How to Get Treatments to Patients Who Need Them Most
ell and gene therapies (CGTs) continue to demonstrate extraordinary potential to transform treatments, particularly for rare diseases and cancer. Yet despite major scientific advances, the field faces persistent barriers that slow progress from discovery to patient access. Manufacturing remains complex and costly, regulatory expectations vary widely across regions, and uncertainty around reimbursement and long-term sustainability continues to deter investment and delay adoption.
- Facilitating chemistry, manufacturing, and controls (CMC) efficiencies
- Enhancing global regulatory harmonization
- Improving access and reimbursement pathways
The discussions revealed a maturing field eager to move beyond identifying barriers toward developing pragmatic, collaborative solutions, highlighting DIA’s role in the process.
For simplicity, this article discusses “cell and gene therapies” together under the CGT umbrella, while recognizing that each involves unique scientific, manufacturing, and regulatory considerations.
Why Progress Still Lags Behind Promise
Even as the number of CGT programs expands, the path to delivering treatments to patients remains uneven. Developers struggle with small batch sizes, limited analytical tools, and constrained viral vector supply chains that hinder manufacturing at scale. Regulatory fragmentation across regions complicates development plans and increases time and cost. In parallel, the infrastructure required to administer these therapies (e.g., specialized facilities, trained personnel, and data systems) remains limited, particularly in low- and middle-income settings or countries with emerging healthcare systems.
These challenges converge on a single issue: how to build a sustainable, globally coordinated ecosystem for cell and gene therapy development and delivery. Against this backdrop, Summit participants focused their discussions on how to translate scientific progress into scalable, sustainable solutions that can reach patients more quickly.
Key Insights from the CGT Summit Discussions
1. Advancing CMC Efficiency
Cell and gene therapies are complex biologics and present unique CMC challenges due to the variability of starting materials, small batch sizes and limited number of batches, maturity of analytical procedures, and complex manufacturing processes.
Variability in starting materials continues to be one of the largest obstacles to consistent manufacturing that impacts both the quality and potency of the final product. Participants emphasized that stronger donor selection and cell source characterization criteria can improve product consistency and potency. However, these materials are difficult to manufacture at scale. Due to the complex manufacturing processes, limited availability of high-quality materials, and the small number of batches that can be produced, it is challenging to demonstrate a product’s consistency in quality, safety, and efficacy (i.e., its comparability) to support process scale-ups and new site introductions. Leveraging tools such as Process Analytical Technology (PAT) enables real-time monitoring and control of manufacturing steps, helping ensure the consistency and quality of complex CGT products. PAT, AI-driven modeling, and automation could improve both scalability and regulatory confidence. Still, comparability remains a regulatory linchpin. Examples from the Foundation for the National Institutes of Health (FNIH) and others demonstrated how early establishment of good manufacturing practices (GMP) cell banks (starting with high-quality research-grade plasmids) can lay a foundation for later phases, supporting faster transitions and cost-effective scaling. In addition, engineering runs and better use of research-grade plasmids may help build the data needed to support process changes across platforms.
An Advanced Therapy Medicinal Product (ATMP) comparability annex to Q5E recently endorsed by the ICH Assembly (the ICH Comparability Annex) could be a potential tool to help redefine how comparability is approached in CGTs. With the expert working group yet to be formed, however, the annex remains in the early stages of development.
Stakeholders discussed the importance of evolving beyond traditional validation paradigms and towards risk-based approaches that accommodate the realities of CGT production. These strategies may include greater reliance on prior knowledge, platform approaches, and concurrent process validation during clinical trials. While analytical technologies are still maturing, there was consensus that investing in these tools early will enable more reliable comparability assessments and real-time release testing.
Next steps: Attendees agreed that the field would benefit from clearer guidance on when and how alternative validation and risk-based approaches can be applied. Professionals in the field are eager to work on rightsizing CMC requirements, to avoid repeated testing for every small patient population. Continued dialogue between developers, regulators, and manufacturing partners is critical to define what constitutes “good enough” comparability for small patient populations, including individualized (n = 1) therapies.
To address starting material challenges, participants suggested that criteria used for antibody drug cell banks be extended to CGTs. Different cell sources, e.g., oncology cells, induced pluripotent stem cells (iPSCs), allogeneic, and universal donor cells, require unique selection and modification criteria, so sequencing and full genomic characterization are becoming increasingly important, particularly when a single donor’s material is used for hundreds of patients. This approach can provide important safeguards, especially given decreasing sequencing costs.
To streamline clinical development, concurrent process validation during trials could at least in part overcome the bottleneck of transferring research-grade materials to GMP-grade for clinical trials, a process that is currently very time- and resource-intensive.
The group also discussed the potential for shared learnings across manufacturing networks, emphasizing transparency and collaboration over proprietary silos to accelerate collective progress.
