The emergence of cell and gene therapies onto the global stage is generating growing excitement, as unprecedented clinical success fuels the expectation of a promising new chapter in medicine. Alongside an extraordinary increase in the number of cell and gene therapies entering clinical trial, there are a lower yet still significant number of companies launching the commercialized manufacture of their cell therapy products.
In a webinar recently hosted by Cell and Gene Therapy Insights,  scientists from both the supply and manufacturing sides of the cell therapy production process discussed their views on how to position a cell based therapeutic for its best chance at success. Now, in this 2-part blog series, we will highlight the insights of these and other industry leaders on overcoming the unique challenges of cell therapy manufacturing.
Anticipating the Needs of the Client
For starting material suppliers, anticipating the needs of the client helps ensure that both volume and regulatory qualification requirements will be met. This involves getting a good “forecast” of supply needs from the client. At HemaCare, good supplier-client communication is considered key to this process. Clients should understand that donor starting material quantity estimates have to cover losses to therapeutic cell isolation and other steps in the cell therapy manufacturing process. They should also factor in material lost to quality assessments and shelf-life, as well as compensation for lot-to-lot variability.
Dr. Dominic Clarke, who heads Global Cell Therapy at HemaCare, believes that a robust donor network is vital to consistently meeting client demand, and is a vital determinant of downstream product quality.
In a recent publication,  Dr. Clarke clarifies how donor material collection centers can best support the quality of the final product:
“Cell therapy manufacturers should ensure apheresis collection facilities maintain a comprehensive quality management program. The quality program should ensure process control is maintained during all aspects of the collection. A strong quality management system along with stringent process control helps to ensure high-quality collections.”
Apheresis and leukapheresis donations are the fundamental “living” building blocks of cell-based therapies. The quality and consistency of these materials will make or break a cellular therapeutic. Nevertheless, quality oversight must be maintained throughout the production process if a high-quality starting material is to be translated into a successful cell therapy. This oversight begins with the transition to a GMP-compliant process.
Transitioning Starting Material Production Processes to GMP
“Consistency is a really important metric for us…for this reason, we follow strict regulatory guidelines overseen by a mature quality management system to help translate our research products into GMP products”- Dr. Sean Kevlahan, Sr. Director of Cell and Gene Therapy at Bio-Techne
One of the most critical factors in producing a successful cell therapy product is consistent access to high-quality starting material. During pre-clinical development, the need to examine multiple therapeutic candidates generally necessitates the use of research use-only starting materials to cut the costs of the comprehensive documentation and performance testing required for GMP compliance. Once a candidate is transferred to the clinic, the process of transitioning to GMP compliance begins.
Dr. Sean Kevlahan, whose company, Bio-Techne, hosted the aforementioned CGTI webinar, knows that it’s important to get things right from the start. He explains that he always chooses reagents that are suitable to scale-up or scale-out, so that he doesn’t have to switch reagents during the translation to GMP. Using GMP-grade materials as early as possible in the process saves time and resources later. When the production process for a successful research candidate is ready for translation to a GMP-compliant process, Dr. Kevlahan has his lab list the reagents and methods for each step, then meticulously make sure that each step is optimized. As a real-world example, he describes the first step for CAR-T cell manufacturing: T cell culture.
“Even one step, for example cell culture, is often full of variables. When culturing cells, we deal with culture vessels, media, cell activation, and timing. Each of those 4 parameters interplays with one another and can affect how cells perform downstream, as well as how many therapeutic cells you end up with.”
The choices made during starting material optimization will affect T cell expansion rate, T-cell phenotype survival, and other important factors. Dr. Kevlanhan’s group needs to make sure that the availability and quality of their T cell starting material is reliable, and that each step of their T cell preparation process is optimized.
These insights from cell therapy authorities help illustrate how the quality and consistency of starting materials and reagents affect the downstream process. Next week in Part 2 of our blog series, please join us as industry experts explain what they look for when choosing a starting material supplier, and what preparations they make to ensure that quality expectations are being met both before and during successful cell therapy production.
- Kevlahan S. Planning for Success: Emerging GMP-Grade Raw Materials & Technologies for Cell Therapy. Cell and Gene Therapy Insights: live webinar. Mar 2019. https://insights.bio/cell-and-gene-therapy-insights/emerging-gmp-grade-raw-materials-and-technologies-for-cell-therapy/
- Clarke D. and Aragon M. Optimizing the Quality of Cell Therapy Starting Materials. RegMedNet. Oct 2018.