Transforming the Treatment Landscape with Tailored Therapies
Patient outcomes are transforming, thanks to innovative, curative, tailored therapies; however, industry needs to address a few pressing issues to ensure the huge promise of these drugs can be achieved.
Traditional blockbuster therapies — high-volume, broad-scope drugs — are being rapidly superseded by high-precision, niche therapeutic platforms that target specific genetic pathways. While this innovative shift toward tailored therapies, such as autologous chimeric antigen receptor T-cell therapies (CAR-T), is providing curative possibilities to patients, there are also various complexities, such as potential discrepancies to access, cost-effective manufacturing solutions, and regulatory harmonization, that need to be resolved to ensure further advancement of the field is successful.
During the latest From Stem to Stern episode, Stuart Lowe, Head — Advanced Therapies at TTP, and Professor Gerhard Bauer, member of the board, Autolomous, Former Director of the UC Davis Good Manufacturing Practice Facility, Founder and President of GBauerGMP LLC, Cell and Gene Therapy, sat down with The Pharma Navigator to offer their insights into the field of tailored/personalized therapies.
Click above to view the video panel discussion or read on for more…
An Era of Innovation
TPN: Drawing upon your experiences, could you reveal what you believe is the reasoning behind the shift by industry into more niche treatment platforms versus the traditional broad-scope blockbusters and also highlight how this shift is impacting the industry?
Lowe (TTP): Yeah, sure, that’s quite a broad trend that you've identified there about the reduction in Blockbuster drugs! I would say, drug development has gotten harder over recent years, and the ‘one-size-fits-all’ drugs are quite rare now. What the dynamic seems to be is that new drug candidates might only be effective for a small segment of the population — maybe you're targeting a specific gene or a specific pathway — and essentially, it's just got more personalized.
I suppose what that means for innovators is that they’re allowed to target those smaller segments of the population. For example, autologous CAR-T, are actually based on a patient’s own immune system, so, can it get more personalized than that? But, this trend has spawned an entire industry, which now has thousands of therapies in trials. So, the shift has actually been really good for overall innovation.
Bauer (Autolomous/UC Davis/GBauerGMP): Let me follow up on that: This is a very important topic that we are touching on. Imagine, 20 years ago, many people were dying of hematologic malignancies, blood cancers, they were just dying. These patients went through many rounds of chemotherapy, they had a miserable life, and, at the end, everybody knew what the outcome would be. This shift to more niche platforms has completely changed the paradigm of having to die from hematologic malignancies, because with individualized therapies, CAR T-cell therapies, we can actually cure people, and this has now been shown over the last 15 years. We have seen people survive over the past 15 years, and live a normal life, and I am so entirely grateful for that.
This ability to cure is the innovation. These therapies are not ‘off-the-shelf’ drugs, they are a completely new development and were actually spawned by academia, which then were taken over by industry and industrialized to bring the therapies to patients. But we are not completely done yet! There's so much more we need to do with these new individualized therapies: More research, more applications, and more broad diversity of such treatments.
The Importance of Improving Accessibility
TPN: Given that we are looking at more curative options now rather than developing a drug that will potentially be taken for a long time, how should companies define the long-term value of these personalized/tailored therapies while also managing to keep costs reasonable?
Bauer (Autolomous/UC Davis/GBauerGMP): Yeah, I was in the middle of this dilemma. So, first, in academia, we tried to develop these therapies for clinical trials. Clinical trials are limited, and of course, they also don’t always provide the full picture, because you often select certain patient populations. But when the therapies became more broadly available, and many more patients would be eligible for treatment, it was found that the therapies are way too expensive. However, the expense has something to do with providing a quality product that has undergone the appropriate testing — which is important because you don't want to harm anybody, particularly when it's a novel treatment as that can set back a field and we don't want that.
Now, we have to think very carefully about how we want to really make this available to many more patients, and possibly worldwide. We have a discrepancy currently between countries that can't afford such therapies, and countries that can afford them. We have a discrepancy between insurance providers that will pay for the therapies and those that will not. We want to close that gap. It is going to be a very important aspect of our industry to get together, find ways to improve manufacturing, make it cheaper, but not letting the quality slide, and making sure that everybody has access to these therapies in the end.
Lowe (TTP): Agreed, and actually, to pick up on what Gerhard was saying earlier about the patients, if you think about that treatment journey — where you're having to go through many rounds of chemo — you might have to do a second line, or you might have to do a third line of treatment. These novel therapies are curative, and people need to price that in a new way, or healthcare systems probably need to think a little bit differently about the value of these therapies. If you think about it, you're replacing almost a lifetime of care with a kind of single shot. It's almost like a shotgun that has a very precise ability to remove disease. So, why shouldn't that sort of approach be smoothed over many years? Why can't we have installment-based payments? Why can't we say, ‘actually, you do need to prove long-term efficacy of the product in order to get the full reimbursement for it’? And those are exactly the sort of models that people are looking at right now.
