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  • AutorenbildJuergen Mairhofer

Cost-effective recombinant protein production with enGenes-eXpress

enGenes Biotech has developed a leading-edge platform for the customized production of recombinant proteins and plasmid DNA that can frequently prove more cost-effective than the development a competing pharmaceutical contract development and manufacturing organization(CDMO) can offer.

These enGenes microbial expression solutions are based on its unique and proprietary enGenes-eXpress bacterial cell line technology platform, enhanced by patented manufacturing processes to leverage the basic -eXpress growth decoupled advantage. The net results are substantially higher soluble product yields and easier downstream processing (DSP), resulting in up to 80% reduction in cost of goods sold (COGS).

Biotech manufacturing challenges

Bioprocesses, harnessing the properties of cells and enzymes through tools such as recombinant DNA to develop novel products, presents a series of challenges, particularly in upstream and downstream processing as well as scale up to industrial viability.

Manufacture of a typical recombinant DNA-derived product will involve up to 20 steps between identifying basic source materials or tissue and final packaging. The initial ten or so steps are concerned with genetic manipulation of the host organism; such as through cloning a gene from DNA into Escherichia coli (E. coli). This will involve genetic engineering at laboratory scale to establish levels of expression available and the stability of the constructed strains, defined as growth and production characteristics of the recombinant cells as a function of the culture environment, with parameters such as cell growth rate, specific productivity, and product yield calculated to measure the performance of the organism.

Once viable culture conditions for production are established, process development will involve using a benchtop bioreactor to establish the ideal inducer, induction strength, temperature, pH, dissolved oxygen concentration, stirrer speed, and other process variables. The challenge here is that moving the cell culture to a stirred bioreactor may not speed the process but harm it. The viability of the process will be defined in measured and calculated parameters such as mass transfer coefficients, mixing time, gas hold-up, oxygen uptake rate, power number, energy dissipation rate, etc. It must also be decided whether the culture is best operated as a batch, semi-batch, or continuous process.

The production strain must then be suitable for tech transfer to CDMO or CRO pilot scale (100- 1,000 litre up to m3-scale) bioreactor, where equipment design or configuration may affect process viability. Full scale contract manufacturing also needs to consider downstream process (DSP) product recovery, which can be a major source of added cost and lost efficiency. For some recombinant-DNA-derived products, DSP purification can account for 80 to 90% of the total processing cost.

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