A current trend in the bioprocessing industry is the implementation of disposables. They usually take the form of filters, mixers, connectors, bottles, tubings, bags, and bioreactors and provide considerable benefit to the manufacturing process. Advantages include reduction of clean-in-place (CIP) or steam-in-place (SIP), elimination of validation, decrease of process time and capital cost, increase of process flexibility, and most importantly, reduction of cross-contamination risks.

As upstream process is migrating toward disposable bioreactors, adapting downstream purification to complete disposable systems is a challenge where multiple processes are involved and high purity is required to meet regulatory standards. Current commercial disposables were devised to meet protein purification needs, while specific targeting toward plasmid-based products has been largely ignored. Therefore, we investigated the employment of disposable modes, typically membrane technology, to replace conventional bead-based chromatography techniques, and integrate these changes into our proprietary DNA production system.

This presentation will provide a case study of application of disposable membrane capsules in the manufacture of plasmid DNA for pre-clinical studies. Two commercially available anion exchange membrane products were compared at the process scale in terms of their DNA binding capacity, contaminant removal and form separation. One of the membrane products was demonstrated to have superior performance especially a high binding capacity ten-fold of typical resins. We successfully scaled it up to large-scale production and implemented in the primary capture and purification of plasmid DNA. Advantages and drawbacks of these membrane products at different production scales will be discussed. Employment of these membrane capsules provides simple, convenient, and economical alternatives to traditional ion exchange chromatography. Most importantly, their flexibility leads to minimized product turn-around time, which could be essential to the manufacture of variable DNA vaccines at large scale in quick response to pandemic threats such as influenza, bird flu, small pox, and other pathogens.