Disadvantages of VHP Pass-boxes

Since the 2010 GMP revision, with stricter sterilization requirements, all materials entering Class B areas must be sterilized. However, traditional moist heat and dry heat sterilizers both have the disadvantage of high-temperature sterilization. Some products that cannot be sterilized at high temperatures can only be sterilized using a low-temperature pass-box. Therefore, the VHP vaporized hydrogen peroxide pass-box was developed.

 

VHP sterilization transfer windows are suitable for sterilizing the surfaces of various items being transferred without leaving residue, making them ideal for transferring items between cleanrooms of varying levels. In 2012, with the rapid adoption of vaporized peroxide (VHP) transfer windows in China, an estimated 100 pharmaceutical companies have achieved new GMP certification for their VHP transfer windows.

Although VHP pass boxes are a mature sterilization transfer solution for today’s pharmaceutical companies, they still have several unavoidable shortcomings:

1. The sterilization cycle for VHP transfer windows remains excessively long. From the start of sterilization to the removal of residual concentrations below 1 ppm, a small chamber typically requires 1.5 hours, while a large chamber can take up to 3 hours. This represents a significant time cost. To reduce sterilization cycle times, some companies may open the VHP transfer window to retrieve materials even when residual concentrations still reach 5-10 ppm. This increases the risk to personnel.
2. The VHP transfer window utilizes a high-temperature flash evaporation method to convert 30% hydrogen peroxide into hydrogen peroxide gas. During the sterilization process, the temperature of the transfer window rises by 5-15°C, making it unsuitable for transferring temperature-sensitive products such as biologicals. If the transfer window is not heated, the high-temperature hydrogen peroxide gas will easily adhere to the stainless steel plate inside the transfer window, causing condensation.
3. Currently, domestic VHP transfer windows utilize the commonly available 30%-35% food-grade (or analytical-grade) hydrogen peroxide solution. 30% hydrogen peroxide is a hazardous chemical, flammable and explosive, and its purchase, transportation, and storage require registration with the local Public Security Bureau. Furthermore, this food-grade or analytical-grade hydrogen peroxide contains many impurities, significantly shortening the lifespan of the hydrogen peroxide flash tray.

Is there a hydrogen peroxide transfer window that can achieve a 6-log sterilization effect against Bacillus stearothermophilus, while shortening the sterilization cycle without increasing the temperature? And without requiring such a high concentration of hydrogen peroxide solution, could this help companies facing urgent time and challenges?

To address the aforementioned drawbacks of VHP transfer honey, let’s first analyze the existing technical difficulties.

Why does the sterilization cycle of a VHP transfer window take so long? Let’s analyze the time distribution of the entire sterilization cycle. The sterilization cycle of a VHP transfer window consists of four steps: dehumidification, conditioning, sterilization, and ventilation. Taking a 3m³ VHP transfer chamber as an example, dehumidification takes approximately 10 minutes; conditioning: approximately 10 minutes; sterilization: approximately 40 minutes; and ventilation: approximately 1.5 to 2 hours (to reduce the concentration to below 1ppm). The total time is 2.5-3 hours.

1. It can be seen that the ventilation stage accounts for two-thirds of the entire sterilization cycle time. Why does ventilation take so long? Based on experiments, the technical department of Anpal Technology Co., Ltd. speculates that the following four factors are the main reasons:

Why does the sterilization cycle of a VHP transfer window take so long? Let’s analyze the time distribution of the entire sterilization cycle. The sterilization cycle of a VHP transfer window consists of four steps: dehumidification, conditioning, sterilization, and ventilation. Taking a 3m³ VHP transfer chamber as an example, dehumidification takes approximately 10 minutes; conditioning: approximately 10 minutes; sterilization: approximately 40 minutes; and ventilation: approximately 1.5 to 2 hours (to reduce the concentration to below 1 ppm). This totals 2.5 to 3 hours.

It can be seen that the ventilation phase accounts for two-thirds of the entire sterilization cycle time. Why does the ventilation take so long? Based on experiments, the technical department of Anpal Technology Co., Ltd. speculates that the main reasons are the following:

• VHP uses a high-concentration 30% hydrogen peroxide solution;
• Thermal evaporation of vaporized hydrogen peroxide easily condenses (from vapor to liquid), which is then slowly released again during the subsequent ventilation process, making it more difficult to remove the peroxide.
• Materials such as HEPA filters easily adsorb hydrogen peroxide.
• The vapor pressure of hydrogen peroxide is lower than that of water.

Many companies internationally are currently seeking to speed up the removal of residual hydrogen peroxide. For example, Metall Plastic Germany has improved its vaporization nozzles and catalysts, but the best results achieved are only a reduction of H₂O₂ to 0.5 PPM in a 5m³ space within 1.5 hours. Bioquell in the UK has devised a method to decompose hydrogen peroxide by spraying a catalase solution. However, because the enzyme is a protein, if it is not completely removed from the microorganisms, it becomes a nutrient for them. Therefore, the catalase solution method is not feasible.

2. Regarding the issue of elevated chamber temperatures, since the principle of VHP is high-temperature flash evaporation, this technical difficulty cannot be overcome. But let’s think about it from another perspective: What is the core purpose of VHP? It’s to transform hydrogen peroxide solution from a liquid phase into a vapor phase! So, is high temperature the only way to do this? Are there other methods?
3. Regarding the issue of hydrogen peroxide, according to national standards, hydrogen peroxide solutions exceeding 8% are hazardous chemicals. So, can the concentration of hydrogen peroxide solution be reduced to below 8%, increasing its purity and addressing the corresponding risks? Wouldn’t this also solve the technical challenge of residual waste removal?
4. With technological advancements, the three drawbacks of traditional VHP pass-through windows are gradually being improved and resolved. Suzhou Baiben Clean Technology Co., Ltd. (drafting unit of the VHP pass-through window industry standard) has recently developed a hydrogen peroxide pass-through window that utilizes cold evaporation technology. This converts hydrogen peroxide solution from a liquid phase into a vapor phase at room temperature, without heating the chamber or condensation. Furthermore, the entire sterilization cycle takes only 35 minutes for small hulls and 60 minutes for large hulls, significantly shortening the lengthy sterilization cycle of traditional VHP pass-through windows. And the sterilization cycle CD is easier to develop and easier to validate.