Unlocking the Potential of Next-Gen Therapies with Advanced Technology
The complexities of next-generation therapies are pushing the boundaries of development and manufacture, leading to an increased need for advanced technologies and novel approaches to processes.
Novel therapeutic modalities, such as cell, gene, and nucleic acid therapies, are offering more effective, personalized treatment options to patients with chronic and/or rare diseases that were, not too long ago, considered to be untreatable. The latest regulatory data (at the time of writing) confirm that approvals of these therapies have generally increased year-over-year, with 45 cell and gene therapy (CGT) products approved by FDA and 27 advanced therapy medicinal products (eight of which have been withdrawn or not renewed) approved by EMA since the noughties (1,2).
However, these “next-generation” therapies, while extremely promising from a treatment perspective, are more complex than traditional drug products, meaning their development and manufacture are inherently more challenging. “Next-generation therapies, particularly those in the [CGT] space, are pushing the limits of what our current manufacturing infrastructure can support,” explains Edwin Stone, CEO, Cellular Origins. “These therapies are incredibly promising, but they’re also incredibly complex. You’re not just making a product; you’re engineering a living, and often patient-specific solution. That introduces variability, tight handling windows, and need for rigorous traceability.”
A Personalization Complication
“Next-generation therapies are significantly more diverse and complex than traditional pharmaceuticals, demanding entirely bespoke approaches to development, manufacturing, and delivery,” confirms David Phasey, Innovation Director, 3P innovation. “A core challenge lies in the fact that the manufacturing route often doesn’t exist — it must be engineered from the ground up for each new therapy.”
This specific hurdle is particularly relevant for cell therapies, Phasey continues. These therapies can be manufactured at the point-of-care, which is completely different to conventional batch-based processes, he adds. “Success hinges on the simultaneous development of the therapy, its delivery mechanism, and the manufacturing process — each of which is novel and interdependent. Most drug developers lack the in-house capabilities or established knowledge base to manage this level of complexity,” Phasey remarks.
“Many CGTs, particularly autologous therapies like CAR-T [chimeric antigen receptor T-cell] therapies, require the extraction, modification, and reinfusion of a patient's own cells,” concurs Oury Chetboun, CEO and co-founder of Seekyo Tx. “This individualized approach complicates standardization, scalability, and even safety, and increases costs. ADCs [antibody-drug conjugates], meanwhile, often rely on identifying surface markers that are not consistently expressed across all tumor cells, limiting their reach.”
The personalized nature of many next-generation drugs, mean they may only be effective in sub-sets of patient populations, notes Dr. Carleen Kluger, Group Leader Clinical Proteomics, Evotec. “In addition, rare diseases which are often caused by very specific genetic variants and affect only a small patient group, require new approaches to develop orphan drugs for thousands of different indications,” she says. “Therefore, already at the discovery stage this aspect of drug development needs to be considered to reflect the highly complex biology during development of screening assays and at the pre-clinical stage, as well as during the manufacturing process.”
Typically, when approaching the development and manufacture of next-generation therapies, companies need “highly specialized infrastructure, state-of-the-art equipment, and rigorously maintained cleanroom environments to ensure product integrity and compliance with stringent regulatory standards,” asserts Jill Makin, CSO, Touchlight. “Establishing and sustaining such sophisticated facilities demands significant financial investment, posing a challenge, particularly for smaller pharmaceutical companies with limited resources.”
Erik Wiklund, CEO, Circio, and co-discoverer of circular RNA, agrees that there are numerous challenges facing the development and manufacture of next-generation therapies. “These modalities often require novel raw materials, specialized delivery systems, and manufacturing processes that are not yet standardized across the industry,” he stresses. “Therefore, manufacturing is often done at smaller scales with highly customized workflows, particularly for autologous cell therapies. The lack of established regulatory frameworks, limited availability of raw materials and skilled talent add further hurdles. In combination, these issues drive up cost, complexity and development timelines.”
The inherently different scientific intricacies of next-generation therapies in comparison to traditional pharmaceuticals has given rise to challenging regulatory pathways, remarks Alexander Seyf, CEO Autolomous. “Demonstrating robust traceability, control, and consistency across the entire lifecycle, from raw material sourcing to final product release, presents a significant hurdle, particularly following manufacturing changes where maintaining product comparability adds further complexity,” he says. “Ensuring chain of identity and custody, upholding stringent quality and safety standards, and mitigating process variability are critical imperatives.”
Additionally, manufacturers are faced with scalability hurdles as a result of the complex nature of the therapies and limitations of currently available infrastructure, Seyf continues. “Many early-stage workflows, developed for academic or research settings, rely heavily on manual processes, hindering standardization and large-scale production. This results in quality inconsistencies, variable yields, and protracted timelines,” he says. “High GMP [good manufacturing practice] operational costs, scarcity of critical materials like viral vectors, and a shortage of skilled personnel further inflate expenses.”
Scalability is a common obstacle for bio/pharma organizations trying to manufacture next-generation therapies, confirms Stone. “Facilities designed for small-scale, manual processing simply don’t translate to commercial production. Labor is stretched, processes are fragmented, and regulatory risk increases. Despite great strides in getting the best out of the manual processes, the field is stuck trying to industrialize therapies using non-industrial tools,” he emphasizes. “There is a smarter way of achieving scale and that’s through automation for scale.”
Bypassing Limitations with Advanced Technologies
With regard to next-generation therapies, companies are approaching drug development much more differently as compared with more traditional pharmaceuticals, notes Max Baumann, co-founder, partner, Treehill Partners. In addition, there are several technological advances available that can help companies overcome the challenges associated with the development and manufacture of these complex drugs.
