At this week’s PAT/QbD meeting, sponsored by FDA and the University of Rhode Island’s College of Pharmacy, there was no question that the speaker everyone was waiting to hear from was Ajaz Hussain, former PAT team leader, Sandoz executive and now VP at Philip Morris International.

He burst energetically up to the podium, briefly recapping the history of why PAT was advanced. At the time, he said, FDA was resisting ICH Q8, although Europe and Japan were embracing it. Industry was stuck in descriptive knowledge, and, when questions of how specifications were set, he quipped, the answer was often “eenie, meenie, meinie, mo.” PAT, further, became a door opener for the Critical Path initiative.

But he minced no words. PAT’s progress on the small molecule front has been very slow, where, in contrast, biopharm has been making great strides, he said. “Is bioprocessing inherently more conducive to PAT,” he asked, citing comparability assessments, which aren’t done for small molecules. 

Look at traditional pharma, he said, where specs are set after clinical trials have been completed and based on compendial standards. It’s no surprise then, he said, that design and design space concepts are not clearly understood.

The comparability approach, as used in Europe in the biosimilars regulatory pathway, summarizes prior knowledge for better regulatory decisionmaking, he said. 

It thus avoids the “Popperian Trap.” (I must have ADD, because I love it when speakers bring up obscure references because they're really teachable moments. . . . I'm sure I was one of many who went running to Google to check up on philosopher Karl Popper, who advanced the idea of “critical rationalism,” which rejects classical empiricism and argues that science is only really science if it is falsifiable (i.e. that it’s being false can be proven). It can lead scientists into disbelieving prior knowledge. OK, I’m still not sure I have it right. In any case, click here for more.

Hussain also managed to refer anyone who missed it (and, unfortunately, that’s a  growing portion of the young people in the U.S.) to Homer’s Odyssey in his use of the term “Procrustean standards,” a colorful reference to Procrustes, who used to lengthen or shorten guests based on whether or not they fit in his bed. A literature nerd, I love it when people have the courage to use that fusty phrase). Ajaz is still a professor at heart.

Most significantly, Dr. Hussain brought up the confusion between PAT and QbD, which need never have existed in the first place. Long before PAT was even used as a term in pharma, he said, regulations called for “quality to be built in by design.”  

Perhaps there have been some political struggles between individuals within FDA over whether QbD or PAT should be the guiding principle? “Look at which offices attend [this meeting] and which do not,” Hussain pointedly said.

Separating the two concepts only deepens the confusion and means that it will take that much longer to convince senior pharma management of the need for change. Isn’t PAT required for QbD? (And PAT needn’t mean expensive analyzers either, as ex-Pfizer/Wyeth PAT and QbD expert Pedro Hernandez, now an independent consultant, mentioned, PAT can even be done with a thermometer and a strip chart . . . the end result is supposed to be process knowledge.)

Clearly, there needs to be an end to political infighting, if it does exist. Unity within FDA is the only way to drive modern thinking forward in the industry.  

And outreach to senior pharma managers is needed, so this meeting was important. A second meeting is planned next year, with NIPTE as cosponsor. Anyone interested in changing pharma’s status quo will want to be there.

AMS