different conditions such as different analysts, instruments, days, or laboratories.

2. Scope

This SOP applies to all personnel involved in method development activities for APIs, excipients, and pharmaceutical formulations who are responsible for conducting and evaluating intermediate precision as part of method validation or verification studies.

3. Responsibilities

• Analyst A and Analyst B: Independently perform the test using the same method on different days or using different instruments.
• Method Development Team Lead: Plans the intermediate precision strategy, verifies experimental conditions, and reviews compiled data.
• QA Reviewer: Audits the precision data for accuracy and completeness and ensures it aligns with validation protocol.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that intermediate precision evaluations are planned, executed, reviewed, and documented in compliance with ICH Q2(R1) guidelines and internal SOP requirements.

5. Procedure

5.1 Experimental Design

1. Use a minimum of two analysts, two instruments, and two days for the study.
2. Conduct the study at the target concentration (100%) using six independent sample preparations per analyst.
3. Ensure consistency in reagents, glassware, and method parameters across the analysts.

5.2 Sample Preparation and Analysis

1. Each analyst shall prepare six replicate sample solutions independently and analyze them as per the finalized method.
2. Record all chromatographic/spectroscopic responses and calculate individual assay or test values.
3. Ensure that each batch includes a system suitability check and meets the predefined acceptance criteria.

5.3 Statistical Evaluation

1. Calculate the % assay for each sample from each analyst separately.
2. Determine the Mean, Standard Deviation (SD), and % Relative Standard Deviation (%RSD) for each set and combined sets.
3. Acceptable %RSD should generally be ≤ 2.0% for assay methods. For impurity methods, acceptance criteria may vary and must be justified.
4. Perform One-way ANOVA if required to assess statistical significance between analyst results.

5.4 Data Compilation and Review

1. Document raw data, calculations, instrument printouts, and observations in Annexure-1.
2. Compile results from both analysts in a comparative format in Annexure-2.
3. Summarize findings and conclusions in Annexure-3: Precision Evaluation Summary Sheet.

6. Abbreviations

• RSD: Relative Standard Deviation
• SD: Standard Deviation
• ANOVA: Analysis of Variance
• ICH: International Council for Harmonisation
• QA: Quality Assurance

7. Documents

1. Annexure-1: Raw Data and Calculations Sheet
2. Annexure-2: Comparative Results Table
3. Annexure-3: Precision Evaluation Summary Sheet

8. References

• ICH Q2(R1): Validation of Analytical Procedures
• USP General Chapter <1225> Validation of Compendial Procedures
• 21 CFR Part 211 – Current Good Manufacturing Practice

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Neha Thakur	Manoj Pillai	Dr. Ravi Mehta
Designation	Analyst	QA Reviewer	Head – AMD
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: Raw Data and Calculations

Sample	Analyst A (% Assay)	Analyst B (% Assay)
1	98.7	98.4
2	99.0	98.8
3	98.6	98.9
4	98.9	98.7
5	98.5	98.6
6	98.8	98.5

Annexure-2: Comparative Results Summary

• Mean (Analyst A): 98.75%
• Mean (Analyst B): 98.65%
• Overall RSD: 0.21%

Annexure-3: Precision Evaluation Summary

The intermediate precision study demonstrates consistent and reproducible results across analysts and days. The %RSD values are within acceptance criteria. No significant analyst-to-analyst variation was observed. The method is considered rugged under intended conditions.

Revision History

Revision Date	Revision No.	Description	Reason	Approved By
01/06/2025	2.0	Enhanced study design to include multiple instruments	Annual Review	Dr. Ravi Mehta
12/08/2022	1.0	Initial SOP Implementation	New Method Validation	QA Head