As the Observatory on Advanced Therapies reveals, “currently all Car-Ts on the market are obtained through a centralized production process”: the biological material taken from patients is sent to “a few highly specialized production workshops” and returns to the patients after a average time of 16-30 days. This wait, however, can easily be prolonged. According to Maria Whitman, global lead of pharma and biotech practice at consultancy ZS Associates, “the complexities of handling and transporting a biologic product, combined with the remoteness of a laboratory or hospital, can add days to , if not weeks.”
Shorten the time
For centers located in the US, the process cannot even begin until the patient’s insurance company has given its approval, a process that can take up to two weeks. Limits in the production capacity of specialized companies can also have an impact: a study published in Frontiers in transplantation states that “patients often wait up to three weeks to access a manufacturing slot, the date on which the company can receive the biological product to start cell production.” Naturally, during this period, the clinical conditions of many patients – who are often treated for very aggressive diseases, such as tumors – can significantly worsen.
The costs of centralized production
Centralized production also involves very high costs, partly due to the need for long special transportation and cryogenic storage of the product. According to various estimates, the cost of a Car-T infusion in the USA is around 4-500 thousand dollars, although the entire treatment (which includes preparation, infusion, hospitalization and management of side effects) can easily reach significantly higher amounts (in 2019 it was calculated as up to one million dollars). These are extremely burdensome costs for the healthcare systems of developed countries but which become prohibitive for the majority of the population of developing countries. As approved Car-T products and their indications continue to increase, scientists are urgently searching for alternative solutions.
Different decentralization systems
The most popular model is the so-called “Point-of-care” (POC), which involves delocalized production near the health center where the patient receives the treatment (if not even inside it), significantly reducing the times and associated risks to cell transport. Two researchers from Harvard Medical School dedicated a study – published in Nature Biotechnology – to decentralized production (local manufacturing). According to their research, this solution “would greatly contribute to meeting growing demand” but to ensure a successful implementation it is essential to leverage new technologies to ensure uniform product quality even in geographically dispersed facilities.
The role of digitalisation
The article suggests the use of “automated cellular manufacturing systems, inline sensors, and process simulation to improve quality control and efficient supply chain management.” There is no shortage of attempts to apply this theory: the startup Cellares, for example, presented its “factory in a box”, a completely closed system that uses software and robotics to automate the processing of cells by eliminating the variability and the risk of human error. Ori Biotech, on the other hand, is studying a robotic system that integrates automation and data analysis and promises to reduce the production time of Car-T therapies to just seven days.
Work out the kinks
The presence of a multitude of production centers also introduces new problems, for example it makes it more difficult for regulatory authorities to carry out effective controls. According to the authors of the study in Nature, this obstacle could be overcome by involving other organizations, such as accreditation bodies, in control activities: according to their calculations, in the United States there are already 116 organizations that comply with the necessary standards. The agency could in turn conduct audits of representative samples of accredited establishments. Finally, they suggest changing regulatory standards “to account for the unique characteristics of distributed manufacturing models.”
