Cell therapies are based on the premise that the patient’s own cells (autologous), or those from a healthy donor (allogeneic), can be genetically re-programmed to combat various diseases. In this form of therapy, patients are injected with living and intact human cells that are deemed to be capable of providing therapeutic benefit. It is important to highlight that cell and gene therapies have been used to treat an array of medical conditions for which no other treatments are available. Considering the vast potential of cellular therapies in the treatment of rare disorders and sufficient body of evidence validating the clinical benefits / therapeutic potential of this complex class of biologic drugs, cell therapy has garnered considerable attention of players engaged in the healthcare industry, in the past few years. The focus of stakeholders has now shifted to optimizing the cell therapy manufacturing process.
The major steps involved in manufacturing of cell therapy products include procurement of source material, cell isolation and selection, cell propagation and differentiation, introduction of transgene, cell expansion, formulation of cell therapy products and cryopreservation. It is worth noting that manufacturing process biologics and cell therapies is considerably complex when compared to small molecule drugs. Further, the development of cell therapy products require a robust population of cells that can be subjected to genetic alterations, without being damaged in this process. In order to address / mitigate the challenges and complexities associated with the current manufacturing protocols and processes related to cell therapies, stakeholders in this domain are reconsidering their present approaches, that are classified under centralized and decentralized strategies, which are applicable to allogeneic and autologous therapies, respectively.
Over the years, several advanced and innovative automation tools and technologies have been developed; these have been demonstrated to hold the potential for significant reduction in the cost associated with the manufacturing of advanced therapy medicinal products, thereby, making such products more affordable. One such emerging concept, namely GMP-In-A Box, offers several advantages, including increased throughput, decreased idle time between batch runs and reduced manual labor.
For the success of cell-based therapies, an effective manufacturing platform and a robust supply chain model is imperative. It is worth mentioning that a sustainable supply chain can actually enable further reductions in the cost of goods and, in turn, prices of such therapies.
Unlike conventional pharmaceuticals, cell therapies require a circular supply chain model. For instance, in case of an autologous cell therapy; the first step involves the procurement of input material (cells) from the patient, since these therapies are developed using the patient’s own cells. The material is then sent to a manufacturing facility and finally, needs to be shipped back to the location of the patient for administration. The key steps involved in the supply chain of cell therapy manufacturing are presented below.
There are various factors that are likely to influence the production and transportation of finished products, which typically depend on the type of manufacturing model used (centralized or localized), supply chain logistics and the import and export requirements of the process. As a result, supply chain risk management is considered to be an essential requirement in the pharmaceutical manufacturing and supply. The key considerations for effective supply chain risk assessment, based on various product characteristics include sensitivity of the product, complexity of the manufacturing process, location of the patient. A typical supply chain model involves numerous stakeholders, patients, providers, collection centers, couriers and manufacturers. However, the lack of automation, outdated analytics and immature supply chain can negatively impact the overall supply chain network of cell therapies. Therefore, it is very important that every aspect of the supply chain network is coordinated in order to establish an ideal delivery system. As a result, in recent years, cell orchestration platforms have emerged as one of the most advanced steps related to supply chain management.
However, there are several hurdles associated with the transition of cell-based therapy products from laboratory to clinical scale, such as regulatory compliance, lack of advanced facilities and infrastructure. Moreover, personnel with high levels of technical expertise and scientific acumen became a prerequisite. In addition, the technology platforms used for the development of such advanced therapy medicinal products (ATMPs) need to be approved by regulatory authorities. Owing to these inherent complexities associated with manufacturing such products, scaling up their production to the commercial level is considered as one of the major challenges in this domain. Some of the key challenges faced by cell therapy manufacturers have been summarized below.
It is difficult to scale-up the manufacturing procedures of cell therapy products. As a result, the mass production of such products is still a concern. Such procedures require sterile and higher-grade clean rooms, along with regular checks on containment levels.
Sophisticated equipment is required for the relocation, transport and multi-site distribution of cell therapy products. Therefore, the facilities where cell-based therapies are to be developed and manufactured should be established at easily accessible locations, such as near airports for overseas transitions.
Setting up cGMP facilities and obtaining the necessary qualifications and certifications is not only challenging, but also requires heavy investments. Moreover, cell production facilities should be equipped with proper storage rooms, clean rooms, cryopreservation rooms and have various other cell processing capabilities as well.
Contamination is a key concern when it comes to manufacturing cell therapy products. To overcome this, manufacturers are required to modify their current procedures in order to incorporate closed manufacturing systems.
There can be limited availability of trained and expertise staff as manufacturing requirements increase. In addition, the cost of manufacturing is extremely high and requires a large work force. There is need to have a cost-effective manufacturing process in order to make the cell therapies easily accessible to the patients.
One of the foremost risk discussed now-a-days in cell therapy domain is defined through capacity shortage.
The enrichment and isolation of mono-nuclear cells, their ex vivo expansion and the availability of raw material are amongst the other most common manufacturing challenges faced by the stakeholders in this industry.
The assays established for traditional biologics are unlikely to be suitable for cell and gene therapies. This is primarily due to the lack of reliable evidence related to the mechanism of action of cell therapies. In addition, the assays used in early stages of cell therapy research are difficult to implement at the commercial scale owing to the inherent complexities of such procedures, coupled to the fact that they are also time consuming and expensive.
Despite the challenges associated with the development and production of such therapies, we believe, that the benefits offered by them outweigh the hurdles. They are likely to serve as important drivers of the industry’s growth. Efforts to introduce automation technologies in cell therapy manufacturing are underway, and if implemented successfully, can significantly help in the elimination of human intervention and reduce the risk of contamination. As a consequence, it is likely to result in a marked increase in product consistency, ensure the maintenance of sterility, and decrease the production time and cost.
In a nutshell, more than 10 cell therapies have been approved globally while numerous other cell-based therapies are being investigated across various stages of development by both industry and academic players. This novel therapeutic modality is expected to soon represent one of the prominent therapeutic options within the mainstream healthcare.