Science Pool

Continuous Biomanufacturing in Agile Production Facilities

Posted by Evotec on Mar 15, 2024 2:20:55 PM

Patients around the world need access to affordable biopharmaceuticals to treat life-threatening conditions. High manufacturing costs can make these medicines unaffordable and limit their use amongst global patient populations. Historically, the biopharma industry has manufactured these medicines in large-scale stainless steel production facilities. Such facilities take years to construct and require over $500M of upfront capital investment. The cost of manufacturing biologics in these production plants is high and especially inefficient when asset utilization is low.

To reduce production costs, the industry increasingly recognizes that the next generation of production facilities must break with existing manufacturing paradigms. New facilities must be small and agile with intensified manufacturing platforms that allow extremely high productivity to meet late phase clinical and commercial demand.

 

Agile J.POD Facilities

Just-Evotec’s J.POD facilities apply modular technology to reduce the footprint of cleanrooms. Our facility design minimizes the expensive utilities needed to run a stainless-steel plant and instead leverages fully single-use and continuous biomanufacturing platforms. We culture mammalian cell hosts in perfusion bioreactors that we connected to a continuous purification train. In this way we can sustain volumetric productivities of over 2 g/L/day and continuously purify antibody during the production run making efficient use of production equipment.

The CAPEX associated with a J.POD facility is less than $200M. Our J.POD Redmond facility is operational in Washington, USA while we will bring a new European facility online in Toulouse, France in 2024. These facilities in two geopolitically stable locations will provide our customers with additional supply chain security.

 

Comparing J.POD to Traditional Facility Designs

Just-Evotec Biologics production engineers use models and associated visualization tools to optimize production costs. These tools show the relationships between facility design, production demand and drug substance manufacturing costs. Our engineers created mathematical models of a large-scale stainless steel and our J.POD facility. They used Net Present Cost (NPC) to compare scenarios. NPC estimates cash flows by computing operational costs and discounting over time using a capital parameter. It does not include revenues in the accounting of cash flows and assumes capital costs incurred at the beginning of the project are sunk costs.

Engineers took the following approach to compare the stainless steel and J.POD facility designs:

  1. They generated 512 different patient population curves. (example is shown in the lower graph of Figure 1)
  2. They estimated bioreactor capacity and utilization needed to deliver the mass of product required by these patient population curves for both facility types. (example is shown in the middle graph of Figure 1)
  3. The engineers ran the model to estimate the manufacturing costs associated with each facility production mass output. (example shown in in upper graph of Figure 1).
  4. The team used NPC calculation to produce a concise estimate of cash expenditures over time and normalized these values by their corresponding mass outputs. They assembled histograms to visualize the underlying statistical distributions behind a particular facility configuration (Figure 2).

 

Fig 1

Figure 1. The determination of manufacturing costs associated with two different biopharmaceutical manufacturing facilities producing sufficient drug product to meet the needs of a specific patient population curve.

Figure 1 shows that a stainless-steel facility has a higher initial cost at Year 0 because of the high capital expense allocation and has higher fixed costs than the J.POD facility over the operating period.

Figure 2 shows the benefits derived from the agility of the J.POD facility design. The NPC over the operating period was lower in the J.POD facility than the stainless-steel facility in every scenario modeled. The width of the NPC distribution for a POD-based facility is narrower than that of a stainless-steel facility. The production costs associated with a J.POD facility are largely independent of capacity utilization because of the lower upfront capital costs. Furthermore, managers have the option to expand capacity if needed by reacting to market demand estimates on a yearly basis. This is a significant advantage of the J.POD facility because managers can tailor plant capacity within the network to the latest market projections, making it more capable of reacting to disruptions or demand fluctuations.

Fig 2

Figure 2: Histogram depicting normalized Net Present Cost (NPC) estimates for both facility types.

 

Agile Efficient Biomanufacturing

J.POD facilities are inexpensive to construct and commission due to their small size and use of single-use technologies that limit the amount of plant utilities needed. We can quickly deploy these assets in response to fluctuations in demand forecasts. Production within J.POD facilities is very efficient due to the continuous manufacturing platform and the ease with which we can modulate capacity to maximize asset utilization. J.POD facilities are leading the transition away from expensive large-scale stainless steel production assets towards more agile and lower cost biopharmaceutical manufacturing. Access to these remarkable facilities is available to Just-Evotec Biologics customers through our innovative partnering arrangements. Together with our partners we are reducing the costs of biologics and making them more accessible to patients around the world.

Read the Full Article Here

Tags: Blog, Biologics