Plasmid DNA development requires great expertise and experience. Selecting a supplier with the quality assurance protocols and Good Manufacturing Practices (GMPs) in place, will prevent you from delays. Also the right supplier will secure the right plasmid for your project in case you don’t’t have one yet.
In this article we are going to speak about some considerations that you should take into account, when you contract pDNA manufacturing service with a CDMO.
Consideration for Plasmid DNA Optimizations
Finding the Right Plasmid
Plasmid DNA is often a highly varied material, developed with unique considerations for bespoke pharmaceutical applications. In response to increased demand for pDNA, 53Biologics have begun pioneering a plasmid service with more utility than ever before.
There are essentially three grades of plasmid DNA:
But within these categories also exist different aspects that you have to consider. For example, commercial-grade plasmids that are intended to serve as raw materials possess regulatory standards much less stringent than plasmids selected to serve as active pharmaceutical ingredients (APIs). That stringency is even greater for plasmids that function as a finished product.
Also, companies must consider other factors inherent to its design, like yield, transient transfection rates, and its capacity to stably transduce cell lines.
For companies at the proof-of-concept stage, plasmid design and antibiotic resistances are very important considerations. The number of generations a backbone is removed from its genesis serves to impact the yield and contamination profile of the pDNA.
Decisions related to these considerations, made as early as possible, can help companies avoid the delays associated with reworking a plasmid that demonstrates suboptimal yield or a tendency toward contamination at later stages of development.
Optimizing Plasmid Production
Poor plasmid design can lead to a range of issues, regarding the integrity of inverted terminal repeats (ITRs) to partial transgene packaging.
Another complex factor is balancing the scale of plasmid manufacture to produce enough material at each stage of development. But the real problem begins with the downstream (DSP) phases. The biggest bottlenecks in pDNA manufacturing are instability during DSP and the identification of issues post-sequencing.
One of the best ways to speed up and avoid these problems is partnering with a plasmid supplier able to support a project’s vertical integration from early stages to clinical and commercial manufacturing. At 53Biologics, we support your pDNA project from the initial steps, even with cell banking generation if you need. Depending on your quality grade, we can develop:
- Non GMP Cell Banks: recommended for research purposes and preclinical studies
- GMP Cell Banks: recommended for clinical studies and commercial market in the research and pleclinical phases all the way through clinical and commercial manufacturing
New Technologies and Innovation for plasmid DNA Optimization
As gene therapies continue to proliferate, innovations to the status quo surrounding plasmid manufacturing are becoming more common.
New technologies that allow users to filter out media and replenish it with new media or are starting to emerge. Things such as single-use disposable fermenters in place of traditional stainless-steel ones or new resins introduced to the DSP process, have helped minimize the potential for contamination.
There are even more promising developments on the horizon like the “doggy bone” DNA technology, a synthetic, rapid, cost-effective alternative to backbone plasmids that eliminates antibiotic resistance genes, which can represent a “contaminant” for plasmids due to their potential to introduce antibiotic resistance in patients.
To be able to take advantage of these innovations, the best option is to partner with a plasmid supplier with the quality assurance protocols and Good Manufacturing Practices (GMPs).
At 53Biologics we have implemented a cost-effective and flexible plasmid DNA manufacturing platform both for research grade and GMP with dedicated quality control testing for R&D, preclinical and clinical trials.
We can help you overcome the challenges associated with the purification of pDNA such us high viscosity, large molecule size, shear sensitivity, and help you obtain pDNA at the purity and scale you need.