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Select contract manufacturing organizations roll out expansions for production of active pharmaceutical ingredients and intermediates.
As contract manufacturers and pharmaceutical companies gather next month in Madrid for CPhI Worldwide, the large trade show for pharmaceutical ingredients, a fundamental question is the health of the custom-synthesis market. "Lumpiness" is a phrase often used to describe the financial state of contract manufacturing, which is subject to the vicissitudes of drug development. This term aptly describes the fortunes of the market this year. First-half results were mixed, with some players reporting a sales decline, and others reporting positive results and expansion plans.
Patricia Van Arnum
Charting a bellwether
Lonza (Basel, Switzerland), one of the largest contract API manufacturers, reported a sales decline of 7.7% to CHF 706 million ($662 million) in its custom-manufacturing business (exclusive synthesis and biopharmaceuticals) for the first half of 2009, according to the company's financial results. In its exclusive synthesis business, stronger sales in peptides and biochemicals offset declines in small molecules. On the plus side, the company's capacity utilization was above 80%, with a pipeline of 225 projects, up from 185 in the first half of 2008.
Lonza is proceeding with several expansions. The first build-out of its large-scale multipurpose current good manufacturing practice (CGMP) active pharmaceutical ingredient (API) plant in Nansha, China, is operating. The second build-out of the plant started up last month. The Nansha site houses administration, research and development (R&D), a kilo laboratory, and small-scale and large-scale production. The installation of a mid-scale multipurpose CGMP API plant at Nansha is under evaluation.
Lonza is also evaluating the addition of another mid-scale plant for highly potent APIs at its facilities in Visp, Switzerland. Last year, the company added large-scale production capacity for high-potency APIs in Visp as well as antibody-drug-conjugation capabilities. Lonza also recently added a laboratory-scale peptide production plant in Nansha. The company is evaluating additional CGMP laboratory-scale production capacity for peptides at its facilities.
(MAGES: ROSEMARY CALVERT, BRAND X PICTURES, DAVID GREENWOOD/GETTY IMAGES ILLUSTRATION: M.MCEVOY)
Lonza is on track with two large-scale mammalian biopharmaceuticals expansions. The company is building a new biopharmaceutical manufacturing facility in Singapore, which is expected to start up in 2011. Another biopharmaceutical plant in Singapore was recently completed and will be ready to hand over to Roche (Basel, Switzerland) in the third quarter of 2009. In 2006, Lonza and Genentech (South San Francisco, CA) formed an agreement providing Genentech the option to purchase Lonza's first Singapore facility. Genentech was acquired by Roche earlier this year. In addition, Lonza is investing CHF 30 million ($28 million) for the first phase of a new cell-therapy facility in Singapore, which will be adjacent to the company's large-scale mammalian manufacturing facility. Construction is expected to begin early next year and be operational in mid-2011.
Lonza also reported that its retrofitted, multiproduct facility in Porriño, Spain, is fully operational and is supporting three customer projects (Phase III and commercial scales). Lonza acquired the mid-scale mammalian biopharmaceutical production plant in Porriño from Genentech in 2006. A new 5000-L line at its biopharmaceutical facility in Portsmouth, New Hampshire, also recently went on stream.
Adding large-scale API capacity in US
Cambridge Major Laboratories (CML, Germantown, WI) dedicated a new 125,000-ft2 large-scale API manufacturing facility in Germantown, Wisconsin, in late July. The facility is designed with six GMP suites capable of producing multiton quantities of APIs and advanced intermediates. The installed capacity is 70 m3 with an expansion capability for an additional 120 m3 .
CML says the new facility is part of its strategy to be a leading Western-based supply option. "Without this site, we would never be considered for large-scale commercial manufacturing," said Michael W. Major, president and CEO of CML, in a July 20, 2009 company press release. "By default, those processes that our chemists developed and produced at smaller scale would be lost to other Western competitors or offshore suppliers as the need for large-scale manufacturing arises. This new facility eliminates those concerns."
The new facility follows recent multimillion dollar investments at the company's development facilities in Europe, which includes new R&D and analytical laboratories and additional pilot-plant capacity. Those investments will add more than 40% to CML-Europe's capacity and enable the facility to produce up to hundreds of kilograms and APIs and intermediates.
