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Analytical Method Development: SOP for Performing Precision Studies in Method Validation – V 2.0

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Analytical Method Development: SOP for Performing Precision Studies in Method Validation – V 2.0

Standard Operating Procedure for Conducting Precision Studies in Analytical Method Validation


Department Analytical Method Development
SOP No. SOP/AMD/361/2025
Supersedes SOP/AMD/361/2022
Page No. Page 1 of 13
Issue Date 01/06/2025
Effective Date 04/06/2025
Review Date 01/06/2027

1. Purpose

This SOP defines the methodology for conducting precision studies during the validation of analytical methods. It focuses on repeatability and intermediate precision to assess the closeness of agreement between independent test results under prescribed conditions.

2. Scope

This procedure

is applicable to all new or updated analytical methods developed in the Analytical Method Development (AMD) department for drug substances and drug products that require quantitative determination.

3. Responsibilities

  • Analytical Chemist: Executes repeatability and intermediate precision tests, compiles results, and performs statistical evaluations.
  • QA Reviewer: Verifies the integrity and compliance of the precision study as per protocol.
  • AMD Group Leader: Reviews the precision report and provides final authorization for inclusion in validation documentation.
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4. Accountability

The AMD Department Head is accountable for ensuring the proper execution and documentation of precision studies as per ICH Q2(R1), USP <1225>, and applicable GMP requirements.

5. Procedure

5.1 Definitions

  • Repeatability: Precision under the same operating conditions over a short interval of time, usually by the same analyst, on the same equipment.
  • Intermediate Precision: Variation within a laboratory caused by different analysts, equipment, or days.

5.2 Repeatability Testing

  1. Prepare six replicates of the test solution at the target assay concentration (Annexure-1).
  2. Perform analysis using the validated method parameters (HPLC, UV, etc.).
  3. Record retention times, peak areas, and any relevant system suitability data.
  4. Calculate mean, standard deviation (SD), and relative standard deviation (RSD).
  5. Acceptance Criteria: RSD should be ≤ 2% unless otherwise justified by product-specific requirements.

5.3 Intermediate Precision Testing

  1. Repeat the precision study on a different day, with a different analyst and equipment if available.
  2. Prepare fresh sample solutions and analyze in triplicate at the same concentration levels.
  3. Combine data from both runs and calculate pooled SD, pooled RSD, and compare variability.
  4. Ensure system suitability is established in each run as per validated method criteria.
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5.4 Data Interpretation

  1. Compare intra-assay (repeatability) and inter-assay (intermediate) data.
  2. Evaluate whether variability is within acceptable limits specified in ICH Q2(R1).
  3. Plot data using control charts or run plots to visualize consistency and outliers.
  4. If outliers are identified, conduct investigation and repeat analysis with justification.

5.5 Documentation

  1. Document each test with unique ID numbers and link to the analytical run log (Annexure-2).
  2. Compile raw data, system suitability data, calculations, and chromatograms in a precision summary report.
  3. Complete Annexure-3 for data tabulation and statistical evaluation.

6. Abbreviations

  • RSD: Relative Standard Deviation
  • SD: Standard Deviation
  • HPLC: High Performance Liquid Chromatography
  • ICH: International Council for Harmonisation

7. Documents

  1. Annexure-1: Precision Sample Preparation Record
  2. Annexure-2: Chromatographic Run Log
  3. Annexure-3: Statistical 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
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9. SOP Version

Version: 2.0

10. Approval Section

Prepared By Checked By Approved By
Signature
Date
Name Swati Kulkarni Ramesh Patil Dr. Neeraj Desai
Designation Analyst – AMD QA Reviewer Department Head
Department Analytical Method Development Quality Assurance Analytical Method Development

11. Annexures

Annexure-1: Precision Sample Preparation Record

Sample ID Analyst Date Target Concentration Volume Prepared
P-361-R1 to R6 Swati Kulkarni 01/06/2025 50 µg/mL 50 mL

Annexure-2: Chromatographic Run Log

Sample Retention Time Peak Area System Suitability Pass/Fail
P-361-R1 6.53 105,430 Pass
P-361-R2 6.55 104,988 Pass
P-361-R3 6.52 105,001 Pass
P-361-R4 6.56 105,350 Pass
P-361-R5 6.54 104,970 Pass
P-361-R6 6.57 105,200 Pass

Annexure-3: Statistical Summary Sheet

Level Mean Area SD RSD (%)
Repeatability 105,156 178 0.17%
Intermediate Precision 105,020 196 0.19%

Revision History:

Revision Date Revision No. Details Reason Approved By
01/06/2025 2.0 Expanded section on intermediate precision, added pooled RSD calculations Annual Review Dr. Neeraj Desai
10/07/2022 1.0 Initial Issue New SOP QA Head
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