CGT manufacturing challenges and opportunities

The cell and gene therapy (CGT) space is something of a mixed bag. While CGT is one of the most exciting therapeutic modalities driving the biopharma space forward by offering personalized, transformative therapies, this sector still has hurdles to overcome before it can be widely commercialized. Major roadblocks in this space include a lack of standardization, steep manufacturing costs, and other challenges related to making products efficiently and at scale.

In the latest episode of Off Script: A Pharma Manufacturing Podcast, we explore what’s driving progress and where the industry is still lagging with Sharon Anderson, VP of Scientific Affairs at the Alliance for Regenerative Medicine. With more than 20 years of leadership experience across cell therapy, immuno-oncology, and manufacturing operations, Sharon brings a unique perspective on the future of the CGT sector. 

During the conversation, Anderson provided her perspective on balancing the need for standardization and scalability while maintaining the personalized nature of the treatments, the pros and cons of centralized and decentralized approaches to manufacturing, and how emerging technologies like automation are paving the way for an efficient future for manufacturing these therapies.

The following interview with Anderson has been edited for clarity and flow:

Andy Lundin: With such an extensive experience across both scientific and operational leadership in cell and gene therapy, you bring a unique point of view to where the field is headed. So, from your perspective, how has the manufacturing landscape evolved and what are the biggest shifts you’ve seen in terms of technology, scale, and quality expectations?

Sharon Anderson: A lot has changed over time and continues to change rapidly. When I first started, a lot of the technology was based on single operations done by manufacturing technologists who had to be highly skilled in biosafety cabinets. Now there’s new manufacturing technologies out there — things like automation — that really have improved cell culture, which is important for both the cell therapy and gene therapy side of things.

Some more recent advancements have included 2D and fixed bed bioreactors, which really help with adherent cell culture, closed system processing units—which are important for making these productions more feasible in less controlled clean room spaces — improved aseptic connections, and automation, like I mentioned.

The quality expectations are interesting too. I’ve seen a lot of improvements in inline monitoring, which helps us with alarming and responding to challenges in our processes. There are also electronic batch records, which is really a huge advancement for anybody who doesn’t want to lug around 20 lbs of paper to record a single operation. 

And with that we’re seeing shorter release times for products — the actual process of getting a product out the door — which I think is really important, both in terms of efficiency for the producer’s side of things, but also on getting those therapies back to our patients faster. And a lot of that is through improved release assays. 

There’s a lot of work that’s been done there, not just in terms of the accuracy of these assays, which has greatly improved, but also in terms of how quickly they can be performed and therefore how quickly the product can be brought back to our patients.

AL: One concept that I’ve been interested in is the paradox of building an industrial scale system for individualized therapies. How do you think manufacturers can balance the need for standardization and scalability while maintaining the personalized nature of the autologous treatments?

SA: I think no matter what autologous treatments will always be personalized. The important part is to continue finding economies of scale which will enable more patients to receive these treatments.

So, reducing variability of starting materials is important here and that really is done through sharing of best practices for quality collection of the starting material. Also, things like understanding the disease state and how it impacts the quality of those collections is important. We want to reduce the frequency of returning to a patient for more material as much as possible. It’s not great for the patient, it’s a more inefficient process for the producers, and it drags down the system, as a whole.

I think there’s a future not too far away where patients can receive individualized therapies that are not autologous, per se. For instance, Baby KJ this year received treatment that was designed just for him. There’s a basis for working toward a platform strategy that allows multiple patients to receive treatment for their specific needs and is not just designed for them.

I think that there’s a whole new world coming to us with these gene editing therapies that are made for one person’s specific mutation, but may apply to multiple patients.

AL: I’d like to talk a little bit about centralized and point-of-care manufacturing for cell and gene therapies. What do you see as the strengths and weaknesses of each approach, and do you believe that the hybrid model is the future of CGT production?

SA: There are strengths and weaknesses to each of these approaches. With a centralized approach you have the potential for higher consistency of manufacturing, and you have reduced fixed costs. Some of the weaknesses around a centralized approach, however, is that you know you have to ship your therapy, and shipments create risk. And if we’re talking about an autologous therapy, that might add time between when you’re collecting and delivering your therapy. And that time is important for our patients and it requires more bridging care.

From a point of care or decentralized approach, one of the strengths is that you can get a treatment more quickly. There are fewer risks for shipment, in terms of errors or delays that might occur, and you may be able to eliminate the need for cryopreservation. Any additional processing steps that autologous therapies have to go through are a potential risk for that product, either in terms of product quality or something going wrong. Anytime you can reduce a step, that’s critical.

On the weaknesses side for a point of care or decentralized approach, you do have additional fixed costs. You have these additional sites that need to be maintained, you need to have staff that know how to operate at each of these sites, and there’s a chance for risks; you could get some inconsistency because you have these multiple locations functioning at the same time. 

