compression or encapsulation.

2. Scope

This SOP applies to the Analytical Method Development and Quality Control departments responsible for blend uniformity analysis in tablet, capsule, and granule formulations during formulation development and batch manufacturing.

3. Responsibilities

• Formulation Team: Provides blend sampling plan and defines critical blend stages.
• Analytical Scientist: Develops and validates assay methods for API quantification in blends.
• QC Analyst: Conducts uniformity testing and records results.
• QA Executive: Ensures proper documentation and regulatory compliance.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that blend uniformity studies are conducted as per validated methods, complying with ICH, FDA, and internal standards.

5. Procedure

5.1 Sampling of Blend

1. Collect a minimum of 10 samples from predefined blend locations (e.g., top, middle, bottom) in the blender.
2. Sample weight: Approximately 1–2 g depending on assay sensitivity.
3. Transfer samples into clean, labeled containers and analyze immediately or store in suitable conditions if delay expected.

5.2 Sample Preparation

1. Dilute accurately weighed sample using suitable solvent/diluent.
2. Sonicate to ensure complete dissolution of API.
3. Filter through 0.45 µm membrane filter prior to analysis.

5.3 Standard Preparation

1. Prepare standard API solution using certified reference material.
2. Ensure concentration range matches the expected blend assay level.

5.4 Analytical Method and Instrumentation

• Assay Technique: HPLC or UV Spectrophotometry based on API characteristics.
• Typical HPLC Conditions:
  • Column: C18, 250 mm × 4.6 mm × 5 µm
  • Mobile Phase: Buffer:Acetonitrile (60:40) or as optimized
  • Flow Rate: 1.0 mL/min
  • Detection: UV at λ_max specific to API

5.5 Calculation and Statistical Analysis

1. Calculate individual sample assay in % of label claim.
2. Determine mean, standard deviation (SD), and relative standard deviation (RSD).
3. Acceptance Criteria:
   • Mean: 95%–105% of label claim
   • RSD: NMT 5.0%
   • No individual result should deviate more than ±10% from the mean

5.6 Validation Parameters

1. Specificity: Ensure no interference from excipients.
2. Linearity: r² ≥ 0.999 over a suitable concentration range.
3. Accuracy: Recovery between 98%–102% at three spiked levels.
4. Precision: RSD ≤ 2.0% for six replicate blend samples.
5. Robustness: Evaluate impact of flow rate and temperature on assay.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• HPLC: High Performance Liquid Chromatography
• RSD: Relative Standard Deviation
• SD: Standard Deviation

7. Documents

1. Blend Uniformity Data Sheet – Annexure-1
2. HPLC Chromatograms and Calculations – Annexure-2
3. Validation Summary Report – Annexure-3

8. References

• FDA Guidance: ANDAs – Blend Uniformity Analysis
• ICH Q2(R1): Validation of Analytical Procedures
• USP <905>: Uniformity of Dosage Units

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Neha Mehta	Rajesh Patil	Sunita Reddy
Designation	Analytical Chemist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Blend Uniformity Data Sheet

Sample ID	% Assay	Deviation (%)	Status
BUA-292-01	98.6%	1.2%	Pass

Annexure-2: HPLC Chromatograms and Calculations

Includes sample chromatograms with peak integration and area reports for standard and sample preparations.

Annexure-3: Validation Summary Report

The method for API distribution analysis in formulation blends was validated in accordance with ICH Q2(R1) and demonstrated specificity, linearity, accuracy, and precision suitable for routine batch release.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added sample location guidance and updated statistical criteria	Annual Review	Sunita Reddy
10/12/2022	1.0	Initial SOP Release	New SOP	QA Head