) Global R&D president John LaMattina will retire from Pfizer by the end of this year, after 30 years with the company. Pfizer has begun a search both inside and outside the company for his successor, and Dr. LaMattina will remain during this period to ensure a smooth transition, according to the company. Chief Financial Officer Alan Levin has resigned after 20 years with the company. 

—Adrian Adams was named president and chief operating officer of 

). Adams joined the company in March 2007 after serving as president and chief executive officer of Kos Pharmaceuticals, Inc. 

) current global head of pharma development operations, Dan Zabrowski, PhD, was promoted to global head of Roche pharma partnering. Zabrowski will oversee the company's strategic alliances with biotech companies and will create new alliances. He joined the company in 1995, after holding a variety of positions in regulatory affairs with Syntex, Inc. 

) promoted Paul Carter to senior vice-president of international commercial operations. Carter joined the company in 2006 as leader of Gilead's European commercial organization. He previously held various positions at GlaxoSmithKline. 

) named Ronald A. Martell president and chief operating officer. Martell joins the company after serving as senior vice-president of commercial operations at ImClone Systems Incorporated.  

) named Nicholas J. Pelliccione, PhD, senior vice-president of regulatory affairs and quality assurance. Pelliccione joins the company from Chugai Pharma USA, where he was senior vice-president of regulatory and pharmaceutical sciences. Pelliccione also spent more than 15 years at Schering Plough Corporation. 

) appointed Michael Graves president and chief executive officer. Graves joins the company after serving as president of the generic product division at Par Pharmaceutical Companies, Inc. 

—Joseph Zakrzewski was appointed chief executive officer of 

). He joins the company after serving as chief operating officer of Reliant Pharmaceuticals. 

) named Amale Hawi, PhD, senior vice-president of pharmaceutical development. In this capacity, Hawi will manage the pharmaceutics and pharmacokinetics groups and will be responsible for preclinical and CMC drug-development strategy. Hawi founded A. Hawi Consulting, Ltd. in 2002 and served as president of the company. She also held various positions at Boehringer Ingelheim Pharmaceuticals. 

) named Eliot Forster chief executive officer. Forster joins the company after serving as Pfizer's head of development for Europe and Asia. 

—Richard A. Krzyzek, PhD, was promoted to vice-president of research for Techne Corporation's (

) biotechnology division. Krzyzek joined R&D Systems, Inc., a subsidiary of Techne, in 1992. He also spent 12 years with Molecular Genetics, Inc. 

) appointed Claude R. Benedict senior vice-president, clinical development and regulatory affairs. Benedict previously served as senior vice-president and head of development at Archemix Corporation and as senior vice-president of global lead optimization, drug innovation, and approval for Aventis Pharmaceuticals. 

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One of the hallmarks of the growth of outsourcing in the pharmaceutical industry has been the evolution of new sourcing models. As outsourcing gains acceptance, pharmaceutical companies and contract service providers experiment with and adopt various approaches to the packaging and delivery of services. The major themes in model evolution include:  

moving from bidding individual projects to establishing preferred provider relationships covering multiple projects; 

various approaches to bundling services together 

 outsourcing the delivery of a single capability in support of multiple projects or studies.

Sourcing models pursued in clinical and nonclinical development services have evolved in somewhat opposite directions. For most of the past 10 years, buyers of clinical research services have preferred to buy contract research organization (CRO) services on a full-service basis. That is, they have tended to buy the range of services needed to complete a clinical study—study management, site monitoring, data management, biostatistics, and medical writing—from a single CRO for a fixed price. By contrast, buyers of nonclinical services have tended to buy the necessary services for a particular drug candidate—process development and manufacturing for active pharmaceutical ingredients, dose formulation and development, clinical packaging, and analytical services—from multiple vendors, each specializing in a particular discipline. 

Today, the trends in the two sectors are moving in opposite directions. Major pharmaceutical companies are embracing a functional outsourcing approach for clinical research under which they contract with a single provider to deliver a particular service in support of all their clinical trials. In the nonclinical realm, the trend is toward a full-service model, often referred to as the one-stop shop. 

