MannKind Corporation's development of an inhalable drug delivery system could improve the quality of life of millions of diabetes patients by relieving them of the daily burden of insulin injections. However, that lofty goal only can be achieved by successfully scaling up research and development results at our Danbury, Ct., pilot plant.
An innovative line of fittings from Versapass, Melbourne, Fla., is helping us in this effort. These fittings provide us the ability to grip and seal probes or dip tubes for variable positioning without damage, distortion or leakage. We can locate the dip tube or probe along its effective length through the fitting and reposition, remove, or replace them repeatedly.
We had been relying upon fixed position fittings that required separate sample probes for each piece of equipment needing headspace oxygen monitoring. Starting in late summer 2010, we installed Versapass fittings on all reactors and other equipment requiring such monitoring (Figure 1). The variable position feature of the Versapass fitting allowed the same probe and oxygen analyzer to be used on every piece of equipment in the plant. We achieved cost savings on inert gas consumption without compromising safety.
"Without the Versapass the effective use of a centralized oxygen analyzer would not have been possible," notes John Pocreva, one of our senior engineers.
The installation was straightforward. We replaced existing flange and sanitary fittings with the appropriate Versapass units. A tee was plumbed into a line and the Versapass fitting was attached, usually with a ball valve between the tee and the fitting. The ball valve provided isolation when the probes or tubing were removed.
Subsequently, we installed additional Versapass fittings to attach variable position tubes to several reactor inlet ports. This allows us to charge liquid either above or below the reaction mixture surface depending upon the position of the tube. Subsurface tube positioning enables easy reaction mixture sampling. These same fittings also serve to position a variety of probes — e.g., for monitoring pH, turbidity, spectroscopic absorption, conductivity and particle size, as well as for any number of process analytical technology (PAT) measurements — at any depth in the reaction mixture, including between different liquid/liquid phases.
More recently, MannKind has used a new multiport Versapass fitting with a separate port between the fitting and vessel connection. Placing one of these fittings on a reactor and one on a charge liquid container with a vapor line between the extra ports keeps the pressure in both vessels balanced as the charge liquid is pumped into the reactor. This new multiport fitting also can serve to establish a recirculation loop for reaction monitoring. The reaction mixture is withdrawn through a subsurface variable position tube and pumped through a sample chamber before returning to the reactor through the extra port. The sample chamber may be set up for any PAT probe, including those where direct placement in the reaction mixture isn't possible.
"The Versapass provided a creative solution to a long-standing problem of charging volatile corrosive liquids," says Rusty Cappadona, our associate director of chemical technology.
The fitting is designed to seal on the same plane as the process side of the fitting, preventing fluid entrapment. All wetted surfaces are constructed of perfluoroalkoxy polymer and type 316 stainless steel or nickel alloy. There are no O rings that can leach, swell or absorb system fluid. The fittings are rated for full vacuum to 100 psig; ambient temperature to 150°C; and clean-out-of-place, clean-in-place and steam-in-place protocols. The Versapass fittings have proven to be extremely robust. Some in use at MannKind are years old and endure multiple daily probe placements and repositionings. Yet, we've experienced no leaks or failures.
"We continue to find new ways to use the Versapass fitting to overcome challenges in the pilot plant," adds Cappadona.
ELLIOTT BAY is Danbury, Ct.-based senior director of chemical technology for MannKind Corp. E-mail him at Ebay@mannkindcorp.com.