pharmaceutical materials including APIs, excipients, and finished products.

2. Scope

This SOP applies to the Analytical Method Development (AMD) department for evaluating material stability, hygroscopicity, and thermal degradation using TGA instrumentation in R&D and routine analysis.

3. Responsibilities

• Analytical Scientist: Responsible for method design, thermal profile evaluation, and interpretation.
• Instrument Analyst: Operates and maintains the TGA instrument, performs calibration and sample runs.
• QA Officer: Ensures review and compliance of validation reports and experimental data.
• Head – AMD: Approves the developed TGA method and validates its implementation in QC or stability labs.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that all TGA methods are scientifically sound, validated, and aligned with ICH and pharmacopoeial standards.

5. Procedure

5.1 Instrument Setup and Calibration

1. Ensure the TGA instrument is calibrated for temperature and weight using certified standards (e.g., calcium oxalate monohydrate).
2. Document calibration data in Annexure-1: TGA Calibration Log.
3. Verify purge gas (e.g., nitrogen or air) is connected and pressure is stable at 50–60 mL/min.

5.2 Sample Preparation

1. Weigh 5–10 mg of powdered sample using an analytical balance.
2. Use pre-tared, clean platinum or alumina crucibles with lids if applicable.
3. Avoid contact with moisture prior to measurement; store hygroscopic samples in desiccators until analysis.

5.3 Method Parameters for Moisture and Volatile Analysis

1. Set temperature program:
   • Start Temp: 25°C
   • End Temp: 150–300°C (depending on analyte)
   • Ramp Rate: 10°C/min
2. Use isothermal holds at 105°C for accurate moisture quantification if needed.
3. Record weight loss and derivative thermogravimetric (DTG) curves.
4. Determine:
   • % Moisture (loss below 120°C)
   • % Volatile (loss between 120°C–200°C)
   • Thermal degradation (onset temperature)
5. Enter all thermal transitions in Annexure-2: TGA Profile Report.

5.4 Method Validation

1. Validate TGA method per ICH Q2(R2) guidelines:
   • Precision – Repeatability of % loss (RSD ≤ 3%)
   • Accuracy – Recovery studies with known spiked water or solvent samples
   • Specificity – Ability to distinguish moisture from solvents
   • Robustness – Evaluate different ramp rates or crucible types
2. Document validation summary in Annexure-3: Validation Log.

5.5 Safety Considerations

1. Ensure the crucibles are cool before removing from furnace.
2. Handle decomposing samples in fume hood if toxic gases are expected.
3. Dispose of thermally decomposed residues as per hazardous waste policy.

6. Abbreviations

• TGA: Thermogravimetric Analysis
• DTG: Derivative Thermogravimetry
• RSD: Relative Standard Deviation
• ICH: International Council for Harmonisation
• SOP: Standard Operating Procedure

7. Documents

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

8. References

• ICH Q2(R2) – Validation of Analytical Procedures
• USP <891> – Thermal Analysis
• European Pharmacopoeia 2.2.34 – Thermogravimetric Analysis

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: TGA Calibration Log

Material	Theoretical Temp (°C)	Observed Temp (°C)	Weight Loss (%)	Analyst
Calcium Oxalate	133	132.8	18.5	Rajesh Kumar

Annexure-2: TGA Profile Report

Sample ID	Moisture (%)	Volatile (%)	Decomposition Onset (°C)	Analyst
API-TGA-22	2.1	3.5	218.6	Sunita Reddy

Annexure-3: Validation Log

Parameter	Result	Acceptance Criteria	Status
Repeatability	RSD = 2.4%	≤ 3%	Pass
Accuracy	98.8%	95%–105%	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added DTG interpretation and expanded volatile content reporting	Annual SOP Review