Standard Operating Procedure for LOD Testing During Drying Stage in API Manufacturing

Department	API Manufacturing
SOP No.	SOP/API/085/2025
Supersedes	SOP/API/085/2022
Page No.	Page 1 of 10
Issue Date	13/04/2025
Effective Date	15/04/2025
Review Date	13/04/2026

1. Purpose

To outline a standard procedure for performing Loss on Drying (LOD) testing during the drying stage of API manufacturing for real-time monitoring of residual moisture and to determine the endpoint of drying.

2. Scope

This SOP is applicable to all API and intermediate drying processes conducted in Fluid Bed Dryers (FBD), Vacuum Tray Dryers (VTD), and Tray Dryers within the API manufacturing facility.

3. Responsibilities

• Production Operator: Collect and weigh samples as per procedure and record observations.
• QC Analyst: Perform LOD testing and verify compliance with limits.
• QA Officer: Review logbooks and ensure procedural adherence.

4. Accountability

Production Head is accountable for sampling and coordination with QC. QC Head is responsible for the accuracy and documentation of test results.

5. Procedure

5.1 Sampling for LOD

1. Ensure drying has reached a steady phase (based on time or visual judgment).
2. Open sampling port or tray cover in a clean area; avoid contaminating the bulk.
3. Collect approximately 2–5 grams of material from at least 3 different trays or regions (top, middle, bottom).
4. Use a clean, dry stainless-steel spatula and sample container labeled with batch number and stage.

5.2 Sample Handling and Transfer

1. Label the sample container with Product Name, Batch No., Sampling Point, Date, and “In-Process LOD”.
2. Transfer the sample to QC immediately; if delay exceeds 30 minutes, store in desiccator.
3. Record sampling details in the “LOD Sampling Log” (Annexure-1).

5.3 LOD Testing Procedure (Gravimetric Method)

1. Use a pre-weighed clean and dry LOD bottle/tin.
2. Accurately weigh ~1 to 2 g of the sample into the container and record weight (W1).
3. Place the container in a hot air oven set at 105°C ±2°C for 3 hours or as per method validation.
4. Remove and cool the sample in a desiccator to room temperature.
5. Reweigh and record weight (W2). Repeat until a constant weight is achieved (≤0.5 mg difference).
6. Calculate LOD using:
   LOD (%) = ((W1 – W2) / W1) × 100

5.4 Acceptance Criteria

1. Compare observed value with specification (e.g., LOD NMT 1.0%).
2. If LOD is within limits, continue drying for additional 30 minutes and repeat sampling for confirmation.
3. If out of limits, continue drying and recheck at defined intervals (e.g., every 30 minutes).

5.5 Cleaning and Documentation

1. After testing, clean the glassware and record cleaning in the laboratory logbook.
2. Ensure all calculations are verified and signed by a second analyst or reviewer.
3. Attach LOD worksheet in the BMR and archive as per QA documentation policy.

6. Abbreviations

• LOD: Loss on Drying
• QC: Quality Control
• QA: Quality Assurance
• BMR: Batch Manufacturing Record
• NMT: Not More Than

7. Documents

1. LOD Sampling Log (Annexure-1)
2. LOD Worksheet
3. Batch Manufacturing Record

8. References

• Ph. Eur / USP General Chapter < Loss on Drying >
• ICH Q2(R1) – Validation of Analytical Procedures
• 21 CFR Part 211 – US FDA cGMP 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: LOD Sampling Log

Date	Batch No.	Sampling Point	Sample Quantity	Sampled By	Sent to QC	Remarks
13/04/2025	API-20250413	Middle Tray	2 g		Yes	For routine drying check

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial SOP Release	New Method Requirement	QA Head
13/04/2025	2.0	Added sampling from multiple tray levels and recheck policy	Audit Observation	QA Head