Stoppering of vials

Figure 34 Freeze-drying plant condenser and shelves cooled with LN2. Clean-in-place system in chamber and condenser. 1, LN2 inlet to condenser and heat exchanger 2, N2 outlet from the condenser and heat exchanger 3, heat exchanger for the brine in shelves 4, brine to and from shelves 5, pressure plate for stoppering of vials 6, piston rod with bellows 7, hydraulic piston for 5 and 6 8, hydraulically operated valve 9, hydraulic system 10 and 13, water and steam inlet 11, pumping system 12, water outlet. (AMSCO Finn-Aqua GmbH, D-50354 Hiirth, Germany.)...

A. Loading and Unloading of Vials, Drying Chamber, Stoppering of Vials... 

High plane parallelism and evenness (<1 mm m ) to permit good stoppering of vials prevention of glass breakage (Figure 14.9). 

Influence of Vial Stoppers on the Residua] Moisture Content... 

The stoppers for vials contain a certain amount of water, which depends on the composition of the stoppers. De Grazio and Flynn [1.86] showed, that the selection of the polymer, the additives for the vulcanization, and the filler influence the adsorption and desorption of water. However even the best possible mixture increases the RM in 215 mg sucrose from 1.95 % to 2.65 % during 3 months storage time at room temperature. Other stopper mixtures show an increase up to 1.7 %. Pikal and Shah [1.87] demonstrated, that the desorption of water from the stopper and the absorption of water by the product depends, in the equilibrium state, on the mass and water content of the stopper and the water content and sorption behavior of the dry product. 

Fig. 1. 100. Water content of 100 mg lactose at +25 °C as function of time. The vials have been closed with 13-mm stoppers of different pretreatment. Pretreatments SV1 steam-Sterilized U, untreated SV8, steam-sterilized followed by vacuum-drying of minimum 8 h. The lines are calculated by a model system (Fig. 4 from [1.87]).

Media-hlled vials (soybean casein digest broth or fluid thioglycollate medium) are hlled on the hlling line, transported to the freeze drier, loaded into the chamber, subjected to a simulated lyophilization process, stoppered, sealed, and incubated for 14 days at 25°C. The minimum number of vials to be used is 5000. 

Test samples (60 vials or stoppers of one size, style, manufacturer, and lot number)... 

Stoppering mechanism functionality to verily that the mechanism will properly insert the vial stoppers over the entire range of vials to be used... 

With a stoppering device vials are closed during SD at certain intervals and analyzed for RM after the end of freeze-drying. 

M. Ribick, M. Jemal, et al., Determination of ehtylenediametetra-acetic acid in aqueous rinses of detergent-washed rubber stoppers of pharmaceutical vials using solid phase extraction and capillary gas chromatography, J. Pharm. Biomed. Anal., 5 687-694 (1987). 

Place the needle through the stopper of the sterile vial, 3. ... 

Worst-case, challenges such as personnel breaks, equipment adjustments, and additional personnel in the fill room will be incorporated into all media fill studies. Stoppers and vials or ampoules will be sterilized. The time between sterilization and the start of the first media fill will be the maximum validated storage time for sterile stoppers, vials, and ampoules, provided the media fills meet all other acceptance criteria. 

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