Standard Operating Procedure for Ensuring Uniform Gelatin Shell Thickness

Department	Capsule Manufacturing
SOP No.	SOP/CM/066/2025
Supersedes	SOP/CM/066/2022
Page No.	Page 1 of 6
Issue Date	01/02/2025
Effective Date	05/02/2025
Review Date	01/02/2026

1. Purpose

The purpose of this SOP is to define the procedure for ensuring uniform gelatin shell thickness during the capsule manufacturing process. Achieving consistent shell thickness is crucial for maintaining capsule integrity, ensuring consistent drug release, and complying with product specifications.

2. Scope

This SOP applies to all capsule manufacturing processes involving gelatin shell formation. It includes the procedures for monitoring, adjusting, and verifying the uniformity of gelatin shell thickness during production.

3. Responsibilities

• Manufacturing Team: Responsible for ensuring that the gelatin shell thickness is uniform and meets the required specifications during production. They must also monitor shell thickness and make necessary adjustments.
• Quality Control (QC) Team: Responsible for performing periodic checks to ensure uniform gelatin shell thickness and verifying that the shells meet the required thickness specifications.
• Quality Assurance (QA) Team: Ensures that the procedure for controlling gelatin shell thickness is followed and that any deviations are documented and addressed.
• Maintenance Team: Ensures that the equipment used to produce the gelatin shells is properly calibrated and functioning to produce capsules with uniform shell thickness.

4. Accountability

The Capsule Manufacturing Supervisor is accountable for ensuring that uniform gelatin shell thickness is maintained throughout the production process. The QA Manager is responsible for ensuring compliance with this SOP and reviewing the inspection results.

5. Procedure

5.1 Pre-Production Setup

Before starting the production process, ensure the following steps are completed:

1. Machine Setup
   1. Ensure that the capsule filling machine is clean and free from residues from previous batches. Perform a thorough inspection of the machine, particularly the parts responsible for gelatin shell formation.
   2. Set up the gelatin preparation system, ensuring that the correct formulation (e.g., gelatin type, plasticizer content, and moisture level) is used to achieve the desired shell properties.
2. Gelatin Solution Preparation
   1. Prepare the gelatin solution according to the formulation and temperature requirements. Ensure that the gelatin concentration and viscosity are within the specified limits to ensure proper shell formation.
3. Documentation
   1. Document the setup parameters, including gelatin solution details, capsule size, and machine settings in the batch production record.

5.2 Monitoring Gelatin Shell Thickness During Production

During the production process, monitor the gelatin shell thickness to ensure uniformity:

1. Regular Thickness Measurements
   1. Use calibrated micrometers or automated thickness measurement systems to check the shell thickness at regular intervals during production. Measure a sample of capsules from the start, middle, and end of the production run.
2. Acceptable Thickness Range
   1. The gelatin shell thickness must fall within the specified range, typically ±0.05 mm of the target thickness. If capsules fall outside this range, take corrective action immediately.
3. Inspection Points
   1. Inspect the shell thickness from various locations around the capsule (e.g., at the top, middle, and bottom) to ensure uniformity. Any significant variation in thickness must be addressed.
4. Automated Monitoring
   1. If available, use automated systems to continuously monitor the shell thickness throughout the production run. Set up alerts to notify operators if the thickness deviates from the acceptable range.

5.3 Adjusting Parameters to Maintain Uniformity

If the shell thickness deviates from the acceptable range, follow these steps:

1. Adjust Machine Settings
   1. Adjust the temperature or speed of the gelatin casting and drying process to control the shell thickness. Typically, increasing the gelatin temperature or slowing down the machine speed may increase the shell thickness.
2. Gelatin Solution Adjustments
   1. If the thickness variation is due to the gelatin solution, adjust its concentration or viscosity. Ensure the solution is mixed properly to prevent inconsistent shell thickness.
3. Re-Check Thickness
   1. After making adjustments, continue measuring the thickness of capsules to ensure that the modifications have successfully brought the shell thickness within the desired range. Verify that the shell thickness is consistent across all sample points.

5.4 Post-Production Review

After completing the production run, perform the following checks:

1. Review Thickness Data
   1. Review the recorded thickness measurements to ensure that they meet the required specifications. Ensure that no deviations were left unaddressed during the production process.
2. Confirm Compliance
   1. Ensure that the final batch of capsules meets the required shell thickness specifications and that any deviations from the specified range were corrected during the production process.
3. Documentation
   1. Document the final shell thickness measurements in the batch production record, including any corrective actions taken during production.

5.5 Equipment Maintenance and Calibration

Ensure that the equipment used to measure and adjust shell thickness is properly maintained:

1. Routine Equipment Calibration
   1. Perform regular calibration of all thickness measurement tools, including micrometers and automated systems. Ensure that calibration is performed according to the manufacturer’s specifications.
2. Maintenance of Manufacturing Equipment
   1. Ensure that all equipment involved in the gelatin shell formation process, such as the capsule filling machine, is well-maintained and regularly serviced. Perform checks on temperature controls, the dosing system, and the drying system to ensure consistent operation.

5.6 Documentation and Record-Keeping

Ensure proper documentation of all activities related to gelatin shell thickness:

1. Thickness Measurement Records
   1. Document all shell thickness measurements, including the results of the sample capsules taken during the production run. Include the batch number, machine settings, and any corrective actions taken.
2. Deviation and Corrective Action Records
   1. Document any deviations from the target shell thickness and the corrective actions taken. Include the time, cause of deviation, and actions implemented to restore uniformity.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QC: Quality Control
• QA: Quality Assurance

7. Documents

1. Shell Thickness Measurement Log (Annexure-1)
2. Deviation and Corrective Action Report (Annexure-2)
3. Calibration and Maintenance Record (Annexure-3)

8. References

• USP <1163> – Pharmaceutical Dosage Forms: Capsules
• FDA Guidelines for Capsule Manufacturing
• International Conference on Harmonization (ICH) Guidelines for Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Shell Thickness Measurement Log

Batch ID	Capsule Size	Measurement Date	Shell Thickness	Operator Name
Batch 001	Hard Gelatin	01/02/2025	0.50 mm	John Doe

Annexure-2: Deviation and Corrective Action Report

Deviation ID	Description	Corrective Action Taken	Action Taken By
DR-001	Inconsistent shell thickness	Adjusted gelatin solution viscosity	Manufacturing Supervisor

Annexure-3: Calibration and Maintenance Record

Equipment ID	Calibration Date	Technician	Calibration Results
Filling Machine 10	01/02/2025	John Smith	Within Tolerance

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial Version	New SOP Creation	QA Head
01/02/2025	2.0	Updated shell thickness parameters	Standardization	QA Head