Will PAT Become Mandatory?

Even though we now have incontrovertible evidence that nobody reads blogs anymore, couldn't condense this one into a chirp or tweet. Please bear with me.

I was genuinely surprised to read the first batch of responses to our latest survey on process control and automation in pharma. What shows up in the first 40 responses is a quiet antipathy to the three-letter acronyms driving modern manufacturing, as embodied in PAT, QbD, CpK (process capability analysis) and SPC (statistical process control). For each of these categories, over one-third of respondents basically said, “we have no interest and we’re not doing it.” For PAT and QbD, the biggest impediments cited were staffing and the knowledge required for implementation.

Of course, these results are extremely preliminary, so pharma may not hate these concepts as much as these responses suggest. I hope that more of you out there will take our survey, whether or not you are wedded to modern manufacturing methods. As cheerleaders for modern manufacturing practices, we need to get a frank look at what’s happening and what the industry really thinks about these approaches.

Speaking of which . . . our sister publication, Control, recently published a cover story on PAT that was interesting for a number of reasons. I had some quibbles with details within the piece, which, for instance, mentions pharma API water emissions as a top quality issue driving PAT . . . there are plenty of better examples of quality control cases out there (heparin, anyone? Or perhaps Chinese talc?). Plus there are examples of PAT implementations that have yielded good ROI.

While the article stated that only a handful of companies are really doing PAT, it also referred to PAT as a “sword of Damocles” hanging over the industry that is “one pen stroke away” from being written into law.

That sounded so dramatic, and so much like wishful thinking on the part of PAT advocates. (More like the letter opener of Damocles if our early survey results are an indication). Or IS it wishful thinking?

The piece also revealed an interesting point: apparently, much of FDA’s PAT Guidance was actually written by . . . Ali Afnan at FDA. A member of the original PAT Team that advocated use of PAT principles, Dr. Afnan had implemented one of the first working examples of NIR PAT at AstraZeneca in Europe (although the installation has not been without its critics). He was often eclipsed by the more politically correct Ajaz Hussain, PAT team leader.

Dr. Afnan has not been one to shy away from controversy. At a recent ISPE meeting, he asked big pharma and bio executives, point blank, why pharma is still at a three-sigma level while electronics is moving to eight sigma . . . but he has kept a low profile for the past few years, so perhaps he will become a bit more vocal about PAT and other issues? Maybe there will be more FDA outreach for PAT under the QbD umbrella?

Interestingly enough, CDER OPS director Helen Winkle will be speaking at the Emerson Users Group meeting in the fall and Dr. Afnan will be on a panel discussing, “How technology impacts the path of molecules to medicines." At first, I did a double-take. FDA rarely speaks at a commercial vendor event. Then I realized: FDA has likely been a user of the software and platforms involved, as part of its training programs.

Perhaps the sword of Damocles is being sharpened and there will be more outreach about pharma PAT. So far, FDA’s process validation guidance draft comes the closest to spelling out any requirements for PAT. At a past webinar, FDA’s deputy officer of compliance, Joe Famulare, ended an upbeat presentation by dissecting the language of a consent decree in the context of the new draft guidance . . . so companies who fail to act based on business benefits may be forced to act.

Perhaps PAT will take on a very different shape within a very different FDA. The unfolding story should be interesting. Stay tuned.

More instructional programs are out there, showing the PAT business case. ABB and Pharmaplan are the latest to collaborate on seminars. Emil Ciurczak just wrapped up a course on PAT for biopharma. We promise to keep you up to date on new information sources. (And those of you who are teaching these courses, please keep us in the loop.) In the meantime, to paraphrase the late comedian, Henny Youngman, take our survey, please.

 

AMS