Driving operational excellence

Manufacturing CGTs involves navigating a complex structure of regulations that can vary significantly from one country to another. The unique nature of CGTs poses challenges for traditional regulatory bodies and their frameworks which are tasked with balancing the need for innovation and ensuring patient safety and treatment efficacy. Compliance with these regulations is paramount not only for patient safety but also for the success of CGT. Unlike traditional drugs, CGTs are living entities that can evolve within a patient’s body. This makes defining and standardising manufacturing processes and quality control parameters a complex task. Regulatory agencies must be able to create flexible yet robust guidelines that accommodate this variability while maintaining rigorous standards. Another challenge for regulatory agencies arises from the long-term effects of CGTs that require monitoring over extended periods and may lead to stricter post-market surveillance. In that context, companies must invest substantial resources in understanding and adhering to regulations and preparing for regulatory inspections and audits. Non-compliance can result in significant costs and delays. 

The initial strategy set-up is crucial to ensure regulatory compliance ease along the entirety of the new product introduction (NPI) lifecycle. Companies manufacturing CGTs invest heavily in process development to understand and document their therapies. This may include comprehensive preclinical and clinical studies that provide robust data on safety, efficacy and potential risks associated with the therapy. The use of quality by design (QbD) as a systematic approach to facilitate continuous improvement throughout a product’s lifecycle is indispensable for CGTs.

Another crucial step for manufacturers is to establish close collaboration with regulatory bodies at early stages of process development. This proactive engagement helps companies to align their strategies with evolving regulatory expectations, ensuring a smoother pathway through the approval process.

Moreover, the use of automation and advanced analytics plays a crucial role in ensuring consistency and traceability throughout the production process. The adoption of automated manufacturing platforms significantly reduces the risk of human error, which can be a costly factor in CGT production. The use of advanced analytics and real-time monitoring enhances the ability to identify and address deviations promptly, however, companies must carefully evaluate the return on investment (ROI) of automation solutions to justify the initial capital expenditure.

CMC burdens in CGT development revolve around maintaining product quality, refining manufacturing processes and adjusting to the dynamic regulatory environment. Compliance is not only a regulatory matter but a pivotal factor affecting overall cost and the timeline for bringing CGTs to market. Early engagement with regulatory bodies, robust investment in process development and leveraging advanced technologies are essential to avoid costly setbacks. Additionally, harmonisation efforts at a global scale can streamline regulatory processes, reducing both time and financial burdens on manufacturers.

Technology plays a pivotal role in streamlining CGT manufacturing processes. Automation and digitalisation have the potential to reduce costs by up to 30%. Leveraging data analytics and machine learning can optimise processes, improve patient outcomes and enable real-time verification of critical quality parameters through in-line analytics. This not only enhances product quality and yield but also reduces production time. We see development of new operating models such as the Integrated Development and Manufacturing Organisation (IDMO) taking the lead to reduce costs and increase standardisation of the process through automated and integrated platforms. Technology platforms such as the commercial lentiviral-based delivery system can also increase process control. It can reduce variability of the starting materials by providing optimised and well-characterised cell lines and vectors that satisfy regulatory requirements to improve bioprocessing yield and reduce development timeline, risk and cost.

The integration of cutting-edge technology not only reduces manufacturing costs but also accelerates time-to-market for CGTs, benefiting both manufacturers and patients. However, companies must invest in workforce upskilling and change management to fully harness the potential of technological integration. Collaborations with technology providers and research institutions can drive innovation in CGT manufacturing. Furthermore, automation substantially increases process capacity, eliminating the need for work to be conducted in shifts. Achieving consistent results is far simpler with machines than with manual operators, who may struggle to replicate the same task identically. Improved process consistency, in turn, leads to greater consistency in critical quality attributes (CQAs). Additionally, automation enhances safety by reducing the risk of potential contamination and variability associated with human manipulation.

As we reflect on the path travelled so far and the road ahead, it is clear that CGTs are reshaping the landscape of medicine. Challenges have been met with innovative solutions, and manufacturing is evolving to meet the needs of patients. With unwavering dedication and a commitment to excellence, the future of medicine is looking brighter than ever.

Early engagement with regulatory bodies, robust investment in process development and leveraging advanced technologies are essential to avoid costly setbacks in CGTs​