Standard Operating Procedure for Review of Regulatory Guidelines before Study Start in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/046/2025 |
| Supersedes | SOP/BA-BE/046/2022 |
| Page No. | Page 1 of 11 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define the procedure for reviewing and aligning with current regulatory guidelines before the initiation of Bioavailability/Bioequivalence (BA/BE) studies to ensure protocol design, conduct, and reporting are compliant with applicable global regulations.
2. Scope
This SOP applies to all BA/BE studies conducted or submitted for approval to regulatory agencies including CDSCO (India), US FDA, EMA, Health Canada, TGA, PMDA, WHO, and others. It includes the pre-study assessment of national and international regulatory requirements, guidance documents, and updates.
3. Responsibilities
- Regulatory Affairs: Conducts regulatory intelligence review, compiles applicable guidelines, and ensures documentation of their implementation.
- Clinical Project Manager: Aligns protocol, ICF, and submissions with reviewed regulatory expectations.
- Quality Assurance: Verifies that regulatory requirements are documented during audits.
4. Accountability
The Head of Regulatory Affairs is accountable for ensuring that the most current and relevant regulatory guidelines are reviewed, documented, and applied before any BA/BE study is initiated.
5. Procedure
5.1 Regulatory Landscape Review
- Initiate regulatory review during the protocol development stage or at least 4 weeks prior to site initiation.
- Access the latest guidance from:
- US FDA (www.fda.gov)
- EMA (www.ema.europa.eu)
- CDSCO (www.cdsco.gov.in)
- WHO Prequalification Programme
- Country-specific regulatory portals for targeted submission
5.2 Compilation of Applicable Guidelines
- Document the applicable guidelines in Annexure-1: Regulatory Guidelines Summary Sheet.
- Include:
- Product-specific guidance (e.g., FDA PSG)
- General GCP and BA/BE guidelines
- Ethics and safety submission rules
- Format and data submission (eCTD, XML, etc.)
5.3 Study Protocol Alignment
- Ensure protocol design complies with relevant pharmacokinetic parameters, statistical methods, and population selection as per guideline recommendations.
- Use Annexure-2: Protocol-Guideline Cross-Reference Table to confirm alignment.
5.4 Impact of Updates
- Monitor for updated guidelines during study conduct and assess their impact using Annexure-3: Regulatory Update Impact Log.
- Communicate changes and take action to amend documents or procedures as needed.
5.5 Filing and Communication
- Store all reviewed guidelines and cross-reference documentation in the Trial Master File (TMF).
- Share the summary with QA and Clinical Teams prior to study start.
6. Abbreviations
- BA: Bioavailability
- BE: Bioequivalence
- FDA: Food and Drug Administration
- EMA: European Medicines Agency
- CDSCO: Central Drugs Standard Control Organization
- GCP: Good Clinical Practice
7. Documents
- Regulatory Guidelines Summary Sheet – Annexure-1
- Protocol-Guideline Cross-Reference Table – Annexure-2
- Regulatory Update Impact Log – Annexure-3
8. References
- ICH E6(R2) – Good Clinical Practice
- US FDA Product-Specific Guidance for BA/BE Studies
- EMA Guideline on the Investigation of Bioequivalence
- CDSCO Handbook for Clinical Trials
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Regulatory Guidelines Summary Sheet
| Agency | Guideline Title | Date Accessed | Applicable Study Area | Reviewed By |
|---|---|---|---|---|
| US FDA | Product-Specific Guidance for Metformin | 10/04/2025 | PK Parameters | Sunita Reddy |
Annexure-2: Protocol-Guideline Cross-Reference Table
| Protocol Section | Guideline Clause | Compliance (Yes/No) | Remarks |
|---|---|---|---|
| Sampling Timepoints | EMA BE Guideline, Section 3 | Yes | Meets 3× t½ requirement |
Annexure-3: Regulatory Update Impact Log
| Date | Guideline Title | Update Summary | Impact on Study | Action Taken |
|---|---|---|---|---|
| 15/04/2025 | FDA PSG Update – IR Tablets | Clarified fasting study requirements | Protocol amended | Version updated and approved |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 15/01/2022 | 1.0 | Initial version | Establish SOP process | QA Head |
| 17/04/2025 | 2.0 | Included EMA, CDSCO, WHO updates and annexures | Expanded global compliance scope | QA Head |