A purpose-built future: 2025 trends for cell and gene therapy

The need for process automation and analytical technology in cell and gene therapies

Currently, there are 38 cell and gene therapies approved by the FDA, many of these having reached commercialization through mostly manual laboratory manufacturing processes. The few that have begun integrating automation and analytics often rely on technologies not specifically designed for cell and gene therapies. These solutions, borrowed from traditional biologics manufacturing, are best suited for large batch production, with basic process parameters and offline critical quality attribute measurements, which limits their effectiveness for cell and gene therapy manufacturing. Moreover, therapy developers often lack the capital to invest in high-tech automation robots during the late-development and early clinical trial stages.

However, it is critical at this juncture to ensure processes being optimized can also be scaled, without needing revalidation. Purpose-built systems can help support a smooth path from R&D to scaled production, be it scale-out for small batch or scale-up for large batch manufacturing. Several key areas in the CGT industry stand to gain significantly from a purpose-built revolution; here are three focus areas to watch in the coming years.

Purpose-built small batch manufacturing systems – for personalized and decentralized therapies

The shift towards personalized medicine necessitates the development of purpose-built small batch manufacturing systems. Traditional large-scale manufacturing processes are not suited for the bespoke nature of personalized therapies, which require flexibility and precision. Meanwhile, batch changeovers are often time-consuming and costly. Whilst this has a minimal impact on the cost per dose in large batch manufacturing, it becomes prohibitive for individualized batches – but this doesn’t have to be the case.

Finding an alternative to large batch manufacturing systems

Systems can be specifically designed for small batches, such as the NANOme® system that we developed with our client leon-nanodrugs. During this development, we helped our client adapt their FR-JET reactor to be suitable for single use, a key step to unlocking their core technology for small batch productions. A key part of the development included focusing design efforts on simplifying user steps, minimizing user interaction time, and ensuring the system was fully closed, the result of which was a user-friendly pharmaceutical aseptic processing system. The NANOme® allows small scale nanoencapsulation with significantly shorter batch/product changeover times and lower operational cost in comparison to conventional systems. Purpose-built platforms such as this can be designed to handle the unique requirements of individualized treatments, allowing for cost efficient production of therapies tailored to each patient’s specific genetic profile.

By designing systems specifically for small batch production, rather than adapting large-batch technologies, and incorporating appropriate use of automation and analytics, we can significantly reduce the costs associated with personalized medicine, making this a much more commercially viable option.

Shifting towards decentralized manufacturing

Centralized manufacturing will remain a cornerstone for CGTs, especially with the recent successes in allogeneic CAR-T cell therapies. However, the shift towards decentralized manufacturing is also expected to continue, driven by the broader trend towards personalized medicine and its unmatched clinical efficacy. The primary challenge here lies in the complexity and cost associated with individualized doses. Additionally, ensuring consistent quality across multiple manufacturing sites adds to this difficulty.

Decentralized manufacturing further enhances the feasibility of this personalized approach by bringing production closer to the point of care. This reduces the time and cost associated with transporting sensitive biological materials and ensures that patients, often with a critical time window, receive their treatments quicker. By leveraging modular and scalable approaches, decentralized manufacturing systems can be rapidly deployed and adapted to meet the evolving needs of the cell and gene therapy industry. This paradigm shift not only improves efficiency but also enhances the accessibility of life-saving therapies.

Purpose-built inline and online adaptations of analytics – for real-time process control

Real-time process control is critical for ensuring the quality and consistency of cell and gene therapies. Traditional offline analytical methods are insufficient for the dynamic and complex nature of cell and gene therapy manufacturing. Cells exhibit a much greater degree of heterogeneity and involve significantly more variables in their processing compared to small molecules and even biologics. Particularly for autologous cell therapies, where the starting material consists of highly variable samples from each individual patient, this contrasts sharply with the precisely controlled starting materials used in traditional one-size-fits-all therapies.

The benefits of purpose built inline and online analytics

Purpose-built inline and online analytical technologies can provide continuous monitoring and control of critical quality attributes (CQAs) at each step of the production process. These advanced analytics aim to enable immediate detection and correction of deviations, reducing the risk of batch failures and ensuring that therapies meet stringent quality standards. By integrating real-time data collection and analysis, manufacturers can achieve greater process understanding and control, leading to more reliable and reproducible outcomes. This approach not only enhances product quality but also accelerates the development and approval of new therapies.

The current limitation lies in the acceptance of these measurements by regulators. Initially, therapy developers are adopting these technologies to enhance their understanding and control of processes for their own development efficiencies. As more data and evidence becomes available, it is anticipated that regulators will gain confidence in their validity for use in real-time quality control and release testing.

Purpose-built data analysis and management – to harness the power of data

With the increased use of purpose-built analytics comes a vast amount of data, which will also require custom management solutions tailored to the needs of the cell and gene therapy industry. The growing quantities of data generated during the manufacturing of cell and gene therapies present both a challenge and an opportunity. Effective data analysis and management are essential for improving process efficiency and product quality. Purpose-built data management systems can handle the complexity and volume of data, ensuring it is stored, analyzed, and utilized effectively.

Utilizing advanced data analysis for cell and gene therapies

Without the appropriate tools, extensive datasets can quickly become overwhelming, turning from a valuable resource into a significant burden and overhead for developers. This is currently holding some therapy manufacturers back from fully adopting the technologies available. However, inefficient data management not only hampers the ability to extract meaningful insights but also increases the risk of errors and compliance issues. This can lead to delays, increased costs and compromised product quality.

By leveraging advanced data analysis techniques, including machine learning, manufacturers can gain deeper insights into their processes, identify patterns and correlations, and make informed decisions. This data-driven approach supports continuous improvement in manufacturing processes. Purpose-built machine learning algorithms can optimize production parameters, predict issues, and support tailored treatments, thereby facilitating personalized medicine strategies.

Data management systems also play a crucial role in regulatory compliance. By ensuring that data is accurate, complete, and traceable, these systems help manufacturers meet stringent regulatory requirements and streamline the approval process. As the industry continues to generate more data, the importance of robust data management systems will only increase.

Cell and gene therapy trends for 2025 and beyond

As the cell and gene therapy industry continues to evolve, the need for purpose-built technology becomes increasingly clear. Small batch manufacturing systems tailored for personalized therapies and decentralized manufacturing, real-time process control through advanced inline and online analytics, and sophisticated data analysis and management systems which utilize machine learning technology, are all critical components for the future of cell and gene therapy manufacturing. This is a move away from the industry’s status-quo and will require upfront capital and time investment, which is undoubtedly a big hurdle, but the time has come to make that investment. The same themes continue to be raised regularly as key challenges in industry reports and whitepapers.

These innovations will not only enhance the efficiency and scalability of production but also ensure that therapies are commercially viable and accessible to the patients who need them most. By embracing these purpose-built technologies, the industry can overcome current limitations and pave the way for the next generation of life-saving treatments. The maturation of the cell and gene therapy manufacturing sector is essential for realizing the full potential of these groundbreaking therapies, ultimately transforming patient care and outcomes.