Point of Diminishing Returns?
Squeezing green efficiencies from upstream bioprocesses is difficult as biomanufacturing is green to begin with, at least compared with small molecule manufacture. Operational efficiencies, process de-bottlenecking, and unit operation schedule optimization can help, as can savings gained through more efficient heating, cooling, and material transfer.
Yet, these have paled against improvements in volumetric productivity, says Joseph Tarnowski, Ph.D., senior vp of biologics manufacturing and process development at Bristol-Myers Squibb. Rising protein titers save not only on ingredients and waste, but they reduce process volumes and processing times. These benefits come at the expense of placing more pressure on downstream operations, which must keep up with upstream output. Another rub of higher upstream productivity that is less easily resolved, is lower utilization of workers and equipment.
Dr. Tarnowski says that BMS is instituting additional efficiencies, like shortening capture chromatography operations or reducing the number of separations steps. Another initiative at BMS involves online mixing of buffers, which conserves process and clean-up water. BMS is also looking into replacing a WFI rinse at the beginning of vessel cleaning with rinsing with softened water. “We’re still consuming water, but it’s not of such high-purity.”
The drive toward sustainability will only work if companies examine the benefits and costs honestly, and if efforts are based on science and sound economics rather than public relations.
Joseph H. Kennedy, Ph.D., principal research scientist at Eli Lilly, has cautioned against a simplistic view of green chemistry, specifically in the preference for aqueous waste streams over organics. For example, recycling for many mixed organic-aqueous solvents may be more problematic than for pure organics. Even 100% aqueous waste streams pose disposal issues since they may not be flushed into municipal sewers but must be dealt with, often as biohazard waste. Companies must remove the water or burn the effluent, solutions that consume copious quantities of energy and carry an independent environmental impact.
Energy consumption, recyclability, and disposal costs, which together reflect environmental burden, should be considered on a case-by-case basis, says Dr. Kennedy. “Innately green solvents may not be all that green,” when all factors are considered—not just the elimination of organic solvents.