By Anna Rose Welch, Director, Cell & Gene Collaborative
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As the past few years of the pandemic have clearly demonstrated, reaching millions of patients is possible when there is multi-stakeholder buy-in and a well-funded and organized manufacturing infrastructure. In the cell and gene space, the good news is that investments in the supportive manufacturing infrastructure are in vogue. The industry’s desire and ambition to reach patients across oceans and continents is also strong. However, COGS remains a limiting factor to earlier and global patient access. That’s why it’s a particularly exciting time to be watching the manufacturing space unfold; companies are dedicating significant brainpower to determining how to reliably and cost-effectively manufacture CGTs in a variety of countries.
One such company is Wugen, which has established a partnership with Shanghai-based Alpha BioPharma to advance Wugen’s allogeneic cell therapy pipeline in several Asian countries. As you can only imagine, this adds additional layers of manufacturing and regulatory complexity for a company striving to establish and scale-up a manufacturing program — especially when that manufacturing process was originally developed within an academic lab.
I was excited to transition my conversation with Ken Chrobak, Wugen’s VP of CMC, from the nuances of working with NK cell culture to the steps he and his team are taking to establish a consistent manufacturing framework that can span oceans and continents.
When I asked Chrobak what it takes to adapt an academic process to one that is more commercially viable, he presented a mind-bogglingly long list of tasks that are, no doubt, much easier said than done. Some of these (multi-faceted) steps include closing and/or automating certain previously manual processes; continuing to fine-tune the expansion process to address and eliminate donor-to-donor variability arising at larger scale; and bulking up and qualifying the analytical package.
“These aren’t show-stopping challenges, but it is still a lot of work to dot all the ‘I’s’ and cross all the ‘Ts,’” he added. “Because this was based on a process that was previously performed by the same operator at a single clinical site at Washington University in St. Louis, we need to make sure that we have a replicable process regardless of who is making it — especially once it’s transferred to CDMOs or facilities overseas that may have higher turnover rates.”
Though consistency is the hallmark of a mature manufacturing paradigm in any nation, establishing this consistency as early as possible will also help the company realize its global commercialization goals. While some countries may permit a product to be manufactured in the U.S. and imported, other countries — for instance, China — require a local manufacturing presence. In these situations, the processes will need to be rigorously developed and documented so that they can and will be performed in the exact same way overseas.
This consistency also hinges upon several other critical factors; for example, Chrobak and his team will need to ensure the necessary raw materials and equipment can be imported or secured locally. (This can be particularly challenging on the raw material side of things, depending on the country.) Equally important, the company needs to evaluate whether the supportive infrastructure for servicing equipment and training operators exists — or will exist — within the country, as these factors also strongly influence the quality of the final product. Hiring consultants and establishing partnerships with vendors that have global distribution centers or facilities overseas are just a few of the steps that have and will continue to be taken as the company’s pipeline advances.
Overall, of all the big steps the company needs to take to achieve a commercially viable manufacturing platform, there is one task that Chrobak singled out as being a top priority: “The more you can engineer the human component out of your manufacturing platform, the better off you are.”
However, to accomplish this finicky necessity, Chrobak emphasized the importance of maintaining a flexible mindset and embracing incremental improvement.
In the CGT manufacturing space, it can be easy to take Ralph Waldo Emerson’s words, “Hitch your wagon to a star,” to heart — especially when establishing the long-term goals for your manufacturing platform. Closing and automating your process is one such goal that must be balanced with the “need for speed,” Chrobak qualified. In some situations, manual processes are more appealing and manageable to navigate when facing an aggressive timeline — especially when the only other (more time-consuming) option may be designing and securing a customized piece of equipment.
In talking to Chrobak, I was reminded of a phrase that was near-and-dear to my heart in my past life in the biosimilar space: companies were often advised to embrace a “step-wise approach” when developing their product. Chrobak’s repeated emphasis on gradual growth toward the company’s commercial — and eventually international — process is the perfect embodiment of a “step-wise” CGT approach.
“When you write your IND and you start a clinical program, you haven’t necessarily established your commercial platform yet,” he concluded. “There are opportunities to constantly improve. So that’s going to be our philosophy: we establish a process that not only works but that we know is safe, because the safety of the patient and the sterility of our product are our top priorities. But we also know that we’re going to expand to larger scales in the future, meaning that we can and will close any gaps we identify along the way as our company, our pipeline, and the CGT industry as a whole grow.”
In our fourth and final piece together, Chrobak continues to discuss the benefits of embracing a “step-wise approach” mindset when developing a CGT manufacturing platform.