Thilly and coauthors introduced closed-vial filling systems, called "Crystal" technology, for aseptic filling of liquid products in Pharmaceutical Technology's 2005 Aseptic Processing supplement (1). Aseptic Technologies (Gembloux, Belgium) has now taken closed-vial technology a step further by developing a process using the closed vial for lyophilization. The technology consists of using ready-to-fill, gamma-sterilized, closed vials and filling them using a needle passing through the stoppper, followed by a laser resealing to restore the closure integrity. The vial body, made of cyclo-olefin copolymer (COC), rather than glass, and the stopper, made of thermoplastic elastomer (TPE), are injection molded and assembled by robots in an ISO 5 (Class 100/Grade A) environment.
The process involves securing the closure integrity with a top ring, and then gamma-irradiating the vial to ensure sterility. The closed vial is then determined to be clean on the inside and sterile and therefore ready for filling. Plastic molding of vial elements allows the vial to have specific functionalities such as an optimized stopper shape and fully secured closure integrity (2).
In the filling line, the TPE stopper is pierced by a special filling needle. Immediate self-reclosing takes place at the needle withdrawal and the piercing trace is resealed with a noncontact laser beam, restoring a continuous upper surface of the stopper. Overpressure inside the vial during filling is eliminated by venting grooves in the outer surface of the needle shaft. A sterile plastic cap is then snapfitted on top of the stopper, which is still inside the barrier. The special cap design protects the piercing target until use by a healthcare professional (1, 2).
The closed-vial, freeze-drying concept
To maintain optimal sterility assurance, an opening in the vial is required but has been limited in this particular process. The vial actually remains closed most of time, especially between the filling station and the freeze dryer's shelf. The opening and closing of the vial is generated by rearranging the movements of the freeze-dryer shelves. When the cycle is finished, the vial closes again before the freeze dryer's door is opened and stays closed until the vial is resealed with a laser and capped. This process has several advantages over traditional glass-vial processing: