignment Log
| Protocol Section | SmPC Reference | Justification | Verified By |
|---|---|---|---|
| Inclusion Criteria | 4.3 | Excludes hepatic impairment | Rajesh Kumar |
Annexure-3: SmPC Control Sheet
| Document Title | Date Retrieved | Retrieved From | Filed By |
|---|---|---|---|
| SmPC – ABC 50 mg | 14/04/2025 | EMA Website | Meera Shah |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 15/01/2022 | 1.0 | Initial SOP | New implementation | QA Head |
| 17/04/2025 | 2.0 | Included annexures and EU-specific submission linkage | Alignment with EU CTR | QA Head |