Process control
To provide enhanced process safety, a new true gas decontamination process is available for aseptic filling lines using nitrogen dioxide (NO2) as the sterilant. Weiler Engineering has pioneered a patent-pending application using this NO2 technology in its ASEP-TECH blow-fill-seal (BFS) systems to offer enhanced sterility assurance for production of pharmaceutical products. The NO2 technology, developed by Noxilizer, is a room-temperature process that combines decontamination of exposed critical zone surfaces with the potential for depyrogenation of these surfaces. Providing an automated gas decontamination process that also offers the potential of endotoxin reduction increases the safety of the pharmaceutical products produced in the ASEP-TECH BFS systems.
In the BFS system, a container is moulded from plastic resin, aseptically filled and hermetically sealed in one continuous, integrated and automated process. The BFS process provides flexibility in container design, high volume product output, low operational costs and a high assurance of product sterility. Packaging liquid pharmaceuticals with BFS technology provides the highest level of sterility assurance available for aseptic filling. As such, the BFS technology is characterised as an “advanced aseptic process” by the FDA and the USP.
Aseptic processing requires rigorous and careful manufacturing practices due to the potential adverse effect on the health care consumer. Regulatory agencies are placing greater focus on improved patient safety, developing standards to ensure sterile, contamination-free products. In particular, regulatory standards increasingly state that pharmaceutical manufacturers should be aware of new procedures designed to improve product safety through the use of enhanced technology. One such procedure is the reduction of pyrogens during the decontamination process.
Pyrogenic contamination comes from endotoxins, which are mainly lipopolysaccharide components of Gram-negative bacterial cell walls, which can cause acute febrile reactions. These endotoxins are heat stable and may be present even when viable organisms are no longer detectable. Endotoxins are impossible to eliminate from filled containers; thus, procedures are generally directed at eliminating endotoxins during the preparation process. The NO2 process offers a new procedure for depyrogenation, efficiently completing the decontamination and depyrogenation in a single, rapid process.
Study results from the first demonstrated decontamination and depyrogenation of the critical zone of an aseptic filling system using NO2 were presented at the 2014 PDA Annual Meeting in San Antonio, Texas. The study was conducted at the Weiler Engineering facility. Weiler worked with Noxilizer, to apply the room temperature, NO2-based technology to the ASEP-TECH system. Weiler utilised a patent-pending design of the ASEP-TECH system with integration of Noxilizer’s NOX FLEX rapid biodecontamination system.
The Noxilizer process is a fast (less than one hour), automated process that yields more than a six log reduction in biological indicator organisms and more than a three log endotoxin reduction. Another feature of the NOX FLEX system verified in this study was the remote operation of the decontamination process with up to 50 metres of conduit between the NOX FLEX unit and the ASEP-TECH system. This capability permits the location of the Noxilizer equipment outside of the cleanroom in which the BFS machine is installed.
The ASEP-TECH BFS System offers advantages for manufacturers with biologic, protein-based and heat-sensitive products. NO2, a rapid and effective sterilant, has been commercialized for decontamination and sterilisation. As a result of the successful collaboration with Noxilizer, Weiler Engineering is now able to offer the NO2 process with NOX FLEX rapid biodecontamination units for its ASEP-TECH blow/fill/seal systems through an exclusive global supply agreement. Noxilizer’s NOX FLEX provides a single-step decontamination and depyrogenation process in a patent-pending application that is expected to broaden the use of ASEP-TECH BFS systems world-wide.
About the authors:
Chuck Reed is director of sales & marketing, Weiler Engineering and David Opie is senior vice president, research & development Noxilizer.