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4.2.2 Transferring the Manufacturing Process
to the GMP Suite
To produce iPSCs for clinical application, the procedures from the preparation
medium to banking the iPSCs should be compliant with GMP standards. GMP com-
pliance procedures request that (1) the laboratory facilities should be designed with
a GMP suite and (2) the procedure should be developed to standard operating pro-
cedures (SOPs).
A GMP laboratory for iPSC production must perform three phases: phase I,
training runs; phase II, engineering runs; and phase III, manufacturing runs. The
training runs are related to training SOPs at the laboratory; engineering runs are the
fi nal evaluation of all prerequisites related to iPSC manufacturing using SOPs.
Manufacturing runs include the production process of iPSCs using the optimized
iPSC manufacturing process established during phases I and II.
4.2.3 Quality Control Testing During iPSC Production
According to GMP-compliant production, quality control (QC) testing is always
required during the production line. QC testing aims to establish the fi nal product
with the highest levels of identity, safety, purity, and viability of the fi nal products.
Multiple QC tests should be performed, including plasmid clearance, karyotype,
STR, sterility, Mycoplasma , and endotoxin tests.
Upon completion of the GMP manufacturing process, a master cell bank of
approximately 100 vials (each vial containing approximately 2 × 10^6 human iPSCs)
should be produced and stored in liquid nitrogen following established protocols.
4.3 Applications of iPSCs in Clinic
4.3.1 Disease Modeling and Drug Screening
4.3.1.1 Disease Modeling
The use of animal models to mimic human disorders has been successfully prac-
ticed in scientifi c and clinical research for years. These models have furthered our
understanding of the causes and mechanisms of diseases, and many therapeutic
drugs have been developed from the results of these analyses. However, preclinical
treatment effectiveness does not always guarantee successful human clinical trials.
For example, congenital megakaryocytic thrombocytopenia (CAMT) is caused by
mutation in the gene encoding MPL (thrombopoietin receptor). Although mutation
of the MPL gene in humans results in signifi cantly reduced platelets and
P.V. Pham et al.