Cancer is relentless. Worldwide, an estimated 19.3 million new cases were diagnosed, and nearly 10 million deaths occurred in 2020.1 The global burden is projected to reach 28.4 million cases by 2040. While the first-line treatment has been surgery, chemotherapy and radiation, these statistics, combined with a deeper understanding of the immune system, are motivating researchers, drug developers and manufacturers to attack the disease in new ways.
A sea change in the way cancer is treated began in 2017 with FDA approval of two chimeric antigen receptor (CAR) T-cell therapies for treatment of children with acute lymphoblastic leukemia (ALL) and adults with advanced lymphomas. The field of immune cell therapy continues to expand: CAR-NK therapies, for example, carry the promise of “off-the-shelf” treatments, being readily available, more cost effective, and potentially offering fewer side effects than CAR-T therapies.
The potential of such precision immunotherapies to deliver durable patient responses is tantalizing. In 2020, the number of CAR-T therapeutic candidates in the collective global pipeline increased by approximately 50% from 2019.2 The predicted annualized growth rate of the CAR-T therapy market is 31% from the period encompassing 2019 to 2030 and will be worth $11 billion by 2030.3
Along with the potential of these therapies come significant challenges for their development. One obstacle garnering significant attention from both biopharmaceutical companies and technology developers is the high cost of goods sold (COGS) incurred during the manufacturing process.4 5
In 2019, it was estimated that the COGS for CAR-T cell manufacturing processes was $95,780 per dose for an autologous therapy and $4,460 per dose for an allogeneic therapy.6 This estimate included the cost of consumables, QC, fill and finish, transport, facility, and staffing requirements. Autologous cell products incur a premium cost for production as they are personalized to the patient, which reduces the risk of host rejection and side effects. On the other hand, while there is a greater risk of host rejection with allogeneic CAR-T therapies, their manufacturing costs are lower due to economy of scale and capacity to prepare multiple doses per batch from an established, validated donor with a known profile. Allogeneic products can also be stored as cryopreserved batches and are available for immediate use, an important resource for emergency treatments. Still, if the trade-off between personalization and cost is patient safety versus accessibility, it becomes clear that much still needs to be done to make both approaches safe and affordable. In the meantime, the immune cell therapy market currently skews heavily toward autologous options, while research and development of allogeneic methods are being tirelessly pursued. Along with the potential of these therapies come significant challenges for their development. One obstacle garnering significant attention from both biopharmaceutical companies and technology developers is the high cost of goods sold (COGS) incurred during the manufacturing process.4 5
The high cost and extended processing time to produce CAR-T cell therapies can be exacerbated due to:
- Inefficiencies in labor in the manufacturing process
- Inadequate process control and challenges in QC
- Lack of raw material consistency that introduces variability
- Supply chain disruptions and logistical challenges
- Overall lack of process knowledge and a means to develop it
These same factors can also impact the consistency, potency, and safety of cell therapy products, compromising patient health.
What can be done to streamline the manufacturing process, make it more robust, and help reduce costs, all while maintaining the quality of immune cell therapies? The answer lies in simplified processes, increased automation, improved consistency of raw materials, integration of unit operations, and use of digital analysis tools that reliably deliver the desired product specifications. This collective imperative may seem like a tall order, especially taken against the rapidly evolving landscape of regulatory requirements. Fortunately, new approaches to the manufacturing of immune cell therapies can be facilitated and de-risked by considering key pain points early and engaging in strategic collaborations with experienced partners.
In this series of articles, we will explore means of addressing these pain points that can enable accelerated and cost-effective manufacturing. Undoubtedly, overcoming these challenges and reducing COGS will play a foundational role in sustaining the momentum achieved in the early days of these revolutionary approaches to defeating cancer.
1. Sung, H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May; 71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID: 33538338.
2. Yu JX, et al. (2020). Cancer cell therapies: the clinical trial landscape. Nat Rev Drug Discov., Sep;19(9):583-584. doi: 10.1038/d41573-020-00099-9
3. Roots Analysis (2019)."The Global T-Cell (CAR-T, TCR and TIL) Therapy Market, 2019-2030 (4th edition). https://www.rootsanalysis.com/reports/view_document/global-t-cell-car-t-tcr-and-til-therapy-market-4th-edition-2019-2030/261.html
4. Simaria AS, et al. (2014). Allogeneic cell therapy bioprocess economics and optimization: single-use cell expansion technologies. Biotechnol. Bioeng. Jan;111(1):69-8. doi: 10.1002/bit.25008
5. Graham C, et al. (2018). Allogeneic CAR-T Cells: More than Ease of Access? Cells. Oct 1;7(10):155. doi: 10.3390/cells7100155
6. Harrison RP, et al. (2019). Chimeric antigen receptor-T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods. Cytotherapy. Feb;21(2):224-233. doi: 10.1016/j.jcyt.2019.01.003