Despite the advances the cell therapy industry has made in recent years, commercially viable manufacturing continues to be an elusive challenge. In order for the cell therapy industry to succeed long-term, it will be crucial to migrate from a clinical-scale process in which tens to hundreds of patient doses per year are made, to a commercial-scale process that can provide thousands of patient doses per year.
For this to happen, the number of batches produced must increase. However, unlike traditional biologics, such an increase in scale will not reap the same economic reward in patient-specific cell therapies. Therefore, the industry must identify further ways to make commercial manufacturing affordable and achieve market success. One way to achieve this increase in scale, without escalating costs, is to use controlled, non-classified spaces (CNC). Although still cleanrooms, these CNC spaces have a reduced burden of monitoring compared to traditional cGMP cleanrooms such as GradeA/ISO 5 through Grade D/ISO 8 as described by Federal Standard 209E that in 2001 was superseded by ISO 14644.
A New Frontier for Cell Therapy
While CNC space is being used more frequently within biopharmaceutical manufacturing, this is a relatively new approach for cell therapy developers and manufacturers. CNC spaces are still cleanable, access controlled and use filtered, ventilated air like the cleanrooms utilized today. One of the biggest risks to using this type of space versus using a cleanroom is if something goes wrong during your process. For example, if there is an unexpected leak, suddenly open manipulation is required. For this you would need a cleanroom space that you could transfer the process to in order to prevent further contamination.
Before this risk can be mitigated the process needs to be amenable to manufacture within the CNC space. The major hurdle for this is being able to have a completely closed system. This is a feature that requires development, sometimes extensive, but is not impossible. Here at PCT we have developed and now manufacture on behalf of a client a completely closed process.
There are a lot of unknowns as we begin to shift into this type of manufacturing space. And at this time, there are no cell therapy manufacturers who are using this approach…yet.
Change is in the Air
With the cell therapy industry advancing so rapidly and the need for these types of products growing at an exponential rate, it is critical for cell therapy developers to explore ways in which to scale their processes while maintaining quality. Surprisingly, it’s relatively straightforward to convert a cleanroom into a CNC space. While you would still need to control the temperature and monitor airflow, you are able to reduce the air change rate (ACR) and the required environmental monitoring (such as microbial and particle monitoring).
By utilizing CNC space, commercial-scale manufacturing would not only be a reality, but the overall cost could be greatly reduced. Lower operating expenses would incur from a reduction in processes such as gowning, HEPA filters and environmental monitoring, which can be costly. Also, you could yield reduced energy consumption through gas and electricity, which can be more expensive than realized. For new facilities, a reduction in the number of HEPA filters, temperature ranges, humidity control and ACR can all provide significant savings.
However, it’s important to note that with change, comes risk.
Moving from standard cleanrooms to CNC spaces would initially create regulatory challenges. The first companies to implement this type of space in cell therapy processes would have to work very closely with regulatory agencies. Nevertheless, because the biopharmaceutical industry is already utilizing similar spaces and creating a path forward, there is most likely existing documentation and regulations that could be used as a great starting point.
At PCT, we recognize the need for new concepts in order to achieve long-term success. We’re here to help answer questions and explore the ways we can begin to utilize CNC space as a way to greatly innovate cell therapy manufacturing. Click the button below to learn more.
