Unlocking The Future Of Cell And Gene Therapies
A conversation with BioPhorum members Dan Hurwit, Amine Djeffal, and Kathy Remington
Advanced therapies — particularly cell therapies and gene therapies — are experiencing rapid and sustained growth, driven by major scientific advances and an expanding pipeline targeting serious and previously untreatable diseases. These products are reshaping treatment paradigms by offering the potential for durable and, in some cases, curative outcomes. As clinical success builds and more therapies progress toward commercialization, advanced therapies are becoming an increasingly important pillar of modern healthcare systems.
However, this continued growth also highlights a significant opportunity and need for further regulatory and technological evolution. Many regulatory frameworks and manufacturing models were not originally designed for highly individualized, complex, and data‑intensive therapies. To fully realize the potential of advanced therapies at scale, ongoing improvement is needed in areas such as regulatory agility, manufacturing innovation, digital oversight, and life cycle management — ensuring patient access while maintaining safety, quality, and sustainability.
These challenges are being explored across the industry, including within the BioPhorum Advanced Therapy Medicinal Products (ATMP) collaboration. We took the opportunity to speak with some members of this collaboration by posing a series of questions to three experts — Dan Hurwit, senior principal scientist at BMS; Amine Djeffal, process expert, regulatory affairs at Sartorius; and Kathy Remington, technical consultant, Scientific and Regulatory Consultancy Group at Millipore Sigma — about issues such as emerging technologies, regulatory challenges, and engagement with regulators in the ATMP space.
Which emerging technologies are having the greatest impact on ATMP delivery and efficacy?
Advances in surface engineering — such as covalent antibody or ligand linkage or the surface expression of targeting moieties — are critical and naturally complement more traditional strategies like rational capsid engineering or directed evolution. Improved targeting expands reach, increases efficiency, and improves the safety profile of both viral and non-viral delivery vehicles.
On the biology side, many next-generation gene editing and gene delivery modalities enable safer, more precise, and increasingly complex edits. This includes multiplexed edits and tunable genetic circuits that better reflect the true biological complexity of disease. As our understanding of genetic disease deepens, we increasingly need tools capable of matching that complexity.
Product quality and consistency, meanwhile, ultimately hinge on a robust understanding of critical quality attributes. Developing that understanding requires extensive experimentation and deep analytics, making high-throughput process development coupled with automation a clear enabler.
The growing application of AI is accelerating progress across all of these areas, influencing design, integration, insight, modeling, and optimization, with natural load balancing across delivery, biology, and manufacturing. In this context, AI acts as a powerful force multiplier for the entire field. While all disciplines will benefit from AI, ATMPs may have the most to gain given the unique challenges around parsimony, knowledge management, and the sheer complexity of genetic medicine. The field remains young relative to monoclonal antibodies and small molecule pharmaceuticals, with less manufacturing experience, less long-term historical data, and less overall mechanistic understanding. AI is well suited to help bridge those gaps. It excels at drawing connections and, as it matures, it will become increasingly critical for understanding and managing biological and manufacturing complexity.
How are manufacturing processes adapting to improve scalability and cost efficiency for ATMP products?
HURWIT: There are four main ways this is happening. First, we are seeing processes move from academic protocols to scalable processes that more closely resemble a mature industry, which is helping drive broader adoption. Second, we are establishing platforms in the true sense of the word — platforms that allow us to accumulate, stack, and leverage legitimate knowledge with speed. Third is the application of lab and process automation, which is driving better space and resource utilization. And finally, there is the continued expansion and maturation of the CGT bioprocess workforce toward a true critical mass.
I think it’s worth noting that I do not see points three and four as being at odds. I don’t believe automation poses an existential threat to the CGT workforce. On the contrary, I think it helps preserve our future — and I think it’s necessary. Right now, the industry is facing a serious bottleneck. In principle, in the face of current and emerging opportunities companies could multiply their current workforces by five times and still have endless experiments to run, design spaces to explore, and new paths to pursue. However, current economic forces make this challenging, if not impossible.
As both the opportunities and the complexities continue to expand — right now, faster than ever — automation is how we actually rise to the occasion.
What innovations in analytics, digital tools, and quality control are essential for complex ATMPs?
HURWIT: To make better medicines, we need better insights, and that means better tools and bolder approaches. In short, we need more, different, cleaner, clearer, relevant data faster, and we need ways to readily access, query, interpret, and leverage it.
So, we need new analytical instruments with higher-fidelity and higher-throughput methods that translate to credible measures of productivity and quality. We need a deeper commitment to quality by design, where we “go strong to the hole” earlier to truly understand the most important attributes. We need automation to drive throughput, AI to accelerate insights, and the digital infrastructure that pulls all this together.
All of this is actually happening right now. It’s a bit chaotic, maybe even disorienting — but it’s happening in meaningful, if modest ways. As the ATMP space has entered into a phase of rapid maturation – more molecules entering later phases or going commercial, a critical mass of expertise focused on identifying and overcoming essential quality and cost challenges that are a filter for long-term viability of these modalities — and as digital tools and AI models grow exponentially more capable, accessible, impactful, and embraced day-by-day, we are on the cusp of it happening in a big way, and that’s very exciting.
What regulatory challenges remain most pressing for global ATMP approvals?
One of the main challenges is the lack of an early harmonized understanding of regulators’ expectations. There is often a constant back and forth with regulators to clarify their expectations. For ATMP products that often address rare diseases, a lack of harmonization delays the whole process of getting these critical medicines to patients. The FDA has recently announced a new, more flexible approach to CMC requirements; this is a step in the right direction, but the broader issue remains.