It’s just that kind of contrast, which Gerhard put so nicely at the beginning, between what it used to be like, that kind of chronic, long-term treatment pathway, with this one shot up front; but, if we can find a way to highlight that the value actually looks really good — because suddenly you're not having to get people come to the hospital, travelling several times a month, and suddenly you're not having to source and store a load of drugs — it's actually much better overall for the healthcare system. So, I think, in the future, we'll find that these therapies actually free up a lot of resources, it's just that people are not used to this way of treating disease right now.
Managing Manufacturing Costs with Automation
TPN: Manufacturing is intrinsically linked to costs, so, in terms of personalized/tailored therapies, what are the biggest hurdles to managing the costs of their manufacture? Are there any specific approaches or technologies that are helping companies in this area?
Bauer (Autolomous/UC Davis/GBauerGMP): I want to start bringing you back many, many years again, to how we manufactured these therapies in academia: We had a flask, a tissue culture flask, where you actually had a screw cap, and you had to pipette in a biosafety cabinet. We had a smaller flask and a bigger flask, and we grew the cells in there and looked at them under the microscope. This work was all done in an open system, because you have to open up the flask — you have to pipette it in, and then pipette it out — and this was extremely time-consuming. Of course, the work was dependent on really well-trained personnel that had very good sterile techniques, so nothing was done to contaminate the flask and the culture, and then testing was required, also by hand, and all of that was a two-week process. This sort of work took skilled personnel from the university and then I also needed to look over everything at the end for quality control (QC) and quality assurance (QA).
Now, take that process and move it over into industry, do you know how much that costs? Also, once you have received regulatory approval, you have to keep the same process that was used when applying for approval, so, you’d have to have that open system, all the way through to the end. And you have to try to manufacture these treatments individually for each patient, which is almost impossible to do!
So, you have to think about how you're going to automate the process: What are you going to do to make the process reproducible? How can you bring the cost down in a way, so you apply the same procedure, but, of course, with the different cells from different patients. And now you need an automated quality control system too, so automated batch records. Batch records are something that are necessary to perform reproducibly, they’re written down, so make them electronic and you can make volumes easier to manage. If you can follow the procedure by just looking at an iPad, or something similar, in a laboratory, then you can automatically check off different parts of the process and have an automated inventory control, for instance.
What automation really boils down to, the most important aspect, is the less human intervention you have with manufacturing, the better it will be for the outcome of the product.
Lowe (TTP): I couldn't agree more with what Gerhard's described. I'm all for helping to remove that kind of operator variability from the process, it's easier to say than it is to achieve in practice, though! However, there are actually a lot of cell-based tools in development, which can handle fragile cells — better cell sorters for fragile cell analytics, image recognition using machine learning and artificial intelligence (AI) to help to stage those incubations.
Thinking about a specific example where we've seen a real impact of automation is in the closure of open processes. So, exactly how Gerhard described, you've got people working in an isolator, if you think about how much those rooms and how much that equipment costs per square foot, it really doesn't make any sense at all for you to be running an industrial process in that area. What you can do instead is have a process that is intrinsically not exposed to the atmosphere, and then you can move that into a completely different, lower-grade cleanroom with lower costs. And this is exactly what we identified with a company that we're working with where there were several different steps of the process, but by incorporating these into single-use disposables, it was possible then to load, leave the room, wait for the process to complete, and then come back and take the product off.
That’s the sort of transformation that automation can achieve — bringing down facility costs, taking out the variability, improving standards, and removing labor from the process. Ultimately, these changes will transform the way that tailored therapies scale, which is really quite exciting.
Possibility of Decentralized Manufacturing
TPN: There has been increased discussion about point-of-care manufacturing as well for these bespoke therapies, but what are the key quality risks associated with this type of manufacturing and how can they be mitigated to ensure patient safety?
Lowe (TTP): It is possible to move away from a very centralized, controlled manufacturing process, when you've been able to train every single operator on the process, and they're all experts. Whereas, I think there is a paradigm where operators are actually able to produce these therapies without needing that sort of training, right? So, we might have people who are not trained in GMP manufacturing, who aren't trained in keeping the environment clean, who don't necessarily have the kind of the regulatory nous.
The solution in the latter instance, and you won't be surprised to hear me say it, is automation. If you have a system that does the same thing every time, with very minimal user intervention, you reduce the need for upskilling, you close the process — so you don't have to worry about the environmental contamination — and all of the quality and regulatory oversight is baked into the fact that the instrument is logging what it's doing — recording and creating digital records.
Bauer (Autolomous/UC Davis/GBauerGMP): Let me play devil's advocate. Decentralized manufacturing is all very nice and good, as long as it works. The moment something goes wrong, and you have an untrained person, you're playing with the life of a patient. Please keep that in mind. You are producing an individualized product for a person. You want to make sure that the product that you're making can go into the patient in spite of any little issues that could arise, we must think of that.
Therefore, I think decentralized manufacturing is a double-edged sword. It's very nice to try and put manufacturing into a decentralized location, maybe right next to the hospital, or in the hospital, and trying to automate this so that you just have to put a bag into a machine, and out comes the final product. I don't think manufacturing is going to happen like that, because it's too dangerous. If I were a patient, I would like to have somebody with knowledge overlook that product, making sure that the product is properly manufactured.
