Now biological agents are the most effective and potentially valuable new therapeutic products, including polypeptides, proteins and antibody drug conjugates (ADC), as well as cells, cell derived products and gene therapy. During the production process, these products are vulnerable to the oxidation or degradation of residual hydrogen peroxide, because some trace hydrogen peroxide (H2O2) will still exist in sterile processing equipment after the completion of the aeration process after purification. For early biological products, a residual level of 100 ppb may be lost. However, for newer products, existing data show that the lower limit of possible loss caused by residual hydrogen peroxide is as low as 30 ppb.
In fact, manufacturers of these biological agents must determine the oxidation sensitivity of products and the upper limit of allowable residual hydrogen peroxide exposure to ensure that the environment of isolators or other sterile processing equipment does not expose products above this threshold.
There are three methods to measure the residual hydrogen peroxide as low as ppb level during and after aeration. In fact, one of the methods is not a measurement method at all – it just depends on the sterilization and ventilation program design, usually your sterile processing equipment. According to the actual requirements, the equipment manufacturer may have carried out a thorough study and designed an adequate aeration process. However, there are two hidden dangers in this method. First, how do you ensure that the hydrogen peroxide adsorbed on some surfaces will not be released during the actual operation (including possible shutdown), long-term operation or repeated operation? If you need to change or re select the procedures or related equipment in the isolator, is there any way to re verify the aeration process? Second, considering the difference between experiment and actual use, the supplier of aseptic treatment equipment may have designed a very conservative and long aeration stage as part of the whole cycle. This means wasting time – time that could have been spent improving productivity rather than waiting unnecessarily.
The second method to measure residual peroxide is to use the wet chemical method technology, which is called peroxidase method. This is a highly sensitive and widely used technology, especially when combined with fluorescence or chemiluminescence detection. It is capable of quantifying hydrogen peroxide on a solid surface (using a rag), directly on a liquid or in the gas phase (by bubbling the gas in water). However, it is not a fast or real-time method, and requires very familiar with chemical expertise and operation. Consumable reagents and containers are used for each sample, which makes it unsuitable for clean room environment. In addition, this method requires frequent calibration.
The third method to measure the residual hydrogen peroxide is to directly use the hydrogen peroxide sensor, which can quickly and continuously measure the hydrogen peroxide concentration in the gas phase. UK Alphasense hydrogen peroxide sensor hydrogen peroxide gas sensor – H2O2-B1. It has the characteristics of good stability, high sensitivity and high cost performance.
In fact, most biopharmaceutical companies are using hydrogen peroxide sensors to ensure the stability of products by ensuring a safe environment for subsequent processing of biological products after sterilization (such as packaging); Similarly, most isolator equipment manufacturers are also using hydrogen peroxide sensors to test and verify their products and designs, or deliver them to users together with the equipment to ensure the safety of sterilization and aeration processes. Therefore, in consideration of the safety and stability of biological agent products, it is indeed the best choice to use hydrogen peroxide sensors to continuously monitor the residual hydrogen peroxide level during ventilation and operation.