There is also the issue of different jurisdictions having slightly different requirements, which causes delays and increases costs. If the U.S. FDA, EMA, and the rest of the world had truly harmonized and clear expectations, it would make it much easier for manufacturers.
It is also important that developers think about the end game from the very start and consider topics such as scalability, variability in raw materials, and appropriate validation. Considering all of these, and more, will reduce timelines and make it easier to achieve the final goal.
All stakeholders — manufacturers, academic scientists, clinicians and regulators, etc. — also need to communicate early and regularly so that everyone is on the same page and moving in the same direction.
ATMPs are inherently complex and variable products, frequently characterized by short shelf lives, patient-specific manufacturing, and evolving processes as programs move from early clinical development to commercialization. Regulators across major regions continue to raise concerns when early-phase manufacturing strategies are not adequately designed with life cycle progression in mind, which can lead to significant delays at later stages.
To de-risk development pathways, early and continuous engagement with regulators is critical. This includes timely scientific advice on product classification, manufacturing strategy, and compatibility assessments. In parallel, clear alignment on potency concepts and expectations for release and stability testing, established early rather than retrofitted later, remains essential to support a robust and approvable CMC strategy.
How should developers engage with regulators early to de-risk development pathways?
DJEFFAL: Developers should make full use of existing regulatory support mechanisms early in development. For example, the FDA’s Regenerative Medicine Advanced Therapy (RMAT) designation and the EMA’s PRIME scheme or early CMC meetings provide structured opportunities to engage regulators well before pivotal development stages. These interactions are valuable not only for potential timeline acceleration but also for stress testing the development strategy against future commercial and post-approval requirements.
Early regulatory engagement should focus on building a shared understanding of the product’s critical quality attributes, anticipated process evolution, and the long-term control strategy. Rather than treating regulatory touchpoints as isolated milestones, sponsors should use them to demonstrate that their control strategy is robust, adaptable, and sustainable as the product moves from early clinical use toward commercialization.
Critically, the commitment does not end at approval. Once a product enters clinical use or reaches the market, maintaining regulatory compliance as processes evolve becomes a central challenge. Establishing alignment on CMC expectations early and revisiting those assumptions as the program matures remains one of the most effective ways to de-risk ATMP development pathways.
REMINGTON: The earlier we engage, the easier it will be. As mentioned, the FDA INTERACT, the EMA’s PRIME, and Innovation Task Force are all avenues that allow earlier conversations with regulators. These programs are great and we hope regulators will continue them and even develop additional routes to enable manufacturers to get the most appropriate advice for their stage of development. Regulators should have some flexibility and understanding that ATMPs are not like the traditional biologics that they have approved in the past. Manufacturers can also learn from each other's experiences. If they have similar products, being willing to be open and communicate with each other would also help.
Do you see any challenges or discrepancies between the FDA and EMA? And how should they be approached?
DJEFFAL: From a global development perspective, one of the key ongoing challenges is the lack of full harmonization across regulatory regions, particularly between the FDA and EMA. While major regions such as the EU, U.S., and Japan have established frameworks for ATMPs, meaningful differences remain in how products are classified, reviewed, and managed post-approval.
These discrepancies can affect expectations around clinical evidence, manufacturing and process changes, control strategy evolution, long term follow-up, and post-marketing commitments. For developers pursuing global approvals, this often results in duplicated effort, additional resourcing, and increased complexity when scaling manufacturing or implementing post-approval changes.
A particularly challenging area is the regulatory management of long-term safety and real-world evidence, especially for cell and gene therapies with potentially durable or permanent effects. Regulators increasingly expect robust long term follow-up strategies, including patient registries and post-authorization safety studies. However, practical implementation is difficult due to small patient populations, even when orphan designation is granted. This highlights the need for more decentralized care models and evolving healthcare infrastructure to support data collection.
Addressing these challenges requires early global regulatory strategy planning and sustained dialogue with agencies to align scientific and CMC expectations where possible. Continued collaboration between regulators, industry, and consortia such as BioPhorum will be essential to drive greater convergence, share best practices, and develop pragmatic solutions that protect patients while enabling timely access to innovative ATMPs — particularly for smaller biotech and academic developers with limited regulatory and operational resources.
What trends do you see shaping the ATMP landscape over the next three to five years?
HURWIT: ATMPs are still in their adolescence, so over this period we will continue to see an expanding suite of technologies. At the same time, there will be some honing and rebalancing as we’re poised for a pretty big influx of clinical data on the newest generation of cell and gene therapies.
With each new generation of therapies, we learn more about safety, efficacy, commercial viability, logistics, etc., and the cohort of drugs entering the clinic now or in the very recent past – i.e., the drugs that we’ll start having readouts on over the next three to five years – are all built on a lot more learning, and perhaps faced a lot more competition, than their predecessors. That’s not to downplay the difficulty or to pretend that there won’t be major letdowns and abject failures. It’s just hard to see the level and pace of engagement, innovation, learning, and progress and not feel bullish.
For some specific examples, I am really excited to see the rise of allogeneic cell therapies and the growing clinical data in both the in vivo and non-viral spaces. We are going to see ATMPs expand into a wider array of disease areas and more complex diseases beyond cancer, autoimmune diseases, etc. It is an exciting time to be in this space.