Bioseparations, the Evolution Continues

But, alas, regulatory uncertainty can make cowards of us all. Demonstrating product equivalence late in development is so costly and risky that many successful biotech companies "just say no"--at least publicly--to downstream process innovation. Future downstream process innovations will probably trickle up into the conservative mainstream from nontraditional biotech areas such as transgenics and gene therapy, as well as from the plasma products industry, which predates fermentation-based biotechnology. But for now, downstream innovations primarily build on decades-old unit operations. Nevertheless, many of these technology tweaks are reducing manufacturing costs and speeding up commercialization, allowing manufacturers to achieve larger economies of scale or to clear regulatory hurdles faster. Because of cleaning costs and associated validation issues, disposable purification equipment often appeals to engineer and accountant alike. From filters and housings to chromatography columns and fittings, disposables are sterile out of the box, eliminate product cross-contamination, and best of all, require no cleaning or cleaning validation. Throw-away equipment is even more appealing when augmented by disposable connectors, valves, and piping. Leading filter and chromatography vendors, including Pall Corp. (East Hills, N.Y.), Sartorius (Edgewood, N.Y.), Millipore Corp. (Billerica, Mass.) and Meissner Filtration (Camarillo, Calif.), are moving headlong into disposables whenever the economics warrant it. Completely disposable downstream processes have not yet hit the big time for bioprocessors, but pieces of the disposability puzzle are filling in. Combinations of disposable filtration systems, chromatography, and concentration/desalting are available for medium-sized and smaller processes. "The decision to go disposable is usually based on the value of product, cost of manufacturing, and, to a certain extent, overhead costs of facility and labor,"says Pall's Derek Pendlebury, Ph.D. "Fifteen years ago everyone we talked to said --great idea, not interested. But increased understanding of true biomanufacturing costs has changed their view," Pendlebury says. Traditionally, purification was be-lieved to make up