Platform Downstream Purification (DSP) processes generally work well for purifying antibodies, predominantly due to the use of an affinity Protein A capture step.  For non-antibody molecules, the DSP typically requires additional chromatography operations to achieve the same impurity clearance.  The storage of intermediate pools in the presence of high levels of host cell impurities can result in the generation of low molecular mass species (LMMS) depending on pool conditions.  Significant work can be required to gain a thorough understanding of the parameters that can improve pool stability and deliver acceptable product quality.<br/>This presentation will discuss the challenges and learnings that occurred during the scale up of a non-antibody purification process.  Unexpected levels of LMMS were generated during the storage of the second chromatography step, whereas all other pools were stable.  Significant work was performed to identify the root cause and determine purification techniques to minimize LMMS generation.  Within 8 weeks of identifying this issue, multiple mitigations were implemented at pilot scale which successfully prevented LMMS generation in subsequent runs.

Rapid downstream process development to prevent low molecular mass species generation for a non-antibody protein

ACS Fall 2021

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