Stability Evaluation of Hydrogen Peroxide Uptake Samples from Monoclonal Antibody Drug Product Aseptically Filled in Vapor Phase Hydrogen Peroxide-Sanitized Barrier Systems: A Case Study

Abstract

During the manufacture of a monoclonal antibody drug product, which was aseptically filled within a vapor phase hydrogen peroxide-sanitized isolator, samples were taken to investigate the hydrogen peroxide uptake behaviors. Surprisingly, the samples had no detectable hydrogen peroxide (most results below the limit of detection). This finding was later attributed to hydrogen peroxide decomposition after the samples were stored frozen at −20°C for two weeks before testing. This case study highlights the criticality of storage conditions for hydrogen peroxide-containing samples and summarizes an investigation on hydrogen peroxide stability in water and in three monoclonal antibody solutions having a wide protein concentration range (30–200 mg/mL). Samples were stored at three temperatures (−70°C, −20°C, or 2–8°C) for up to 28 days to assess the impact of protein concentration and storage temperature on hydrogen peroxide decomposition rates. Hydrogen peroxide degraded slightly more rapidly with increasing protein concentration independent of storage condition. When stored at −20°C, hydrogen peroxide was least stable and degraded faster than when stored at 2–8°C. Hydrogen peroxide was most stable when the samples were stored at −70°C. Overall, this case study brings the hydrogen peroxide stability issue to the attention of process development scientists and engineers and offers a valuable lesson learned during process development.

LAY ABSTRACT: The use of vapor phase hydrogen peroxide as a sanitizing agent for isolator and cleanroom decontamination has become common in recent years. Because of the potential impact of residual hydrogen peroxide on biopharmaceutical product quality, hydrogen peroxide uptake behaviors and mechanisms during the manufacturing process within these barriers need to be evaluated and understood. Samples taken from various small-scale and manufacturing-scale hydrogen peroxide uptake studies are often stored frozen before testing. This case study reports an important and interesting finding about hydrogen peroxide stability in samples collected for hydrogen peroxide uptake investigation, and it demonstrates the relationship between hydrogen peroxide stability and storage temperature, storage duration, and monoclonal antibody concentration. The approach and outcome of this study are expected to benefit scientists and engineers who develop biologic product manufacturing processes by providing a better understanding of drug product process challenges and appropriate sample storage.