Case Study: Meeting the GMP Cytokine Need for Cell Therapy Manufacturing

A customer focused on autologous T cell therapies targeting solid tumor cancers was progressing into clinical trials and needed to transition from research-grade to GMP-grade cytokines. Concurrently they wanted to improve their methods of cytokine supplementation to reduce cytokine waste, improve concentration accuracy across lots, and reduce process risk by defining methods for closed-system cytokine addition. They were already using research-grade cytokines from Bio-Techne.

• Transition plan for GMP cytokines — For each cytokine, we provided certificates of analysis, stability data, and bioactivity documentation for comparison with research-grade cytokines. The customer confirmed that the GMP-grade cytokines of interest are produced with the same clone and manufacturing process as the research-grade cytokines. Next, we provided three lots of each GMP cytokine for performance equivalency and lot-to-lot consistency testing.
• Cytokine use and waste reduction plan — The customer was ordering cytokines in vialed amounts larger than required for a single process addition. This resulted in the discarding of unused reconstituted cytokine. We provided options for reducing waste, including custom filling by activity (IU) per vial as well as off-the shelf cytokines in smaller vialed amounts.
• Closed-system plan for GMP cytokines — Looking to commercial manufacturing, this customer was interested in reducing process risk by implementing closed-system addition of GMP cytokines. We provided some prototype closed-system cytokines in bags for the customer to evaluate for ease-of-use and performance equivalency. We are open to partnering with companies to identify the best solution for closed-system cytokine addition for cell therapy manufacturing.

Converted from research-grade to GMP cytokines — The customer generated data showing comparable bioactivity of GMP and research-grade cytokines. Additional data showed consistent lot-to-lot performance of GMP cytokines in their process. Together, these data allowed them to document and justify their transition to GMP.

Enacted plan to reduce cytokine waste — The customer identified that 2 of 3 GMP cytokines were available off-the-shelf at smaller sizes that met their activity per vial requirements. Switching to smaller vialed amounts helped reduce cytokine waste. For the remaining cytokine, the customer is pursuing custom vialing to deliver process-fit activity per vial, thus eliminating waste for that GMP cytokine.

Exploring option for closing cytokine supplementation — The customer is open to working with Bio-Techne to explore options for future closed-system cytokine addition.