Development of a rapid sanitization solution for silica-based protein A affinity adsorbents

Area of Science:

• Bioprocess Engineering
• Chromatography
• Microbial Control

Background:

• Protein A chromatography media require regular sanitization for optimal performance and longevity.
• Traditional sanitants like sodium hydroxide (NaOH) are incompatible with silica- or controlled pore glass (CPG)-based adsorbents due to high pH instability.
• Benzyl alcohol is a common alternative but often requires extended contact times for effective microbial reduction, impacting manufacturing throughput.

Purpose of the Study:

• To develop a novel, synergistic sanitant solution for Protein A chromatography media.
• To reduce sanitization cycle times while maintaining adsorbent stability and achieving effective microbial log reduction.
• To support increased manufacturing throughput for monoclonal antibody therapeutics.

Main Methods:

• Development of a new sanitant solution, PAB, comprising phosphoric acid, acetic acid, and benzyl alcohol.
• Evaluation of microbial kill kinetics and sanitization efficacy of PAB.
• Assessment of adsorbent stability and process compatibility under PAB treatment.

Main Results:

• The PAB sanitant solution demonstrated improved microbial kill kinetics, enabling effective sanitization in 2-3 hours at room temperature.
• The new solution maintains acceptable adsorbent stability, crucial for silica- and CPG-based chromatography media.
• Achieved desired microbial log reduction values, addressing limitations of existing sanitization protocols.

Conclusions:

• The PAB sanitant offers a significantly faster and effective method for sanitizing Protein A chromatography media.
• This advancement is particularly beneficial for high-throughput manufacturing of monoclonal antibodies.
• PAB provides a viable, efficient alternative for sanitizing sensitive chromatography adsorbents.