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Pharmaceutical Technology's Manufacturers' Rankings
Pharmaceutical Technology's Second Annual Manufacturers' Rankings reveal key trends about the pharmaceutical industry's sales growth, product and company positioning, and the manufacturing activity of the top companies. Led by a recovery in the US market, global pharmaceutical sales growth increased at a healthy rate in 2006, although the industry still has not returned to the double-digit growth it once enjoyed. The top 10 product rankings for the global and US markets remained fairly steady, although 2006 saw the entry of two biologic-based products in the global top 10. On the innovation front, the number of new molecular entities (NMEs) from Big Pharma continues to be modest. The manufacturing activity of the pharmaceutical majors reflects these trends as companies proceed with expansions in biologics manufacturing and rationalize small-molecule capacity.
Pharmaceutical industry growth
Product positioning for the top spots
Global sales. On a sales basis, the top 10 selling products accounted for $60 billion or nearly 10% of the global market, according to IMS. Sales of the top 10 global products grew 8% in 2006, slightly above the 7% growth for the global pharmaceutical industry as a whole (see Table I).
Despite declining sales resulting from generic competition, Merck & Co.'s Zocor still ranked among the top 10 selling products in the United States, although US sales declined from $4.4 billion in 2005 to $3.1 billion in 2006. TAP Pharmaceutical Products's Prevacid also made the top 10 US product rankings despite a sales decline from $3.8 billion in 2005 to $3.5 billion in 2006.
And three products—Amgen's "Epogen," AstraZeneca's "Seroquel," and Merck & Co.'s "Singulair"—made the top 10 in USrankings but not globally in 2006.
Manufacturing activity in Big Pharma
Pfizer. Pfizer announced plans earlier this year to reduce its workforce by 10%, exit five manufacturing facilities, rationalize R&D operations, and restructure its US pharmaceutical operations. The announcement comes as the company expects its 2007 and 2008 revenues to be comparable to 2006 levels.
Since the Pharmacia integration begun in 2003, Pfizer has been reducing the number of its plants to bring capacity in line with product demand, to eliminate duplication, and to improve manufacturing efficiency. By the end of 2009, the number of global plants will have been cut by almost 50%, from 93 to 47. This reduction includes rationalization of its internal manufacturing networks and the sites included in the sale of its consumer healthcare business to J&J.
In February, Pfizer reported it would close a portion of its active pharmaceutical ingredient (API) plant at Ringaskiddy, Ireland, and would pursue the sales of its API facility in Loughbeg, Ireland, a portion of the API manufacturing facility in Little Island, Ireland, and a facility for sterile liquids in Nerviano, Italy, subject to consultation with works councils and local labor laws.
In January, Pfizer reported plans to close its manufacturing sites for solid-dosage drug production and packaging in Brooklyn, New York, and for animal-health sterile products in Omaha, Nebraska. It also plans to sell its combined API and drug-product operations in Feucht, Germany, subject to consultation with works councils and local labor laws. Pfizer also is phasing out a manufacturing facility in Groton, Connecticut. The plant makes APIs for human- and animal-health products, and the manufacture of those products will be transferred to other plants.
In 2006, Pfizer sold four facilities: a sterile production and API facility in Cruce Dávila, Puerto Rico, to Abraxis Biosciences, Inc. (Los Angeles, CA); an API facility in Augusta, Georgia, to Xethanol Corp. (New York); an API and finished-drug manufacturing plant in Uppsala, Sweden to Kemwell Pvt. Ltd. (Bangalore, India); and its API, finished dosage, and packaging facility in Morpeth, United Kingdom, to NPIL Pharma (Mumbai, India).
The sale of Pfizer's consumer healthcare business to J&J included finished-drug product plants in Parsippany, New Jersey; Lititz, Pennsylvania; Caringbah, Australia; Cali, Colombia; Orleans, France; Cape Town, South Africa; and Helsingborg, Sweden, as well as an associated gum-production operation in Esbjerg, Denmark.
Pfizer is planning to close its Ann Arbor, Esperion, and Kalamazoo, Michigan, research sites, but will continue to maintain a large manufacturing and animal-health presence in Kalamazoo. It is also proposing to close research sites in Nagoya, Japan, and Amboise, France, subject to consultation with works councils and local labor laws.
