Justin Carbungco, associate director, small-scale commercial manufacturing, Samsung Biologics

Carbungco began with what he described as a lingering question: Which is better, single use or stainless steel? He focused on cost comparisons for stainless-steel and single-use systems, including some factors for companies considering clinical and contract manufacturing.

Implementation of single-use systems is estimated to grow to ~US$33 billion by 2027. The year-end growth rate as of 2020 will be about 10.85%. For biopharmaceutical manufacturers, most single-use systems are implemented at small or clinical scale, with stainless steel remaining more prominent for manufacturing capacities greater than 2,000 L.

Key factors for deciding which system to use include balancing operational and implementation costs and assessing technical and economic feasibility, acceptable levels of product or process risk, process continuity and implementation strategies, and basic logistical approaches for using systems in day-to-day operations. Economic factors include cost of goods, labor, and utilities. For supply-chain management, stainless-steel systems are less dependent than single-use systems on consumables.
Precommercial capacity, especially for upstream processing, currently is dominated by single-use systems. Titers from production bioreactors have been increasing and now average five to 10 g/L. But single-use implementation downstream has not had much growth because yield improvement is only about 5%. The most practical limit for single-use systems (the current “sweet spot”) is at the 1,000-L to 2,000-L scale. Systems larger than that are reported to be unwieldy and hard to install for use in day-to-day operations. That, of course, may change as the technology is improved and refined.

For scalability, single use leads in small-capacity operations, whereas stainless steel is still more cost effective for large-scale manufacturing, reducing costs by $60–$100/g from those of large-scale single-use operations. Single-use systems still are confined primarily to products from mammalian cells, whereas stainless-steel systems can be used both for mammalian and microbial products.

Carbungco spoke further about relative costs. For single-use operations, the cost of consumables (e.g., filters and bags) will grow over time. But single-use systems can reduce utility costs — electricity, clean-in-place and steam-in-place (CIP and SIP) systems, and so on — and therefore occupy a smaller facility footprint than do stainless-steel systems. Stainless steel, on the other hand, is a single, hard-piped installation that cannot offer the flexibility of modular adaptations.

Assessing risks and associated costs focuses attention on reducing turnover times and preventing contamination. Using disposable systems is the most effective way to eliminate cross contamination from product to product or batch to batch, whereas stainless-steel systems must undergo CIP and SIP operations, pressure testing, and other processes to mitigate contamination. Stainless-steel systems, on the other hand, do tend to be more robust in resisting equipment damage, whereas detecting microscopic damage to single-use systems can be harder during normal inspections.

Carbungco spoke about supply-chain management issues thus far during the COVID-19 pandemic, noting that the entire industry’s supply chains have been compromised severely. Manufacturers and vendors have had to accommodate working operations to comply with government recommendations about practices such as social distancing, reduced work hours, and reduced labor forces in certain parts of the world. Samsung has noticed a kind of hoarding mentality compounded by a higher demand for consumables from vendors. Industry-wise, companies want to prevent interruptions in production and manufacturing schedules, but the supply is not adequate for that higher demand. Lead times have been increasing from three or four months to five or six months or even longer. If new equipment is purchased, lead times could increase to up to a year.

A Samsung task force currently is assessing critical risk factors in the company’s supply chain in relation to the COVID‑19 pandemic. Carbungco works in a small contract manufacturing organization for Samsung Biologics, which houses two 1,000-L stainless-steel production bioreactors and two single-use 1,000-L production bioreactors. The group works closely with the company’s large-scale contract manufacturing organization to accommodate a full range of client processes.

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