Overcoming Bottlenecks in Personalized Medicine Manufacturing

In a video interview with Pharma Commerce, Jason C. Foster, CEO of Ori Biotech, describes how the current state of cell and gene therapies (CGTs) shows promising potential, particularly in curing cancer and rare diseases. These therapies are safe and effective, with evidence demonstrating their curative capability. However, their widespread adoption is hindered by challenges in manufacturing at large scales and at affordable costs, limiting patient access. While three CGT products have advanced from last-line to second-line therapies, the number of patients receiving treatment has remained relatively unchanged, signaling that access, not prescription willingness, is the primary issue.

Only about 10,000 patients were treated with CGTs in 2024, out of a much larger global pool of patients who could benefit, with access in the United States at just 20%, and far lower in other regions. The real obstacle is the inability to produce these living, often personalized therapies at the scale needed for broader distribution. Many existing production processes rely on outdated technology that cannot meet the demand or provide the level of access needed.

This situation creates a vicious cycle: limited access leads to doubts about the commercial viability of these therapies, affecting investment in future innovations. CGTs cost billions to develop, and investors and companies require financial returns to continue funding new therapies. If the therapies cannot reach the market or gain sufficient coverage, the commercial future of CGTs is uncertain, risking investment in this area and potentially diverting capital to other treatment modalities. Overcoming these manufacturing and access barriers is crucial for unlocking the full potential of CGTs and improving patient outcomes globally.

Foster also comments on the manufacturing bottlenecks; regulatory hurdles; role of automation; and economic and healthcare system challenges pertaining to CGTs.

A transcript of his conversation with PC can be found below.

PC: What are the primary factors causing manufacturing bottlenecks in this space, and how can the industry overcome them in order to scale up production?

Foster: There're really three problems that need to be solved simultaneously, Unfortunately, it's not just one. Throughput is one, so how many doses can we just physically manufacture? There are costs, because obviously high cost of goods often drives high prices to the end payer. The third is quality.

We need to make sure that we're addressing throughput, costs, and quality all at the same time. If you only address one, let's say we can make lots of products, but they still are half a million to $5 million a patient, it’s still going to be difficult to get access. Maybe we can address costs, but if we can only make 10s of products or hundreds of products, we're not going to treat more patients. It's this kind of ability to address all three of those things that’s just truly required. So ultimately, the bottlenecks in the process consists of a couple unique factors. Obviously, we discussed that this is a circular supply chain. It's a personalized medicine that starts with a patient and ends back with that same patient. That's totally unique, because there's nothing we've ever had to face before. When you're stamping out tablets putting them in bottles, and sending them to pharmacies, that's a very kind of well-established and understood supply chain. Similarly, with biologics, we figured that out, but those are generic, not with a capital G, but a little G. They can apply to any patient. That same medicine goes to all the patients, and it's universally applicable. In this case, if you make a product for you, it's no good for me, and that has its own implications, because we have to make sure and get back to that exact patient and there's a lot of steps along the way.

The true bottlenecks today are several-fold, so that circular supply chain is challenging. It's not insurmountable, but it's challenging when you have to harvest the patient cells in one country, freeze them, transport them to an airport, fly them halfway across the world, process them for three, four, or five weeks, freeze them, and fly them back. That kind of logistics increases the complexity and cost, but as we look to the throughput question, how we just get more doses through the system, it's really the part of the process that is the bottleneck. When you're making a CAR-T therapy as an example for you, we would take your patient, your immune cells. We'd freeze them. We'd send them to a manufacturing facility somewhere. We would thaw them. We would choose the cells we want. We'd select them, and then we would wash and concentrate. All of those steps in the upfront that we're preparing the cells, getting them ready, that takes about six hours or so.

The next steps include the activating of the cells to get them ready to grow, the genetic reprogramming. You'll be very familiar with the challenges around viral vector manufacturing and how we actually create a CAR-T cell, in this case, out of a T-cell, which has to do with it, the DNA, the transfer from the viral vector, and then the expansion steps. Upfront took about six hours. That bit takes about 240 hours, so 10 days or so. And if you look at the bottleneck, something that takes 240 hours, clearly is always going to be the bottleneck, if you've got six-hour processes running. So what we need to do—and what the IRO platform that Ori has launched recently intends to do—is address that core bottleneck, those steps that are the longest, the most labor-intensive, and the most expensive. If we address that bottleneck well, which we think we are able to certainly help—and I'll tell you why I think that, and how that works exactly—addressing that bottleneck alone can move us 10x higher throughput. So we get the same footprint, the same clean room, and we can make 10 times the number of doses, while at the same time cutting cost of goods by 50%.