The system and process in detail
The system.
A small, disposable device called the penetrator reopens the piercing trace made by the filling needle. This penetrator is
installed on top of a regular closed vial by a light snapfit over its existing top ring. Made of medical-grade, high-density
polyethylene (HDPE), the penetrator is gamma-irradiated to avoid contamination during lyophilization. The penetrator has an
internal cone with an open tip located above the piercing spot.
Vertical downward movement of the freeze-dryer shelf, carried out before the freezing phase, pushes the penetrators down.
At the same time, the front ring of the open tip pushes (but does not pierce) the surface surrounding the piercing trace.
This push reopens the piercing trace and generates a passage for the water vapor during freeze-drying. The size of the cone's
pushing front ring on the penetrator is large enough and tolerant enough to accommodate the needle piercing.
Shelves are kept down during the three lyophilization phases (freezing, sublimation, and secondary drying) to keep the stopper
open and allow gas to exit. At the end of the secondary drying phase, when temperature is back in the 25–35 °C range, the
shelves are lifted to their initial position. The resilience of the deformed stopper push up the penetrators while the stopper
opening recloses and reseals itself.
The process.
The entire process can be separated into three steps: vial-filling, lyophilization, and vial-closing and capping (see Figure
1). Each is described below.
Figure 2: Lyophilization process: (1) A vial and the penetrator, (2) penetrators are placed on the vial with a placement tool,
(3) vials are introduced inside the lyophilization unit and the shelves are moved down to break the bridges, (4) the shelf
reopens the piercing trace to allow lyophilization, (5) the shelf is moved up, and (6) the penetrator is withdrawn. (ALL
FIGURES ARE COURTESY OF THE AUTHORS.)
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The vial-filling step is identical to the classical filling process described by Verjans et al. and Thilly et al. (1, 2).
The same vial is loaded on the filling equipment and the vial is filled by a needle piercing through the stopper. The only
modification is that the needle has a slightly larger diameter (11G gauge instead of 13G) and its tip configuration is trocar,
giving a precise cut in the elastomer, with the shape of a three-branch star. These two features facilitate future reopening
of the stopper. As with liquid-filling needles, the stopper's elasticity allows it to immediately self-reclose after filling.
After filling, the process changes radically as the immediate laser resealing and capping are eliminated and replaced by the
positioning of the penetrator on top of the vial with a placement tool (see Figure 2, positions 1 and 2). The vial, still
closed, is then conveyed to the freeze dryer's loading unit and onto the shelves (see Figure 2, position 3).
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