These opposing trends reflect some very different dynamics in these two sectors of the pharmaceutical services industry. The rise of functional outsourcing in clinical research is being driven primarily by the industry's embrace of clinical information technology (IT). This change brings with it the need for new areas of expertise such as systems integration as well as new opportunities to realize cost savings by offshoring software development and data processing. Creating a single data infrastructure for all clinical trials facilitates using clinical data for applications beyond the study for which it was collected, including strategic planning, marketing, and disease modeling. Contracting with a single, dedicated information technology services provider to build and maintain the clinical data infrastructure offers the promise of best-in-class capabilities and cost savings across all clinical operations. 

The functional outsourcing model in clinical research has been adopted in several major pharmaceutical companies, including 

(Madison, NJ), and based on discussions at April's 

 conference in Orlando, Florida, more companies appear to be adopting it. Furthermore, the model is moving beyond data management into other clinical research areas: Wyeth has struck a deal with 

 (Dallas, TX), a clinical CRO, to provide site monitors for clinical trials, and the company recently contracted with 

(Plantation, FL) to provide logistics for distributing clinical supplies to investigator sites. 

One interesting implication of the trend toward the functional model is that it has opened the door to new competitors in the clinical research sector. IT outsourcing giants 

(Mumbai, India) have become important players in clinical data management, and it is widely speculated that Federal Express and UPS will join DHL in competing with established clinical packagers and couriers. That specter of increased competition from global leaders has traditional CROs very worried. 

Functional outsourcing has been the rule rather than the exception in nonclinical outsourcing. The reason has little to do with the cost and performance advantages being pursued in clinical research, however.  

Instead, the predominance of the functional model in nonclinical development reflects the fact that the component disciplines of nonclinical development have very different and specific technical and operation bases and require expensive specialized capital infrastructure. (Clinical research requires very little capital investment, and its human resource requirements can be met with job-specific training in most cases.) Nonclinical services companies have traditionally been unwilling or unable to make the capital investments and assemble the expertise necessary to offer a full-service nonclinical offering. An early effort to assemble a full-service nonclinical offering, Oread, flamed out more than  five years ago because it couldn't support the cost of maintaining so many capital- and technology-intensive capabilities. 

The return of the one-stop-shop model in recent years reflects two major trends in the pharmaceutical industry. The first is the renewed support for early-stage companies developing new drug candidates and their focus on getting to proof-of-concept (positive results at Phase IIA) as quickly as possible. Venture-backed early-stage companies account for over 50% of the new drug candidates in early development (preclinical through Phase IIA), and their development programs are geared toward achieving proof-of-concept as quickly and cheaply as possible. Most of these companies lack the facilities and breadth of scientific and development know-how to manage a program to proof-of-concept, let alone to commercialization. The full-service nonclinical CROs are promising these early-stage companies a quick and cost-effective route to proof-of-concept by providing a turnkey offering with complete nonclinical capabilities and project-management skills to tie it all together. 

The second trend is the interest of private equity investors in the pharmaceutical services market. The nonclinical contract services business is highly fragmented and presents many acquisition opportunities for private equity investors looking to build a large CRO operation by buying up a number of smaller operations. The full-service CRO presents a logical model around which to build an acquisition strategy. 

As the pharmaceutical service industry continues to mature, we will see many variations of the basic full-service and functional models. Early-stage and virtual companies will tend toward the full-service model for both clinical and nonclinical services. That's because they need the regulatory and project-management expertise embedded in the full-service model along with the basic technical disciplines. 

Large pharmaceutical companies are likely to use a hybrid approach, mixing and matching the models as appropriate to meet their objectives of greater flexibility and lower costs. In clinical research, data management, clinical supplies logistics, and central laboratory services will be sourced largely on the functional model, but study management and monitoring services could be provided by full-service CROs with expertise built around specific therapeutic areas. In the nonclinical area, services that are closely linked, (

 formulation and clinical supplies manufacturing, may be sourced on a full-service basis) but we expect functional capabilities to count more heavily in nonclinical sourcing arrangements.

 is president of PharmSource Information Services, Inc., and publisher of 

Outsourcing

Preferred models for clinical and nonclinical services move in opposite directions.

Functional Versus Full-Service Outsourcing Models

) signed a definitive agreement to acquire two pharmaceutical manufacturing sites, along with additional land for future expansion, in Aurangabad and Navi Mumbai, India. AMRI will acquire the assets, including facilities, employees, products, and equipment of Ariane Orgachem Pvt. Ltd. in Aurangabad and Ferico Laboratories Ltd. in Navi Mumbai for approximately $11 million in cash. All of the facilities are currently owned by the Runwal Group (

) and manufacture a range of pharmaceutical intermediates and bulk active ingredients.  