A follow-up to this discussion will include additional perspectives from CDMOs, or Contract Development and Manufacturing Organizations, and smaller biotech companies to expand the industry knowledge base and foster shared solutions for CGT CMC challenges. CDMOs support biopharmaceutical companies by providing specialized expertise and infrastructure for product development, manufacturing, and sometimes testing, which is particularly valuable for small or emerging companies lacking in-house capacity. Insights from discussions with CDMOs and small biotech companies will inform future conversations and initiatives aimed at harmonizing regulatory expectations and accelerating product development for advanced therapies.
2. Moving Toward Regulatory Convergence
Achieving regulatory harmonization for cell and gene therapies (CGTs) remains a major challenge due to the absence of global consensus on definitions, approval pathways, and technical standards. This fragmentation creates complexity for developers seeking to advance therapies across regions and can slow the pace of global patient access. As scientific understanding and manufacturing capabilities continue to evolve rapidly, regulatory frameworks are also adapting—often at different speeds—underscoring the need for greater alignment and clarity worldwide.
Differences in regional requirements for preclinical testing, manufacturing, and clinical trial design add further complexity. These inconsistencies are particularly difficult to navigate in the context of CGTs, where developers often work with very small patient populations and compressed development timelines. Because the field is still relatively new, regulatory expectations are maturing alongside the science, and guidance continues to evolve in real time.
Summit participants agreed that early and transparent communication between developers and regulatory authorities is critical to navigating this evolving landscape. Establishing regular mechanisms for dialogue can help sponsors anticipate expectations, align development approaches, and even contribute to the evolution of emerging standards. For example, since some degree of testing variability is inevitable, a shared potency matrix, endorsed by multiple regulatory bodies, could promote greater consistency in how product potency is evaluated across regions.
Participants also emphasized that while each patient is different, the manufacturing process should be consistent. Developers are expected to demonstrate process consistency rather than product uniformity, recognizing that biological variability in patient-derived starting material will always exist. Maintaining well-defined, validated steps and process controls ensures that such variability does not compromise the safety, potency, or overall performance of the final therapy.
To support global regulatory convergence, participants proposed the creation of pilot programs to test new approaches for assessing manufacturing changes or comparability standards in a structured, collaborative way. These pilots could help determine when process adjustments truly have no impact on product safety or efficacy and identify areas where current testing requirements could be streamlined. A regulatory sandbox (i.e., a controlled environment where regulators and developers can experiment with new methods under close supervision) was viewed as a promising mechanism to enable such pilots. Within this framework, stakeholders could safely explore innovative regulatory approaches, such as risk-based assessments, data sharing, and regulatory reliance, before integrating them into broader policy or guidance.
Finally, participants noted that regulatory innovation should be inclusive of clinical and economic perspectives. Physicians can provide critical real-world insights into how therapies perform across patient populations, while pharmacoeconomic and societal cost analyses can help ensure that new regulatory models support both innovation and equitable patient access.
Next Steps: Important next questions will center on how regulatory bodies can collaborate more effectively, share best practices, and work towards global harmonization of standards in this rapidly evolving field. Strengthening such collaboration could also open the door for scaling up regulatory reliance frameworks, an approach long advocated by many organizations, such as the ICH, WHO, ARM, and FNIH working groups, to promote efficiency and transparency—particularly in the context of platform technologies and master file systems.
A comparison, or crosswalk, of expedited pathways implemented by various agencies could help identify opportunities for convergence and provide valuable insights for regulatory planning by CGT developers. Such efforts would not only streamline development but also enhance predictability and coordination across regions, benefiting the field as a whole.
Finally, participants underscored the importance of aligning regulatory approval pathways with reimbursement requirements. Greater coordination between regulators and policymakers responsible for market access and pricing could help ensure that the same evidence supporting regulatory approval also facilitates timely patient access to these transformative therapies.
3. Expanding Access and Reimbursement Pathways
Even when therapies receive regulatory approval, access remains uneven. High manufacturing and administration costs, limited infrastructure, and complex reimbursement landscapes restrict availability, especially in low- and middle-income countries. The specialized facilities required and the individualized nature of many cell and gene therapies lead to extended production timelines and high costs, and many regions lack the necessary infrastructure, including specialized treatment centers and skilled personnel, to handle the complexities of CGT administration. Varying regulatory standards and a lack of harmonization across countries can further delay approvals and limit access to innovative treatments.
Patient engagement and access to CGT therapies are often hindered by a lack of social support for patients in need (e.g., travel and lodging) and sufficient public awareness and understanding of the benefits and risks associated with cell and gene therapies. Eligibility criteria for patients in need as well as limited funding for research, development, and implementation of cell and gene therapies, particularly in low- and middle-income countries, further exacerbate access disparities.
