Microbiological integrity

Thirty year s ago there would have been a limited set of equipment in the quality control laboratory of the majority of fruit juice and soft dr inks factories. This would probably have consisted of a reffactometer, a burette, a spectrophotometer, an instrument to measure the level of carbonation and some equipment for checking the microbiological integrity of the product. However, with the move to larger... 

There are no standard methods for verifying microbiological integrity of container-closure systems. Documents such as that published by the Parenteral Society in 1992 ° and the PDA in 1998 may be helpful in relating microbiological integrity to secondary physical tests, but they do not specify detailed microbiological test methods. 

All biochemical reactions are enzyme-mediated. The rate of an enzyme reaction depends on the substrate concentration at the location of the enzyme and thereby on the diffusion rate of a substrate to the enzyme. It is therefore important to permanently obtain an intimate contact between a cell or enzyme and substrate molecules. Additionally, the product generated in the bioreactor has to be extracted because it may under certain conditions inhibit its own production. In some processes there may also be even a prepurification in the bioreactor itself. If living micro-organisms have to be applied, it is necessary to provide sufficient nutrition and respiration gases in case of aerobic fermentation. All other reaction parameters such as temperature, pH-value and reaction time have to be controlled precisely. In many cases (generally with modem processes) the maintenance of microbiological integrity (sterile process) is absolutely mandatory for a successful fermentation. 

Other containment systems must be specified in similar levels of detail if there is to be consistent assurance of maintenance of microbiological integrity. 

Some degree of evaluation of the microbiological integrity of the vial/ closure system can be made from the specified characteristics of the two components, In the first instance it would be reasonable to have a clear picture of the quality characteristics of the vial flange and the vial neck that affect con-tainer/closure integrity concurrently to have a clear picture of the quality characteristics of the closure. 

Other physical tests may allow routine in-place evaluation of the microbiological integrity of vials. Headspace gas analysis is one such method. Many sterile products are held under nitrogen or some other gas in vials. The gas content of the headspace should, with a perfect seal, remain constant over time rather than becoming equilibrated with the atmosphere under a less than perfect seal. This type of analysis is amenable to chemical methodology and is likely done routinely in pharmaceutical production for reasons other than evaluation of microbiological integrity. 

Detection of pinholes in flexible packaging is therefore an important aspect of the physical evaluation of their potential to maintain microbiological integrity. It is usually a specialized activity left to the manufacturers of packaging films. 

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