As part of the purchase, AMRI will obtain additional land in Aurangabad with plans to invest approximately $15 million to expand capabilities there over the next three years. The proposed expansion includes increasing capacity, as well as bringing these facilities into compliance with US Food and Drug Administration regulations for manufacturing clinical trial materials and commercial drug substances. Subject to customary closing conditions, the transaction is expected to close during the second or third quarter of 2007. 

) plans to further expand its manufacturing facility in Milford to enhance its capabilities in siRNA and aptamer manufacturing. Avecia expects the new facility and equipment to be on line by September 2007. As part of the expansion, the company will install new large-scale cleavage-deprotection vessels and equipment to enable large-scale siRNA manufacture. 

—As part of its global initiative to align with customers worldwide, 

) inaugurated its newest Life Sciences Center of Excellence in Bangalore, India. The center includes a proteomics laboratory, a validation laboratory, and a training facility to support Indian and regional customers.   

) is moving the operations of its Dayton, Ohio manufacturing plant to its recently acquired facility in South Haven, Michigan. The company expects to begin the move before the end of the second quarter of 2007. As part of the move, Albemarle will reduce personnel at its facility in Dayton. Some employees will be moved to South Haven or other Albemarle sites. 

) opened a new biotechnology production center in Basel today. The facility will manufacture the anticancer drug "Avastin" (bevacizumab). The Roche Group plans to inaugurate a second new facility in Penzberg, Germany this July. Together with the Basel site, these two facilities will supply Avastin and "Herceptin" (trastuzumab). The first batch of Avastin from Basel is scheduled for delivery in 2009. Until then, 

) will establish a new clinical packaging and logistics facility on the east coast of the United States and build a larger, more modern facility in Deeside, United Kingdom. The US facility will be located near Philadelphia and will accommodate formulation development, analytical testing, and manufacturing operations. The 400,000–500,000-ft

  site is expected to be completed by the summer 2008. The site in Deeside also is expected to be completed in 2008. 

) is expanding its manufacturing capacity for the intermediate tetrahydrofuran (THF) by 30,000 tons per year. The decision to expand is a response to growing demand for THF in the European pharmaceutical industry. The expansion will raise the company's total annual production of THF to 210,000 metric tons. 

) plans to start large-scale production of antibody drug conjugates by investing in a new production unit and in supporting development and analytical laboratories, in Visp, Switzerland. Construction of the commercial-scale plant in Visp began in the last quarter of 2006. Stage I is expected to be on line in 2008. The plant will initially be capable of producing over 100 kg of antibody drug conjugates per year, and future expansion plans are built into the design. Currently Lonza is operating laboratory scale production and will bring small-scale pilot facilities on stream in 2007. 

) began construction of a $100-million research and development expansion at its facility in Waltham. The 132,000-ft

  facility is scheduled for completion in mid-2009. Once complete, it will accommodate up to 100 additional researchers. 

) is doubling its manufacturing space with an expansion that began in mid-2006. The company is installing two new stir-tank bioreactors and relocating, upgrading, and tripling the size of its process development laboratory. 

) opened its specialist design and manufacturing facility for CGMP-grade nanoparticles in Bilbao, Spain. The facility, Midatech Biogune S.L., is the world's first CGMP-grade manufacturing plant for the production of nanoparticles at a scale commensurate with pharmaceutical applications, according to the company. Midatech Biogune initially will focus on designing and manufacturing nanoparticles to supply Midatech Group's nanotechnology project. 

) received a $9.8-million coinvestment from Endless LLP (Leeds, UK, 

) and NorthStar Equity Investors (Newcastle, UK, 

). Excelsyn plans to use most of the investment to upgrade and expand its pharmaceutical development and manufacturing facility in Holywell, United Kingdom. The first phase will be completed in 2007, and the second phase is scheduled for completion in 2008. 

) completed the initial phase of construction on its new CGMP manufacturing facility. The warehouse and materials-management section of the facility are now complete, and the active pharmaceutical ingredient (API) and aseptic fill-and-finish wings are still under construction. The API facility houses a fermentation train leading to a 1000-L scale batch production with downstream processing facilities. The aseptic fill-and-finish wing will include automated vial and syringe filling, inspection, and labeling equipment capable of producing batch sizes larger than 100,000 units. Construction of the 30,000-ft

  facility began in January 2007. Once completed, Althea will occupy a total of 80,000 ft

), is expanding construction at its manufacturing facility in West Chester, Ohio. The expansion increases the company's total investment to approximately $400 million. 

