Decisions made during the conceptual design of a manufacturing asset for cell therapy products (CTP) have consequential impacts on not only facility capital costs, but also on the cost of goods (COGs). During clinical trials, there is tremendous focus on trial costs as companies move into phase 3 trials. Decisions made years before in facility design can impact these per-patient values more than many might think.
The design of a manufacturing process for any biopharmaceutical product involves a proven methodology that includes criteria such as operating costs, capital investment costs, and manufacturing reliability and efficiency.
Costs for raw materials, reagents, starting materials, labor, utilities and consumables will be driven by market conditions, and there is little impact that can be influenced to reduce/improve this market reality. But the facility attributes that impact day-to-day operational costs and manufacturing efficiency, once established, will become the baseline. Speed to market, flexibility and efficiency, and regulatory qualification/compliance are impacted as COGs are baselined.
Developing a COGs model
Implementing COGs analysis during early phase facility planning sheds light on areas of operational cost risk, future per-patient trial costs impacted by facility attributes and identification of options for consideration in equipment selection and facility design. By looking at COGs distribution for each clinical phase, it can be easy to see where facility design decisions have the greatest impact. The costs from personnel, materials/supplies, equipment and facility attributes significantly impact overall operational costs.
Developing COGs values that are specifically driven by the attributes of the process-facility relationship will focus on a set of inputs and outputs that have a direct day-to-day impact on operational costs and manufacturing efficiency. The key is to have a tool that will provide the necessary data for evaluation while also making the data accessible during the design phase of the project. As design attributes change, so will the data. The tool should be ‘user friendly’ and easy to implement.
The inputs required to evaluate manufacturing costs should include:
- Personnel requirements
- Unit operational data
- Batch size
- Operational scale
- Qualification data
- Materials and consumables
For early phase design development, the focus will be on defining the established fixed costs that can be supported with available data. This will include:
- Equipment sizing/vendor data: In the model process, all unit operations are performed in single-use components. This is driven by scale of operation, flexibility, and level of automation. For this model, unit operations are assumed to remain manual-focused during the clinical manufacturing phases, as many CAR-T operations are today. Key information would include: product protection via equipment solution (BSC/isolator); cell processing via cell enrichment, cell washing; concentration; filling; and cryo storage.
- Utility consumption: Load calculations based on facility attributes such as HVAC unit sizing/zoning and average energy cost (localized).
- Area sizing/classification in regards to energy usage intensity and operations schedule
- Cost of consumables — such as bags, micro beads, bottles, pipettes and tubing — based on target manufacturing outputs.
There will also be a need to identify key assumptions necessary to complete the COGs model. You will need to factor in batch targets based on manufacturing time durations, testing requirements, headcount full-time equivalent, energy costs, annual maintenance costs and unscaled facility costs (tax rates).
The cost of any form of biological product is weighed against its therapeutic cost-benefit analysis and by assessing the relative costs of manufacturing. The affordability of many CTPs is often driven by factors related to development, clinical manufacturing logistics, and facility optimization. Specific factors to consider include analytical testing, operational attributes, product protection strategy, manufacturing logistics and technology solutions.
Since many CTP processes are not yet considered ‘robust’ due to their lack of manufacturing support data, the question around COGs is not always given its appropriate emphasis during early phase design activities — but it should be.