Overcoming cell product manufacturing challenges

Angharad Baldwin speaks to Massimiliano Cesarini, Global Sales Manager of the Isolation Technology Division at Comecer, about increasing the manufacturing capacity of cell cultures using a cleanroom production facility alternative

There is growing interest in advanced therapy medicinal products (ATMPs), medicines for human use based on genes, tissues or cells, based on their promising therapeutic potential. Massimiliano Cesarini believes that many of these treatments are very close to patient approval, which will lead to mass production facility requirements to make them.

ATMPs, says the European Medicines Agency, offer “groundbreaking new opportunities for the treatment of disease and injury.” These advanced therapy products are classified into three main types — gene, somatic-cell and tissue-engineered — are subject to European legislation and must comply with Annex 1 and 2 good manufacturing practices (GMPs) to be commercialised, which has meant their production has been compared with traditional sterile pharmaceutical production.

“For the treatment of rare diseases, the amount of cell culture that’s required is limited; but, when considering the cell therapy products required for diseases such as cancer, conditions that affect large populations, the quantities of cells required are incredibly high,” comments Cesarini, “which means bigger and more cell factories are needed.”

“Living cells used in these products must be viable, pure and, most importantly, free from external contamination,” comments Cesarini. “Large quantities need to be produced without compromising on quality — and the price needs to be feasible so healthcare organisations such as the NHS can afford the treatments,” he says.

Cesarini explains: “Although the small-scale production of these cell products is quite straightforward, the transition to mass production is far from simple, requiring additional classified spaces. For manufacturing capacity to be increased, production facilities must either be expanded or the process made faster.”

Expanding a cleanroom facility is a difficult and costly task; when the new materials required, time taken for expansion and loss of continuity in production is considered, it also has arduous logistical considerations.”

Comecer has addressed this challenge with an integrated modular system. According to the company, its FlexyCult grade A incubation system, which comprises a combined isolator and incubator, achieves aseptic manipulation and cell culture expansion. Modular and expandable, Comecer believes it can be used for mass production, offering a viable alternative to expensive cleanrooms and significantly reducing the production costs of ATMPs.

Cesarini comments: “The sterility is superior because of the segregated environments in which the cells are manipulated; plus, the cells are also separated from the operator. H2O2 sterilisation can be done in the incubator when it’s empty, which has been found to be very effective.”

He continues: “The energy requirement of the FlexyCult, which can be installed in a grade D environment, is smaller than that of running the same procedure in a grade B cleanroom, as is the volume of air exchanged. Consequently, the operational costs to run the same facility capacity in terms of power consumption and environmental monitoring requirements are less. Operators can also work without special sterile gowning, saving costs in wearables and time for gowning/degowning.”

Drawbacks of this isolator approach include the retraining required for operators to work in a closed environment, when previously they were accustomed to open spaces. Comecer hopes to address this challenge and others that may occur by partnering with academic institutions, ATMP developers and manufacturers to troubleshoot potential issues. The company also hopes to improve the process of raw material introduction and implement automation to reduce labour costs.

Companies