The manufacturing facility is in the process of being equipped to manufacture the company's long-acting release formulation of exenatide, which is being developed to treat Type 2 diabetes. The expanded facility is expected to create up to 500 jobs over the next three years. 

) broke ground for its $750-million biologics manufacturing facility in Devens, Massachusetts. The $750-million investment is BMS's single largest capital investment in its history.  

The new, large-scale, multiproduct bulk facility is modular in design to accommodate potential future expansion. Phase I of the project calls for the construction of four main buildings: a manufacturing structure that will house six 20,000-L cell-culture vessels and one purification train; a central utility building; an administrative and quality-control building; and a warehouse and storage structure. The facility is projected to be operationally complete in 2009, and BMS plans to submit the site for regulatory approval in 2010.  

Phase I of the facility will require a workforce of approximately 350 employees. Future expansion of the site, including several additional buildings, could lead to a total of 550 or more employees. Any expansion will depend on the demand for BMS's biologic drugs and regulatory approval of investigational compounds.  

				The facility will support increased production capacity for "Orcencia" (abatacept), BMS's first internally discovered and developed biologic medicine, and also will manufacture commercial quantities of compounds currently in development should those compounds receive regulatory approval BMS currently manufactures biologic compounds in a company-owned facility in Syracuse, New York, and finishes and packages biologic compounds in Manati, Puerto Rico. The Syracuse site was not designed to accommodate large-scale commercial production but  will continue to serve as a center in process development and early-product launch for BMS's biologic compounds. 

The Manati facility, which also is wholly owned by the company, will continue to finish and package biologic compounds. In March 2006, the company announced a $200-million investment to expand this facility to accommodate increased filling and finishing needs.  

BMS also has biologic manufacturing agreements with third-party partners 

) inaugurated a $200-million expansion of its production facilities in Montes Claros, Brazil. The 37,000-m

  plant will formulate and fill insulin into 3-mL "Penfill" cartridges, which are used in the pen systems marketed by Novo Nordisk. Approximately 95% of the total volume produced in the Montes Claros plant will be exported to other countries such as Germany, Austria, the United Kingdom, Ireland, Australia, New Zealand, Canada, and later on to several developing countries. Novo Nordisk expects to increase the number of employees at the site from the current 400 to 750 by the end of the year.  

				The new plant is Novo Nordisk's largest manufacturing facility outside Denmark and is the largest single investment in the history of the pharmaceutical industry in Brazil, said Novo Nordisk in a company release. Novo Nordisk also recently approved an additional investment of $50 million for the construction of a manufacturing facility in Montes Claros for "FlexPen,"a prefilled insulin pen. The new FlexPen facility is expected to become operational by 2009. 

), a pharmaceutical process development and bulk active ingredient manufacturing affiliate of 

) plans to expand its pharmaceutical manufacturing facility in Florence, South Carolina. The $60-million investment will involve the construction of a new multipurpose production unit in an existing manufacturing building. Roche also plans to add 25—30 new positions at the facility. Construction is scheduled to begin in mid-2007 with completion slated by the end of 2008. 

A roundup of manufacturing and service expansions

Expansions

) together with its subsidiaries,  signed definitive agreements to acquire 

), a multinational generic manufacturer with established subsidiaries, manufacturing and products across the United States, Israel, Canada. North America represents more than 90% of Taro's sales. This all-cash deal is subject to Taro shareholder approval and requisite regulatory clearances. In addition, to provide immediate liquidity for Taro, Sun Pharma will provide interim financing to the extent of $45 million. 

Taro reported 2005 sales of $298 million and profit of $5.7 million. Taro's financial statements for 2003 and 2004 were required to be restated by the audit committee of its board of directors in view of errors in estimating the chargebacks from wholesalers and the actual inventory in the drug distribution chain. As reported on March 20, 2007 by Taro, it expects to report a substantial loss for the year ended December 31, 2006.  

) completed its acquisition of Instituto de Pesquisa Clinica de Sao Paulo, Ltd., a contract research organization providing clinical development services in Brazil.  

