The process for producing Xeragenx recombinant human intrinsic factor (rhIF) and binding it to vitamin B12 for a finished dosage form is completed over several steps.
The first step is the generation of plant biomass that expresses the human intrinsic factor protein. Transgenic Arabidopsis seeds are germinated and plants are grown in an indoor chamber environment with controlled conditions for light, temperature, irrigation, and humidity. The rhIF protein is expressed in the plant biomass sufficient for harvest after several weeks.
At the conclusion of the growth cycle, the plants are harvested using a cutting device and the biomass is mechanically homogenized in the presence of a buffered solution. The homogenate is then centrifuged to separate the supernatant, containing soluble host cell proteins and rhIF, from the solid plant material. The plant lysate is then filtered to remove any remaining particulates leaving a clarified lysate that is the liquid plant starting material for creation of the drug substance.
An affinity chromatography column is prepared by linking the vitamin B12, Hydroxocobalamin (OHCbl), as an affinity ligand to a proprietary resin. The clarified plant lysate is then loaded onto the affinity column to bind the recombinant human intrinsic factor (rhIF) protein to OHCbl. The OHCbl (rhIF-bound) drug substance material is then eluted and filtrated from the column, and finally concentrated and sterile filtered for packaging.
The OHCbl (rhIF-bound) liquid drug concentrate is processed into an active granulate intermediate for use in XGX-001 and other finished dosage forms. The final XGX-001 product is a tablet that is enteric coated to ensure the OHCbl-rhIF complex is first released in the upper duodenum.