The context
Current technology for cell and gene therapies (CGTs) is unsuitable for large-scale production. This is partly because there is no common standard for the industrial manufacturing of CGTs nor any common reference frame for designing a company-specific production facility.
To help fill this gap, BioPhorum’s Cell & Gene Therapy Commercialization Workstream has published a set of process maps for cell therapy and gene therapy. These represent example processes, unit operations, and platform technologies being used in CGT manufacturing. They can be used as an educational tool and will accelerate collaboration projects, process improvements, and product commercialization.
The story
“I brought some internal process maps to the team, which then developed them into comprehensive process map documents for cell therapies and gene therapies,” said Magnus adding that the wide expertise of the team was crucial to their development. “The BioPhorum team consisted of experts from different fields who brought their experience to the project. These included specialists in GMP requirements, bio-safety levels, architecture, processing, and cost calculations.”
We used our internal process maps in 2019 when we wanted to build a production facility for bioreactorsJørgen Magnus, Strategic Program Manager at Bayer’s Cell and Gene Therapy Unit
The outcomes
“At that point, we did not know what future programs we would have or where this facility would be – in the US, Europe or wherever. So our first step was to conduct a feasibility study where we calculated the cost and timeline to build it.
“Of course, we had to design it according to what we thought our requirements would be, i.e., how many patients we would treat, which was around 4,000 patients. At a high level, the results were a projected $100m capital cost and a three-year build time, based on our Berkley, California site.” Magnus said these figures were critical to making an investment decision and allowing a proper engineering study to take place before building the facility.
“As a basis for this type of decision, you need a complete overview of the different processes that you will have. For example, if the equipment you’re buying is specific for one type of expression system or whether you can use it for the different types of processes, and how flexible your facility will be with a certain type of equipment.”
After deciding on the equipment you need, Magnus added that the next step is to design the facility, e.g., the processing floors for the bioreactors, the downstream equipment, filling rooms, buffers, media preparations etc. “This is how the BioPhorum process maps can be used, as the starting point of an engineering study.”
Benefits
“The maps give you a complete overview of the different types of processes and help you go into more specific design details, e.g., what type of equipment and its scale,” said Magnus. Example process maps include those for cell bank and plasmid preparation for transient transfection in gene therapy, and autologous and viral gene editing in cell therapy.
“They also help users connect the number of patients that need treatment with the size of your equipment and, ultimately, your facility. For example, if you want to treat 4,000 patients per year, the size of the bioreactor is one of the main design criteria for the facility because everything else is sized according to that. In that whole calculation, the process maps are very helpful.”
He suggested that it is hard to quantify the cost savings from using the process maps, other than to say that time is money, and the maps will definitely speed up the early phase of engineering projects.
At the start of a new project, there are always a few months when the team is just trying to understand it. This phase goes much faster when you can put the process maps on the table as they let you understand how a process works without having to do extensive researchJørgen Magnus, Strategic Program Manager at Bayer’s Cell and Gene Therapy Unit
Lessons learned
Magnus said that the first step should always be to understand the facility design process. “Some people might say they have a piece of land and they want to put a facility on it, so let’s see what we can fit into that building. But this is the wrong way to do a feasibility study. Instead, you should start with what you need the building for. So the question is, how many patients would you like to treat and with what kind of processes?”
He added that you should always start with your core process then design everything around that, e.g., your utilities and other requirements. “Then you go into the facility requirements, cleanroom classification, bio-safety levels, etc. After that, you go to the next layer, which is the building itself. So, you should go from the inside to the outside.”
The process maps now use improved navigation, e.g., clicking on a high-level process box that takes you to a detailed process map. “Looking ahead, I can see that the process maps could be made even better by including more detail on the processing steps and the equipment that we suggest for each one. At the same time, a second version could include more simple presentations to make them easier to read.
“BioPhorum’s CGT process maps can be used for designing a company-specific process and production facility,” said Magnus, “and are a great first step towards industry standardization.”
