Bridging the Gap Between Early-Stage Gene Therapy and Clinical Trials

Find out how TKD’s process improvements addressed manufacturing challenges, enabling the production of clinical material.

Gene therapies present a notorious challenge to GMP workflows. The manufacturing processes for gene therapies often have poor scalability and irreproducible results due to the nature of the therapeutic vectors. Recent reports on current gene therapies in clinical trials have suggested thousands of liters of cell culture are required to produce clinical material for trials involving just 40 patients. The amount of time and resources required to scale a process for generating clinical grade gene therapy material is often the limiting factor in the success of a gene therapy trial.

At TKD Solutions, we have first-hand experience with clients who have come to a standstill in their gene therapy production due to poor scalability of their manufacturing processes. One such client was struggling to even produce clinical trial material. When TKD Solutions joined the team to investigate the problem, no Drug Product was available for use in our client’s clinical studies after 4 years of failed batches. We were tasked with identifying the manufacturing problems, implementing process improvements, and advising our client in producing clinical trial material.

To begin our task of solving the gene therapy production challenge, we investigated historical manufacturing data. We reviewed GMP SOPs, batch records, analytical SOPs and reports, and quality data on early characterization. Our first assessment showed disorganized GMP data and analytical methods that were not robust. With decades of experience in cell and gene manufacturing, we understand how biologically inefficient gene therapy manufacturing can be; and we know to combat the biological inefficiencies, processes must be robust and controlled early in development to maintain reproducibility for scale-up and clinical material supply.

We used our initial assessment of the gaps in the process to implement process controls. We developed a QbD strategy to make our client compliant with FDA standards, and we used our client’s historical data to redevelop analytical methods for improved robustness. Our QbD approach also guided CQA determination and allowed us to recommend additional analytical methods to further control the process for reliable manufacturing. Through data analysis and on-site CDMO oversite, we were able to identify gaps in the process and implement process improvements.

Our process improvements led to the first successful gene therapy batch in 5 years for our client. We were able to find the root cause of our client’s failed batches, and we were able to implement a robust process for clinical material in 1 year. We increased our client’s yield 10-fold from their previous batches, and we made their program commercially viable by allowing the clinical trials to resume and reducing their manufacturing time and costs. By greatly improving our client’s yield, we saved our client $900 million in production costs for their clinical trials.

At TKD Solutions we understand that gene therapy manufacturing is challenging regardless of the vector. We know it is essential to establish a compliant process as soon as tox/preclinical material production begins. We believe establishing process controls and consistency early enables a smooth transition to later stage clinical trials. We believe addressing safety concerns, mechanism of action studies, and CQAs early in a process will mitigate risk and cost in late stage programs.


Learn how we can support your cell and gene therapy manufacturing needs.