by demonstrating similarity using appropriate statistical tools and regulatory acceptance criteria.

2. Scope

This SOP is applicable to all oral solid dosage forms developed in the Analytical Method Development (AMD) department, where comparative dissolution testing is required as part of formulation development, stability studies, or regulatory filings.

3. Responsibilities

• Analytical Scientist: Performs the dissolution runs, compiles raw data, and conducts statistical analysis.
• Group Leader: Reviews the test design, f2 values, and trend analysis.
• QA Executive: Reviews report and ensures alignment with regulatory guidance.
• Formulation Scientist: Provides development batch and reference product details.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that CDPs are developed, analyzed, and reported in accordance with global regulatory expectations and internal quality systems.

5. Procedure

5.1 Batch Selection

1. Select batches for comparison:
   • Test batch (development or exhibit batch)
   • Reference product (marketed formulation, innovator)
2. Ensure both products are stored and handled under recommended conditions before testing.

5.2 Method Selection and Pre-Test Checks

1. Use a validated or discriminatory dissolution method approved by QA.
2. Verify:
   • Sink conditions
   • Filter compatibility
   • System suitability

5.3 Dissolution Testing

1. Perform dissolution on 12 units each of test and reference using:
   • USP Apparatus I (Basket) or II (Paddle)
   • Standard media (e.g., 900 mL, pH 1.2, 4.5, 6.8, as applicable)
   • Sampling at 6–8 time points (e.g., 5, 10, 15, 30, 45, 60 mins)
2. Analyze samples using a validated quantification method (e.g., HPLC, UV).

5.4 Data Analysis and Similarity Factor

1. Calculate mean % release for each time point.
2. Determine similarity factor (f2) using:
   
   f2 = 50 × log{[1 + (1/n) Σ (Rt − Tt)²]⁻⁰·⁵ × 100}
   • Where Rt and Tt are reference and test % release at time t
3. Acceptability Criteria:
   • f2 ≥ 50: indicates similarity
   • CV% at early time points ≤ 20%, at other time points ≤ 10%
4. Document analysis in Annexure-2: f2 Calculation Sheet.

5.5 Reporting and Interpretation

1. Compile data tables and graphical profile overlay in Annexure-3.
2. Summarize:
   • Batch details
   • Method parameters
   • Release trends
   • Conclusion on similarity
3. Review by QA and approval by AMD Head before use in regulatory submissions.

6. Abbreviations

• SOP: Standard Operating Procedure
• CDP: Comparative Dissolution Profile
• f2: Similarity Factor
• QA: Quality Assurance
• CV%: Coefficient of Variation

7. Documents

1. Comparative Dissolution Data Sheet – Annexure-1
2. f2 Calculation Template – Annexure-2
3. Overlay Graph and Conclusion Report – Annexure-3

8. References

• FDA Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms
• WHO TRS 992 Annex 7: Multisource Pharmaceutical Products
• 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	Ashwin Menon	Priya Vaidya	Sunita Reddy
Designation	Analytical Research Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Comparative Dissolution Data Sheet

Time (min)	% Release – Test (Mean ± SD)	% Release – Reference (Mean ± SD)
10	42.1 ± 2.1	41.8 ± 1.9
30	88.6 ± 1.1	89.3 ± 0.9
45	96.7 ± 0.8	97.2 ± 0.6

Annexure-2: f2 Calculation Template

Calculated using Excel spreadsheet template coded: AMD/CDP/F2/2025/01

Annexure-3: Overlay Graph and Conclusion Report

Graphical representation generated using validated software. Overlays stored in digital archive under folder: AMD/CDP/Levofloxacin/May2025

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Updated to include f2 calculation annexures and WHO TRS reference	Annual SOP Review	Sunita Reddy
10/04/2022	1.0	Initial SOP Release	New Document	QA Head