—Following its acquisition of the research bioproducts and microbial biopharmaceutical business of 

) announced it will consolidate all US microbial activities in Hopkinton, Massachusetts. Lonza will invest more than $30 million in its Hopkinton site to support its microbial process development and manufacturing growth plans. Both the commercial operations and biopharma service activities in Baltimore, Maryland will continue to run for as long as necessary, anticipated to be until early 2008 to allow for securing sufficient supply of all existing commercial products currently manufactured at the site and to ensure a fully compliant technology transfer to Hopkinton.  

The relocation from Baltimore and the subsequent development of the Hopkinton site may result in as many as 250 additional jobs in Hopkinton. Lonza will offer job opportunities to the affected employees of Baltimore in its other US sites, namely in Hopkinton and the closely situated Lonza Bioscience headquarters in Walkersville, Maryland. Lonza's microbial pharmaceutical business produces therapeutic proteins, fragmented antibodies, vaccines, and other biopharmaceuticals based on microbial expression platforms.  

) signed a share purchase agreement under which Mylan will acquire all of Merck's worldwide operations within Merck Generics, the company's generics business. The $6.7-billion, all-cash transaction is expected to close later this year, subject to regulatory review. Merck Generics has a product portfolio comprising 400 substances, dosage forms, and drug delivery systems.  

In a prepared statement, Karl Ludwig-Kley, chairman of the executive board at Merck KGaA said the company will now focus its resources on growing its pharmaceuticals and chemicals business sectors. In 2006, Merck's generics division accounted for 29% of Merck Group sales and 28% of the group's operating result, with sales rising 6.9% in 2006. Merck Generics employs nearly 5000 people worldwide.  

Mylan operates through Mylan Pharmaceuticals (generic pharmaceuticals), Mylan Technologies (transdermal patches, generic and brand-name), and UDL Laboratories (supplier of unit dose pharmaceuticals). Mylan also owns a controlling interest in Matrix Laboratories, which produces active pharmaceutical ingredients.  

) received and is reviewing a takeover offer made by 

), an investment company led by Bjorgolfur Thor Bjorgolfsson, Actavis's chairman. Novator is offering EUR.98 (approximately $1.30) per share. 

) plans to sell its custom manufacturing business to 

) to focus on its core competencies in colors, surfaces, and performance chemicals. The custom manufacturing business supplies intermediates and active ingredients for the agrochemical, pharmaceutical, and polymer industries. The transaction value was not disclosed. Last year, Clariant sold its pharmaceutical fine chemicals business to the private equity firm 

(Johannesburg, South Africa). The $70-million acquisition makes Ranbaxy the fifth largest generic pharmaceutical company in South Africa and gives the company local manufacturing capability. 

) acquired the biopharmaceutical contract manufacturing organization 

) plans to sell its pharmaceutical manufacturing facilities in Baudette, Minnesota to 

). ANI will assume current manufacturing and packaging activities performed at the facilities and will serve as a contract manufacturer to Solvay for products currently manufactured and packaged in Baudette. ANI also will provide laboratory services to Solvay. 

) received a request for additional information from the 

) Schering-Plough still expects the transaction to close by the end of 2007. 

for $265 million. Negma is the fourth largest independent, integrated pharmaceutical group in France. Wockhardt now owns five pharmaceutical companies in Europe. 

A roundup of company moves and positioning from the pharmaceutical and biotechnology industries and contract service providers.

Mergers, acquisitions, and restructuring

				A spate of recent or planned expansions in biologics production capacity mark the strategy of several biotechnology and pharmaceutical majors as they expand their internal manufacturing networks and partner with select contract manufacturing organizations (CMOs). 			

) with several key projects underway or recently completed for bulk biologics production. 

Genentech is expanding its Vacaville, California facility by constructing an additional manufacturing facility adjacent to the existing facility as well as office buildings to support added manufacturing capacity. Construction, qualification, and licensure of the new Vacaville plant is expected by the end of 2009. In  the fourth quarter of 2006, Genentech received US Food and Drug Adminisration approvals for yield improvement projects at its manufacturing plants in Vacaville related to  the  production of "Rituxan"  (rituximab), according to the company's 2006 annual report. Rituxan is Genentech's top-selling drug with 2006 US sales of $2.07 billion. 

The company also received FDA licensure of 90,000 L of biologic capacity at its Oceanside, California manufacturing facility in April 2007 for bulk production of "Avastin" (bevacizumab). Avastin is one of Genentech's top-selling drugs with US 2006 sales of $1.7 billion.  

