One of the key production challenges was to develop a solution to manage large populations of adherent cells in multiple parallel containers as a single batch. The consequences of a batch loss due to contamination or operator error is significant.

Loss of a final product batch can amount to several thousand doses, while loss of a working cell bank batch could ultimately amount to the loss of several hundred thousand doses and of course the associated significant delays to therapy.

The first step in automating the process was to envision how it could be transformed from an open process performed in a Class A environment to a closed process. The cell culture containers used in this application are too heavy to be handled by a person when filled, and concurrent cube orientation and fluid transfer during seeding and harvest would be impossible without automation.

The solution involved a combination of automated physical manipulation of the cell culture containers together with automated fluidics and medium conditioning. This enabled four, 100-layer cell culture containers to be handled concurrently with associated process monitoring to ensure consistent conditions and maintain single batch integrity.

Our automated manufacturing approach enabled the recruitment of employees with skills and aptitude suited to consistency while achieving complex, concurrent, rapid actions in a highly repeatable manner. At the operator interface level, the automation guides the operator through the SOP and creates the batch record at the same time.

At the equipment control level, it enables multiple, complex actions to occur in precise timing that would be unrealistic for operators to perform reliably in a manual setting.