Standard Operating Procedure for Review of Bioequivalence Waiver Justifications (BCS Class I) in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/049/2025 |
| Supersedes | SOP/BA-BE/049/2022 |
| Page No. | Page 1 of 11 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To establish a standardized procedure for evaluating, documenting, and reviewing requests for bioequivalence (BE) waivers based on the Biopharmaceutics Classification System (BCS) Class I criteria in support of regulatory submissions.
2. Scope
This SOP applies to all oral immediate-release (IR) solid dosage forms intended for biowaiver submission using BCS Class I justification across regulatory regions including US FDA, EMA, CDSCO, and WHO PQ.
3. Responsibilities
- Regulatory Affairs: Coordinates the biowaiver request, compiles documentation, and verifies that justification aligns with regional regulatory guidance.
- Formulation Scientist: Provides data related to solubility, permeability, and dissolution profile.
- Quality Assurance: Reviews and verifies the integrity of submitted supporting data.
4. Accountability
The Head of Regulatory Affairs is accountable for ensuring biowaiver justifications are scientifically sound, well-documented, and in compliance with the relevant guidelines before submission.
5. Procedure
5.1 Initial Feasibility Review
- Confirm the product is eligible for BCS Class I waiver:
- High solubility: Soluble across pH 1.2–6.8 at the highest strength
- High permeability: ≥85% absorbed or human mass balance data available
- Rapid and similar in vitro dissolution
- Document eligibility in Annexure-1: BCS Waiver Eligibility Checklist.
5.2 Compilation of Supporting Data
- Gather and validate:
- Solubility data at 37°C across multiple pH conditions
- Permeability data from literature or validated in vitro/in situ models
- Dissolution profiles of test and reference products in 0.1N HCl, pH 4.5, and pH 6.8 buffers
- Prepare Annexure-2: Comparative Dissolution Data Table.
5.3 Similarity Factor Evaluation (f2 Test)
- Calculate similarity factor (f2) for each media:
- If f2 ≥ 50, profiles are similar
- Use three batches of test and reference products
- Document f2 results in Annexure-3: f2 Similarity Evaluation Sheet.
5.4 Biowaiver Justification Preparation
- Summarize findings in a justification report including:
- Introduction and product classification
- Solubility and permeability data with references
- Dissolution comparison with statistical support
- Conclusion and regulatory citations
- Attach Annexures 1–3 to the justification report.
5.5 Review and Approval
- Route the final justification through QA for verification.
- Approval by Regulatory Affairs head documented in Annexure-4: Biowaiver Approval Log.
6. Abbreviations
- BA: Bioavailability
- BE: Bioequivalence
- BCS: Biopharmaceutics Classification System
- IR: Immediate Release
- f2: Similarity Factor
7. Documents
- BCS Waiver Eligibility Checklist – Annexure-1
- Comparative Dissolution Data Table – Annexure-2
- f2 Similarity Evaluation Sheet – Annexure-3
- Biowaiver Approval Log – Annexure-4
8. References
- US FDA Guidance for Industry – Waiver of In Vivo Bioavailability and Bioequivalence Studies
- EMA Guideline on the Investigation of Bioequivalence
- WHO Technical Report Series No. 937, Annex 8
- ICH M9 – Biopharmaceutics Classification System-Based Biowaivers
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: BCS Waiver Eligibility Checklist
| Criteria | Requirement | Status | Remarks |
|---|---|---|---|
| High Solubility | Soluble in 250 mL at pH 1.2–6.8 | Yes | Data from 3 pH ranges |
Annexure-2: Comparative Dissolution Data Table
| Batch | pH | Time Points (min) | % Released |
|---|---|---|---|
| Test-001 | 1.2 | 5, 10, 15, 30 | 91%, 96%, 99%, 100% |
Annexure-3: f2 Similarity Evaluation Sheet
| Batch Pair | Media | f2 Value | Conclusion |
|---|---|---|---|
| Test vs Ref | pH 6.8 | 65.8 | Similar |
Annexure-4: Biowaiver Approval Log
| Date | Product | Reviewed By | Approved By | Status |
|---|---|---|---|---|
| 15/04/2025 | XYZ 500 mg IR Tablet | Rajesh Kumar | Dr. Sunita Reddy | Approved |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 12/01/2022 | 1.0 | Initial release | New regulatory requirement | QA Head |
| 17/04/2025 | 2.0 | Included annexures and ICH M9 reference | Guideline update | QA Head |