of spectral similarity between test samples, reference standards, and placebos to support identity, conformity, or specificity conclusions.

2. Scope

This SOP applies to all FTIR analyses conducted using KBr pellet or ATR techniques in the AMD laboratory for Active Pharmaceutical Ingredients (APIs), excipients, intermediates, and formulations. It covers spectrum comparison, overlay assessment, and reporting requirements.

3. Responsibilities

• Analytical Chemist: Prepares and scans samples, performs spectrum overlays, and documents comparison outputs.
• Reviewer: Verifies match percentages, peak alignments, and interprets deviations.
• QA Officer: Reviews documentation and ensures regulatory compliance.
• Head – AMD: Approves final interpretation and method development conclusions based on comparison data.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring the integrity of FTIR spectral comparisons and their scientific justification within development reports and validation documents.

5. Procedure

5.1 Sample and Reference Preparation

1. Prepare test sample, reference standard, and placebo (if applicable) using the approved FTIR method (ATR or KBr pellet).
2. Ensure all samples are dried appropriately and prepared under similar environmental conditions.
3. Label all spectra with unique identifiers, date, analyst initials, and method used.
4. Document in Annexure-1: Sample Preparation Log.

5.2 FTIR Scanning Parameters

1. Set instrument parameters uniformly for all spectra being compared:
   • Scan range: 4000–400 cm^-1
   • Resolution: 4 cm^-1
   • Number of scans: 32–64
2. Perform background correction before each sample scan.
3. Export spectra in compatible formats (e.g., ASCII, .spc) for overlay comparison.
4. Document scan parameters in Annexure-2: Scan Settings Log.

5.3 Spectral Overlay and Match Assessment

1. Use FTIR software (e.g., OMNIC, Spectrum, or instrument manufacturer software) to overlay test and reference spectra.
2. Align spectra at a common baseline and adjust scaling if necessary (without distorting original values).
3. Focus on fingerprint region (1800–600 cm^-1) for match analysis.
4. Key match parameters:
   • Peak positions within ±5 cm^-1
   • Peak intensities within ±10%
   • Absence of additional peaks in test spectrum
5. Record visual overlay and software-calculated match percentage (target ≥ 95%).
6. Document in Annexure-3: Overlay Evaluation Sheet.

5.4 Fingerprint Region Comparison

1. Assign functional groups to key peaks based on known IR absorption ranges.
2. Compare the number, position, and sharpness of peaks between test and reference.
3. Note any peak shifts or missing peaks and investigate possible causes (e.g., polymorphism, moisture, processing).
4. Capture observations in Annexure-4: Fingerprint Interpretation Sheet.

5.5 Reporting and Conclusion

1. Summarize comparison findings:
   • Overlay match percentage
   • Key spectral differences (if any)
   • Confirmation of identity or deviation reason
2. If results support conformity, the FTIR spectrum may be included in the analytical method or COA specification.
3. Record final remarks and reviewer approval in Annexure-5: Comparison Summary.

6. Abbreviations

• FTIR: Fourier Transform Infrared
• ATR: Attenuated Total Reflectance
• KBr: Potassium Bromide
• API: Active Pharmaceutical Ingredient
• cm^-1: Wavenumber
• SOP: Standard Operating Procedure

7. Documents

1. Sample Preparation Log – Annexure-1
2. Scan Settings Log – Annexure-2
3. Overlay Evaluation Sheet – Annexure-3
4. Fingerprint Interpretation Sheet – Annexure-4
5. Comparison Summary – Annexure-5

8. References

• ICH Q2(R1) – Validation of Analytical Procedures
• USP <197K> – FTIR Spectroscopy Identification
• Instrument Manufacturer 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: Sample Preparation Log

Sample ID	Material	Method Used	Operator	Date
FTIR-100-01	Ibuprofen	ATR	Rajesh Kumar	19/05/2025

Annexure-2: Scan Settings Log

Scan Range	Resolution	No. of Scans	Mode	Background Done
4000–400 cm-1	4 cm-1	64	Absorbance	Yes

Annexure-3: Overlay Evaluation Sheet

Test vs Reference	Match %	Baseline Aligned	Conclusion
FTIR-100-01 vs REF-IBU	97.2%	Yes	Acceptable

Annexure-4: Fingerprint Interpretation Sheet

Wavenumber (cm-1)	Functional Group	Test Peak	Reference Peak	Status
1710	C=O Stretch	1710	1709	Match
2955	CH Stretch	2955	2956	Match

Annexure-5: Comparison Summary

Analyst	Observation	Conclusion	Reviewed By
Sunita Reddy	Spectrum matched with minor baseline shift	Confirmed	QA Officer

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added overlay match criteria and expanded fingerprint assessment annexures	Annual SOP Review