Last year, Genentech formed a supply pact and the option to purchase a new large-scale mammalian cell-culture manufacturing facility with the CMO 

). In December 2006, Lonza acquired Genentech's cell-culture manufacturing facility (40,000 L of biologic manufacturing capacity) in Porriño, Spain and at which Lonza will continue to manufacture Avastin bulk drug substance for Genentech under the terms of a supply agreement. Genentech also has an option to purchase from Lonza between 2007 and 2012 Lonza's 80,000-L large-scale mammalian cell-culture manufacturing facility currently under construction in Singapore. The facility is expected to be licensed for the production of Avastin in 2010. 

In mapping out other biologics production projects, Genentech announced in March that it was entering into a land-lease agreement in Singapore for the construction and development of a 1,000-L 

 manufacturing facility. The approximately $140-million facility will be dedicated to the bulk drug production of "Lucentis" (ranibizumab). Construction on the facility is expected to begin in the second quarter of 2007 with licensure anticipated by early 2010.   

 In 2006, FDA granted approval for the manufacture of Herceptin (trastuzumab) bulk drug substance at 

) production facility in Andover, Massachusetts. Herceptin is one of Genentech's key products with 2006 US sales of $1.23 billion.  

In September 2006, Genentech acquired land in Hillsboro, Oregon for the construction of a new fill-and-finish, warehousing and related office facility. Genentech broke ground in December 2006 and FDA licensure is anticipated in 2010. Genentech also selected the Hillsboro, Oregon site as the location for a new West Coast warehouse and distribution center. Construction will begin in the second quarter of 2007 and the facility is expected to be completed and fully operational in the third quarter of 2008. 

Also, in April 2007, Genentech received FDA licensure for a third aseptic fill line, which will fill both liquid and lyophilized products for commercial use, on its South San Francisco campus.  Construction began in the third quarter of 2005. 

) has two major expansions underway. Earlier this year, Amgen revised its schedule for completing a new manufacturing facility in County Cork, Ireland. In 2006, Amgen announced plans to invest more than $1 billion in new process development, bulk protein production, and fill-and-finish facilities, with an initial target of beginning operations in 2010. An Amgen official explained that the amount of additional capacity Amgen intends to develop in Ireland, the overall capital investment, and the number of staff it plans to employ have not changed, but the company will stagger and extend its time lines to allow for a more efficient project execution. In addition, Amgen will continue to monitor business needs to determine whether it needs to accelerate the construction start. The bulk-manufacturing capacity is scheduled to be operational in 2012, and regulatory licensure of the facility is anticipated for 2013. The process-development laboratories will be constructed in conjunction with the bulk facility or as needed to support the start-up of the manufacturing capacity. The fill-and-finish capacity is scheduled to be operational by 2013, with regulatory licensure anticipated by 2014. 

Amgen is further investing more than $1 billion to build a new bulk-protein manufacturing facility in Juncos, Puerto Rico, for "Neupogen" (filgrastim), "Neulasta" (pegfilgrastim), "Epogen"(epoetin alfa), and "Aranesp" (darbepoetin alfa). The company will construct a new formulation, fill, and finish facility as well. 

) is proceeding with the construction of a large-scale biologic manufacturing facility in Hillerod, Denmark to produce "Tysabri"(natalizumab) and other products in the company's pipeline. After voluntary suspension of Tysabri, Biogen Idec decided to proceed with the bulk manufacturing component of the facility and to add a labeling and packaging component, according to the company's 2006 annual report, although it decided not to proceed with the fill-finish component of the project. Biogen Idec's board of directors authorized an additional $225 million to be spent on the project on top of the $275 million initially spent on the project, according to the company's 2006 annual report.   

Tysabri is manufactured in Biogen Idec's Research Triangle Park, North Carolina, facility. Tysabri was initially approved by the FDA in November 2004 and was voluntary withdrawn by Biogen Idec in February 2005. FDA approved resumed marketing of the drug in June 2006.  

), is moving ahead with an expansion in Ireland. Earlier this year, the company announced that it will invest EUR 60 million ($81 million) for a new  pharmaceutical plant at Grange Castle Business Park, Clondalkin, Dublin, Ireland. The development of the new Dublin facility will involve the relocation of the company's current facilities and more than 80 staff from Sandyford Industrial Estate to Grange Castle Business Park. The company is relocating from Sandyford as its current facilities have reached maximum capacity and are no longer able to meet its growth targets and manufacturing requirements, according to a release from the Irish Development Agency (Dublin, Ireland, 

). The target completion date for construction of the new facility is late 2008. 

