Therapeutic Dose: The Man Behind the Curtain

Adopting PAT and QbD can be done, with legislative encouragement

By Emil W. Ciurczak, Contributing Editor

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If you are like most humans, in late August you were glued to the TV, watching the Olympics from Beijing. There were wonderful feats of athleticism, heartbreaking “near-misses,” and touching affection among athletes of the world. Two things in particular struck me as curious: the news that CDs of the opening ceremony were already on sale the day before the event; and the controversy regarding the ages of the female Chinese gymnasts.

These things got me thinking about problems Pharma has been encountering in outsourcing to China: counterfeits and government collusion. In our (capitalistic) rush for profit, we are ignoring the “man behind the (bamboo) curtain” to a great degree. We are building plants overseas and then sending production protocols and proprietary methodology to the people operating those plants. The point is not that manufacturers shouldn’t be outsourcing—to China or elsewhere—but that they should do so more cautiously and wisely.

I am an optimist by nature; I don’t think any dog will bite me; I trust strangers; I like to think that we are all capable of heroic acts. But I often doubt the judgment of pharmaceutical executives on issues related to the longterm health of manufacturing. PAT is another such issue. Having been at many, many PAT-QbD conferences, one would think that a large number of companies are going full-tilt to implement projects in these areas.

Ironically, I speak with scientists from various facilities (other than those at “flagship” sites of large PAT-heavy manufacturers) and am told they have no PAT projects happening at their sites. At the prime of Pharma expansion (just a few years back), Pfizer had 82 sites, with other major players not far behind in numbers. Some investigation will show that most sites, even sites of the first adapters of PAT, are still “PAT-less.” The reasons are complex and numerous; one person or organization cannot address them all.

The most popular approach to on-line measurements is still spectroscopy: NIR, MIR, Raman, UV/Vis, LIF, THz und so weider. Even the largest companies supplying spectroscopic instrumentation (e.g., ABB, Bruker, Thermo), when combined, do not have the revenues generated in a single year of sales of a Viagra or Lipitor. The companies resemble pilot fish around sharks in the ocean.

They do not have the resources to make all the custom instruments needed for all pharmaceutical sites worldwide. Their expert staffs are very, very limited—and young . . . in some cases, I have shoes older than applications people. And the cause is not helped by larger drug companies poaching top talent from instrument companies as soon as these professionals are experienced. Were there enough staff and resources within the instrument community to provide the technology required for truly worldwide PAT, their cause would likely still be frustrated by the pharma executive mindset, loath to invest in PAT in the face of continuing profits.

Any executive looking beyond the next quarter to the next quarter century would scream, “Do PAT! Do QbD!” However, the conservative nature of the industry comes to the fore here. Many see PAT as “changing horses in midstream” and QbD as something that will delay an NDA. Once upon a time, many other systems (cGMP, for instance) were new and revolutionary and “could never catch on.” Somehow, Pharma (and the FDA) managed to learn and integrate HPLC to a point where it is now ubiquitous. PAT and QbD can be done.

It will take work and will power, but one day they could be as commonplace as all the other “new-fangled” ideas we now take for granted. How? Ajaz Hussain, who spearheaded the PAT movement during his time at FDA, once told me that he had one regret about the PAT Guidance: when he wrote that the Guidance wasn’t law, he should have added, “yet.”

If there were a push by Congress or will by FDA (with EMEA, of course) to make PAT (and QbD, of course) the law of the land, suddenly, it would be quite possible. Human nature is such that we need prodding to do the right thing (remember Mom saying, “Eat your veggies, dear”?). We simply need legislation that will make us eat out spinach, er, adopt PAT.

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