Ever wanted to know how to manufacture stem cells under cGMP-compliant conditions? Well, contract manufacturing organisation (CMO) Lonza has published an A-Z guide to producing clinical-grade iPSCs in the Stem Cell Reports Journal.
Entitled ‘cGMP-Manufactured Human Induced Pluripotent Stem Cells Are Available for Pre-clinical and Clinical Applications,’ the paper details Lonza’s processing flow from defining tissue requirements to the characterisation and viral testing of stem cells made at its Walkersville, Maryland facility.
“iPSC MCBs [master cell banks] have to be generated using a robust, reproducible, and cGMP-compliant manufacturing process, applying best practices for cell culture, documentation, and quality control,” the authors state.
Lonza’s iPSCs use CD34+ cells from a fresh umbilical cord blood unit.
“Sourcing from cord blood when using an optimized and reproducible integration-free method allows one to develop a bank of well characterized and tested pluripotent cells that can be used for differentiation into clinically relevant cells.”
Procuring raw materials
But while the CMO offers a step-by-step guideline, it warns that this alone “will not be sufficient to ensure clinically relevant products, nor will adding certification or training complete the process,” in appeasing regulators.
An iPSC manufacturer must conform to regulations surrounding the procurement of human donor tissue, while control material must be developed to generate convincing data on in-process testing, lot-to-lot variability, and release assays - themselves needing to be developed and validated.
“There were three levels of concerns we had to address during the derivation process,” the firm says, the first asking: “Was the process of obtaining tissue compliant with the new guidance provided by the FDA and compatible with the final donor consent rule?”
“The second issue was keeping a backup tissue sample and multiple clones of iPSC lines from the same donor.” Lonza opted against this for its first line it generated, but said for the actual therapy, each group will prefer generating its own lines.
“We expect, however, that, if they opt to use the described process and SOPs, then their cost will be significantly lower, and that the FDA will accept much of the pre-clinical data that have been generated with this line.”