Now personally, I don’t believe that the hybrid model is a solution for every therapy. And how I look at it is that CGT is a bit like real estate. We must consider things like the location of your starting material, the location of your production capacity — that includes the space, workforce, and technology — and the location of your patient population and where they are going to be treated.

And as you’re evaluating each of these, each of the models will have merits and risks. Depending on what your product is and what your manufacturing approach is, you have to select the right one to be most efficient.

AL: Experts often point to variability and product quality as major bottlenecks to scaling. What kinds of analytical or process innovations are most promising in improving consistency across batches and sites?

SA: Variability is always a concern when we’re scaling. Personally, I’m super excited for things like automation, digital analytics, and biosensors.

I’ve seen firsthand how real time monitoring of CGT processes can save a batch. Those ongoing monitoring tools to control variability are super critical and I really think that there’s a lot to that.

I think in five to 10 years I could see the technology becoming even more automated. And I think that will happen in two ways, one of which will be the field as a whole learning these processes, more standardization, using consistent equipment, and that sort of thing. The other way will be through machine learning, which I think is an important potential future pathway and certainly one that the field is looking at as a whole to see if there are more efficient practices that can be done.

AL: What is the state of AI and machine learning in this space? Do you have a sense of what that looks like now and where it might be heading.

SA: I think it’s a little early to say, but I do know that now is the time to act on these technologies. On a smaller scale, we’ve already done modeling and simulation in terms of identifying efficient uses of available equipment. I know that modeling and simulation has been a very reliable tool that we’re currently using. So, in that case, the learning starts now.

AL: Given the complexity of CGT logistics, what are the most critical steps the industry needs to take to create a more resilient, patient-centered global supply chain?

SA: As a whole, CGT has a very complex global supply chain; there’s no doubt about it. For example, some materials that we may need for one of our processes may only be supplied through a certain country. The cost of goods of these supplies needs to be considered, as well, and resilient supply chains are important. 

We can’t get to a point where we aren’t able to deliver a product to a patient; our patients are relying on us. Not just for creating these hopeful and exciting solutions to their challenges, but also to provide them reliably.

Our patients count on us to be as efficient as possible so that the lowest point of entry is available for patients to receive therapies that could be very life changing.

AL: On the topic of cost of goods sold and barriers to patient access, what are some practical strategies or technological breakthroughs that could help drive down manufacturing costs without compromising safety or quality?

SA: I think an early understanding of what drives costs in your processes is really important. Once you’ve got a grasp on where costs being accrued in your process, you can start generating potential competition or alternatives around those costs.

A frequent source of costs are media, media that goes into either growing your cells or generating your cell lines that create your products. For media suppliers, I’d really encourage them to understand the feasibility of generating powder formulations of their proprietary solutions. Oftentimes, liquid solutions are leveraged early in a development process to get quick wins: get a product out the door, get some proof of concept, and that sort of thing. But these liquid or frozen liquid solutions are really difficult in terms of scaling and cost effectiveness. Because then you have to store and manage these really heavy shipments. 

As you get to a later phase commercialization, if it’s possible to have a powder formulation, encouraging your media suppliers to start those early I think is really important. It really drives down costs and allows you to have a better approach there.

Also important is identifying anywhere we can work with governmental agencies to promote the production of those critical raw materials. Earlier we talked about the importance of location, and a key location to consider is the location of your raw materials. Where are your starting materials coming from?

Let’s say you obtain a liquid raw material from the other side of the world and you have to ship it across the world to get your process done. That is really quite a challenge. And so, working with your own governmental agencies to promote the production of whatever is truly a critical raw material closer to your production facilities could help drive down some of those costs.

AL: As the Alliance for Regenerative Medicine works to advance the field, looking ahead, what does CGT 2.0 look like to you? What are the most exciting innovations or collaborative efforts that could redefine how we make and deliver these therapies?

SA: We’ve already had an exciting year in 2025. We had Baby KJ provide hope for advancing platform gene-editing technologies. We saw CRISPR editing in a commercial setting — we’ve got proof of concept and we’re generating further safety data — and we have some big wins around removing some of the restrictions around CAR-T, such as shorter duration requirements for patients to be close to their treatment facilities and reduction of driving restrictions. It’s all based on this improved knowledge of what we know CAR-T product delivery looks like and what it means for our patients. 

I see us building on that and continuing to see progress in these therapies. I think what’s next is we continue to see new disease states that we can affect positively. I see us using new methodologies, such as in vivo gene editing and hypoimmune cell therapies, that could help take us truly off the shelf for allogeneic instead of having to have patients, receiving immunosuppression to receive them. 

And then we’re seeing new regions stepping up. So new regions around the world being able to receive these therapies and so many more things. This field is super exciting. I’m excited to be part of the work at the Alliance for Regenerative Medicine to pull all of these really important stakeholders together and really unite us around the focus of getting these really modernized treatments out to our patients.