I have been so concerned about PAT’s and QbD’s effect on pharmaceutical process improvement, that I have forgotten to look at the underlying technology and the benefits that analytics has reaped from spinoffs in aviation and space travel, and telecommunications. Unlike Tang, the ersatz orange drink that owed its success almost solely to its being the astronauts’ main refreshment (it couldn’t have been loved for its taste), technical improvements from spinoffs have transformed modern analytics, enabling results to be obtained less expensively, much faster and with minimal waste or environmental impact.
Like Tang, miniaturization, perhaps the most dramatic of these improvements, has its roots in the space race. At the time, the USSR had more powerful rockets than the U.S., which allowed the Soviets to launch that big, clunky “beep-beep” Sputnik, based largely on vaccum tubes. Our much smaller rockets could not carry as much weight, so we had to miniaturize components. The transistor, itself a telecommunications spinoff, was incorporated into everything, leading, eventually to the inertial guidance systems used by nuclear subs and missiles, and, more recently, to modern heart pacemakers.
“What does this have to do with PAT?” you may well ask. Quite a bit. In our quest for smaller, faster, wireless, self-contained spectrometers, for instance, we have spawned a generation of handheld instruments. Portable NIR and Raman devices are available for field work, not only for drug counterfeiting, but in forensics, agriculture, textiles, and a number of other fields.
Miniaturization and high throughput have also changed chromatography. The need for speed has pushed the development of UPLC devices that allow an analyst to separate dozens of compounds in seconds, cutting down on the biggest QC and clinical bottleneck” analysis time. In the past, at one company, I can recall making many, many batches of the same product, running 10 samples of 20 batches each night, tied up several HPLCs all night, every night. The solvent costs alone (not just the cost of buying, but also also storing and disposing of them) were incredible and didn’t even take into account space and electrical requirements for the lab.
With a UPLC, the same number of assays can be performed in a few hours by one instrument, using 1/100th (or less) of the solvent previously squandered. (In light of the recent acetonitrile shortage, this is significant.)
Going back to spectrometers, while getting faster, smaller, and, in some cases, better, today’s instruments also cost less. Previously, a lab manager might have to choose between a Raman or an NIR system. Now, he or she can have both for about the same cost and without dedicating 10-15 linear lab bench space for them! Better still, method transfer is so much simpler. Instead of trying to transfer a method from a benchtop to a process model, the method can be developed on the same model.
Ion mobility, a spinoff of homeland security, and a mainstay at airports today, has been born again as a pharmaceutical cleaning validation tool. Instead of looking for trace explosive on a potential terrorist, it has found a home in production, searching for residual detergent and drugs on process equipment. Instead of swabbing a spot, bagging a sample, labeling the sample, sending it to the lab for GC or LC analysis and waiting a day or two for results, any number of swabs may be taken and processed on the spot. This allows a piece of production equipment to be put into service immediately, lowering overhead costs, and effectively giving us more equipment without having to buy more equipment.
I have already mentioned the use of the “process signature,” used in production to predict such things as dissolution rates, applied to counterfeit warfare. The same spectrometric “signature” that tells us that a product meets spec can also tell if it is the real thing, in the field.
Yet another benefit of all this progress is that modern instrumentation is within the budget of most colleges. We are only helping ourselves when students graduate already knowing how to (correctly) use NIR and Raman. Think of the savings from a shortened learning curve!
So, except for some TV shows, aren’t spinoffs great? We have only ourselves to blame if we don’t take full advantage of these advances.