The need for intensive inpatient treatment, specialized storage, and transportation can pose significant logistical challenges, especially in rural areas. Adequate data infrastructures to protect sensitive genomic information are needed to ensure patient privacy and facilitate research.
Next Steps: Future efforts will focus on approaches to turn insights into coordinated actions, such as streamlining regulatory and reimbursement processes, including the harmonization of standards across countries to facilitate global access to innovative advanced therapies. Companies and patients will both benefit from having an integrated regulatory strategy that helps characterize new assets and accelerates their development.
To reduce costs upfront, it’s important to explore alternative manufacturing models, such as decentralized manufacturing or partnerships with academic and research institutions. Developing creative financing mechanisms, such as public-private partnerships or dedicated funding initiatives, can also make cell and gene therapies more affordable and accessible to patients who need them.
Investing in the development of specialized healthcare infrastructure, including decentralized treatment centers that alleviate travel burden, skilled personnel, expanded access to clinical trials, social support, and patient education, will be crucially important to ensure equitable access to cell and gene therapies.
Remaining Challenges and Looking Ahead
Because each cell or gene therapy batch is often derived from a small number of samples, the amount of product available for testing is extremely limited. Unlike traditional biologics, developers cannot easily produce large quantities of identical material for analytical studies or validation exercises. This scarcity makes it difficult to perform the full range of tests typically used to confirm product consistency and comparability.
As a result, developers must find ways to extract the maximum possible information from minimal samples while still meeting rigorous quality standards. It is critical to continue developing characterization strategies that can later support scale-up, real-time release testing, and other analytical or process changes. Additionally, refined approaches are needed to demonstrate comparability between nonclinical and clinical batches.
Given both the small data sets and the inherent variability of starting materials, sponsors still struggle to establish critical quality attributes (CQAs) and define appropriate acceptance criteria early in development. Building consensus on how to interpret limited data will be essential for maintaining product quality without imposing infeasible testing demands.
Investing in the development of specialized healthcare infrastructure, including treatment centers and skilled personnel, can make a crucial difference for ensuring equitable access to cell and gene therapies. That approach can also be paired with working to raise public awareness and understanding of cell and gene therapies while building trust and encouraging participation in clinical trials and treatment. Stakeholders have to make sure that ethical concerns are addressed, including long-term effects and the potential for unintended consequences from CGT use, to build public trust and ensure responsible innovation. Additionally, we have to work on implementing standards for robust data protection measures to support genomic research while ensuring consistent patient privacy.
The Summit underscored both the complexity and the urgency of advancing CGT development. It also reinforced that no single stakeholder group can solve these challenges in isolation. Addressing these challenges requires a multifaceted approach involving innovative manufacturing, regulatory harmonization, and equitable funding models. While existing consortia and organizations are already exploring aspects of these issues, participants agreed that a coordinated, global approach will be key to accelerating progress.
In line with this need, DIA is currently focused on organizing a global public-private partnership to address these challenges and complement the work of other consortia in the field. The Summit conversations served as a reminder that the field’s greatest promise lies not only in its scientific potential but also in its capacity for shared problem-solving, turning innovation into access for all patients who need it most.
Acknowledgements
We gratefully acknowledge the many experts who contributed their time, insight, and experience to the DIA Cell and Gene Therapy Summit held in June 2025. Their thoughtful discussions, diverse perspectives, and shared commitment to advancing innovation in this field were instrumental in identifying the key themes and next steps highlighted in this summary. We extend special thanks to the following participants:
Kristina Adams, Sarepta Therapeutics Inc.; Yoojin Ahn, Regenerative Medicine Acceleration Foundation; France Bui, 99 Consulting LLC; Rosa Canet-Avilés, CIRM; June Cha, FasterCures, Milken Institute; Sandeep Dhall, Jaguar Gene Therapy; Carla Fiankan, Adverum Biotechnologies, Inc.; Kira Gillett, FNIH; Brittany Goode, Vertex Pharmaceuticals; Ann Gorman, AviadoBio Ltd; Ralf Herold, European Medicines Agency; Huong Huynh, Critical Path Institute; Laura Lasiter, AstraZeneca; Kyounglim Lee, Regenerative Medicine Acceleration Foundation; Michael Lehmicke, Alliance for Regenerative Medicine; Purva Pandya, Bayer LLC; So Ra Park, Regenerative Medicine Acceleration Foundation; Allison Radwick, U.S. Pharmacopeia; Anna Somuyiwa, Centre for Innovation in Regulatory Science (CIRS); Barry Ticho, Stoke Therapeutics; Sherie Toth, AbbVie; Katie Wachtel, Akouos; James Witty, Vertex Pharmaceuticals; Dan Zhang, Hillgene Biopharma; Sophie Sommerer, Health Canada; Bradley Watts, Conner, Strong, and Buckelew; Lana Shiu, Kite Pharma.