Longer operating time and the highest level of pharmaceutical safety is what is on offer from the latest generation of sterility test isolators STISO. This is mainly due to DECOpulse®, the highly efficient, award-winning bio decontamination system. STISO also scores high points for its ergonomic design and the "Plug & Test" principle.
Sterility testing is central to the aseptic processing of drugs, which must be carried out in strict accordance with regulatory requirements. Common practice is for sterile tests to be carried out under conditions that are as similar as possible to those encountered during production – for example, inside isolators or even with sterile workbenches in the laboratory. Where isolators are used in production, the use of sterility test isolators is advisable since, compared to sterile workbenches, these isolators offer considerably higher safety for avoiding false-positive tests. The tests are mainly performed with gloves on the sterility test isolator, so ergonomic factors also need to be taken into account to ensure that the operator's processes are as simple as possible. The STISO sterility test isolator also satisfies these high requirements most effectively. The newly integrated DECOpulse® bio-decontamination system also provides the highest level of safety and efficiency. So what exactly makes the DECOpulse® system stand out? This question can be answered by taking a look at the development of the new system.
A physical phenomenon provided the idea and basis for the realisation of DECOpulse®: H₂O₂ can evaporate at room temperature if the pressure in the liquid phase is high enough. Since the geometrical shape has an effect on internal pressure through surface tension, according to the Young Laplace equation, a micro-sized droplet or "sphere" of H₂O₂ would be suitable. In this case, the liquid H₂O₂ which is initially still visible as a spray mist (aerosol), would evaporate and thus no longer be visible to the human eye. The question is how to achieve this small microdroplet diameter and, above all, what effects does it have in practice with pharmaceuticals? DECOpulse® works with several injection nozzles in the isolator. As was previously the case, these are mounted as direct injection nozzles in the plenum and above the CG diaphragm (membrane) for indirect injection. H₂O₂ is introduced into the isolator via twosubstance nozzles, together with pharmaceutical compressed air as carrier gas. Here, the critical factors are the nozzle geometry, as well as numerous otherparameters that need to be satisfied during injection to ensure the desired droplet sizes and turbulence for distribution in the plenum. A specific control system, for the valves, for example, and a "loop" through which the injection nozzles are supplied with the medium are further elements of DECOpulse®, which has a patent pending. One important aspect is that the H₂O₂ vaporizes and thus the general principles of gas phase decontamination systems take effect. Above all, the resulting processes of adsorption and desorption of the H₂O₂ molecules ensure an even distribution on the surfaces in the isolator room. The size distributions of the droplets produced were determined during the development phase. This has ensured that with properly selected operating parameters, the achieved microdrop size is actually below the desired d < 3 μm. The diffraction of laser radiation at the microdroplets was measured to determine the corresponding size distribution. An example of the distribution is shown in Fig. 1. In this case 99.9 percent of the microdroplets in the final system have a diameter d < 3 μm!
By taking measurements at different distances from the nozzle, the evaporation of the droplets can also be determined. By means of light scattering, the eye can perceive how the H₂O₂ spray mist moves away from the nozzle and gradually "disappears" as the microdroplets change into the gas phase. Thus the evaporation of H₂O₂ is achieved as desired with no active heating. Evaporation is achieved by atomizing the liquid, which is why Metall+Plastic calls this process "Atomization-driven Evaporation". In addition, the R&D team of Metall+Plastic has researched the spatial distribution of H₂O₂ in a typical isolator geometry and the homogeneous surface wetting. As a comparison, bio decontamination with DECOjet. and the flash evaporation system integrated here was used, which can be described as a hitherto market-leading system from Metall+Plastic which will continue to be installed upon request.
Background: The more the internal pressure in the ("micro") drop increases, the smaller its diameter is. According to the Young LaPlace equation, the microdroplet diameter d must be < 3 μm so that the internal pressure is greater than the atmospheric pressure (approx. 1 bar) and thus the desired evaporation can occur.
