A non-linear path to the development of advanced downstream bioprocessing solutions

By Christie Childers, Senior Downstream Scientist, Astrea Bioseparations

Pivot to plasmid

If you asked me when I was very young what I wanted to do, I would have said forensic science. But by the time I was doing my undergraduate degree, I had changed my mind a few times. I eventually settled on a love for neuroscience and everything to do with the brain. So, I studied addiction behavior in rats as my undergraduate honors project with Dr. Karen Brebner at St. Francis Xavier University. I thought I would keep that up with graduate studies but, towards the very end of my undergraduate degree, I was introduced to an eclectic supervisor who offered me a role in his molecular biology lab. So, I pivoted my focus at the last minute and ended up having an amazing time doing my master’s and PhD in the Storey Lab. We looked at how some mammals and frogs could change their enzyme function with post-translational modifications to adapt to hibernation, freezing in the winter or long droughts. It was all pretty cool, pun intended.

I thought I was going to extend my study of enzyme regulation at the NIH, but I decided to cut that postdoc position short when we were sent to work from home by COVID-19. I had known I wanted to look for an industry position and the chaos of that time sped that decision up. This second major focus pivot led me to a downstream processing R&D role at CPI in the Northeast of England. My first big project was in the unfamiliar territory of purifying a large-scale batch of plasmid DNA (pDNA). Thankfully, I was able to apply what I knew about lab work and learn a whole lot about biologic manufacturing on the run. Looking back, the biggest lesson I learned at CPI was how to successfully integrate my workflow with that of the upstream and analytical teams. Science is incredibly collaborative, and being able to work in a team can make the work much smoother and more fun.

When I joined Astrea Bioseparations in May 2023, I began work on an exciting AstreAdept® nanofiber-based product called pDNAHERO®. As the name suggests, it was developed specifically to streamline pDNA processing, which perfectly aligned with my skillset at the time.

Using hydrophobic interaction to capture pDNA is nothing new, but the use of a nanofiber matrix in pDNAHERO® offers a key differentiator: high-speed performance. Processing time may not be such a challenge at the smaller R&D scale, but, as you scale up toward commercial manufacture, hours become days. And time spent in the GMP suite is expensive.

The power of the platform

Most mAb-based therapy development travels well-known ground, relying on proven approaches to large-scale up- and downstream processing. The mAb field has already matured to the point where established contract development and manufacturing organizations (CDMOs) can confidently say to customers that they will supply a new product within a 15-month time frame. There are nuances, of course, as well as the constant pursuit of perfection in terms of performance, speed, and cost. But it is fair to say that platform processes reign supreme in the world of mAbs and is the goal of most, if not all, up-and-coming modalities.

Cell and gene therapy products, like CAR-T therapies, mRNA vaccines, and lentiviral vectors, might not be at a gold standard universal platform process just yet, but, as the right tools and approaches are developed (AstreAdept® fiber being a good example), they seem destined to follow in the footsteps of mAbs. CDMOs in particular are likely to be the first in line to adopt and establish platform processes that reduce development time and provide greater confidence, in terms of hitting production timelines. And drug developers are always keen to drive down the cost of goods.

The sci-fi-esque days of “input target sequence here; collect pDNA or mRNA product there” don’t seem all that far away. Right now, my days are spent working away on a prototype unit that feels very much like a natural evolution of the AstreAdept® range. Watch this space!

Learn more about AstreAdept® nanofiber-based technology here.