2/3 March 2021
Nitrogen often comes in contact with a product during manufacturing and is therefore relevant for its quality, especially when it comes to the manufacture of sterile products. Nonetheless, the use of nitrogen is significantly less specified than that of pharmaceutical water. Parameters and limits have to be defined by the pharmaceutical users themselves.
Like with pharmaceutical water, the first sources of information are pharmacopoeias. The European Pharmacopoeia defines two types of nitrogen: “medical nitrogen” and “nitrogen with low oxygen content”. As the name suggests, the first is used for medical purposes, e.g. in hospitals. The latter can be used for the inertisation of oxygen-sensitive pharmaceuticals, for example. There are no parameters for water content, oil or particles, however. It seems inadequate that the only specification is 99.5% purity for nitrogen with low oxygen content. The remaining 0.5% could, depending on manufacture, storage and distribution, very well consist of water, oil, etc.
This nitrogen quality is also interesting when it comes to the use of nitrogen generators (molecular sieve technique), though. Those can be a suitable alternative for the well-known compressed-gas bottles in many use cases.
As is the case with compressed air (see also Requirements for compressed Air in the Pharmaceutical Industry), the pharmaceutical user has to define their own specifications depending on application and product risk. The 2010 ISO 8573-1 can be useful here. A specification according to class 2 is helpful in most cases – this excludes particles > 5 µm. Microbiological limits can be defined in accord with the class of purity in which the nitrogen is being applied.
In conclusion, nitrogen may be seen as an excipient, even though the amount of it remaining in a finished product is insignificant compared to classic excipients like lactose. Therefore, the EG Guideline 2015/C 95/02 can be consulted for risk assessment concerning contamination or for qualification requirements