pH Criticality Across Traditional Production Stages: 

• In the upstream suite: The yeast expresses the GLP-1 peptide in a methanol fed-batch regime with precisely controlled carbon uptake. The pH setpoint, therefore, is strictly controlled; pH = 5.0-6.0 with a deadband of 0.2-0.5. For pH measurement, and since SIP cycles are in effect like in any other biopharma fermenter, the sterilizable METTLER TOLEDO InPro™ 3253i SG sensor with solution ground (for minimizing offset and drift) is highly suitable.

• In media and buffer formulation tanks: It is also critical to monitor pH in-line to enhance formulation efficiency. Here, since there are no SIP cycles and only CIP is in effect, the non-sterilizable InPro 3250i SG suffices.

• After post-harvest operations and in the DSP suite: In-line pH indicators determine successful capture and elution steps in ion-exchange chromatography steps. Similarly, pH spikes trigger successful TFF polishing and UF/DF formulation steps. Here also, since steaming is not usual, the InPro 3250i SG or InPro 3100i SG is sufficient. You may, however, have some specialized pipelines that indeed require SIP for the DSP pipelines. In these cases, the InPro 3253i SG would be required.

• Further complementary steps: Including deletion of the first tag amino acids, positional substitutions, and linker conjugation. However, these steps are fast and based on intensified scales, usually in SU platforms that are run blind without in-line monitoring.

In all of these steps, perhaps with the exception of final formulation, pH poses as a Critical Process Parameter (CPP). Monitoring and controlling it in real time and in situ is necessary. Since SIP is rare in these fast unit operations, the InPro 3250i SG would be suitable.