In recent years, GEN has reported on single-use bioprocess bags, connectors, sensors, and tubing many times. The benefits of disposables are, by now, well known and do not require repeating. An early knock on disposables was their limited volume, but the debut of 2,000 L bioprocess containers, accompanied by dramatic improvements in protein titers from cell cultures, dramatically expanded the scope of disposables. Yet, Sartorius Stedim Biotech estimates that single-use equipment has penetrated less than 20% of its potential biomanufacturing market.
One GEN reader, T&C Stainless CFO Todd J. Cook, takes issue with the single-use mania, citing environmental and cost issues and arguing—with some justification—that reporting on disposables paints an unduly rosy picture. “I have watched the growth of single-use systems from the beginning, and I do realize they have their place. Stainless does cost more in the startup phase of a [biopharmaceutical] product, but it must be less costly during manufacturing due to the ongoing cost of bags, and their subsequent disposal as hazardous waste.”
Cook recognizes the need for flexibility in one-off processes, in multiproduct facilities, or early in development when the cost of investing in stainless equipment may not be justified. But stainless steel is preferred in single-product plants, particularly immediately post-approval. “I know of stainless systems that have been in use for 20 years or more. The cost of single-use systems during that period would be vast.”
But proponents of single-use equipment point out that bioreactors are just one variable in the cost equation. Cleaning materials used to sanitize steel tanks, including high-purity water, are expensive and carry a significant carbon footprint and time investment that rapidly adds up. The cost of electricity that powers a facility during downtime adds to the environmental impact per batch. Then there are the substantial human resource costs associated with documentation and cleaning/validation operations.
Plastics have environmental consequences as well. Plastics manufacture carries a significant carbon footprint, uses nonrenewable feedstocks, and involves environmentally unfriendly disposal. “I was in the plastics industry for 15 years before my present position,” Cook told GEN, “and have seen the cost associated with producing plastics from crude oil, the production of the product itself, and the cost of disposal. Recycling [of bio-bags] is out; landfills are not an option due to the fact that the bags are biohazards, and even if they could be put into a landfill they never break down. That leaves incineration, which is costly and not environmentally friendly.”
Single-use process bags provide fewer paths for problem recovery, observes George Moyer, director of business development at Broadley-James. For example, if a 1,000 L stainless steel CHO culture foams and fouls an exhaust filter, it is possible to isolate or change the filter. “With a single-use bioreactor, if you foul a filter and you don’t have a replacement read to uncap and install, the game is over. The run is finished.”
Another potential issue arises from contaminated batches, and how to dispose of the culture. “With steel tanks you press the ‘auto-sterilize’ button and run the fluid down the drain,” Moyer says. “Disposables require the use of a chemical disinfectant, which may or may not be effective.”