Controlling High Mannose Glycan Level and Optimizing Titer Through a Balanced Modulation of Cell Culture Process and Medium Changes

High mannose glycoform may be an important quality attribute that can affect the efficacy of therapeutic monoclonal antibodies. Meeting comparable high mannose glycan level (%HM) is often important when developing a commercial process to replace the early phase clinical process. Strategies were developed to tune the %HM in order to meet the comparability range while at the same time increasing titer for the commercial process. The strategies utilized a combination of process optimization and medium modification in order to produce the desirable %HM profile. In several process instances, titer had to be sacrificed in order to meet the desirable %HM level; however, this was overcome by modulation of certain medium components. Yet, precise balance between process and medium needed to be made in order to achieve the most desirable state for both titer and %HM. Overall strategies and learning on taking this dual approach to controlling the %HM while improving titer will be discussed.