Just as the biotechnology majors are investing in internal manufacturing capacity, so are the pharmaceutical majors, with several projects announced or recently completed.  

) opened in April 2007 a $450-million, 330,000-ft

  biologic manufacturing facility in Barceloneta, Puerto Rico, to support the long-term supply of its biologic agent, "Humira" (adalimumab).  

) broke ground this month for its $750-million, large-scale, multiproduct, bulk-biologic manufacturing facility in Devens, Massachusetts—the single largest capital investment in its history. Phase I of the project calls for the construction of four main buildings: a manufacturing structure that will house six 20,000-L cell-culture vessels and one purification train, a central utility building, an administrative and quality-control building, and a warehouse and storage structure. The facility is projected to be operationally complete in 2009, and BMS plans to submit the site for regulatory approval in 2010.  

The facility will support increased production capacity for "Orcencia" (abatacept), BMS's first internally discovered and developed biologic medicine, and also will manufacture commercial quantities of compounds currently in development should those compounds receive regulatory approval. BMS has biologic manufacturing agreements with third-party partners 

BMS currently manufactures biologic compounds in a company-owned facility in Syracuse, New York, and finishes and packages biologic compounds in Manati, Puerto Rico. The Syracuse site was not designed to accommodate large-scale commercial production but will continue to serve as a center in process development and early-product launch for BMS's biologic compounds. The Manati facility, which also is wholly owned by the company, will continue to finish and package biologic compounds. In March 2006, BMS announced a $200-million investment to expand this facility.  

Several large-scale vaccine production expansions are underway as 

 Novartis is building a cell-culture-derived influenza-vaccines manufacturing plant in Holly Springs, North Carolina. Novartis will spend approximately $600 million, including a $220-million award from the US Department of Health and Human Services, to complete the site. The plant is expected to produce about 50 million doses of seasonal trivalent flu vaccines annually for the US market. The site also is designed to produce 150 million monovalent vaccine doses annually within six months of an influenza-pandemic declaration. In parallel, Novartis is making additional investments to expand capacity for flu cell-culture vaccine production in Marburg, Germany.  

 Merck & Co. invested $300 million to construct a 272,000-ft

  vaccine-production plant in Durham, North Carolina. The plant is scheduled to be complete and operational by the first quarter of 2008. Following validation, the first vaccines should be available by the first quarter of 2009. The plant is expected to eventually produce more than two thirds of Merck's annual live-virus vaccine stock, which could amount to more than 25 million doses per year. The facility will produce "Zostavax," Merck's new shingles vaccine, and a vaccine for measles, mumps, and rubella. 

In addition to the $300 million for the new vaccine facility in Durham, Merck is investing $100 million to increase vaccine-manufacturing capacity at the facility. The 115,000-ft

  expansion will provide room for sterile processing, formulation equipment, lyophilization equipment, automatic inspection equipment, testing laboratories, and high-speed packaging. The new phase of construction is scheduled to begin in the fall 2007 and be completed by 2010. 

 GSK is investing £100 million ($200 million) for a vaccine-manufacturing plant in Singapore for the primary production of pediatric vaccines. GSK also is investing more than EUR 500 million ($680 million) in its St-Amand-Les-Eaux, France, vaccine-manufacturing plant to increase formulation, filling, freeze-drying, and packaging production. The facility is expected to be operational in 2011 and will produce vaccine for cervical cancer, meningitis, pneumonia, and influenza. Also, GSK opened an EUR 100-million ($136-million) primary production facility in Gödöllö, Hungary, for manufacturing diphtheria, tetanus, and pertussis antigens used in several pediatric vaccine combinations. 

 Sanofi Pasteur is building a $160-million vaccine-manufacturing facility in Swiftwater, Pennsylvania, which will double its US production capacity. Sanofi also is investing EUR 160 million for a formulation-filling facility in Val de Reuil, France, and will expand cell-culture based virology production at its facility in Marcy l'Etoile, France. 

), two major insulin producers are proceeding with expansions.  

 Novo Nordisk. inaugurated a $200-million expansion of its production facilities in Montes Claros, Brazil. The 37,000-m

  plant will formulate and fill insulin into 3-mL "Penfill" cartridges, which are used in the pen systems marketed by Novo Nordisk. Approximately 95% of the total volume produced in the Montes Claros plant will be exported to other countries such as Germany, Austria, the United Kingdom, Ireland, Australia, New Zealand, Canada, and later on to several developing countries.  

