Cell and gene therapies (CGT) are gaining greater popularity in the community as viable regenerative medicine options. Although there has been a lot of progress made in a relatively short amount of time, there are challenges to overcome before these treatments can become more mainstream. As a solution to the concerns with rapid, scalable manufacturing, many pharma companies are partnering with contract development and manufacturing organizations (CDMO), which are companies within the pharmaceutical industry that provide drug development and manufacturing services.
CGT CDMO has been a tremendous help to many organizations, but there are still other factors to consider and hurdles to overcome before these therapies can be more widely and easily available.
Challenges in the GMP Cell Therapy Manufacturing Process
There are several bottlenecks that stand in the way of a seamless process in manufacturing cell and gene therapies.
Cell Processing Safety
Manufacturing a cell therapy is a complex process that involves many sequential steps that need to be executed precisely, from collecting and preparing the sample to cell washing and cryopreservation (storage). Each of these steps, especially if done manually, involve a great deal of labor and, therefore, are exposed to a high risk of contamination.
Cell Manufacturing Capacity
As cell and gene therapies grow in popularity, there are many treatments already on the market and a large number of potential ones set to be brought to market in the future. To date, five CAR-T therapies have been approved by the FDA and it is expected that another 10-20 will be approved each year. Given the current facilities available, there is not enough supply to meet the future demand, even through CDMO partnerships.
Over 65% of CGTs will be outsourced to CDMO companies, however, only 5-10% of the required capacity for manufacturing exists for the next 10 years. In fact, the current wait for manufacturing capacity is 12-18 months. These manufacturing capacity issues will be exacerbated by accelerated FDA approvals as more and more CGTs are brought to market.
Currently, many CGTs are invested heavily in their Research and Development needs. The discovery of new treatments and of the methodologies needed to prepare them for safe and effective patient use is where the majority of the energy and money is dedicated in this field. In order to grow, however, there needs to be a greater investment in engineering technology that will make scaling-up and improving yields possible.
GMP Regulatory Hurdles and Approvals
A unique challenge faced by CGTs is the need to meet quick turnaround times while still meeting strict Good Manufacturing Practice (GMP) regulations. For example, in autologous (patient-derived) therapies, there needs to be a link between the logistics of the collection, storage and patient treatment of a therapy and the manufacturing process. Without this link, it is difficult to meet the safety requirements under the GMP.
In addition, GMP regulations don’t just require a quicker turnaround for the vein-to-vein loop (an industry term referring to the time and process between collection of the sample and patient treatment), but they also require manufacturing costs to remain reasonable. This, in turn, makes the treatments themselves more affordable for patients.
The Costs and Affordability of Cell Therapies
Two critical and unmet needs in the manufacturing of CGTs are costs and affordability. Currently, the drug costs for the two approved CAR-T cell therapies in the U.S. are $475,000 and $373,000 per dose, making them among the most expensive drugs on the market. The manufacturing costs for each dose of some CAR-T therapeutics exceeds $100,000, 70% of which are attributable to the labor and GMP facility costs alone. Until these costs can be brought down to a more reasonable level, it will be difficult for these life-saving treatments to become mainstream.
ThermoGenesis and the future of GMP Cell Therapy Manufacturing
ThermoGenesis Holdings Inc. offers global infrastructure and proprietary manufacturing technologies to help alleviate some of the challenges that developers of CGT therapies face. A proprietary technology like the CAR-TXpress Platform provides high efficiency manufacturing for cGMO grade cell therapies. This state-of-the-art technology increases manufacturing efficiency while reducing manufacturing costs. Our BioArchive System also provides storage solutions for cell samples. It is the number one ranked cryostorage system for clinical grade cell therapies and offers the best cell viability in the industry. Our BACS technology is a novel, closed, semi-automated system that allows the selection of specific cell types. This is an excellent solution for CGT therapies that are in the development phase.