As it has rationalized facilities, Pfizer acquired from Sanofi-Aventis the Frankfurt, Germany, insulin-production business and facilities it previously had owned jointly with Sanofi-Aventis as part of its $1.4-billion acquisition of the rights to manufacture and sell "Exubera" inhaled insulin.
GSK. GSKis investing EUR 250 million ($335 million) in its production site at Currabinny, County Cork, Ireland, through 2012 to support production for lapatinib, the API in "Tykerb," a new oral treatment for breast cancer.
In biologics, GSK announced several projects for vaccine production. It 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.
In April, GSK completed a 30,000-ft2 expansion of its Aiken, South Carolina, manufacturing facility to improve capacity in several processes such as dry-powder blending, tablet compression, tablet coating, and tablet printing.
Sanofi-Aventis. Like other pharmaceutical majors, Sanofi-Aventis is reducing its manufacturing network. The company plans to close its manufacturing site in Waterford, Ireland, according to news reports. The plant manufactures mature and over-the-counter products, including "Essentiale" and "Flagyl." The manufacture of these two products will be taken over by Sanofi plants in France and Germany. The Waterford plant is expected to close by the end of the year.
Sanofi 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.
In March 2006, Sanofi-Aventis acquired an additional 25% stake in Zentiva for EUR 430 million ($577 million), becoming that company's largest shareholder. Zentiva is a pharmaceutical company that develops, manufactures, and markets branded, low-cost pharmaceutical products. The company employs nearly 5000 people and has manufacturing plants in the Czech Republic, Slovakia, and Romania.
Novartis. 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.
In 2006, Novartis invested approximately $101 million to expand capacity at its Grimsby, United Kingdom, production facility to support the technical launch of its blood-pressure medicine "Tekturna–Rasilez" (aliskiren). In addition, the company invested $58 million to fund a chemical-operations production facility in China to support early-phase development activities and more than $61 million to construct a new pharmaceuticals plant in Singapore.
AstraZeneca. Earlier this year, AstraZeneca announced a new productivity initiative to improve asset utilization in production operations. The plan, which will be implemented during the next three years, involves the rationalization of production assets and a proposed reduction of approximately 3000 positions, subject to requisite employee consultations.
As part of this global restructuring effort, AstraZeneca announced plans to exit its Plakstadt, Germany, and Mississauga, Canada, sites. The plan for Plankstadt, which is used for bulk production, formulation, and packaging and currently employs 400, is to either close or sell the site by the end of 2009. Products currently manufactured at the site include "Casodex" (bicalutamide), "Zoming" (zolmitriptan), "Crestor" (rosuvastatin), and "Tenormin" (atenolol). The Mississauga packaging facility will close within the next 18 months, affecting approximately 120 employees.
AstraZeneca's operations in the United Kingdom, Sweden, and the United States also will undergo staff reductions. About 700 job cuts will be phased in during the next three years at its plant in Macclesfield, Cheshire, United Kingdom. At its Södertälje, Sweden, facility, 850 jobs cuts are anticipated. Södertälje is AstraZeneca's largest production site and employs roughly 4500 workers. The job cuts are scheduled to take place during 2008 and 2009, with full effect by 2010. In addition, 450 jobs at the Swedish manufacturing site will be cut in 2007 as part of a previously announced reduction.
AstraZeneca's US operations announced plans for a 400–450-person headcount reduction by 2010 to support its goal of improving productivity by 25–30%.
AstraZeneca opened a $32-million tablet factory near Cairo, Egypt, in December 2006, representing its first manufacturing investment in the Middle East. The new facility began production this year. The 7000-m2 plant has three production lines with an annual capacity of 250 million tablets that could be expanded to 400 million tablets.
AstraZeneca will close its formulation and packaging plant in Pandaan, Surabaya, Indonesia, this year. Also, in 2007, AstraZeneca opened a new $15-million, 8000-m2 process R&D laboratory at its R&D center in Bangalore, India.