 Eli Lilly completed a $1-billion expansion of its Puerto Rico manufacturing operations in August 2006, which includes new bulk capacity for "Humalog" (insulin lispro [rDNA origin] injection). The company also is adding a new assembly line at its device-assembly operation in Indianapolis. One of the first products made on the assembly line will be its new prefilled insulin pen, "HumalogMirioPen." The product is currently under FDA review and is expected to be launched later this year. 

Other biotechnology investments by Eli Lilly include an expansion of its site in Kinsale, Ireland, to manufacture active pharmaceutical ingredients for future biotechnology products. Lilly is also expanding its Indianapolis, Indiana, parenteral operations so that the site can convert the biotechnology APIs made in Kinsale into their final-dosage forms. In October 2006, Eli Lilly completed the first phase of a $560-million expansion to its biotechnology complex in Indianapolis, which included the opening of a bioproducts pilot-manufacturing plant that makes small-scale amounts of drugs for use in clinical trials and a research-support facility. Construction of a third facility, a bioproducts R&D laboratory, was completed earlier this year.  

Global Feature

Reflecting strong growth prospects for certain biologic-based drugs, the biotechnology and pharmaceutical majors are proceeding with a strategy of expanding their internal manufacturing networks and partnering with select contract manufacturing organizations (CMOs).

Mapping a Biologics Supply Strategy

) for the development, GMP manufacturing, and regulatory documentation support of MORAb-028, a therapeutic antibody targeting advanced melanoma and other cancers. MORAb-028 is a human IgM monoclonal antibody that specifically recognizes a cell surface antigen overexpressed on a significant fraction of metastatic melanoma, brain cancers, and non-small cell lung carcinoma. MORAb-028 is being prepared to enter clinical evaluation in 2008. 

) entered into a collaborative agreement with 

) to develop and commercialize human antibody therapeutics for treating cancer and autoimmune disorders. The companies will use Medarex's "UltiMAb" human antibody development system and will share all development and commercialization responsibilities for any antibody-based therapeutics that result from the collaboration. 

) to provide engineering, procurement, validation, and site-support services for a cell-culture manufacturing facility in Hillerod, Denmark. The facility, the first of its kind in Hillerod, will produce the multiple sclerosis treatment "Tysabri" (natalizumab). The facility is scheduled for completion in 2009. 

). The agreement covers the reciprocal supply of products for biopharmaceutical process applications between Sartorius and 

), an affiliate of Thermo Fisher. TC Tech will supply Sartorius with disposable process containers through 2007 and with disposable process containers assembled with Sartorius filter capsules until 2012. Sartorius will continue to supply TC Tech with filter units for an additional five years. 

Chalfont St. Giles, United Kingdom (May 3)

) that gives NorDiag access to GE patents for the biomagnetic isolation of nucleic acids. The agreement gives NorDiag the rights to isolate and purify nucleic acids using GE's proprietary magnetic separation technology 

) signed a process-development and CGMP production agreement with 

). Diosynth will develop a process to produce clinical trial material for VGX's biological therapeutic drug candidate VGX-100.  

) "CaptureSelect" custom affinity ligands were selected by 

) for vaccine purification. CaptureSelect ligands are manufactured using a high-yield, animal-free, yeast-based expression system. They offer high stability and specificity for the process-scale purification of some vaccine products. 

) for use with PR-171, proteasome inhibitor that could treat certain cancers. Captisol improves water solubility, bioavailability, and complexation characteristics of insoluble or unstable drugs. The agreement gives Proeolix global rights to Captisol to formulate PR-171. 

), licensed its "Pfenex" expression technology to 

). VGX plans to use the technology to produce a proprietary therapeutic protein for cancer therapy. Pfenex produces large yields of soluble, correctly folded therapeutic proteins, thus avoiding the refold step. The proteins produced also are easy to handle and enable a clear path through the purification process, according to Dowpharma. 

The latest pacts from the pharmaceutical supply chain.

PTSM: Pharmaceutical Technology Sourcing and Management-05-30-2007

People

Functional Versus Full-Service Outsourcing Models

Expansions

Mergers, acquisitions, and restructuring

Mapping a Biologics Supply Strategy

Agreements and contracts