COVER STORY
Assistance from contract manufacturing operations, such as this one operated by Rhodia in Annan, Scotland, is crucial to small biotechnology firms.
PHARMA OUTSOURCING A look at three pharmaceutical outsourcing relationships shows that change is a constant in the biotech industry
T
H E B I O T E C H N O L O G Y INDUSTRY IS A PLACE O F C O N -
stant flux. Companies are formed, disbanded, and acquired. People move from firm to firm, job to job, gaining experience and contacts along the way. It can be a difficult industry to serve, especially if the service being provided is one as critical as contract development or chemical manufacturing. Managers and corporate directions may change, but the biotech industry's demand for high-quality chemistry services remains the same. In the pages to follow, C&EN presents three case studies of the relationship between a biopharmaceutical company and a pharmaceutical chemistry provider. Belying the biotech industry's discovery-oriented image, none of the three biotech firms proHTTP://WWW.CEN-ONLINE.ORG
filed developed its own drug. Rather, the compounds were licensed or acquired from other firms or institutions. Uncertainty is created when a drug in development changes hands, but as these stories show, the successful service provider must be able to weather change and even use change to its advantage. • NEW LIFE An abandoned drug is revived by the big-company scientist who developed it. PAGE 34 • VIRTUAL PLAY Experienced hands start a new company to develop a promising compound. PAGE 39 • SHIFTING FORTUNES A service provider must adapt when a key customer is acquired. PAGE 43
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COVER STORY Rubin, meanwhile, left Abbott in 1993 to spend three years as director of early clinical development and clinical pharmacology at what is now GlaxoSmithKline. He then worked for Sepracor for six years as executive vice president of R&D. While he was at Sepracor, the company sold SepraChem, its chiral chemistry subT S NOT OFTEN THAT SOMEONE CAN sidiary, to the contract research and proinflammation, mucus production, and the further a company's ambitions while duction firm ChiRex. Sepracor went on to closing of the airways in asthmatic patients. employ ChiRex as the manufacturer for advancing a more personal project at CTI believes that zileuton's activity against the same time. But if Paul Rubin is sucseveral ofits new active pharmaceutical ina range of leukotrienes differentiates it cessful in commercializing the asthma gredients (APIs). In 2000, ChiRex was acfrom montelukast, the active ingredient quired by Rhodia, where it is now part of drug zileuton, he will have managed to acin Singulair, a Merck drug that is the most complish both of these goals. Rhodia Pharma Solutions. Rubin left Sepracor in August Rubin is president and chief 2002 to join CTI as president executive officer of Critical and CEO. CTI had been formed Therapeutics Inc. (CTI), a small ayear earlier by three intensivebiopharmaceutical company in care experts: Mitchell P Fink of Lexington, Mass. And in his dual the University of Pittsburgh's quest, he is leveraging two School of Medicine; Kevin J. strengths from his past: an intiTracey ofthe North Shore-Long mate knowledge of zileuton and Island Jewish Medical System's a good working experience with Institute for Medical Research; the pharmaceutical services firm and Harvard Medical School's Rhodia Pharma Solutions. H . Shaw Warren. They had From 1987 until 1993, Rubin, pooled their collective scientifa medical doctor, was in charge of ic discoveries and won initial fia group at Abbott Laboratories HANDS ON An operator at Rhodia's Annan, Scotland, nancing from HealthCare Venresponsible for the development facility works with material in a contained offloading unit tures and M P M Capital. of zileuton. When the drug was When Rubin came aboard, the compaapproved in 1996 as Zyflo, it became the frequently prescribed leukotriene recepny was developing the drug candidates on only Food & Drug Administration-aptor antagonist. Singulair, according to CTI, which it had been founded: critical care disproved product that works by blocking the blocks only one of the two known recepease products that work by regulating the activity of5-lipoxygenase, the main enzyme tors and for just a single leukotriene. b o d / s inflammatory response. However, responsible for the formation of a family Despite zileuton's apparent therapeuhe saw an opportunity to accelerate CTI's of lipids known as leukotrienes. tic advantages, Rubin says Abbott failed to path to profitability by licensing zileuton Leukotrienes are known to cause many promote it heavily and, after about a year, from Abbott and marketing it to asthma of the biological effects that contribute to ceased all sales calls for the drug.
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Yuhan does not make a competing H I V drug, and the plant near Seoul at which the work is being done is not used to manufacture yuhan products, other than some antibiotics that are made in a separate building. Gilead was not interested in pursuing a comarketing agreement on emtricitabine. While joint marketing alliances such as the one with Abbott were a key means for Triangle to bring drugs to market, Gilead has 13 sales offices around the world and only comarkets H I V drugs in Asia, Prisbe says. According to Robert B. Miller, Abbott's program manager for pharmaceutical R&D, the alliance with Triangle was essentially a comarketing agreement, but manufacturing was "key to taking the project forward. They were making tens of kilos. We moved it into a process that we hoped would get up to 25 tons." Miller acknowledges that Gilead's concerns about contracting with the services division of a large drug company are typical, but not necessarily deal breakers. iCWe have been asked about the priority issue on anumber ofoccasions," he says. "Invariably the answer we give is that the project that gets the priority is the project that needs the most work." In 2003, Miller says, Abbott's biggest job was done for a third party HE ADDS that Abbott has also become more flexible, strategically in its contract process R&D work since forming the alliance with Triangle. "In the model going forward," he says, "we develop a process and transfer it to the eventual manufacturer. We are evolving to a multiservice offering as opposed to a one-stop shop." Gilead made one more change. Having resolved patent issues with Glaxo in 2003, the company switched to a more economic menthol-based diastereomeric chemistry to promote stereoselectivity eliminating the use of PLE in emtricitabine production altogether. Prisbe emphasizes that the change of manufacturer does not reflect on Abbott's performance. Rather, Gilead, which does its own R & D and process development, prefers to work with small, "boutique" contractors that he says have extremely focused expertise and are more flexible and transparent than large contract manufacturers. "There is nothing wrong withAbbott, or with DSM and Lonza," Prisbe says. "But the firms we contract with tend to be smaller." He says Gilead has contracted with Aerojet Fine Chemicals for energetic chemistry, Raylo andlbrcan for nucleotide work, EaglePicher for cytotoxics, PPG-Sipsy for chiral reductions, and Pfanstiehl Laboratories for carbohydrates.—RICK MULLIN
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