Can the management style known as Six Sigma help improve the probability of a drug’s commercial success, or do its black-belted acolytes punch holes in the creative process needed for innovative R&D discovery?
The latter question was posed to Kevin Duffin, senior fellow, translational sciences at Eli Lilly – and a Six Sigma practitioner – at the conclusion of a Drug Information Association (DIA) panel on Monday. During the panel, Duffin unveiled a formula he uses at Lilly to “apply industry probabilities to drug design,” the goal being to increase commercial potential, while reducing costs and shorting cycle times in the early stages of drug discovery.
The particular equation that Duffin suggested had to do with locating a “sweet spot” based on the ratio between a compound’s molecular weight (which correlates with bioavailability, he said), and its lipophilicity, or ability to dissolve in fatty oil. Too much molecular lipophilicity affects the proteins in water, leading to potential off-target responses, said Duffin.
The current industry trend, per Duffin, is the heavier the molecular weight, the higher its lipophilicity. While the “IP police” wouldn’t let Duffin discuss particular Lilly compounds, he said the company falls in line with the trend. For Duffin, the proper ratio for locating the sweet spot is a molecular weight less than 400, and a lipophilicity measure (known as ClogP) of less than three, combined with several other “desirable guidelines.” In response to the question of whether this kind of criteria-setting inhibits creativity in the lab, Duffin said “some love it and some hate it,” adding that Lilly CEO John Lechleiter “is embracing Six Sigma” as a tool to make the discovery process more efficient. The financial benefit of the sweet spot ratio has already saved Lilly upwards of $7.3 million, and has upped the chances of a given drug’s approval by 2%. If that doesn’t seem like much, consider that fact that the average drug candidate has only a 10% chance of approval, according to Duffin.
Michael Walega, a Six Sigma Master Black Belt at Covance, a CRO, said all parts of his company, “from preclinical through phase 4,” are steeped in the ways of Six Sigma. He called for a reevaluation of organizational culture in industry, based on four steps: awareness, motivation, competency, and implementation.