MANUFACTURING

Production and Qualification of GRNOPC1
GRNOPC1 is a cryopreserved cell population containing a mixture of oligodendrocyte progenitor cells and other characterized cell types that are produced by a specific differentiation protocol from a master cell bank of H1 undifferentiated hESCs that has been qualified for human use. GRNOPC1 is produced under current Good Manufacturing Practices (cGMP) in Geron's qualified manufacturing facilities. The GRNOPC1 manufacturing process in Geron's clean room suites has been inspected and licensed by the state of California.

The manufacturing process consists of three stages: 1) numerical expansion of undifferentiated hESCs obtained from the qualified H1 hESC master cell bank, 2) differentiation of the expanded hESCs into GRNOPC1, and 3) harvest, formulation, fill and cryopreservation of the GRNOPC1 drug product. The manufacturing protocol specifies the sequential addition of biologicals and growth factors to induce the expansion and progressive differentiation of undifferentiated hESCs into the GRNOPC1 drug product. A significant portion of each manufacturing run of GRNOPC1 is retained and subjected to extensive quality control testing to ensure the identity, sterility, viability and cellular composition of each manufacturing run before the product is released to the sites for clinical use. GRNOPC1 product that has passed all such specifications and has been released is available for the approved clinical trial. The current production scale is sufficient to supply all clinical trial needs. The existing qualified H1 master cell bank of undifferentiated hESCs could potentially supply sufficient starting material for GRNOPC1 manufacturing to commercially supply the entire spinal cord injury market in the United States for more than 20 years.