For example, modeling and simulation approaches are being used to reduce potential failures early on in the process. “Organ-on-a-chip platforms now enable human-relevant disease modeling, effectively bypassing the limitations of inter-species differences in preclinical safety and efficacy testing. Regulation is only very slowly following these approaches, and true ‘wins’ yet need to be reported,” Baumann says. “Digital twin technology and real-time analytics simulate processes, predict equipment failures before they occur, and accelerate technology transfers between development and production phases.”
Then, there are tools like artificial intelligence (AI) and machine learning (ML), which are having a significant impact throughout the development lifecycle, Baumann continues. “AI and ML are revolutionizing drug development by predicting drug-target interactions, optimizing manufacturing schedules, and detecting defects in real time, substantially reducing trial-and-error approaches in R&D,” he specifies. “In many instances, we see that AI is not yet being used with maximum effect, and while the technology keeps developing seemingly at the speed of light, humans do require time to adapt their workflows and embrace change.”
In addition to AI, automation and closed-system production processes will be imperative for companies to overcome the challenges associated with the manufacture of next-generation therapies, Wiklund asserts. “AI and ML can improve process optimization and real-time monitoring to enhance batch consistency. Automation helps reduce variability and contamination risk, which is particularly relevant for gene and cell therapies that currently require substantial manual handling. Closed-system platforms can support scalability and allow CDMOs to handle complex, small-batch production more efficiently,” he says.
“For manufacturing, automation and digitization are diminishing the need for manual steps and specialized personnel, leading to improved scalability and consistent batch quality,” agrees Seyf. “Real-time data capture within electronic batch records and advanced reporting and analytics empower optimized production, early deviation flagging, and faster, more informed decisions. Furthermore, technologies such as closed-system manufacturing and modular facilities are increasing capacity, minimizing variability, and accelerating global technology transfer.”
Key Players in Driving Innovation Forward
“CDMOs are critical partners in the process as they have the ability to cut across multiple approaches and be partners from early stages of product development,” asserts Miguel Forte, President, ISCT, board member of ARM and CEO of Kiji Therapeutics. “The process development part of [a CDMO’s] value proposition is key, particularly to early-stage start-ups that need a partner that helps channel the product development and has access to multiple innovative technological approaches.”
By leveraging advanced technologies, CDMOs are ensuring that they can provide enhanced efficiency, scalability, and flexibility to next-generation therapy innovators, stresses Chetboun. “Implementing unified digital platforms enables CDMOs to streamline operations, accelerate technology transfers, and lay the groundwork for AI-ready manufacturing,” he says. “This approach facilitates real-time monitoring and control, enhancing product quality and regulatory compliance.”
“CDMOs are looking to differentiate from one another due to current over-capacity in the industry and are well placed to assess new technologies due to their experience across a range of manufacturing processes and technologies,” reveals Jon Ellis, CEO, Trenchant BioSystems. “Development of new technologies could be streamlined by collaboration between technology companies and CDMOs to ensure new platforms meet technical and functional requirements. Collaboration across the industry to share knowledge and non-proprietary data would reduce inefficiency.”
For Makin, the implementation of advanced technologies by CDMOs is synergistic with the progression of next-generation therapy innovation. “One major area of innovation is the integration of synthetic DNA technologies, which enables therapeutics to move from R&D to GMP without the complexities of legacy systems,” she remarks. “Cultivating regulatory engagement when adopting innovative solutions enables next generation medicines to progress through clinical development.”
Another key facet of partnerships in relation to driving forward next-generation therapy innovation is the provision of standardized platforms — which are needed to ensure quality and adaptability — that they offer, notes Kluger. “Fully integrated drug discovery and development programs drastically reduce the time needed to de-risk a candidate and transform it into a successful drug,” she says.
“Once the drug development process becomes more complex and individualized, there is also a higher need for cost-efficient manufacturing at high success rates,” Kluger adds. “Having cell line development, process development, as well as clinical and commercial manufacturing under one roof provides the infrastructure needed for continuous manufacturing of next-generation therapies, thus pioneering access to affordable biotherapeutics.”
Approaching a Significant Transformation
“Manufacturing ability and scaling capacity still represent a challenge and are associated with relatively high costs,” Forte emphasizes. “Developments in making the manufacture of gene therapies more affordable and with higher capacity is a must to enable the translation of these products in therapeutic realities.”
According to Baumann, it is looking likely that industry is approaching a significant transformation with AI revolutionizing many aspects of development processes over the next few years. “Whether this transformation occurs within established players or through market disruption by new entrants remains uncertain, but AI adoption continues growing across engineering domains and will inevitably transform the CDMO sector,” he says.
“Advanced technologies hold the key to transforming the potential of cell and gene therapies into a scalable, globally accessible reality,” exclaims Stone. “But to deliver meaningful impact, they must be applied with a deep understanding of the sector’s unique challenges, including biological complexity and regulatory demands.”
Furthermore, to be able to scale-out these advanced therapies successfully, a novel approach to automation that offers flexibility, which is not afforded by the automated solutions that have served traditional biomanufacturing, is necessary, Stone confirms. “What cell and gene therapy needs isn’t just more modular automation,” he summarizes, “it needs a shift towards manufacturing designed with the same scalability, agility, and intelligence that industries like silicon fab, automotive, and even lab automation have mastered.”
References
FDA. Approved Cellular and Gene Therapy Products. FDA.gov (accessed May 22, 2025).
EMA. CAT Quarterly Highlights and Approved ATMPs. Committee Report, EMA.europa.eu, Feb. 10, 2025.