Expanding high-potency capacity
SAFC (St. Louis, MO) has invested more than $75 million in developing its high-potency manufacturing capabilities in recent years. These investments include a $4.5-million project to add a CGMP pilot-plant and kilo-laboratory capacity at Madison, Wisconsin, completed in early 2008; a $29-million investment to expand bacterial and fungal fermentation-derived high-potency capacity at its facility in Jerusalem, scheduled for completion in 2009; a $30-million investment to build a commercial-scale high-potency API facility at Madison; and a high-potency bioconjugation suite in St. Louis that was validated in early 2008.
In January 2009, SAFC began operations at a 7000-ft2 laboratory complex in Carlsbad, California, next to its viral production substance facility, which the company gained by acquiring Molecular Medicine Bioservices. Commissioning of the new laboratories follows SAFC's 2008 announcement of a $12-million expansion at the site to construct two fully segregated manufacturing suites, which are scheduled to be operational by the end of 2009.
In September 2008, SAFC began operations at a new reactor at its site in Arklow, Ireland, which increased its large-scale API capacity by 15% and the site's total capacity to 96,000 L. The investment complements two additional expansions: the building of a $2.25-million, 15-kg pilot-scale filter dryer designed to double the facility's capacity for small-scale API manufacturing, which is scheduled to be commissioned in the third-quarter of 2009; and a $1.8-million expansion of the site's CGMP warehouse capacity.
SAFC is proceeding with its first greenfield manufacturing project in China, a $25-million investment in Wuxi for a large-scale, non-CGMP multipurpose plant to produce raw materials, intermediates, and final products to support SAFC Pharma, SAFC Supply Solutions, and SAFC Hitech. The Wuxi site will include a manufacturing plant and analytical, packaging, and warehousing facilities. The first construction phase is expected to be completed by 2010. Future development phases at the site will support SAFC's parent company, Sigma Aldrich's research chemicals business by further expanding analytical, packaging, and warehousing facilities.
Rounding up other expansions
Saltigo (Langenfield, Germany) completed a EUR 10 million investment ($14 million) in early 2008 for a CGMP plant in Leverkusen, Germany, for producing advanced intermediates and APIs. The unit has annual capacity of more than 200 metric tons. In 2008, Saltigo expanded its early-phase facility in Redmond, Washington. The expansion includes two CGMP-compliant kilo laboratory systems and a pilot plant for investigational new drugs and intermediates from benchtop to a scale of 400–800 L.
Cambrex (East Rutherford, NJ) opened a new $20-million CGMP large-scale API manufacturing facility in Karlskoga, Sweden, in March 2009. In 2008, Cambrex added a new 11,500-ft2 facility in Charles, City, Iowa, with five process development/kilo laboratory production suites for high-potency APIs as well as enhanced facilities for analytical development and quality-control activities. It also expanded its high-potency micronization facility in Charles City.
Cambrex made other investments in its API business in 2008. It increased the capacity of its API finishing facility in Milan, Italy, by 20–30% and added to its small-scale development capabilities by acquiring Prosyntest (Tallinn, Estonia).
Hovione (Loures, Portugal) reported sales growth of 21% in the fiscal year ended March 31, 2009, and is expanding as well. In 2008 Hovione invested in particle-design technologies and in new production lines, at it facilities in Hisyn, China, and in Portugal. Also in 2008, Hovione acquired from Pfizer (New York) manufacturing facility in Cork, Ireland. The facility has a 427-m3 of production capacity and spray-drying capabilities.
In July 2009, Novasep (Pompey, France) acquired Henogen (Charleroi, Belgium), a contract manufacturer of bioprocess development and manufacturing services. In 2008, Novasep added a pilot-scale continuous chromatography unit in its facility in Chasse sur Rhône France, for supplying enantiomers for clinical supplies. It operates six facilities that manufacture APIs and advanced intermediates, and four integrate chiral separation services.
Finally, Helsinn (Biasca, Switzerland) is planning to expand the development and manufacturing services at its advanced synthesis site in Switzerland.
Patricia Van Arnum is a senior editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, firstname.lastname@example.org