Still the One
Drug makers have, for decades, recycled solvents from manufacturing operations. Recently rising costs for the acquisition and disposal of common solvents have created an opportunity to recycle at the laboratory level as well.
A number of companies provide equipment and services related to solvent recycling. Clean Harbors Environmental Services will pick up spent solvents from manufacturers and recycle them.
Most stills are not industry-specific. CBG Biotech, for example, produces general-purpose recycling distillation units that cost between $8,000 and $40,000, depending on capacity and features. The CBG stills are green as they do not use cooling water, and the heat of vaporization is recaptured as the fluid condenses. With the aid of vacuum distillation, the stills can recycle solvents with boiling points of up to 300ºC.
CBG claims that its distillation units can reduce solvent consumption and recycling each by about 95%. For solvents like xylene and ethanol, recycling reduces purchases to negligible levels, saving about 93% of purchase costs.
Additional savings in solvent-related storage, handling, ordering, and administrative activities improve the economics even more. “It’s not unusual for customers to see a six- to twelve- month payback,” says Gerald Camiener, Ph.D., technical director.
Recycling is not a panacea, since the distillate is of slightly lower purity than the original feedstock. For HPLC solvents, which are frequently mixed with water, potential recyclers should be aware that common solvents like ethanol and acetonitrile distill as azeotropes. Ethanol water distills as a 5% water azeotrope, isopropanol-water is 12.6% aqueous, while the acetonitrile isotope consists of between 14% and 16% water.
Pharmaceutical/biotech labs are quite finicky about HPLC-grade solvents, so most distillates will be repurposed. One of CBG’s customers dilutes the isopropanol-water mixture down to 70% and uses it for disinfection. Other firms may use the acetonitrile-water mixture for chemical reactions, or perhaps use a secondary azeotrope to remove the water. “How customers used recycled solvents depends on their prejudices, and their ingenuity,” Dr. Camiener notes.
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.