PharmExec Blog

DIA: Does Six Sigma Stifle R&D Innovation?

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.

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4 Comments

  1. Arthur Fernandez
    Posted June 23, 2011 at 9:29 am | Permalink

    I’m not sure this article explored the question sufficiently…here’s an interesting article on Japan’s take on Six Sigma:

    http://www.fastcompany.com/magazine/98/debunk.html

  2. Tom Chapman
    Posted June 28, 2011 at 4:25 am | Permalink

    I think the calculation has to be a lot more complex than molecular weight and lipophilcity. For a better idea go and look at some supercritical fluid extractions which rely just on these two factors plus flow rate and see what variety you can get.

  3. Posted June 28, 2011 at 8:55 am | Permalink

    Tom,

    Thanks for your comment. The calculation is indeed more complex, and is used in concert with other guidelines as mentioned. Attendees of the panel were given to understand that the molecular weight/lipophilicity ratio is a crucial one in locating the “sweet spot” for potential candidates.

  4. Stephen Robinson
    Posted June 29, 2011 at 8:59 am | Permalink

    I can see that the “sweet spot” ratio is a useful heuristic for medicinal chemists, however turning to the question in hand, two notable academics (Amabile and Khaire, 2008) point out evidence that over-emphasis on efficiency/continuous improvement by managers tends to hamper innovation over the long term, or in other words, organisations get “better and better at doing the wrong thing”.

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