Stability Evaluation of Hydrogen Peroxide Uptake Samples from Monoclonal Antibody Drug Product Aseptically Filled in VPHP-Sanitized Barrier Systems

Abstract

During the manufacture of a monoclonal antibody drug product aseptically filled within a vapor phase hydrogen peroxide-sanitized isolator, samples were taken to investigate the hydrogen peroxide uptake behaviors. The results surprisingly yielded no detectable levels of hydrogen peroxide. This finding was later attributed to hydrogen peroxide decomposition after samples were stored frozen at -20oC for two weeks before testing. This case study highlights the criticality of storage conditions for hydrogen peroxide-containing samples and summarizes a comprehensive investigation on hydrogen peroxide stability in aqueous samples and in samples containing monoclonal antibody with 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 more rapidly with increasing protein concentration independent of storage condition. When stored at -20°C, hydrogen peroxide was least stable and degraded faster than storage 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.