Collaboration Aims To Transform the Manufacturing of Cell Therapies

Due to the complexity of the cell therapy products and patient-specific variability, product quality and consistency are significant challenges in manufacturing. In-process controls and analytics are critically important in ensuring a consistent drug product.

By developing and integrating current and new analytical technologies into patient-scale cell therapy manufacturing workflows, Agilent and Lonza aim to increase access to safe and efficacious cell-based therapies.

To learn more about this collaboration, the challenges faced in cell therapy manufacturing and how these can be overcome, Technology Networks spoke to Yama Abassi, head of strategic marketing and business development, PLXA- Cell Analysis Division at Agilent Technologies.

Ash Board (AB): Why are product quality and consistency such significant challenges in cell therapy manufacturing?

Yama Abassi (YA): Cell therapy is a novel, personalized medicine which is becoming increasingly complex as the range of disease and conditions that could be treated with cells expands and different processes evolve. Cell therapy is not only used for treatment of cancer but also genetic diseases, autoimmunity, infectious disease and even considered for chronic diseases such as certain cardiac conditions.

There are various challenges to maintaining product quality and consistency in autologous cell therapy manufacturing. In autologous cell therapy, every batch is specific to the individual, meaning that we only have one opportunity to successfully manufacture safe, consistent, and high-quality cell therapy products. Cells taken from individuals will not only have genetic and phenotypic differences but will be influenced by the individual’s unique medical history. It’s vital to understand the functional status of the cells during manufacturing, which can be achieved by integrating cellular analytics into bioreactors to provide information about the cell status in real-time. The individuality and variations in starting material of cells coupled with potential changes in cell quality during manufacturing makes identification of critical quality attributes (CQA’s) of paramount importance.

Having the right tools and equipment and validated CQA such as those that inform on immune cell persistence and potency during the manufacturing process, is vital for scientists to be able to produce safe and efficacious cell therapy products.

AB: Can you talk to us about the importance of in-process controls and analytics in the manufacture of cell therapy products?

YA: The motto in the field is that the ‘process is the product’, so it’s very important to get that process right. To have effective personalized therapies, you must personalize the manufacturing process itself.

In-process monitoring of the actual cell therapies happens rarely in cell manufacturing at present but will grow in scale in the future. Successful in-process monitoring during cell manufacturing helps to control cell quality over time, gain a better understanding of how the cells will behave once they are manufactured and administered to the individual.

The bioreactor engineering process needs analytics throughout the entire workflow so scientists can monitor for CQAs in real time, and ultimately produce a high-quality product which will act in the way intended.

AB: How does an understanding of CQAs enable the manufacturing process to be directed in real-time?

YA: It’s important to have a solid understanding of the attributes of the cell. There are so many different facets to the cell itself. Those facets are measured by critical quality attributes. Whether a cell originates from an autologous donor or from a stem cell, the critical quality attributes determine whether the cell will provide therapeutic effect in a safe manner.

Real time analytics of CQAs throughout the manufacturing processes determine whether the cell is ready for use and meets certain predetermined standard. Current processes use production quantity and time in the bioreactor to determine when the cell manufacturing process should finish. Having in-process analytics will help scientists better control the manufacturing process to produce optimal cell therapy products on a bespoke individual basis.

AB: Can you explain how integration of Agilent’s analytics technologies and techniques into Lonza’s Cocoon platform will benefit manufacturers of cell therapies?

YA: Cell therapy manufacturing is still in its relative infancy. Our partnership with Lonza, the largest CDMO in the world, will bring industry leading experience in biologic molecule manufacturing to cell therapy manufacturing through their Cocoon® bioreactor to our business. In turn, we will support Lonza with our broad range of analytical measurement tools for every step of the cell manufacturing process.

Previously scientists preferred to use molecular or non-functional measures in cell manufacturing due to their reliability and controllability. However, we’re now learning that persistence and potency can only be measured by functional assays which provide a relevant measure of a cell’s behaviour once administered to the individual. Agilent has the right analytical technologies for providing consistent and real-time functional measurements in a variety of applications, such as assessing bioenergetics and metabolism for investigating persistence or real-time killing assay for measuring potency.

The question is, “can a functional measure be repeatable and reliable?” We believe that with more advanced tools like flow cytometers and state-of-the-art mass spectrometers, we can provide functional measures which weren’t available previously.

Our work with Lonza will place Agilent sensors within the Cocoon® bioreactor workflow, and together we will research which key measurements are critical for different stages of the cell manufacturing process. Understanding exactly what to measure during these workflows is poorly understood, and our work with Lonza will fast track comprehension across the scientific community for advancing the production of safe and effective cell products.

AB: What impact do you see this having on the manufacture of autologous cell therapies?

YA: There is currently a failure rate of around 3 - 10% where cells do not meet the quality needed for use. In-process monitoring will increase the percentage of good quality cells available at the end of the manufacturing process.

Firstly, through increased analytics capabilities, we will be able to standardise and better understand key CQAs for producing more reliable and safe cellular therapies. Secondly, by reducing failure rates, cell manufacturing workflows will become more efficient, scalable, and affordable.

AB: The integration is set to deliver the first “fit-for-purpose” solution for scaled manufacturing. Can you expand why this has not been possible before, and what impact it will have on the industry?

YA: Cell therapy manufacturing is a new territory. Traditionally pharma and biopharma has been focused on small molecule production and biologics like antibodies and proteins. We have not been faced with the challenge to create fit-for-purpose cell therapy solutions until now.

Developing a “fit for purpose” solution means creating measurements designed to work within a bioreactor workflow which guide decision making as far as quality, potency, safety, and purity of the cells are concerned.

Both Agilent and Lonza are aware that there is nothing like this available to date.

Our first step will be to implement off-line or at-line analysis – to make it more automated and easier to feed samples into the bioreactor. Once we have a better understanding of the critical parameters needed for every manufacturing run or critical measurements, the second step will be to make them in- or on-line so they are able to measure within that bioreactor environment.

We believe that the fruits of our partnership will be provide a solution which can support the production of cell therapy products in a scalable and effective way, in turn transforming the future of medicine.

Yama Abassi was speaking to Dr. Ash Board, Editorial Director at Technology Networks.