Formulation and Quality Control
Figure 6
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Purified pDNA is formulated into the buffer of choice by a disposable scaled-down version of the previous hollow fiber membrane
assembly (Figure 6). The pDNA is formulated at the desired concentration in the appropriate solution (normally isotonic) requested
by the sponsor. The choice of filter membrane is also critical to avoid unnecessary losses of plasmid by nonspecific binding.
Table 1. Final QC release testing and specifications for clinical grade pDNA
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The final product is fully tested, and satisfies current recommended guidelines (Table 1). Limited in-process QC testing is
performed because of the continuous nature of the process.
Conclusion
The continuous process is suitable for the rapid turnaround required for the preparation of these vaccines at a low cost.
It is aseptic, contained, and completely disposable to avoid product cross contamination. It has been estimated that on current
demand, with two operators in two cleanrooms, up to 40 individual vaccines could be manufactured annually.
By careful design, it is possible to eliminate some of the main obstacles and limitations normally associated with conventional
processes (e.g., to reduce the reliance on high-tech equipment and to eliminate the use of column chromatography). The process
has been shown to achieve a recovery of pDNA of greater than 45% from bacterial lysate with the quality of the final product
satisfying current regulatory requirements.
Paul Lloyd-Evans, PhD is an operations manager, Denise A. Phillips is a production supervisor, Antony C.C. Wright is a production scientist, and R. Keith Williams is a business development manager, all at the Clinical Biotechnology Centre, Bristol, UK, 011.792.89388, paul.lloyd-evans@nbs.nhs.uk
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