Invetech cell therapy formulation and fill platform

The high cost of producing new cell therapies, particularly gene-edited cell therapies such as CAR T-cell therapy, for example, are notoriously expensive. Advancements in manufacturing are driving costs down, but not at the required pace. The complex manufacturing process that these biological treatments require means that their price is currently at a premium. In this article, we focus on ways to drive down the cost of manufacturing autologous cell therapies, as explained in a recent Cell & Gene Live event.

The ‘Can Innovation Drive Down Cell Therapy Manufacturing Costs?’ on-demand webinar featured panelists Dr. Mark Gilbert, SVP of R&D of Acepodia; Thomas Lequertier, Head of Cell Therapy Manufacturing Unit of Celyad Oncology; and Ludek Sojka, Ph.D. Chief Technology Officer of SOTIO, who discussed how both autologous and allogeneic cell therapies alike are impacted by the high cost of manufacturing.

The why behind cell therapy manufacturing’s hefty price tag

Cell therapy laboratory

Most cell therapies today are produced one dose at a time, using the patient’s own cells as the starting material. This approach is very labor-intensive, failure prone, and extremely difficult to scale with manual methods. And so it goes with autologous cell therapy manufacturing, as it comprises many handling steps (e.g. density gradient cell processing, washing, and feeding) that require considerable labor-intensive interventions from skilled operators.

Skilled labor tends to be the greatest cost followed by materials, which include solutions for processing and QC testing. “The main challenge that we face with autologous CAR T-cells is that they are single-lot products,” says Gilbert. “Therefore, every time we develop a product, we must perform all of the quality testing; we have to repeat multiple steps within manufacturing in order to produce that product. Plus, we incur the complexity of gene modification.” Gilbert notes the surprising aspect that has added or contributed greatly to the cost of manufacturing is the use of viral vectors. Additional expenses are incited, because regulatory authorities treat viral vectors not as a key raw material but rather as a drug substance.

The global viral vector manufacturing market accounted for $227.63 million in 2017 and is expected to reach $1013 million by 2026 growing at a CAGR of 18.0% during the forecast period. According to APNews, based on geography, North America holds the major market share during the forecast period owing to rise in research activities, many regenerative medicine companies, increase in the prevalence of target diseases and availability of funds.

A shortage in manufacturing capacity

If North America holds the major market share, where does it stand on capacity? According to McKinsey & Company, a shortage of manufacturing capacity and talent is exacerbated by logistical issues. The industry faces a well-known viral-vector capacity constraint and a limited number of third-party suppliers, so manufacturers must either invest heavily to build in-house production or lock down contracts with viral-vector manufacturers.

In addition, the lenti- or AAV-based approaches are often time-consuming and inefficient. And, the logistics for manufacturing and delivering cell and gene therapies are always hard. Especially with autologous cell therapies, supply chains require a high degree of logistical precision, which is harder in the absence of local manufacturing capacity.

The process can be slow – often too slow for patients in the late stages of a disease. But further delays can be caused by any number of local issues when so many different personnel are involved at different sites, using different systems, and when several different couriers might be involved. The slightest disruption — a patient’s apheresis appointment delayed, for example — can disrupt the entire supply-chain flow.

McKinsey & Company further states that the sensitivity of supply chains has been highlighted during the COVID-19 crisis, when two-thirds of cell therapy companies surveyed reported supply-chain disruptions because of travel restrictions.

True innovation for autologous manufacturing

Cell therapy manufacturing

For autologous cell therapies, the major pain points are patient-to-patient variability in the starting material, multiple manufacturing spaces to increase throughput, and variability in the overall yield of the final cell product. There are many closed system and automated technology solutions being developed that will provide incremental improvements to process robustness, reproducibility, and sterility assurance. These technologies may also reduce labor needs per batch helping to reduce costs.

“I do believe that innovation will come incrementally to autologous cells,” explains Gilbert. “But when you are talking about true innovation, think back to the first principles of cell source and look for pools of allogeneic cells as a source or a cell line. NK cell lines that are available offer that opportunity. The second piece is the complexity of genetic modification — if there is a way to avoid genetically modifying cells yet redirect them to the target for a reasonable period — that becomes a real innovative shift from a regulatory standpoint and will probably reduce costs significantly.”

The importance of partnership

The typical early-stage cell therapy company lacks the resources for implementing internal manufacturing capabilities. Instead, they outsource to fulfill their manufacturing demands, particularly during pre-clinical and early stages of clinical development. Different products have different needs, but Cell & Gene Live panelists strongly suggest that biotechs identify a reputable market partner that focuses on automation.

For autologous therapies, the patient stands at the beginning and end of the supply chain, and therefore, proximity of manufacturing to patients is key to reducing complexity. The partnership should be comprised of a fully integrated offering, including logistics, scheduling, distribution, chain of custody, chain of identity, etc.

“Of course, before you identify a market partner, be sure to evaluate the products already on the market,” explains Gilbert. “There are different products that allow for very efficient culturing of cells. We evaluate those products, those devices, first. And then, we potentially work with the partner to focus on the automation aspect to develop something more specific for the products.”

“Some manufacturing solutions require cell therapy manufacturers to modify their process to fit the manufacturing system, leading to costly qualification and possible re-validation activities,” says Anthony Annibale, Global VP, Commercial, Invetech. “Instead, by using configurable platforms that can be programmed to fit the manufacturers’ unique processes allow for increased inter-batch consistency, increased cell recovery, and viability while being cost-effective over the long-term.”

The shifts in the industry toward improving manufacturing efficiencies will lead to a positive change in the cost structure of personalized medicine. Specifically, this will allow for more cost-effective manufacturing of autologous cells.

Cell and gene webinar

Watch the full webinar on Cell& on demand.

This article was originally published on Cell & Gene and has been republished with the permission of Cell & Gene.  

Byline: Erin Harris, Editor-In-Chief, Cell & Gene