to the Analytical Method Development (AMD) department for characterization of APIs and formulations, especially for confirming crystal structure, phase purity, and polymorphic transformation during stability and manufacturing processes.

3. Responsibilities

• Analytical Scientist: Plans and executes XRPD experiments, data interpretation, and documentation.
• Instrument Operator: Calibrates, aligns, and operates XRPD instrument as per method parameters.
• QA Officer: Reviews analytical reports and validation data to ensure GMP compliance.
• Head – AMD: Approves method validation and ensures regulatory readiness of XRPD characterization data.

4. Accountability

The Head of AMD is accountable for the integrity and scientific validity of XRPD methods used in regulatory submissions, product development, and quality assurance.

5. Procedure

5.1 Instrument Calibration

1. Perform daily calibration using certified silicon or corundum standard.
2. Verify peak positions and intensities with acceptance criteria (±0.2° 2θ shift).
3. Record in Annexure-1: XRPD Calibration Log.

5.2 Sample Preparation

1. Grind sample uniformly using mortar and pestle if needed; avoid over-grinding.
2. Spread sample evenly on zero-background sample holder (glass or quartz-based).
3. Level surface to prevent diffraction anomalies.

5.3 Method Parameters

1. Instrument Settings:
   • Radiation: Cu-Kα (λ = 1.5418 Å)
   • Voltage/Current: 40 kV / 30 mA
   • Scan Range: 2θ = 3° to 40°
   • Step Size: 0.02°
   • Scan Speed: 1.0°/min
2. Collect diffraction patterns for each sample in triplicate.
3. Use internal standard (e.g., NaCl) for peak alignment verification if required.

5.4 Data Interpretation

1. Compare peak positions and intensities to reference library (e.g., PDF from ICDD).
2. Match pattern to polymorphic forms identified during development.
3. Overlay reference patterns with test sample using XRPD software (e.g., HighScore Plus).
4. Document in Annexure-2: Diffraction Pattern Record.

5.5 Method Validation

1. Validate per ICH Q2(R2) and internal quality protocols:
   • Specificity – Confirm unique diffraction peaks of polymorphs
   • Precision – Reproducibility of peak position (RSD ≤ 0.2%)
   • Robustness – Scan rate and sample holder variation
   • Detection Limit – Minimum crystallinity detectable
2. Record results in Annexure-3: Validation Summary Sheet.

5.6 Application Examples

1. Identification of polymorphic form in new API batch.
2. Comparison of reference and stress-tested material for phase transition.
3. Monitoring batch-to-batch crystal form consistency during scale-up.

6. Abbreviations

• XRPD: X-ray Powder Diffraction
• API: Active Pharmaceutical Ingredient
• RSD: Relative Standard Deviation
• PDF: Powder Diffraction File
• ICDD: International Centre for Diffraction Data
• SOP: Standard Operating Procedure

7. Documents

1. XRPD Calibration Log – Annexure-1
2. Diffraction Pattern Record – Annexure-2
3. Validation Summary Sheet – Annexure-3

8. References

• ICH Q2(R2) – Validation of Analytical Procedures
• USP <941> – X-ray Powder Diffraction
• European Pharmacopoeia 2.2.33 – XRPD
• ICDD PDF-4+ Database

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: XRPD Calibration Log

Standard Material	Theoretical 2θ (°)	Observed 2θ (°)	Δ (°)	Analyst
Silicon	28.44	28.43	0.01	Rajesh Kumar

Annexure-2: Diffraction Pattern Record

Sample ID	2θ Range	Major Peaks (°2θ)	Match Reference	Analyst
API-XP-109	3–40	11.2, 14.6, 21.7	Polymorph-II	Sunita Reddy

Annexure-3: Validation Summary Sheet

Parameter	Result	Acceptance Criteria	Status
Precision	RSD = 0.13%	≤ 0.2%	Pass
Peak Match Score	98.6%	≥ 95%	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Expanded validation parameters and included polymorph tracking log	Annual SOP Review