blending stages prior to tablet compression or capsule filling. It ensures content consistency, quality control, and compliance with regulatory requirements.

2. Scope

This SOP applies to all blend assay method development activities undertaken by the Analytical Method Development department for solid oral dosage forms including tablets, capsules, granules, and premixes. It encompasses new product development, scale-up, and technology transfer phases.

3. Responsibilities

• Analytical Scientist: Responsible for method design, execution, optimization, and validation.
• Formulation Scientist: Coordinates sampling during blending and provides blend composition details.
• QA Representative: Reviews method validation protocol and ensures compliance with GMP standards.
• Instrumentation Officer: Ensures instrument calibration and readiness for method development.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring the developed blend assay method meets ICH Q2(R1) criteria and is suitable for routine in-process quality control operations.

5. Procedure

5.1 Method Design and Planning

1. Obtain formulation composition including percentage of API, excipients, and expected potency per unit dose.
2. Evaluate sample matrix complexity and potential interference from excipients.
3. Select suitable analytical technique (e.g., HPLC, UV, NIR) based on sensitivity, specificity, and matrix compatibility.

5.2 Sample Preparation Strategy

1. Establish sampling procedure to collect representative blend samples from multiple points (top, middle, bottom) of the blender.
2. Optimize sample extraction method ensuring complete dissolution of API and minimal matrix interference.
3. Develop sample dilution protocol to bring API concentration within the linear range of the instrument.

5.3 Method Development Steps

1. For HPLC methods:
   • Select appropriate mobile phase, column, flow rate, and detection wavelength.
   • Inject placebo and API standard solutions to assess specificity and retention time.
   • Inject blend samples and evaluate peak purity and resolution.
2. For UV methods:
   • Scan full spectra of blend vs. standard to identify λmax.
   • Check baseline drift, stray light interference, and absorbance linearity.

5.4 Method Optimization

1. Assess method repeatability and recovery by spiking known amounts of API into blend matrix.
2. Adjust injection volume, run time, and gradient (if HPLC) based on resolution and tailing factor.
3. Minimize solvent use and method runtime to improve efficiency for routine application.

5.5 Validation of Method

1. Validate method as per ICH Q2(R1) guidelines covering:
   • Specificity: Confirm absence of interference from excipients.
   • Linearity: Prepare 5–7 concentration levels, calculate correlation coefficient (r² > 0.999).
   • Accuracy: Perform recovery studies at 50%, 100%, and 150% levels.
   • Precision: Assess repeatability (intra-day) and intermediate precision (inter-day, analyst-to-analyst).
   • Robustness: Alter minor parameters like flow rate, temperature and observe impact.
   • LOD/LOQ: Determine using signal-to-noise ratio (LOD ≥ 3:1, LOQ ≥ 10:1).

5.6 Documentation and Reporting

1. Document all raw data, chromatograms, spectral overlays, and calculations in method development notebook.
2. Prepare Method Validation Report (Annexure-2) including summary tables and validation outcome.
3. Submit report to QA for approval and archiving.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• HPLC: High-Performance Liquid Chromatography
• UV: Ultraviolet Spectroscopy
• LOD: Limit of Detection
• LOQ: Limit of Quantitation

7. Documents

1. Blend Assay Method Development Protocol – Annexure-1
2. Method Validation Report – Annexure-2
3. Linearity and Accuracy Calculation Sheet – Annexure-3

8. References

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

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Deepika Iyer	Neeraj Sinha	Dr. Harshita Goyal
Designation	Method Developer	QA Reviewer	Head – AMD
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: Blend Assay Method Development Protocol

Protocol detailing method objective, sample details, target analyte, instrument parameters, trial sequence, and acceptance criteria.

Annexure-2: Method Validation Report Summary

Parameter	Result	Acceptance	Status
Linearity (r²)	0.9995	≥ 0.999	Pass
Accuracy	98.5% – 101.2%	98% – 102%	Pass
Precision (RSD)	1.3%	≤ 2%	Pass

Annexure-3: Linearity and Accuracy Calculation Sheet

Includes raw values, dilution factors, absorbance or peak area, regression equation, slope, intercept, recovery %, and SD.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2025	2.0	Updated sampling strategy, robustness section	Annual SOP review	Dr. Harshita Goyal
10/03/2022	1.0	Initial Release	New SOP	QA Head