Is Scalability Possible for Patient-Specific Cell Therapy?

The traditional method of achieving scale in manufacturing is, typically, to increase production capacity so that more product can be sold. For example, with medicines such as aspirin, the manufacturer can achieve an economy of scale by maximizing the number of doses they make. Since these products have a long shelf life and can be administered to nearly anyone (assuming the patient doesn’t have an allergy), making more doses increases the profit potential of the product. While “over-the-counter” products can use this method to increase production, patient-specific cell therapy (PSCT) products cannot.

Unlike OTC medicines such as aspirin, which can be used almost universally, patient-specific cell therapy products are collected either from the patient or a matched donor—meaning that there’s a 1-to-1 collection and treatment ratio. It doesn’t matter if the harvested cells are enough to make one treatment or 1,000 treatments—that batch of cells is only going to be used for one patient.

With this in mind, a common question would be “is scalability even possible for patient-specific cell therapy products?”

Yes, it is possible to achieve scalability in limited ways with PSCT products, but it requires a different approach from the one typically used with over-the-counter biologics. In the case of PSCTs, this is called “scale-out” rather than “scale-up”. Here are a few methods that cell therapy developers can use to achieve scalability with their patient-specific products:

Use a CDMO to Offset the Cost of Excess Capacity

One of the major challenges in achieving commercial scale for a PSCT product is the fact that demand for the product will fluctuate. It is entirely possible to go from needing to manufacture 20 doses in a month to only needing to make 1 dose a month or vice versa. And, because the product has to be collected from the patient or a matched donor, there is no stockpiling doses in advance to prepare for busier months.

Some cell therapy developers might want to add extra manufacturing capacity so they can meet demand during peak periods. However, this extra capacity would go to waste during the slower months—increasing the cost of goods (COGs) for the cell therapy product substantially. One way to avoid this problem is to use the services of a contract development and manufacturing organization (CDMO).

A CDMO helps minimize the risk of excess capacity costs while improving the scalability of a patient-specific cell therapy product in a couple of ways:

1. The addition of the CDMO’s facilities helps developers increase their overall manufacturing capacity and distribution area.
2. When demand for the cell therapy product is low, the CDMO can potentially shift focus to other products, so their production capacity isn’t sitting idle.
3. CDMOs house experts with a wealth of knowledge which can prove instrumental in improving the manufacturability of your product.
4. Often, CDMOs will already have invested in capital and infrastructure, therefore reducing the cost of starting manufacturing.

However, this does require choosing the right manufacturing partner to ensure that the manufacturing process is scalable, consistent, and able to produce a product that matches your definition.

Reducing Cost of Goods Per Dose

Another key method for improving the scalability of a PSCT product is to minimize the cost of goods as much as possible. Reducing the COGs for a patient-specific cell therapy product helps to improve the long-term viability for the cell therapy product.

There are many ways to optimize the cost of goods for a cell therapy product, including:

• Creating Closed Systems to Optimize Processing Space. Normally, cell therapy manufacturers cannot share the space being used to make one patient’s batch with batches for other patients. However, by creating closed systems for cell therapy manufacturing, it is possible to share one processing or operating space between multiple products simultaneously. This helps improve scalability by increasing the number of patients that can be processed at once.
• Integrating Multiple Steps to Simplify Processes. Many processes involve steps that use different devices and apparatuses. By finding ways to combine steps or simplify processes (such as the authors of this paper on anti-CD19 CAR T cells propose), cell therapy developers can reduce the time and resources spent on manufacturing individual product doses.
• Using Automation Tools in Cell Therapy Manufacturing. In PSCTs, when you automate something, you can potentially cut process time and save money. Automating even a simple task can be an enormous time-saver. And, automation isn’t necessarily limited to the manufacture or processing of cell therapy products. For example, automating data collection can save time and reduces human error deviations when the volume of production is large enough. Considering that a single deviation can cost 8-10 hours of labor to rectify, using automated electronic batch records to prevent deviations can provide significant savings.
• Elimination of Extraneous Processes. In some cell therapy manufacturing processes, there may be quality control (QC) steps that were added at one point which may not be necessary or even helpful at a later stage. It’s important to take a look at each step of the manufacturing process and ask: “Why are we doing this? Can this be done in another way?” Eliminating extraneous processes helps to simplify the overall manufacturing process and reduce costs.

All of these methods can be used to address the cost of goods in a cell therapy manufacturing process—which is a cornerstone of the Development by Design (DbD) process. One key part of DbD is making sure that these COGs issues have been addressed as early as possible in the development cycle. This way, time, money, and effort may be spared during later cycles.

Using Cryopreservation to Improve Scalability

Cryopreservation of cell therapy products is catching on as a solution to the problem of scalability for patient-specific products. The process of preserving cells at low temperatures to extend their viability offers several potential benefits, including:

• Increased Distribution Area. Being able to freeze cells to extend their useful life makes it easier for a single manufacturing center to cover a larger area. Shelf lives of mere hours can be extended to several days. This helps increase scalability without the expense of adding new manufacturing facilities.
• Improved Flexibility of Transport Timing. When a cell therapy product’s shelf life is measured in hours, that puts tight restrictions on when the product can be manufactured and shipped. By cryopreserving cell therapy products, it is possible to extend the product’s useful life long enough to make logistics for shipping standardized—which is a must for reducing the COGs in manufacturing.
• Less Risk of Drops in Demand. With a larger distribution area comes a larger pool of potential patients for a cell therapy product. This helps to somewhat alleviate the risk of a sudden drop in demand for a product.

However, cryopreservation isn’t a perfect solution, there are risks and challenges involved in the process.

For example, cryopreservation has to be available at both ends of the supply chain to achieve maximum impact. If you need fresh, live cells from the patient but cannot get them, that will still limit the reach of a patient-specific cell therapy product.

Additionally, the cost of developing a preservation process that’s compatible with your cell therapy can be significant because it adds new unit operations to both your cell collection and product distribution.

Finally, because there will be new processes to preserve collected cells and to thaw final product cells at the clinical site, there may be a need for extra training at the clinical sites to reduce the likelihood of damaging the cells—the transition from the frozen state to the thawed state (or vice versa) can cause damage if mishandled or used on the wrong cells. This can impact the function of the final product cells.

When considering the use of cryopreservation for a cell therapy, it’s important to make that choice early on in clinical development. This is because the introduction of cryopreservation late into the development cycle may means making major changes to the product’s definition—creating a large amount of difficult and delicate work that brings with it comparability risk for your manufacturing process.

Need help in achieving larger scale and/or commercially viable manufacturing with a patient-specific cell therapy product? Contact the experts on the PCT services team today for advice and information about how you can improve scalability for your cell therapy product. Or, read chapter one of our guide on developing commercially-viable cell therapies at the link below: