non-destructive analysis of blend uniformity, moisture content, and identity verification.

2. Scope

This SOP is applicable to the Analytical Method Development (AMD) and manufacturing support teams responsible for deploying NIR-based tools for monitoring critical quality attributes (CQAs) during blending, granulation, drying, and tablet compression stages.

3. Responsibilities

• Analytical Scientist: Designs and validates NIR methods, prepares calibration models, and interprets results.
• Instrument Analyst: Operates NIR spectrometer, ensures calibration and maintenance, and captures IPT data.
• QA Officer: Reviews validation data and monitors GMP adherence.
• Head – AMD: Approves final method and ensures alignment with regulatory expectations.

4. Accountability

The Head of AMD is accountable for ensuring NIR methods are validated, compliant with ICH and PAT guidelines, and effective for real-time process monitoring.

5. Procedure

5.1 Instrument Calibration and Setup

1. Calibrate wavelength accuracy using certified reference materials (e.g., polystyrene or SRM standards).
2. Verify photometric response, noise, and resolution specifications per instrument manufacturer instructions.
3. Record all calibration results in Annexure-1: NIR Calibration Log.

5.2 Sample Preparation

1. Use representative samples from various stages (pre-blend, post-blend, granules, tablets).
2. No dilution or sample treatment is required; ensure uniform surface for consistent spectra.
3. Use sample cup, glass vials, or inline probes as per instrument configuration.

5.3 Method Development Parameters

1. Wavelength Range: 800–2500 nm (or instrument-specific range).
2. Resolution: ≤ 10 nm spectral resolution.
3. Scans per Spectrum: 32–64 scans to reduce noise.
4. Integration Time: Adjust based on signal-to-noise ratio and sample reflectance.
5. Collect reference spectra from authentic samples with known properties.

5.4 Calibration Model Building

1. Use chemometric software (e.g., Unscrambler, SIMCA) to build calibration models.
2. Apply multivariate methods such as PLS (Partial Least Squares) or PCA (Principal Component Analysis).
3. Include minimum 20–30 representative samples spanning expected concentration ranges.
4. Validate model by comparing predicted vs. actual values (R² ≥ 0.98, RMSEC ≤ 5%).
5. Save and secure calibration model; document in Annexure-2: Model Development Sheet.

5.5 Method Validation

1. Validate per ICH Q2(R2) and EMA PAT guidelines:
   • Specificity: Differentiate between active and excipient spectra.
   • Linearity: R² ≥ 0.98 across working range.
   • Accuracy: Recovery within 95%–105% against reference method.
   • Precision: RSD ≤ 3% for repeat measurements.
   • Robustness: Assess under varying environmental/light conditions.
2. Summarize in Annexure-3: NIR Validation Summary.

5.6 Application in In-Process Testing

1. Use NIR for:
   • Real-time monitoring of blend uniformity.
   • Moisture tracking during fluid bed drying.
   • Content uniformity during compression or coating.
   • Rapid ID testing of incoming materials at warehouse.
2. Integrate with control systems for automatic release or rejection.
3. Maintain results and logs in Annexure-4: In-Process NIR Test Record.

6. Abbreviations

• NIR: Near Infrared Spectroscopy
• PAT: Process Analytical Technology
• RSD: Relative Standard Deviation
• PLS: Partial Least Squares
• PCA: Principal Component Analysis
• SOP: Standard Operating Procedure

7. Documents

1. NIR Calibration Log – Annexure-1
2. Model Development Sheet – Annexure-2
3. NIR Validation Summary – Annexure-3
4. In-Process NIR Test Record – Annexure-4

8. References

• ICH Q2(R2) – Validation of Analytical Procedures
• FDA Guidance for PAT – A Framework for Innovative Pharmaceutical Development
• USP <856> – NIR Spectroscopy
• EMA QbD and PAT Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: NIR Calibration Log

Date	Standard Used	Wavelength Accuracy (nm)	Status	Analyst
18/05/2025	Polystyrene Film	+0.6 nm @ 1900 nm	Pass	Rajesh Kumar

Annexure-2: Model Development Sheet

Model ID	Application	Sample Size	R²	RMSEC	Status
NIR-BLEND-23	Blend Uniformity	30	0.989	4.1%	Valid

Annexure-3: NIR Validation Summary

Parameter	Result	Criteria	Status
Precision	RSD = 2.1%	≤ 3%	Pass
Accuracy	97.2%	95%–105%	Pass

Annexure-4: In-Process NIR Test Record

Batch No.	Stage	Result	Acceptance Limit	Status
BLND/2025/117	Post-blend	98.6%	95%–105%	Complies

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Included PAT applications and inline validation steps	Annual SOP Review