TC BioPharm eliminated approximately 200 steps from its allogeneic CAR-T biomanufacturing process, reducing hands-on manufacturing time by half and cutting production costs to a fraction of the industry standard. Consequently, the company says it can produce allogeneic gamma delta T cells for $300 to $500 per dose—significantly less than the industry norms of $250,000 to $500,000. Batch manufacturing of approximately 300 doses can be frozen for years.

The manufacturing process is linked to process development, and results from a detailed Quality-by-Design approach that streamlines technical transfer and minimizes risk of failure. Key points are expansion of viable cells in a closed system, continual process monitoring, and risk mitigation strategies to reduce product variability. “Identifying critical quality attributes is absolutely essential,” Angela Scott, COO and co-founder of TC BioPharm, points out.

Manufacturing has evolved from an autologous fresh product to a universal frozen donor program. During that time, “We developed a miniature ‘in-a-dish’ version of the manufacturing process. It uses 1/30 the volume of the full manufacturing process,” Scott continues. In the autologous process, this was used for patient selection, but in the frozen allogeneic process it is used to select the most potent, prolific cells for expansion.

Eliminating multiple connections and tubing

TC BioPharm uses a closed system of G-Rex flasks for cell expansion, transitioning from traditional media bags. This eliminates multiple connections and tubing. It also reduces the risk of contamination in connecting one receptacle to another and eliminates dozens of open-and-close manipulations, further decreasing risks, while also removing the need for multiple validation steps.

After expanding the gamma delta T cells, unwanted alpha-beta cells are labeled and removed using a CliniMACS system. “Once we have our population of gamma delta T cells, we fill into our final product containers,” according to Scott. “Off the shelf, there are not many pieces of equipment that give you a fully closed system.”

Many respected companies list pieces of a kit that are GMP-compliant but, she stresses, “The onus is on you to ensure they actually are GMP compliant.”

Her team assesses equipment in detail to understand its exact and identify potential points of risk and how they may be mitigated. By considering critical quality and process attributes and incorporating scale-up, shelf-life, closed manufacturing, and product packaging considerations into those early decisions, Scott says TC Biopharm minimizes the need to redesign its manufacturing processes to future proof potential issues.

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