Standard Operating Procedure for Leak Testing of Filled Containers

1) Purpose

The purpose of this SOP is to establish a standardized procedure for leak testing of filled containers to ensure their integrity, prevent contamination, and ensure compliance with regulatory requirements for ocular dosage forms.

2) Scope

This SOP applies to all filled containers, including vials, ampoules, syringes, and bottles, containing ocular dosage forms produced within the pharmaceutical manufacturing facility.

3) Responsibilities

The responsibilities include the proper testing, documentation, and handling of filled containers. Quality control personnel are responsible for conducting the leak tests and recording the results. Production personnel are responsible for presenting filled containers for testing and maintaining accurate records.

4) Procedure

4.1 Preparation for Leak Testing

1. Ensure that the testing area is clean, well-lit, and free from distractions.
2. Calibrate the leak testing equipment according to the manufacturer’s instructions to ensure accurate results.
3. Gather all necessary testing tools, such as vacuum chambers, dye solutions, and gloves.
4. Record the batch number, product name, and quantity of containers to be tested in the testing logbook.

4.2 Leak Testing Process

1. Vacuum Decay Method
   1. Place the filled container inside the vacuum chamber.
   2. Seal the chamber and apply a vacuum according to the equipment’s specifications.
   3. Monitor the pressure inside the chamber for a predetermined period.
   4. If the pressure remains stable, the container is considered leak-free. If the pressure changes, the container may have a leak.
2. Bubble Emission Method
   1. Submerge the filled container in a tank of water or dye solution.
   2. Apply a vacuum or pressure to the container to force any leaks to emit bubbles.
   3. Inspect the container for any visible bubbles indicating a leak.
3. Dye Penetration Method
   1. Apply a dye solution to the exterior of the filled container.
   2. Place the container in a vacuum chamber and apply a vacuum to draw the dye into any leaks.
   3. Inspect the interior of the container for any visible dye penetration indicating a leak.
4. Set aside any containers with identified leaks in a separate, labeled area for further investigation.
5. Continue the leak testing process until all containers in the batch have been tested.

4.3 Documentation

1. Record the results of the leak testing in the testing logbook, including the number of containers tested, the number of leaks found, and the types of leaks identified.
2. Ensure that all records are signed and dated by the personnel responsible for the testing.
3. Attach a copy of the testing log to the batch production record for traceability.

4.4 Handling of Defective Containers

1. Isolate defective containers in a designated area to prevent them from being mistakenly used or distributed.
2. Investigate the cause of the leaks and document the findings in a deviation report.
3. Determine the appropriate disposition of defective containers, such as rework, reinspection, or disposal, based on the severity and nature of the leaks.
4. Implement corrective and preventive actions (CAPA) to address the root cause of the leaks and prevent recurrence.

4.5 Review and Approval

1. The quality assurance department should regularly review testing procedures and records to ensure compliance with SOPs and regulatory requirements.
2. Any discrepancies or deviations should be investigated, documented, and resolved promptly.
3. Review and update the SOP as necessary to reflect any changes in procedures, regulations, or industry standards.

5) Abbreviations, if any

CAPA: Corrective and Preventive Actions

6) Documents, if any

1. Testing logbook
2. Batch production record
3. Deviation report

7) Reference, if any

GMP Guidelines for Leak Testing of Parenteral Products

8) SOP Version

Version 1.0