compatibility of pharmaceutical materials.

2. Scope

This SOP applies to the Analytical Method Development (AMD) department for the use of DSC in analyzing raw materials, active pharmaceutical ingredients (APIs), excipients, intermediates, and drug formulations during development and stability studies.

3. Responsibilities

• Analytical Scientist: Develops and validates DSC methods, prepares interpretation reports.
• Instrument Analyst: Calibrates, maintains, and operates DSC instrument as per protocol.
• QA Officer: Reviews method validation and thermal analysis reports.
• Head – AMD: Authorizes finalized methods and ensures regulatory compliance.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that DSC methods meet GMP and ICH Q6A requirements for physical characterization of pharmaceutical substances.

5. Procedure

5.1 Instrument Preparation and Calibration

1. Ensure DSC instrument is calibrated using certified reference materials (e.g., indium, zinc).
2. Record calibration temperatures and enthalpy values in Annexure-1: Calibration Log.
3. Verify nitrogen purge and cooling system readiness.

5.2 Sample Preparation

1. Weigh 2–5 mg of accurately prepared sample using an analytical balance.
2. Place in pre-cleaned, crimped aluminum pans with tight-sealing lids.
3. Use matched reference pan (empty) for all runs.

5.3 Method Development Parameters

1. Set scanning temperature range based on sample properties:
   • Typical range: 25°C to 300°C
2. Set heating rate:
   • Standard: 10°C/min
   • Slow heating (e.g., 2°C/min) for polymorphic or excipient interaction analysis
3. Use nitrogen as purge gas at a flow rate of 50 mL/min.
4. Program DSC for single or multi-heat cycles if needed (e.g., heat-cool-heat profile).

5.4 Analysis and Interpretation

1. Start run and monitor baseline stabilization.
2. Identify peaks corresponding to:
   • Melting point (endothermic)
   • Glass transition temperature (Tg)
   • Crystallization (exothermic)
   • Polymorphic transitions
3. Measure:
   • Peak temperature (Tm)
   • Enthalpy change (ΔH)
   • Tg (midpoint of baseline shift)
4. Document all thermal transitions in Annexure-2: Thermal Profile Report.

5.5 Method Validation

1. Perform validation per ICH Q2(R2) and instrument-specific SOPs:
2. Parameters:
   • Precision – Repeatability of Tm and ΔH (RSD ≤ 2%)
   • Specificity – No signal overlap in matrix-excipient mixtures
   • Robustness – Confirm results across heating rates or pan types
3. Summarize validation data in Annexure-3: Validation Report.

5.6 Safety and Cleaning

1. Ensure pans are crimped tightly to avoid sample leakage.
2. Wear gloves when handling hot crucibles or after thermal run.
3. Dispose used pans as per waste handling SOPs.

6. Abbreviations

• DSC: Differential Scanning Calorimetry
• Tg: Glass Transition Temperature
• Tm: Melting Temperature
• ΔH: Enthalpy Change
• RSD: Relative Standard Deviation
• SOP: Standard Operating Procedure

7. Documents

1. Calibration Log – Annexure-1
2. Thermal Profile Report – Annexure-2
3. Validation Report – Annexure-3

8. References

• ICH Q6A – Specifications: Test Procedures and Acceptance Criteria
• ICH Q2(R2) – Validation of Analytical Procedures
• USP <891> – Thermal Analysis
• European Pharmacopoeia 2.2.34 – Differential Scanning Calorimetry

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Calibration Log

Material	Reference Temp (°C)	Observed Temp (°C)	ΔH (J/g)	Analyst
Indium	156.6	156.4	28.5	Rajesh Kumar

Annexure-2: Thermal Profile Report

Sample ID	Melting Point (°C)	ΔH (J/g)	Tg (°C)	Crystallization (°C)	Analyst
API-DSC-2025-02	143.2	22.6	59.4	NA	Sunita Reddy

Annexure-3: Validation Report

Parameter	Result	Acceptance Criteria	Status
Repeatability of Tm	RSD = 1.2%	≤ 2%	Pass
Recovery	98.6%	95%–105%	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added enthalpy and multi-cycle profile validation	Annual SOP Review