In practice, to conduct the measurement, a few elements are needed:
- Vacuum source: vacuum can be provided by a dedicated vacuum pump, by a vacuum source provided as utility, by a vacuum generator based on Venturi effect.
The choice can be done considering cost, vacuum flow rate required and speed of measurement, vacuum level to be reached, stability of supply. - One or more measuring chambers (sometime called ‘tools’) properly designed to fit the format and type of container to be tested
In case of automated equipment for online hi-speed measurement, an array of multiple identical chambers can be used, with automation built to position each sample, close the chamber, run the measuring cycle, reopen the chamber, pick the tested sample and deliver it to the line if good, or to discard if defective. - The measuring unit itself, made of devices for vacuum admission/release and control (valves and regulators) vacuum sensor(s) for continuous vacuum measurement internal testing device, electronics, etc. This is the core of the equipment and can represent the key for accurate and highly sensitive results.
- The chamber design can widely vary, depending upon the sample type, size, content, and eventually the area to be tested. The accuracy and expertise of manufacturer in chamber design can represent a significant fraction of the total equipment, and it is a key factor for the result.
- The different measurement phases, the parameters control (vacuum and time) and the results are managed by PC and/or PLC. This assures reproducible measuring procedure and data control, in order to meet strict requirements in terms of data traceability and integrity.
- Before the conditions for measurement cycle are decided, some proper method development must be performed. In this phase, user must decide the level of measurement vacuum decay accepted (MALLS) to qualify the sample as ‘pass’. Samples measured above the MALLS level will be classed as ‘fail’.
- To develop the method, also called recipe, it can be useful to have a few samples the have artificially generated defects of known entity (size), as well as suitable devices to simulate controlled flow rate. These are typically calibrated orifices or hi-precision adjustable flow controller tools.
General rules for the proper Vacuum Decay measurement
The Vacuum Decay can detect leaks of gas or vapour. If the product inside the container is liquid, and the leak (the ‘hole’) is in a position on the container that is below the air/liquid interface, then the detection can only take place if there is a significant evaporation of the liquid through the defect.
To obtain this effect, the testing vacuum must be high (low pressure) so that evaporation is accelerated. If the measurement in the headspace (gas) is sufficient, then vacuum levels such as 500- 300 mBar absolute can be enough to get good method.
For this reason, oil- based samples might have a too low vapour pressure and do not evaporate, thus Vacuum decay might not be the suitable method, if defects are in the liquid region.
The samples must be clean and dry: humidity on the outside of the container can cause false positive,
care must be taken when samples come from a fridge.
Samples that are filled under partial vacuum condition (e.g. from a freeze drying process) might suspected to be difficult if not impossible to test, because the internal low pressure prevent the gas to escape towards the dead volume of the chamber, so no pressure increase (= Vacuum decay) can be observed. However, it is reasonable to assume that, if there was vacuum inside the container at time of the sealing, but there is a defect, after some time the outside air must have entered the container, until it is in equilibrium with outer atmosphere.
Therefore, the problem (false negative) is restricted to online equipment measuring Vacuum Decay immediately after the sealing of samples under vacuum, while is not in practice affecting lab testing on bench-top instruments.
Conclusions
The Vacuum Decay method has a very broad field of use, both in bench-top and online solutions, with some limitations for specific containers or conditions. With suitable definition of measurement procedure, it can be applied both to large and small defects, on liquid and non-liquid containing samples, flexible or rigid walls.
Vacuum decay is by definition a deterministic method as it produces immediate numerical, reproducible data, it is non-destructive (the same sample can be retested many times), it is not operator dependant and no sample preparation is needed. The product inside the container is not subject to any physical or chemical stress.
The equipment can be properly calibrated, and results compared to between different labs and instruments.
For all the above reasons, combined with the affordable cost of acquisition and ownership Vacuum decay will remain the preferred choice for deterministic testing of pharma containers.
