Abstract
In the past years, the demand for small batches of clinical grade plasmid DNA has been growing. For that purpose, we designed and qualified a scaled-down Good Manufacturing Practices (GMP) production method, able to produce small batches (1-4 mg) of plasmid. The developed method does not require any complex production equipment and utilizes only disposable production materials, which makes it easy to implement and simplifies line-clearance. We have successfully used this method to produce several small batches of two different plasmids. The produced plasmids, both formulated in an Electroporation Buffer, are mixed and filled into small, single-use, aliquots. Quality control confirmed the robustness of the developed method and a stability study showed that the final formulation is stable for at least two years. The final patient formulation will be subsequently used in a phase I/II clinical trial in which retina cells of patients with Age Related Macular Degeneration, are transfected. The presented production method can be generically used for other plasmid constructs and final formulation designs.
Highlights
Both gene therapy and cell therapy have become attractive treatment options in a wide variety of diseases over the past decades (Ginn et al, 2013; Gorabi et al, 2018; Melero et al, 2014)
Quality control analysis of the Master Cell Bank (MCB) and bulk miniplasmids pFAR4-Pigment epithelium-derived factor (PEDF) and pFAR4-SB100x and control samples taken during the production processes, were all conformed to specifications, demonstrating that the used production method is robust
We have described a fully disposable, small scale plasmid DNA production method
Summary
Both gene therapy and (stem) cell therapy have become attractive treatment options in a wide variety of diseases over the past decades (Ginn et al, 2013; Gorabi et al, 2018; Melero et al, 2014). Good Manufacturing Practice (GMP) grade plasmid DNA is required. We have previously described a method to produce large scale (>100 mg) batches of plasmid DNA that we used for DNA vaccination purposes at our institute (Quaak et al, 2008; Samuels et al, 2017). Besides for clinical phase I/II studies, small aliquots of plasmid can be useful for animal experiments and pilot studies in which only small amounts are required. For this purpose, a small scale manufacturing process was developed. The production method is a scaled-down version of a previously described GMP production process (Quaak et al, 2008)
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