QRM Process

Who Really Designed the Design Space?

Quality by Design is a great idea for Pharma, but some dispute its industry origins

By Steven Kuehn, Editor-in-Chief

I do enjoy a little controversy, especially when it involves the origins of trusted engineering methods and practices. No matter the industry, debates of this character often swim below the surface of technical discourse only to breach for some air when advances or claims of innovation receive fresh scrutiny and perhaps some revisionist hindsight by the engineering/technical community.

Apparently, a bit of a debate is occurring between the Pharma and Chemical process engineering communities as to the origins of the design space concept and its application to pharmaceutical manufacturing process in the context of Quality by Design (QbD). I became aware of the “controversy” after publishing “Who Designed the Design Space?” — a column written by Ronald Snee, reprising a blog he posted on a respected Pharma industry website last year.

Snee’s take on QbD history walked one through R.A. Fishers’s pioneering work on statistical design of experiments (DOE) in the ’20s and the discipline’s further development, including seminal commercial application of its fundamentals by two engineers at Imperial Chemical Industries looking to optimize chemical production process through response surface methodology (RSM). Snee credits Merck scientist Joe Schwartz with introducing RSM to Pharma in the early 1970s as a means to optimize formulation process. According to Snee, FDA’s Ajaz Hussein picked up the ball about 12 years ago, introducing the discipline (coined as QbD by Juran in 1992) as the overarching system to pursue and assure pharmaceutical process quality.

Snee makes a subtle point, he said RSM never gained any real traction with Pharma in that era because “Apparently the process improvement need wasn’t yet identified in Pharma to improve its processes …” In hindsight, that’s quite an understatement. It’s at that point in time I see where the seeds of today’s controversy might have been planted.

One of my contributors told me, “The irony is, that before Ajaz Hussein suggested QbD to FDA — which is an application of chemistry and chemical engineering fundamentals — those fundamentals were well known and practiced in chemical engineering in the ’70s.”

At the crux of his critique was his impression that Snee’s column perpetuates the myth that QbD, statistical process optimization and its supporting design space framework are fresh ideas when in reality (and any chemical engineer worth his or her salt knows) they are just jargonistic new labels for Fisher’s DOE principles, codified by DuPont in “Design of Experiments” in 1974. “We were taught that every process you develop and design has to be such that you have complete command and control [of a process] to produce the same quality,” whether continuously or from batch to batch, said my colleague. “Please do not call fundamentals of chemical engineering new. We all know Pharma is a few generations behind and needs to catch up … giving fancy names [to things] has become Pharma’s habit as it considers itself well above its roots.”

To a degree I understand the frustration, because it appears that in the 1970s the Pharma process engineering community had a chance to embrace the chemical industry’s well defined and commercially applied process optimization principals, and for reasons I can yet fathom fully, chose to either ignore or reject them. Snee wrote, “Sometimes a new idea can take a generation or more before it becomes standard practice.” Well, that’s true, but I don’t think he meant that the idea or concept was actually “new” — more likely it was new to Pharma, back in the day, and only now being accepted doctrinairily by the industry. But I understand that for those ChemE’s who cut their teeth on DOE, listening to Pharma’s process engineering community prattle on about QbD and design space like it was some home-grown concept after rejecting its core principals for so long, could be a trifle annoying.

Free Subscriptions

Pharma Manufacturing Digital Edition

Access the entire print issue on-line and be notified each month via e-mail when your new issue is ready for you. Subscribe Today.

pharmamanufacturing.com E-Newsletters

A mix of feature articles and current new stories that are critical to staying up-to-date on the industry, delivered to your inbox. Choose from an assortment of different topics and frequencies. Subscribe Today.