<br/>Transfer and scale-up of a biological therapeutic manufacturing process is often required when clinical development programs transition from early to late stage clinical trials. An initial assessment of a therapeutic protein manufacturing process as run at a CMO identified several limitations in processing capabilities if it were to be run in our 15K RTP manufacturing facility. The downstream facility fit challenges/limitations that were identified centered largely around the harvest, the capture column load UF/DF, and two downstream columns. The harvest was challenged with an extremely large depth filtration area, along with a high buffer volume for the capture column load UF/DF unit operation, while the capture column was development with a unique pH slope change for end of eluate collection, and the first polishing column was run using a linear gradient with the eluate collection stop calculated upon mass load.  To enable running this process in our 15K facility, several processing options were explored with the requirement of maintaining product quality comparability. Process modifications were initially tested at bench scale to assess the impact to product quality and ease of processing, and then verified at pilot scale. Modifications made to the original CMO process included alteration of the harvest flocculation and clarification operations, replacement of the pH dependent eluate collection with a fixed volume collection, and implementation of an isocratic and fixed volume elution in place of a linear gradient with the calculated end of eluate collection criteria.<br/>

A case study of tech transfer and growing pains: Shoehorning a process to fit a facility

255th National Meeting (2018)

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