Using Closed-Vial Technology in Aseptic Filling - Pharmaceutical Technology

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Using Closed-Vial Technology in Aseptic Filling
Closed-vial technology is an alternative to traditional glass vial filling that reduces the risk of contamination for the patient, simplifies the filling process, and provides easier handling for healthcare providers.


Pharmaceutical Technology
Volume 36, Issue 5, pp. s36-s40

Containment


Figure 4: A closed-vial filling system surrounding a robotic filling line.
The closed vial acts as a mini-isolator because exposed surfaces are limited to the stopper top surface and the needle. In contrast, in a traditional glass vial, the inside of the vial, the inside surface of the rubber stopper, and the needle are exposed until the vial is stoppered. The closed vial filling system (CVFS) offers a new barrier or containment concept, in which only closed containers are handled (6, 7). The CVFS is suitable for installation in an ISO8 cleanroom, as illustrated in Figure 4, in which a robotic filling line is surrounded by a CVFS.

The advantage of the CVFS over the traditional isolator is its simplicity, in that it can be sanitized with classical sporicidal agents and does not require vapor hydrogen peroxide sanitization. The CVFS uses unidirectional, HEPA-filtered laminar airflow that exits through the bottom of the system, which helps maintain laminar flow and prevent turbulence. Isolators are still mandatory when the safety of the operator must be ensured (i.e., with highly potent drugs such as cytotoxics). Such isolators must be installed in an ISO9 cleanroom.

The advantage of the CVFS versus the Restricted Access Barrier System (RABS) is that in the CVFS, operator access is only possible via gloves, and the barrier environment is never compromised by door opening. Material entry is limited to secured processes such as rapid transfer ports, airlocks, and e-beam irradiation units. With these limitations, an ISO8 clean room environment for the surroundings is sufficient to ensure the ISO5 quality inside the barrier.

Lyophilization with closed-vial technology


Figure 5: In a lyophilization chamber, shelves push on the penetrator plate to reopen the piercing trace and allow sublimated water to evacuate.
Closed-vial technology has also been developed for lyophilized products (8). Lyophilization is performed through the piercing trace, which is reopened inside the lyophilization chamber. After vial filling, a penetrator plate with multiple funnel shapes that fit on top of each vial is placed on a set of prearranged, bee-nest vials. As shown in figure 5, the vial/penetrator plate assembly is placed inside the lyophilization chambers and the shelves are moved down, thus pushing down the penetrator plate and reopening the piercing traces. The lyophilization cycle is launched while keeping the piercing trace open to allow evacuation of the sublimated water. At the end of the cycle, the shelves lift up and the natural elasticity of the stopper causes it to regain its initial shape and push the penetrator plate up. After exiting the lyophilization chamber, the vials are laser resealed and capped.

The lyophilization cycle with closed vials is very similar to that of glass vials, except that the primary drying phase is longer. Tests show that closed-vial technology produces an improved cake surface, suggesting that the lyophilization process is more homogeneous. In the closed vial system, vials are more stable than in glass vial systems. The bee-nest assembly increases vial stability and the absence of contact between the shelves and the stoppers prevents stopper sticking. These factors reduce the risk of a vial falling down and knocking other vials on the shelf over.

Validation

Changes to the container design and process that occur when using closed-vial technology must be validated. To ensure that the technology is suitable for product approval, a series of tests that meet the required standards from Pharmacopeia and International Conference Harmonization (ICH) guidelines should be performed on the container materials, the properties and characteristics of the container closure, the processing technology, and the performance of media fill.


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