consistency of active ingredient distribution within and across containers.

2. Scope

This SOP applies to the Analytical Method Development (AMD) team responsible for assessing content uniformity and/or weight variation in semi-solid dosage forms during formulation development, batch release, and stability testing.

3. Responsibilities

• Analytical Scientist: Conducts the test and evaluates data against acceptance criteria.
• QC Analyst: Prepares individual dosage units, performs sample analysis, and records results.
• QA Executive: Reviews the results for compliance with internal and regulatory standards.

4. Accountability

The Head of Analytical Method Development is accountable for implementing and validating the dosage uniformity method and ensuring compliance with regulatory guidelines such as USP <905> and ICH Q6A.

5. Procedure

5.1 Definitions

Dosage Unit: A specified quantity of semi-solid formulation (e.g., 1 g or 2 g) withdrawn consistently from different locations of the container.

5.2 Sample Selection

1. Select 10 dosage units randomly from a single batch (entirely filled containers).
2. Collect from the top, middle, and bottom to account for any stratification.

5.3 Sample Preparation

1. Weigh 1.0 g (or labeled unit dose) from each selected container into a suitable volumetric flask.
2. Add diluent (e.g., methanol:water), sonicate for 10–15 minutes, and dilute to volume.
3. Filter through 0.45 µm membrane before injection.

5.4 Standard Preparation

1. Weigh accurately known quantity of reference standard and dilute to match expected concentration of test samples.
2. Filter through 0.45 µm filter and inject along with test samples.

5.5 Analytical Method

1. Use validated HPLC or UV method for assay.
2. Record absorbance or peak area and calculate the percentage of label claim for each unit.

5.6 Acceptance Criteria (USP <905>)

• 10 units must fall within 85%–115% of label claim.
• RSD ≤ 6.0% for assay results.
• If one result is outside 85%–115% but within 75%–125%, test an additional 20 units.
• Content uniformity passes if not more than 3 of 30 units fall outside 85%–115% and none outside 75%–125%.

5.7 Method Validation

1. Precision: Intra-day and inter-day RSD ≤ 2.0%
2. Linearity: r ≥ 0.999 across 50–150% of target concentration
3. Recovery: 98%–102% across various matrix levels

5.8 Documentation

1. Record individual sample weights, absorbance/peak area, and calculated assay values.
2. Attach chromatograms or UV spectra along with calculation sheets in Annexure-1.

6. Abbreviations

• HPLC: High Performance Liquid Chromatography
• RSD: Relative Standard Deviation
• QA: Quality Assurance
• AMD: Analytical Method Development

7. Documents

1. Dosage Unit Assay Log – Annexure-1
2. Validation Summary Report – Annexure-2

8. References

• USP <905>: Uniformity of Dosage Units
• ICH Q6A: Specifications for New Drug Substances and Products
• EP 2.9.40: Uniformity of Dosage Units

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Neelam Joshi	Varun Iyer	Sunita Reddy
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Dosage Unit Assay Log

Unit No.	Weight (g)	Peak Area	% Label Claim	Status
1	1.02	15432	99.2%	Pass
2	0.98	15012	98.6%	Pass
3	1.01	15500	99.5%	Pass

Annexure-2: Validation Summary Report

The method was validated across 3 batches of ointment product O-258. Results met criteria for specificity, linearity, precision, and accuracy. The method is suitable for routine batch release and stability testing.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added clarification on extended testing and updated annexures	Annual Review	Sunita Reddy
01/04/2022	1.0	Initial Release	New SOP	QA Head