Challenges in Advancing Cell and Gene Therapy: Balancing Innovation, Legislation, and Production hurdles
In the rapidly evolving landscape of advanced therapies, a significant focus lies on addressing regulatory challenges, particularly in manufacturing quality, process consistency, and regulatory clarity. The sector faces a unique set of hurdles, with concerns about the adoption of AI in regulatory settings adding to the mix.
Key regulatory challenges include stringent Chemistry, Manufacturing, and Controls (CMC) expectations. The FDA now requires more comprehensive, higher-quality data for gene and cell therapy approvals, especially regarding process performance, product characterization, batch-to-batch variability, purity, and potency. About 40% of early-stage investigational new drug applications get rejected on CMC grounds, causing delays and cost increases.
Advanced Therapy Medicinal Products (ATMPs) face varied regulatory requirements, with differing stances between EMA and PIC/S on facility design and GMP guidelines. Novel frameworks, such as the UK’s new legislation (2025) enabling point-of-care manufacturing, add further regulatory complexity.
Moving therapies from clinical trials to commercialization involves scaling while maintaining quality under intensifying regulatory scrutiny, particularly in the US and Europe. This drives the need for strategic regulatory planning to handle increasing filings and disparities between regional regulations.
Regarding AI use in regulatory settings for advanced therapies, AI tools like FDA’s Elsa system aim to optimize regulatory processes but currently have limited capabilities and are not fully reliable. Primary concerns centre on human oversight and accountability, legal responsibility, and the potential abdication of human expertise.
These concerns reflect a broader tension between leveraging AI’s potential efficiency gains and maintaining the rigorous scientific and ethical standards necessary in the advanced therapies sector.
The path to success for the CGT industry lies in balancing innovation with safety, efficiency with access, and global collaboration with domestic capabilities. Domestic manufacturing for CGTs may require significant automation and scale to compete with global alternatives, potentially changing the fundamental nature of how these products are made.
Patient access is a critical challenge, given the high costs and manufacturing complexities associated with personalized CGTs. The loss of expertise at the FDA, with a workforce being cut by 19%, is causing procedural changes, such as an increase in committee reviews, which can slow down the approval process and potentially prevent drugs from ever going to market.
The deployment of Elsa within the FDA has generated both excitement and concern across the CGT industry. Philip Vanek, ISCT’s chief commercialization officer, believes that advanced CGTs will fundamentally change treatment paradigms beyond traditional palliative care approaches.
However, companies are slowing investments and hiring due to uncertainties in policy changes. The tariff situation has been detrimental for investors due to its unpredictable rollout and communication. The Most Favored Nation (MFN) policy is creating complexity for the CGT industry.
Supply chains for advanced therapies are global by necessity, involving raw materials that may not be readily available domestically. Legal accountability is another concern, as regulatory agencies making life-or-death decisions based on AI-generated reports could potentially abdicate human expertise.
Drug pricing is a complex issue in a complex ecosystem, not a single actor issue. Bringing manufacturing back to the United States for advanced therapies is a challenge due to unique complexities and development times.
The advanced therapies sector must manage evolving, demanding manufacturing and regulatory standards with the added complexity and cautious integration of AI tools, balancing innovation with responsibility and patient safety. The decisions made in the coming months will test the industry's resilience and present an opportunity to build a more sustainable, accessible future for these life-saving therapies.
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