As a small leakage from the silicone oil tubes in pharmaceutical freeze dryers may go undetected for several cycles, it provides a major threat to both product safety and the economic performance of the installations.
Product losses due to coolant contamination in freeze dryers are best minimized by employing an in situ detector for the presence of coolant vapors within the unit. Without an inline detection, traces of oil are eventually found through quality control checks after an unknown number of batches may have been contaminated. This uncertainty forces the rejection of all suspect batches. Conversely, if an oil leak is detected upon occurrence by an inline detector, only the batch in process is lost.
Mass spectrometry (MS) is a powerful detection tool for contaminants that should be applicable in environments such as freeze dryers. Quadrupole mass spectrometers (QMS) are widely used in a number of industries for inline contaminant detection and process control purposes. Certain requirements must be met by any QMS unit used in pharmaceutical manufacturing applications. The detector must be capable of untended, automated operation over prolonged periods of time with minimal maintenance. In operation, it should have sufficient versatility to reliably monitor the freeze drying chamber, not only for contaminant silicone oil signatures, but also for process states such as drying end-point detection. The QMS system should be easily integrated into the manufacturing site’s product management system (PMS) without the need for validation of software/setup revisions. Obviously, for the application under consideration in this note, the QMS system should have sufficient flexibility to fulfill any unique requirements present in pharmaceutical production equipment for freeze drying/sterilization procedures.
The major benefits of the technology are:
Silicone Oil Detection: it is possible to detect even small traces of silicone oil leaking within the freeze dryer during the operating cycle. No additional product is at risk as the leak would have been detected immediately.
Moisture Content: An additional benefit comes from being able to predict the freeze drying curve of the product through the moisture content in the chamber. Freeze drying behaviour for each batch can be compared with a ‘qualified batch’ to confirm that the process is progressing normally.
Chamber Leak Tests: If during the test a leak is detected it is necessary to perform a helium leak test to find the source of the leakage. Using standard external equipment for helium leak testing sometimes takes several hours to set up; however, some supplier has the system permanently connected to the chamber so the helium leak test can begin instantly, detecting leaks much faster thereby saving valuable time.