Breaking Down Regulatory Challenges in Cell Therapy Production

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 Many existing production processes rely on outdated technology that cannot meet the demand or provide the level of access needed.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: How are regulatory hurdles impacting the advancement of CGTs, and what changes would you like to see along that front in order to accelerate patient access?

Foster: I think on the regulatory side, the regulator has been incredibly supportive of advanced therapies and rethinking the way to conduct business as usual. They've offered to combine Phase I, II, or Phase III together, so that we can get faster through the clinical trial process. As an example, thinking about the ethical concerns around double-blind, placebo-controlled trials in late-stage cancer patients—it’s probably not ethical to put some of them on placebo, so they've been quite forward-looking and forward-thinking.

Recently, the US FDA has put forward something called the Advanced Manufacturing Technology designation, which will allow platforms like Ori’s to essentially put a master file, a dossier, in with the agency. They'll review it, and they'll be aware of the system, which will help speed up the application for companies that are using it, ultimately trying to get those products to patients more quickly. I think the regulator has been very supportive of the industry, and Peter Marks and his team at CBER (Center for Biologics Evaluation and Research) have done a great job in my opinion.

There's a couple things still left to do I would argue, globally and also within the US market. One is this idea of comparability is still kind of a question mark. Not to get too technical, but let's say we put a product in (Product A) and we say, this is how we're going to make it. We're going to make it using these tools and this process, and that's generally what your dossier says. It says it's effective and safe for patients to do it this way. If you want to change something about that process, the perceived bar is very high, so if I'm using a 15-year-old technology but better technology comes out, my ability to switch from one to the other is very difficult, and it's seemingly very high-risk, and the bar is quite high, because we have to show the process is comparable. If we improve it too much, it becomes a different process, and you have to go back and start over—do your critical trial over again—which logically doesn't make any sense, but it's the way the regulatory construct works. This ability to take advantage of new technologies is very difficult, and so we're stuck with these old, decades-old processes with decades-old tools that aren't performing. They aren't delivering enough doses for patients, they aren't delivering cost-effective therapies to the market. I think that transition process, the definition and the understanding of how to transition to a newer process that is better in various ways, and how to smooth that, is a way that the regulator could certainly help us solve that market access problem and scaling up these production processes. That’s one way.

Another way, I would suggest—and this has been debated for years and years—is obviously therapy developers go through essentially the same process to get a drug approved in the US, and then they have to do the same thing in Europe, and then maybe they have to do the same thing in the UK, and then maybe they do the same thing in Australia. But effectively, they're using the same processes. They're looking at the same criteria. Is it safe? Is it effective? What does the clinical data look like? What a gigantic waste of resources and time. You have patients that are literally dying on the waiting list, but having each regulatory authority set slightly different rules—but also with the same end in mind—it just doesn't seem like a good use of all of our time and all of our skills and efforts. Some sort of a mutual recognition, which has been discussed for many years, I think would be quite helpful.

And then the last I would offer up is that circular supply chain we discussed—where your cells might get on an airplane and fly halfway across the world—that kind of logistical complexity will never scale. If you have to transport cells via airplane here, there, and everywhere, it's always going to be expensive, it's always going to be complicated. It's never really going to be super cost-effective, where you could have this as a first- or second-line therapy. We've talked a lot in the industry about distributed manufacturing, so instead of having a centralized facility where all the cells come in from all over the world, you might move those facilities out in kind of a hub-and-spoke model, closer to the patient, closer to the hospital, minimizing logistics time, minimizing complexity, so that we cut vein to vein times for patients. These are very sick people at the end of the day, and they need their therapies quickly. This idea of distributed manufacturing has taken hold in the hearts and minds of the industry, but the how to get it done, what it really looks like, and the how do we sort of think about this from a regulatory perspective hasn't really been clarified.

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: How are regulatory hurdles impacting the advancement of CGTs, and what changes would you like to see along that front in order to accelerate patient access?

Foster: I think on the regulatory side, the regulator has been incredibly supportive of advanced therapies and rethinking the way to conduct business as usual. They've offered to combine Phase I, II, or Phase III together, so that we can get faster through the clinical trial process. As an example, thinking about the ethical concerns around double-blind, placebo-controlled trials in late-stage cancer patients—it’s probably not ethical to put some of them on placebo, so they've been quite forward-looking and forward-thinking.

Recently, the US FDA has put forward something called the Advanced Manufacturing Technology designation, which will allow platforms like Ori’s to essentially put a master file, a dossier, in with the agency. They'll review it, and they'll be aware of the system, which will help speed up the application for companies that are using it, ultimately trying to get those products to patients more quickly. I think the regulator has been very supportive of the industry, and Peter Marks and his team at CBER (Center for Biologics Evaluation and Research) have done a great job in my opinion.

There's a couple things still left to do I would argue, globally and also within the US market. One is this idea of comparability is still kind of a question mark. Not to get too technical, but let's say we put a product in (Product A) and we say, this is how we're going to make it. We're going to make it using these tools and this process, and that's generally what your dossier says. It says it's effective and safe for patients to do it this way. If you want to change something about that process, the perceived bar is very high, so if I'm using a 15-year-old technology but better technology comes out, my ability to switch from one to the other is very difficult, and it's seemingly very high-risk, and the bar is quite high, because we have to show the process is comparable. If we improve it too much, it becomes a different process, and you have to go back and start over—do your critical trial over again—which logically doesn't make any sense, but it's the way the regulatory construct works. This ability to take advantage of new technologies is very difficult, and so we're stuck with these old, decades-old processes with decades-old tools that aren't performing. They aren't delivering enough doses for patients, they aren't delivering cost-effective therapies to the market. I think that transition process, the definition and the understanding of how to transition to a newer process that is better in various ways, and how to smooth that, is a way that the regulator could certainly help us solve that market access problem and scaling up these production processes. That’s one way.

Another way, I would suggest—and this has been debated for years and years—is obviously therapy developers go through essentially the same process to get a drug approved in the US, and then they have to do the same thing in Europe, and then maybe they have to do the same thing in the UK, and then maybe they do the same thing in Australia. But effectively, they're using the same processes. They're looking at the same criteria. Is it safe? Is it effective? What does the clinical data look like? What a gigantic waste of resources and time. You have patients that are literally dying on the waiting list, but having each regulatory authority set slightly different rules—but also with the same end in mind—it just doesn't seem like a good use of all of our time and all of our skills and efforts. Some sort of a mutual recognition, which has been discussed for many years, I think would be quite helpful.

And then the last I would offer up is that circular supply chain we discussed—where your cells might get on an airplane and fly halfway across the world—that kind of logistical complexity will never scale. If you have to transport cells via airplane here, there, and everywhere, it's always going to be expensive, it's always going to be complicated. It's never really going to be super cost-effective, where you could have this as a first- or second-line therapy. We've talked a lot in the industry about distributed manufacturing, so instead of having a centralized facility where all the cells come in from all over the world, you might move those facilities out in kind of a hub-and-spoke model, closer to the patient, closer to the hospital, minimizing logistics time, minimizing complexity, so that we cut vein to vein times for patients. These are very sick people at the end of the day, and they need their therapies quickly. This idea of distributed manufacturing has taken hold in the hearts and minds of the industry, but the how to get it done, what it really looks like, and the how do we sort of think about this from a regulatory perspective hasn't really been clarified.