pharmacopeial and ICH requirements.

2. Scope

This SOP is applicable to the Analytical Method Development and Quality Control departments involved in the routine testing, validation, and development of content uniformity methods for hard gelatin and soft gelatin capsules.

3. Responsibilities

• QC Analyst: Performs content uniformity testing of individual capsules as per validated method.
• Analytical Scientist: Develops and validates the method for content uniformity.
• QA Executive: Verifies compliance with acceptance criteria and ensures accuracy of records.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring method accuracy, regulatory compliance, and timely reporting of content uniformity results.

5. Procedure

5.1 Sampling Plan

1. Randomly select 10 individual capsules from the finished batch for testing.
2. Ensure each capsule is intact, free of leakage, and representative of the lot.

5.2 Sample Preparation

1. Individually weigh and empty each capsule into a volumetric flask.
2. Dissolve contents using a suitable diluent (e.g., methanol, buffer solution).
3. Sonicate if necessary to ensure complete dissolution and filter using 0.45 µm filter.
4. Make up to volume and dilute further if required to reach assay concentration.

5.3 Standard Preparation

1. Prepare a stock solution of known concentration using API reference standard.
2. Prepare working standard in the same diluent used for sample preparation.

5.4 Instrument Conditions

• HPLC Column: C18, 250 mm × 4.6 mm, 5 µm
• Mobile Phase: Buffer:Acetonitrile (65:35 v/v) or as optimized
• Flow Rate: 1.0 mL/min
• Detection: UV at λmax specific to the API (e.g., 254 nm)
• Injection Volume: 20 µL

5.5 Evaluation Criteria

1. Calculate the content of API in each capsule using the calibration curve.
2. Acceptance Criteria (USP <905>):
   • 9 out of 10 units must be within 85%–115% of label claim.
   • If 1 unit falls outside this range but within 75%–125%, test 20 additional capsules.
   • Content uniformity passes if not more than 3 of 30 units are outside 85%–115% and none outside 75%–125%.

5.6 Validation Parameters

1. Specificity: No interference from capsule excipients.
2. Linearity: r² ≥ 0.999 over a range of 50%–150% of label claim.
3. Accuracy: Recovery of 98%–102% across three levels.
4. Precision: RSD ≤ 2.0% for six replicate capsules.
5. Robustness: Evaluate impact of minor method variations.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• HPLC: High Performance Liquid Chromatography
• RSD: Relative Standard Deviation
• QA: Quality Assurance

7. Documents

1. Capsule Content Uniformity Log – Annexure-1
2. Standard and Sample Chromatogram Set – Annexure-2
3. Method Validation Report – Annexure-3

8. References

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

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Preeti Mehra	Rahul Nanda	Sunita Reddy
Designation	QC Analyst	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Capsule Content Uniformity Log

Capsule No.	% Assay	Limit	Status
1	99.2%	85–115%	Pass
2	97.8%	85–115%	Pass

Annexure-2: Chromatogram Set

Includes representative chromatograms for standard and 10 capsule samples. All peaks meet system suitability criteria (retention time, resolution, tailing factor).

Annexure-3: Method Validation Report

The method for content uniformity of capsules was validated for specificity, linearity, accuracy, and precision. Results comply with ICH and USP guidelines. Approved for batch release testing.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Expanded sample criteria, included soft gelatin capsule applicability	Annual Review	Sunita Reddy
15/06/2022	1.0	Initial SOP Release	New SOP	QA Head