Chemical indicators that react by colour to H₂O₂ were placed at identical and in particularly hard-to-reach points in the isolator. Examples of these are corners or zones at and between glove openings (Fig. 2). The result are manifest in the truest sense of the word. The goal is to change the magenta colour of the indicators to yellow; which indicates complete wetting with H₂O₂. If one observes two cycles with a short comparable injection time, this is not completely successful in flash evaporation regardless of indicator placement. Multiple indicators retain their original color. In contrast, Atomization-driven Evaporation with DECOpulse® produces complete coverage: All the indicators are yellow, only one of them still shows a minimal presence of magenta. This convincingly demonstrates the very uniform wetting with H₂O₂ that can be achieved with the new system, even in complex geometries. This comparison is particularly meaningful where pharmaceutical safety is concerned. Furthermore, the D-values of the two systems were examined using biological indicators. In this case, the comparison yields a value of 0.86 min for Flash Evaporation, whereas Atomization-driven Evaporation with DECOpulse® takes only 0.47 minutes.
Fig. 2: Flash Evaporation (top): The chemical indicators here stay primarily magenta. (Dotted boxes: Air return ducts. Comparable biodecontamination cycles with 11- and 10-minute injection time of H₂O₂).
In Atomization-driven Evaporation (DECOpulse®) magenta turns yellow – the chemical indicators change colour even in difficult locations. This confirms consistent wetting with H₂O₂.
Another comparison: Aerosols and micro-aerosols, both of which are currently in use in today's bio-decontamination systems, have diameters (d) of about 100 μm to 1,000 μm and about 10 μm to 100 μm respectively and therefore do not directly vaporize at room temperature. The structure means that a more uneven distribution then takes place, especially in complex geometries. Thus there is a basic physical system difference and advantage for DECOpulse® compared to other aerosol-based systems.
It is also interesting to note that DECOpulse® (in comparison to DECOjet®) reduces the use of H₂O₂ by about 40 percent. This is particularly visible in the shorter aeration time as part of the decontamination cycle (Fig. 3). The curves in the diagram diverge significantly from each other from a concentration of 200 ppm. DECOpulse. demonstrates a time advantage of approx. 21 minutes for reduction to 1 ppm. A further 30 minutes are saved in the subsequent investigated range of reduction from 1.0 to 0.1 ppm. In practice, H₂O₂ concentrations ranging from 0.1 to 0.03 ppm are currently demanded. We expect that, even at these extremely low concentrations, the trend towards saving time will continue and even accelerate. (The times given are based on comparable bio-decontamination cycles with a 10-log reduction when the isolator is loaded). The reduced use of H₂O₂ also results in lower outgassing effects, which reduces the risk that H₂O₂ residues will affect the sterile testing process and also reduces material stress.
D-value: Sterility is taken to mean the absence of microorganisms. 100 percent sterility cannot be obtained in practice, so the decimal reduction time D (D-value) is a common standard. In pharmaceutical sterile processing, the minimum requirements are a 4-6 log reduction. In individual cases up to 12 log reductions are required.
Fig. 3: The time advantage in ventilation: This effect is particularly visible at concentrations of 200 ppm and below.
The curves of the Atomization-driven Evaporation and the Flash Evaporation (DECOjet®) move apart. (Remark: The peak in the progression of the red curve at approx. 2.5 min is the result of the process-related rinsing of the decontamination system with compressed air.)
Pharmaceutical safety is significantly increased, cycle times are significantly reduced – thus STISO with DECOpulse® , has positioned itself as the benchmark system. By the way, the jury of the Interphex Exhibitor Awards has also recognized the advantages of DECOpulse® and has awarded the system the "Biotech Innovation Award 2019". But the STISO with DECOpulse® has even more advantages to offer. A sterility test isolator is ultimately a workstation, so it is important to be able to work there comfortably and in safety for several hours. While the STISO was still in the development phase, Metall+Plastic commissioned an ergonomic study. This has led to some important benefits: Today, about 95 percent of all potential operators reach all areas of the system using glove access. The STISO working positions can be adjusted for sitting and standing, and the angled front glass creates more distance to the glass, which also facilitates better ergonomic posture when working on the sterility test isolator.
The STISO can be designed in a modular way with a flexible number of glove accesses, with or without material transfer chamber or, if required, with left or right wall connection. The greatly simplified ("Plug & Test") installation is facilitated by eliminating connections to the building services engineering. All it needs are power, compressed air and cold water connections. The STISO is unaffected by possible fluctuations in room temperature. The integrated heat exchanger system simultaneously ensures that no heat is released into the room and pressure conditions remain constant. The glove test plates are equipped with a Wi-Fi function for wireless testing. A self-test ensures that the glove tests are carried out correctly. The first STISOs with DECOpulse® were delivered in late 2019. Right now, there are many more STISOs with DECOpulse. in the pipeline or under construction – as well as many production isolators with DECOpulse® as the new standard.