Analytical Method Development (AMD) laboratory.

2. Scope

This SOP applies to all qualitative and semi-quantitative morphological evaluations conducted within the AMD department to support material characterization, method development, and formulation development.

3. Responsibilities

• Analytical Scientist: Prepares samples and performs morphological evaluations using microscopy.
• Instrument Operator: Calibrates and operates SEM or optical microscope as per protocol.
• QA Officer: Verifies records and compliance with analytical documentation standards.
• Head – AMD: Approves the morphological characterization report and ensures regulatory adherence.

4. Accountability

The Head of Analytical Method Development is accountable for the accuracy, compliance, and interpretability of morphology assessment results.

5. Procedure

5.1 Sample Preparation for Optical Microscopy

1. Weigh approximately 1–5 mg of powder and evenly spread on a clean glass slide.
2. Use immersion oil (if required) to enhance contrast for smaller particles.
3. Place a cover slip gently without compressing the sample.
4. Label the slide with sample ID and date of preparation.
5. Log details in Annexure-1: Optical Microscopy Sample Log.

5.2 Sample Preparation for SEM Analysis

1. Mount a small quantity (~1–2 mg) of dry powder onto carbon tape fixed to an SEM stub.
2. If required, coat the sample with gold or platinum using a sputter coater (for non-conductive materials).
3. Document sputter coating parameters (voltage, duration) in Annexure-2: SEM Sample Preparation Log.

5.3 Instrument Setup and Observation

1. For optical microscopy:
   • Use magnifications ranging from 100X to 1000X.
   • Capture images using camera software.
2. For SEM:
   • Set accelerating voltage (e.g., 5–15 kV depending on material type).
   • Adjust working distance and focus using standard procedure.
   • Capture images at multiple magnifications (e.g., 500X, 1000X, 5000X).
3. Ensure calibration is verified using a reference grid or standard particles before each session.
4. Log in Annexure-3: Instrument Configuration Record.

5.4 Morphology Evaluation Criteria

1. Visually assess the following parameters:
   • Shape: spherical, rod-like, irregular, plate-like
   • Surface texture: smooth, rough, porous
   • Agglomeration: presence or absence
   • Particle integrity: cracked, fractured, uniform
2. Record observations along with captured images in Annexure-4: Morphology Assessment Worksheet.

5.5 Reporting and Documentation

1. Compile a summary of morphology, include:
   • Microscope/SEM images (annotated)
   • Table of morphological attributes
   • Interpretation on formulation or processing impact
2. Submit the morphology assessment report for QA and Head–AMD review.
3. Maintain records for minimum 5 years or per GMP data retention policy.

6. Abbreviations

• SEM: Scanning Electron Microscopy
• API: Active Pharmaceutical Ingredient
• AMD: Analytical Method Development
• GMP: Good Manufacturing Practice
• SOP: Standard Operating Procedure

7. Documents

1. Optical Microscopy Sample Log – Annexure-1
2. SEM Sample Preparation Log – Annexure-2
3. Instrument Configuration Record – Annexure-3
4. Morphology Assessment Worksheet – Annexure-4

8. References

• USP <776> – Optical Microscopy
• USP <823> – SEM Technique Validation
• ICH Q6A – Specifications: Test Procedures and Acceptance Criteria

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Optical Microscopy Sample Log

Sample ID	Slide ID	Magnification	Prepared By	Date
API-MO-118	SLD-001	400X	Rajesh Kumar	18/05/2025

Annexure-2: SEM Sample Preparation Log

Sample ID	Stub ID	Coating Type	Duration	Operator
API-MO-118	STB-006	Gold	90 sec	Sunita Reddy

Annexure-3: Instrument Configuration Record

Instrument	Magnification	Voltage	Calibration Status	Verified By
JEOL JSM-IT200	5000X	10 kV	Valid	QA

Annexure-4: Morphology Assessment Worksheet

Sample API-MO-118 exhibits elongated rod-like particles with rough surface texture and minor agglomeration. No evidence of particle fracture was observed. Particle shape consistent with expected API crystallinity.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Updated SEM coating process and added image annotation requirement	Annual SOP Review