A new concept in aseptic filling: closed-vial technology

Jan 01, 2006
Volume 18, Issue 1

Aseptic filling has been well-established for several decades, but regulatory requirements have become more and more restrictive over time. For example, authorities have requested increased environmental safety in the filling area, with very strict requirements regarding eliminating potential contamination agents and reducing particles, in addition to revising product formulations to eliminate preservatives. These recommendations have led to two major improvements: better air quality control to reduce contamination risk and new container designs.

Containment technologies reduce the risks associated with the human presence in Class 100 clean rooms. The isolator appears to be the best solution in terms of quality, although it is the most complex for pharmaceutical manufacturing, especially for conducting multiple and difficult validation experiments; performing controlled vapour-phase hydrogen peroxide sterilization; maintaining delicate pressure balances; and controlling the complex airflow patterns generated in the closed environment.

Faced with the complexity of using isolators, manufacturers have developed open barriers, particularly the restricted access barrier system (RABS), which consists of a barrier system with hard walls (allowing access only through gloves), but which is in fact an open system. The RABS is based on the principle of a regular air flow pushing all possible sources of contamination to the bottom and then outside the barrier without any air recirculation. The sterility assurance level inside a RABS appears to be similar to that of an isolator.

Since the classical ampoule was introduced, several new container designs have been configured such as the vial, the cartridge, and more recently, the prefilled syringe. All these containers have been developed in response to one key concern: ease of use throughout the supply chain. The vial, for example, is a more-solid container with a reduced risk of generating glass particles, and the prefilled syringe eliminates handling during drug administration. Nevertheless, because all these containers remain open during aseptic filling, they do not succeed in significantly reducing the risk of contamination from the environment.

This article presents a new concept: closed-vial technology, which is based on a vial that is supplied closed and sterile and therefore ready-to-fill. This sterile vial, which functions like a mini-isolator, is filled in a Class 100 environment inside a RABS.

The closed-vial concept

The principle of the closed-vial concept can be summarized as follows:

  • The body of the closed plastic vial is made of cycloolefin copolymer (COC), a plastic material that can be molded into shapes that are not feasible with glass and that allows for tighter seals between parts of the vial, thus improving closure integrity.
  • Closed vials are clean and do not require washing before filling. The vial body and the stopper are molded and assembled in a Class 100 environment, leading to extremely low particle levels inside the container.
  • The vial is sterile. After assembly, the closed vial is sterilized in a gamma-irradiation unit to secure the absence of vial contamination, eliminating the vial washing and depyrogenization step in the filling line.
  • In the filling process, a needle penetrates the closed vial through the stopper. After the liquid is delivered, the needle's path is resealed with a laser beam to restore closure integrity. Stopper integrity can be achieved because the stopper is made of a thermoplastic elastomer, which can remelt and fuse when the temperature is increased.

The closed vial

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