Candidate Commercialization: A Helping Hand

In today’s busy biopharma market, speed is of the essence – and demand for COVID-19 interventions means that it’s more important than ever to find ways to safely accelerate the development and manufacture of antibody drug candidates for multiple indications through immunotherapy. Here, Kenneth Lee, Head of Commercial Division, Americas, GenScript ProBio, explains how he helps biopharma, biotech and academic institutions to optimize their manufacturing processes.

At least in the media, development and commercialization typically take a backseat to discovery. What are your thoughts?

You are spot on – almost daily, we hear of promising novel drug candidates celebrated in newspapers. But in many cases, that ends up being the first and the last time we hear about them. Developing a latent breakthrough into a good business project is just as important as making the discovery in the first place. And process development and manufacturing play a key role in minimizing costs and optimizing quality attributes to transform the good science into a good business. At the end of the day, a medication should not just be safe and effective, but also affordable.

How do you help customers?

GenScript ProBio offers one-stop development and manufacturing solutions designed to get drugs to the market fast and affordably, while meeting necessary regulatory and quality guidelines in the US, EU, China, and APAC. We work with customers all the way from cell line development to process development to GMP production. In cell line development, we transfect plasmid DNA into a host cell genome and then screen a large number of clones to select the best one based on productivity, chronology, and stability. Once identified, each hit is confirmed, validated, and characterized using a variety of functional assays. Upon completion, we expand and scale up the single best clone, then optimize additional downstream processes before moving into GMP manufacture for clinical studies.

GenScript ProBio has performed around 200 elite optimization projects and 50 CMC projects, including projects that have obtained IND approval.

What are the main challenges faced during process development?

One clear challenge is maintaining productivity at scale. Better productivity means a high yield; a higher yield means more product per batch; fewer batches mean lower prices. Another challenge is batch failure and contamination. It is vital to have a strict and robust process over the entire course of manufacturing. Fed-batch cultures have a success rate of over 90 percent, whereas the spin filter perfusion approach has a much lower success rate due to the extended culture periods increasing the risk of contamination.

And, of course, cost is often a concern. In GMP production, my advice is to carefully gauge the quantities you need for each step of your development. For example, at the IND filing stage, you might want to manufacture just a bit more than you need for phase I, so that you can use that buffer for the PK/PD/tox studies. This way, you can hedge the risk of overproduction in case you don’t succeed.

Every molecule is different. Although working with an established and proven set of cell lines and processes is considered best practice, it’s important to be open to experimenting as much as possible when it comes to upstream process development like media and cell culture conditions, so that you can make informed decisions on maximizing productivity and robustness. GenScript ProBio offers “in process consulting” to ensure our clients make the best decision at each step based on data from previous steps.

What investments have you made to increase capacity?

From a production point of view, we will make an additional 2,200 L available by Q4 of 2020, and are building new global commercial production capacity that will be tens of thousands of liters in size by late 2022.

As well as conventional development and manufacturing services, we now offer regulatory consulting and documentation services that are not typically offered by CDMOs.

As a CDMO, it is important for us to grow with our customers. We have served our customers well throughout development and into clinical manufacturing, but the new capacity will allow us to help our customers be ready for global commercialization of their products.

How has COVID-19 affected business?

COVID-19 does not affect our supply chain as we have global operation in CDMO perspective and we keep up our promise to serve our customers as planned. We are also collaborating with many different companies on COVID-19 solutions and working on a number of drug development and manufacturing projects in this area.