BY PACKAGING


Gas Cylinder

Gas Cylinder – usually cylindrical, suitable for compressed, liquefied or dissolved gas, fitted with a device to regulate the spontaneous outflow of gas at atmospheric pressure and room temperature.

General case: cylinders of single gases

Validation of the cylinder filling process is performed by a weighing (or double weighing) control, including the calculation of the mean, standard deviation and coefficients of variation, or by pressure if justified.

This validation should ideally be presented for all types of cylinder, but at least for critical types of containers. A bracketing approach may be used as a function of the capacity, material used for construction and whether fitted with a built-in pressure regulator or a residual pressure valve. If needs be, for each type of alloy used, a single validation can be performed on one cylinder of this alloy, on the condition that this is justified.

Validation can be performed by determining the amount of gas contained in a cylinder compared with a reference cylinder filled with the charge of gas to avoid the problems of fluctuations in pressure as a function of temperature. The reproducibility of filling is also verified whatever the composition of the finished product batch (homogenous or heterogeneous).

For compressed gases, the temperature and pressure stabilisation time after filling which depends upon various capacities, nature of material, thermal exchange, ambient temperature (and any variation in it during the stabilisation time), rate of filling of the cylinder, airflow over the cylinder and its proximity to any adjacent filled cylinders is specified, unless otherwise justified. Cylinders, which have been returned for filling, are prepared in accordance with Annex 6 of the GMP.

The integrity of the filling system to indicate leak tightness to prevent possible contamination of the system under vacuum or an estimate of the yield accounted for losses as an annual average is provided. The tolerated limits of temperature and pressure are provided (specifying especially the hydrostatic pressure test and the bursting pressure of the cylinder). On the safety level, any problems of possible overload of compressed or liquefied gas are addressed.

Other containers for single gases

In the case of cylinder bundles and mobile evaporators, validation of the filling procedure is also performed by weighing or by pressure if justified.

In the case of fixed evaporators, validation can consist of the absence of impurity enrichment due to the formation of degradation products with time, to trapping because of the temperature and to transfers from one container to another during the manufacturing process or during sampling. It is specified whether the impurities remain at the same proportions between the gaseous and liquid phases as the container is emptied. The minimal threshold for filling the fixed evaporator is specified to avoid any risk of impurity enrichment.

Analytical Procedure

In the case of liquefied gases, the nature of the phase (liquid or gaseous) is indicated, as is the method of sampling for the control. In the case of impurities that are preferentially present in the gaseous phase and eliminated to a large extent during the first drawing off (e.g. nitric oxide in medical nitrous oxide), the order of analyses is specified.

Medicinal gases are often packaged in a wide range of containers:

        − compressed gas cylinders,

        − liquefied gas cylinders, with or without a dip tube,

        − cylinder bundle,

        − mobile evaporator,

        − fixed evaporator,

        − mobile cryogenic container,

        − fixed cryogenic container.

A variety of reference codes exist, depending on the supplier, capacity and material, particularly in the case of cylinders. For each reference and each capacity, the water capacity of the container (in L), the amount of gaseous product released at 1atm and 15°C (in m3), and the weight of product stored (in g for compressed gases or in kg for liquefied gases) are provided, together with the accepted deviations. For liquefied gas cylinders, the pressure remains constant then falls suddenly at the end of use. Therefore, only the weight monitors the state of filling. The filling pressure (at 15° C) is justified in comparison with the weight formula.