of sterile injectable products, including raw materials, intermediates, and final product testing. It is applicable to Quality Control (QC) laboratories and R&D departments.

3. Responsibilities

• Analytical Development Team: Develops and drafts validation protocol.
• QC Analyst: Executes validation experiments.
• QA Officer: Reviews protocols, reports, and ensures compliance.
• Head QC: Approves validation outcomes and final reports.

4. Accountability

The Head of Quality Control is accountable for the execution and approval of all method validation activities.

5. Procedure

5.1 Preparation of Validation Protocol

1. Define scope, objective, responsibilities, and timelines.
2. List materials, equipment, instruments, and acceptance criteria.
3. Include ICH validation parameters such as accuracy, precision, specificity, linearity, LOD, LOQ, robustness, and system suitability.

5.2 Execution of Validation

• All experiments must be performed using GMP-compliant practices and documented in real-time.
• Each validation parameter should be tested as described below:

5.2.1 Specificity

• Demonstrate method can distinguish analyte from degradation products, excipients, and matrix.
• Run placebo, blank, and spiked solutions.

5.2.2 Linearity

• Prepare at least 5 concentration levels of standard solutions across the intended range.
• Plot calibration curve and calculate correlation coefficient (r ≥ 0.999).

5.2.3 Accuracy

• Perform recovery studies at 3 different concentrations (e.g., 80%, 100%, 120%).
• Acceptable recovery: 98–102%.

5.2.4 Precision

• Evaluate repeatability (intra-day) and intermediate precision (inter-day or analyst-to-analyst).
• RSD should not exceed 2.0% unless specified otherwise.

5.2.5 Detection and Quantitation Limits (LOD & LOQ)

• Determine using signal-to-noise ratio or standard deviation method.
• LOD: S/N ≥ 3; LOQ: S/N ≥ 10.

5.2.6 Robustness

• Assess effect of small deliberate changes in method parameters (e.g., pH, temperature, mobile phase composition).
• Results should remain within acceptable limits.

5.2.7 System Suitability

• Check resolution, tailing factor, number of theoretical plates, RSD of injections.
• All criteria must comply with method-specific limits.

5.3 Documentation

1. Record all raw data in laboratory notebooks or approved data sheets (Annexure-1).
2. Compile and analyze results using statistical tools.
3. Prepare final validation report and submit for QA review (Annexure-2).
4. Maintain records for minimum five years or as per retention policy.

5.4 Revalidation

• Revalidate the method when there are significant changes to:
  • Analytical procedure or equipment
  • Manufacturing process or formulation
  • Analyst or laboratory transfer

5.5 Change Control

1. Initiate change control before modifying any validated method.
2. Assess impact and decide whether full or partial revalidation is needed.

6. Abbreviations

• SOP: Standard Operating Procedure
• QC: Quality Control
• QA: Quality Assurance
• LOD: Limit of Detection
• LOQ: Limit of Quantitation
• RSD: Relative Standard Deviation
• ICH: International Council for Harmonisation

7. Documents

1. Validation Data Sheet – Annexure-1
2. Validation Summary Report – Annexure-2
3. Change Control Log – Annexure-3

8. References

• ICH Q2(R1) – Validation of Analytical Procedures
• USP General Chapters <1225>, <1226>
• FDA Guidance for Industry on Analytical Procedures and Methods Validation

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	QC Analyst	QA Executive	Head QA
Department	Quality Control	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Validation Data Sheet

Parameter	Tested By	Date	Result	Remarks
Linearity	Anil Rathi	20/06/2025	r = 0.9998	Complies
Precision	Shweta Mehta	21/06/2025	RSD = 1.2%	Complies

Annexure-2: Validation Summary Report

Report ID	VAL-2025-16
Method Validated	Assay by HPLC
Validated By	QC Department
Reviewed By	QA Department
Approval Date	24/06/2025

Annexure-3: Change Control Log

Change ID	Description	Date	Status
CCL-204	Adjustment of flow rate in assay method	15/06/2025	Closed

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/02/2022	1.0	Initial SOP Release	New Method Validation Requirement	QA Head
24/06/2025	2.0	Included revalidation and system suitability	Annual Review	QA Head