Six Sigma, Here We Come

Nov. 25, 2003

Manufacturing in the pharmaceutical industry is poised for a quality revolution. As dwindling new product pipelines stall revenue growth at many companies, management is pushing cost containment and efficiency improvement in order to protect profit expectations. Add to this a rash of high profile time-to-market delays, product recalls and eye-popping settlements related to manufacturing violations, and even denizens of the executive suite are beginning to recognize the strategic importance of manufacturing competence.

And if management is pushing manufacturing to be more efficient, the U.S. Food & Drug Administration (FDA) is pulling from the other side. Regulators' move to "risk-based" manufacturing practice guidelines and endorsement of process analytical technologies (PAT) are indicative of a recognized gap between current pharmaceutical manufacturing practice and its unrealized potential.

And that gap is in quality. I don't mean that the safety of the public is affected by quality issues--the final quality of our drug supply remains second to none. What's needed, rather, is a fundamental shift from a reliance on post-production quality assurance methodologies to a quality systems outlook targeted at rooting out process and product variability at all stages of the manufacturing process. That's how drug makers will begin to improve manufacturing efficiencies and reduce unit costs.

The father of quality, W. Edwards Deming, long ago linked the need for inspection to excessive process variability. "Ceasing dependency on inspection means you must understand your processes so well that you can predict the quality of the output from upstream activities and measurements," he wrote. "To accomplish this, you must have a thorough understand of the sources of variation in your processes then work to reduce variation."

Dr. A. Peter Green, Pfizer vice president of pharmaceuticals sciences, looks to increasingly intertwined co-development efforts of researchers and manufacturing professionals to increase that understanding. The ability of products and processes to tolerate variations in uncontrollable parameters such as raw material composition, Green describes as robustness: the more robust a process, the more unanticipated variations can be accommodated without affecting the attributes of the final product.

"Today, we need improved robustness of product at launch, to be able to improve robustness faster, and to achieve higher levels of robustness," he said at a recent address to the Chemical Marketing & Economics Group of The Chemists' Club of New York, acknowledging the lower quality and higher variability tolerated in pharmaceutical manufacturing processes compared with other industries. "Co-development will be the foundation for a process to be right the first time," he said.

Granted, pharmaceutical manufacturers have a bigger job ahead of them relative to other industries where quality systems methodologies such as Six Sigma have been developed and refined. Process improvements must be weighed against the antithetically opposed priorities of process validation. No change is necessarily good if it triggers an expensive revalidation of an already proven process.

Today, however, FDA is giving clear indications that it wants to help drug makers better negotiate its sometimes over-onerous validation procedures, and to pursue process improvements that make business sense. While hurdles remain, it's clear that quality systems methodologies--and the manufacturing competence they foster--will be increasingly important survival skills in the competitive years ahead.