Editor’s Note: The following is from our PharmaQbD archives, initially published late in 2009 prior to our platform change. Consultant John E. “Jack” Carroll has a very good feel for how manufacturers are struggling to implement PAT and QbD, and thus this deserves a fresh look.
By John E. Carroll, CEO, Carroll Ventures, Inc.; Managing Partner, Cadrai Technology Group
In discussion surrounding PAT and QbD lately, I have heard many drug industry professionals allude to a lack of buzz-word specificity, the need for understanding the big picture, and the need to integrate these new quality initiatives.
My company, Cadrai Technology Group, teaches on-going courses, both public and private, as well as webinars that address key quality management issues. We find some interesting attributes among the participants in these courses.
The courses in question cover implementation of PAT and QbD principles for both small-molecule and biologic drug manufacturing. Companion courses cover diverse but related topics—risk management, various instrumental analytical methods and utilitarian issues such as process validation, using DQ to advantage and experimental design and deployment.
All of these courses are accredited and so draw participants who need recurrent training. Most, however, attend because they are involved with new or emerging PAT programs. More recently, the “draw” has been QbD, although their companies understand that concept only dimly.
Participants usually have some level of supervisory or functional responsibility and come from the analytical, formulation, drug development, scale-up and production sectors. We occasionally host QA personnel and, rarely, discovery staff. Professionally, they are chemists or pharmacists with the occasional chemical engineer.
Contents of the courses evolve continually: each revision reflects student review of the course immediately taken and also the changes that occur as Quality Systems evolve and mature. About 20% of the participants at each course are newly charged with “getting a PAT program going,” with no time or resources allocated, or even a clear goal. They are doomed to fail and, as later contacts confirm, they do.
Why PAT Stalls
As the training material evolves, we find these startling situations:
- A dearth of understanding about the sensors and instruments that may come into play as their PAT programs take shape.
- Pronounced evidence of the “silos”—lack of continuity between functional departments and what is more evident, comfort with that situation.
- A fundamental lack of awareness regarding the overall fiscal picture, or the sustainability situation of their respective companies, markets and products. A concomitant is the belief that the industry’s high profits are evidence that efficiency improvement is nice, but not earth-shaking. By and large, the training participants misuse ROI and have little understanding about the import of slow inventory turn and large work-in-progress numbers.
- We find a big disconnect between the PAT and QbD in-crowd and those trying to learn the “art.” The principles are sound, obviously, but the buzz-words are understood differently between the mavens and learners.
- We find palpable inertia in making the jump from QA comfort with GMP and ICH quality thrusts.
- Last but certainly not least, we find a big knowledge gap in understanding current technology in process control and process robustness.
To be fair, these facets don’t apply to every participant. We encounter many attendees who have successfully merged their company and product needs with a well-thought-out program. But these attendees are still the exceptions rather than the rule.
I believe that PAT programs that are sufficiently resourced will succeed: even moderate improvements in low-efficiency pharma manufacturing deliver tangible benefits. As quality systems progress into the ICH Q8 through Q11 realm, however, these disconnects will erect much bigger barriers. There’s a need for an enlarged and common dialogue in both training and practice.
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