Filling Line Nitrogen Purge Qualification

Nitrogen purge qualification shows that a filling line consistently brings headspace oxygen in each vial down to its target level before the vial is closed. For oxygen-sensitive formulations, that target protects product quality from the moment of filling. This case study describes how one filling line went from no better than 5% to the targeted 2% headspace oxygen.

The study was performed with rapid, non-destructive headspace oxygen analysis in an at-line set-up, with samples measured immediately from the line. It shows how data exposed the cause of poor purging, ruled out a fix that looked reasonable on paper and confirmed the solution. For more on the application, see our overview of oxygen monitoring in pharmaceutical manufacturing.

The client had an existing filling line with a pre-purge and a post purge, in which nitrogen was blown into the vials after filling. The aim was to reduce headspace oxygen to 2%, but the line could do no better than 5%.

The cause was a ‘dead space’ between the post purge and stoppering. During that residence time, nitrogen escaped from the open vials before they were closed. Frequent line stoppages added a second problem: vials that lost their nitrogen headspace during a stoppage had to be identified and rejected.

The filling line manufacturer suggested a nitrogen overlay system in the dead space: a nitrogen ‘tunnel’ meant to keep the vials blanketed until stoppering.

At-line measurements showed the opposite effect. With the overlay installed, headspace oxygen could not be purged below 7%. The overlay caused turbulent gas flow around the open vials, pulling surrounding air into the headspace and preventing efficient purging. Without actual headspace measurement data, a change like this could easily be assumed to help.

The solution was an extended post purge arm. Purging closer to stoppering reduced the residence time, so less nitrogen could escape before the vial was closed. With the extended arm, the client achieved the targeted 2% headspace oxygen.

Use of an at-line headspace oxygen analyzer during the study enabled:

• Efficient purge optimization and validation
• Optimal purge performance at about 2% headspace oxygen
• Validation of a software solution to reject a fixed number of vials after a line stoppage
• Ultimately, a significant reduction in production downtime

Qualification is one step; the line still has to perform every day. Line stoppages will still happen, and with the validated software solution a fixed number of vials is rejected after each stoppage, so vials that may have lost their nitrogen headspace are removed from the batch.

At-line configurations of the FMS-Oxygen Headspace Analyzer let operators determine headspace oxygen quickly and accurately. This streamlines filling line optimization and qualification during set-up, and enables in-process control measurements during routine production.

Oxygen control does not end at stoppering. See how headspace oxygen is tracked after filling in our article on oxygen monitoring during shelf life, and how headspace analysis supports another manufacturing-floor application in automated media fill inspection.

Download the case study for the filling line schematics and the residence time data, or talk to one of our application scientists about headspace oxygen measurements on your filling line.