So, I think we’ll have a combination of approaches. We're going to have places of excellence, I believe, where therapies should be manufactured. There may be many places of excellence, because now we can actually afford it as we may not need to build such an expensive cleanroom and we can manufacture in a lower-grade environment, for instance, ISO 8. Additionally, we're going to have a closed system, and we're going to have a wonderful product that's going to be coming out, which is really good at the end, for which we must have quality control and quality assurance.
On the quality point, I have another issue in that it is not standardized at the moment. We must standardize our QA/QC on such product manufacturing, and this can only happen with an electronic system, it is not possible on paper. There are systems out there where we can use a standardized protocol, standardized quality control, batch records, and everything. We need to share those systems with everybody else so we get onto one common denominator, and that would also help us to continue in the right direction.
In summary, it's good to think about decentralized manufacturing, maybe in the far future it's even possible, with a lot of AI oversight — AI can actually replace some of this quality control that's being done with humans currently — but it's going to take a little while. We also have to make sure that we are standardized with our procedures.
Greater Harmonization Required
TPN: How are the regulators adjusting for the niche target audience of these personalized therapies so that they can perform an appropriate evaluation?
Bauer (Autolomous/UC Davis/GBauerGMP): They're not at all! I have seen over the past few years, actually, a divergence of all the regulatory affairs everywhere. Nowadays, Europe and the UK are talking a little bit, but also sometimes not; America and Europe are not talking and neither are we talking to Asia or Australia. So, what is happening currently? Everybody is trying to do a very good job, in their own way, but is that going to be helpful for everybody? I don't think so.
In the long run, we will need to get to a point where we actually can harmonize our regulatory affairs. What we would like to do, in the industry, is to produce a product that you can export to other countries, or we want to import other things from other countries, which is not so easy at the moment and has become even more difficult.
So, I would say regulation is something that we absolutely need to work on, this needs to be harmonized, and we need to, again, find ways to infuse a system electronically, that will allow us to regulate harmoniously even better.
Lowe (TTP): It’s a real shame that there isn't more harmonization, because the opportunities are fantastic. I was talking to a rare disease executive the other day, just after the news about baby KJ came out (1), and he was so excited about the opportunity to turn an N of 1 into a more standardized process that could be regulated like a platform. I mean, to standardize the process would involve approving the diagnostic pathway — you'd have to feed it into the therapy design and think about where and how the manufacturing is done — so, it's not an easy thing to regulate, but with the right frameworks, it could be possible.
I'm hoping that some of the bigger players, who are well invested in personalized therapies, could have that level of influence with the regulators across the world. Essentially, what they want, and what we all want, is the ability, if somebody's come up with a really innovative pathway that enables this almost miracle cure for an individual, to kind of pick that innovation up and place it in a different jurisdiction without having to reinvent the wheel.
What the Future Holds
TPN: Finally, what do you anticipate is going to happen over the course of the next couple of years in terms of personalized/tailored therapies?
Lowe (TTP): I'll pick up from what I was saying about the potential, I think the benefits of personalized therapies are way too significant to be ignored, what is happening is that the industry is maturing. If you look back at monoclonal antibodies, it took decades to solve their commercialization challenges, and in the advanced therapies industry, we're already seeing end-to-end platform automation companies. What needs to catch up, I think, is maybe the next generation of manufacturing equipment that goes into these platforms: they need to be smarter; they need to be automation-friendly; and they need to be able to cope with the full diversity of cell therapies that are coming out.
I'd say, if I'm kind of giving advice and saying what I'd like to see, then it’s automation baked into the design of these processes and a bit of future-proofing. So, that process needs to be able to adapt to a new type of equipment coming out, or a new analytical technique for the for the QC. Embedding that level of flexibility in some of these systems is really important. And, just finally, to talk about cross-disciplinary collaboration, so you'll hear Gerhard from an academic background and immunology, and I'm a physicist, but both trying to tackle the same challenge. I think it is going to take this level of cooperation in order to solve some of the fundamental problems in scaling for the industry.
Bauer (Autolomous/UC Davis/GBauerGMP): I'm a filmmaker and I like to talk to a lot of people with my films, and I have done this in a way so that people can understand what I'm talking about visually. So, I like to apply a very similar approach in cell and gene therapy. I'd like to tell everybody what the advantages are to produce an individualized therapy, and what we can do, because it's curative in many ways. It's all new, but it's going to be marvelous what we can achieve in the future.
Also, there's something called Act for Hope coming, which is an initiative built by Autolomous (2). This collaborative initiative is trying to get everybody together to brainstorm to find out what we need, what needs to be made, and then, I think, in the long run, we want to make equipment, materials, and reagents that everybody can use in a standardized fashion. If we can achieve this standardization and we can really implement the process that we have so painstakingly developed together, everybody should profit from that, and profit in a way that we can actually treat the patient and cure the patient.
References
Ledford, H. The Baby Whose Life was Saved by the First Personalized CRISPR Therapy. Nature, News Feature, Dec. 8, 2025.
Act for Hope. The Story Behind Act for Hope. Article, Sept. 11, 2025.
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