pH inactivation of SARS-CoV-2 and SARS-CoV in virus spiked protein A eluates from a mAb purification process

Area of Science:

• Biopharmaceutical Manufacturing
• Virology
• Process Chemistry

Background:

• Biopharmaceutical manufacturing often uses low pH treatment to inactivate enveloped viruses.
• Chromatography resins cleaned with sodium hydroxide (high pH) can also inactivate viruses.
• Murine leukemia virus is a model for assessing viral inactivation in manufacturing.

Purpose of the Study:

• To evaluate the susceptibility of SARS-CoV-2 and SARS-CoV to low and high pH conditions.
• To assess viral inactivation in the context of monoclonal antibody production.
• To compare the efficacy of pH-based viral inactivation for novel coronaviruses versus other enveloped viruses.

Main Methods:

• Testing SARS-CoV-2 and SARS-CoV inactivation at various low pH levels (e.g., pH 3.0, 3.4, 3.8).
• Assessing viral inactivation under high pH cleaning conditions (ca. 13.4) using sodium hydroxide.
• Utilizing protein A eluate material from a monoclonal antibody production process.

Main Results:

• SARS-CoV-2 was effectively inactivated at pH 3.0 and moderately at pH 3.4, but not at pH 3.8.
• Low pH was less effective for SARS-CoV inactivation compared to SARS-CoV-2.
• Both SARS-CoV-2 and SARS-CoV were inactivated at high pH (ca. 13.4).

Conclusions:

• Low and high pH treatments are effective viral inactivation strategies in biopharmaceutical manufacturing.
• SARS-CoV-2 demonstrates susceptibility to low pH inactivation, informing process development.
• These findings are crucial for ensuring viral safety in biopharmaceutical production involving novel coronaviruses.