A new approach to decontamination coupled with depyrogenation comes to blow-fill-seal processes.
Blow-fill-seal (BFS) equipment manufacturer Weiler Engineering Inc. is equipping its ASEP-TECH blow-fill-seal systems with the NOX FLEX Rapid Biodecontamination system from Noxilizer Inc. The company had sought an alternative to the traditional approaches of using preproduction manual sanitation or steam sterilization of the BFS fill system shroud, which encompasses the fill needles and electronic modular dosing system.
“The critical filling zone of a BFS machine is the enclosed area comprising the fill system shroud,” explains Chuck Reed, Weiler Engineering’s director, sales and marketing. “Weiler Engineering sought a non-aqueous solution to provide additional measures of safety to the BFS process by integrating a gas sterilization process into the fill system shroud of the ASEP-TECH Blow-Fill-Seal System. The unique characteristics of nitrogen dioxide provide this solution. Weiler’s patent-pending STERI-Shroud design incorporates the use of the NOX FLEX system by Noxilizer. The NOX FLEX system is an automated process, which eliminates the variability imposed by human interaction with the manual sanitization method.”
Noxilizer’s automated room-temperature NO₂-using technology requires less than one hour for decontamination. Test results from a recent study presented by Noxilizer and Weiler Engineering at the April 2014 PDA Annual Meeting showed “a more than a 6 log reduction in biological indicator organisms (Geobacillus stearothermophilus) and more than a 3 log endotoxin reduction,” the companies report.
“Endotoxins, or pyrogens, are mainly lipopolysaccharide components of Gram-negative bacterial cell wall fragments, which can cause acute febrile reactions (i.e., fever),” explains Reed. “These endotoxins are heat stable and may be present even when viable organisms are no longer detectable.” In layman’s terms, they are residues of dead micro-organisms that may induce fever and are dangerous to patients receiving a drug through parenteral administration. Endotoxins are impossible to eliminate from filled containers; thus efforts are generally directed at eliminating endotoxins during preparation processes, the companies tell PMP News.
The NOX FLEX system performs both decontamination and depyrogenation in a single-step process. Weiler and Noxilizer believe that such an approach could meet a growing need in pharmaceuticals. “A growing share of all medicines are biologics, including proteins and monoclonal antibodies,” observes Reed. “BFS technology and the ASEP-TECH Blow-Fill-Seal System STERI-Shroud with NOX FLEX in particular, is well suited for the aseptic processing of biologics, vaccines, and other protein-based materials. These products are particularly sensitive to residual sterilant in the filling environment. NO₂ has been demonstrated to have a fast aeration rate with negligible residuals, making the Noxilizer process ideal for all drug processing."
When asked what changes to BFS machinery were made to accommodate the NOX FLEX system, Reed reports that “the STERI-Shroud is a completely new, patent-pending design based on strict processing parameters which incorporate the NOX FLEX NO₂ process. As a result of these process constraints, the STERI-Shroud is available for new ASEP-TECH BFS systems only.” The new decontamination/depyrogenation process is designed to coincide with the normal cycle time of the clean-in-place/sterilize-in-place process for sterilizing of the product path in the BFS machine. During the decontamination process, the NO₂ is introduced to the sealed shroud and recirculated for the exposure period. “Standard validation processes must be followed to ensure compliance with regulatory authorities,” Reed continues. “The challenge studies that have been conducted support the process with a strong scientific basis.”
The technology could be well timed. “Regulatory agencies continue to focus on improved patient safety and are developing standards to ensure sterile, contamination-free products,” says Reed. “In particular, regulatory standards state that pharmaceutical manufacturers should be aware of new procedures designed to reduce risk to the product through the use of enhanced technology. One such procedure is the reduction of pyrogens during the decontamination process.”
Weiler and Noxilizer expect the first ASEP-TECH BFS systems equipped with STERI-Shroud to be delivered in calendar year 2015.