J&J. In addition to the facilities gained with its $16.6-billion acquisition of Pfizer's consumer healthcare business, J&J started the construction in April 2007 of a new building on its Spring House, Pennsylvania, campus to add approximately 150,000 ft2 in new laboratory, clinical development, and office space to its existing facilities. The site will become Johnson & Johnson Pharmaceutical Research & Development's East Coast hub for discovery research and early clinical development upon its completion in 2009.
Merck. Merck & Co. is continuing its global-manufacturing restructuring program, first announced in late 2005, under which it plans to close or sell five of its 31 manufacturing facilities and two preclinical sites by the end of 2008. The manufacturing sites to be rationalized are located in Ponders End, United Kingdom; Okazaki, Japan; Kirkland, Quebec, Canada; Albany, Georgia; and Danville, Pennsylvania. By the end of 2006, Merck had sold its bulk manufacturing facility in Ponders End to the contract manufacturing organization Aesica (Cramlington, UK), exited manufacturing sites in Okazaki, Japan, and Kirkland, Canada, and exited two preclinical sites in Okazaki and Menuma, Japan. With this restructuring, Merck eliminated 4800 positions companywide by the end of 2006 as part of an overall plan to reduce its workforce by 7000 by the end of 2008.
While it is rationalizing certain facilities, Merck is proceeding with investments in vaccine production. The company invested $300 million to construct a 272,000-ft2 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-ft2 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 fall 2007 and be completed by 2010.
Roche. Roche Pharmaceuticals is investing roughly CHF 2 billion ($1.6 billion) in manufacturing infrastructure projects, which includes CHF 800 million ($659 million) in major biotechnology facilities to produce the APIs in "Avastin" (bevacizumab) and "Herceptin" (trastuzumab) in Basel, Switzerland, and Penzberg, Germany, which are scheduled to be operational by 2009. Roche also is investing in new formulation, filling, packaging, and logistics facilities for injectable and infusable medicines in Kaiseraugst, Switzerland, and Mannheim, Germany, and in a facility in Toluca, Mexico, for the formulation of highly potent drugs such as "Xeloda" (capecitabine).
Roche Carolina Inc., a pharmaceutical process development and bulk API manufacturing affiliate of Roche Holding Ltd., plans to expand its pharmaceutical manufacturing facility in Florence, South Carolina, by investing $60 million in a new multipurpose production unit within an existing manufacturing building. Construction is scheduled to begin in mid-2007 to be completed by the end of 2008.
Roche also announced earlier this year that it has sufficient production capacity for its antiviral drug "Tamiflu" (oseltamivir) for treating the H5N1 avian-influenza virus. Its manufacturing network for the drug includes eight Roche sites and 19 external manufacturing partners located in nine countries, giving it annual production capacity of more than 400 million courses. Roche has government orders for 215 million treatments and is tailoring its production schedule while maintaining stocks of intermediates and APIs. It said gearing production up to full capacity will be triggered by one of two events: Roche inventories of oseltamivir, the API in Tamiflu, dropping below target levels or the World Health Organization declaring the pandemic has evolved to phase 4 (human-to-human transmission).
Eli Lilly. Eli Lilly is investing in its biologics-manufacturing facility to support its emerging biotechnology pipeline that is anticipated to produce one new product per year, on average, beginning in 2010. Biotechnology-based programs and drug candidates now make up more than 30% of the company's drug portfolio and pipeline.
Specific biotechnology investments include an expansion of its site in Kinsale, Ireland, to manufacture APIs 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. Both expansions are part of a $1.5-billion investment in the company's biotechnology capabilities announced during the past five years.
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. These investments follow the recently completed $1-billion expansion of its Puerto Rico manufacturing operations in August 2006, which includes new bulk capacity for "Humalog" (insulin lispro [rDNA origin] injection).
Eli Lilly is also adding a new assembly line at the company's 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.
Also, in response to excess capacity in Lilly's small-molecule API operations, a voluntary exit program was offered to 250 employees at Lilly's Tippecanoe manufacturing site in Lafayette, Indiana. About 1000 employees work at the site, and 200 accepted the program.
Eli Lilly is also closing its manufacturing plant in Basingstoke, United Kingdom, effective April 2008. The site now produces 56 million packs of finished product per year with an annual volume of 1.5 billion does. The site manufactures the finished product for "Cialis" (tadalafil), "Evista" (raloxifene), "Strattera" (atomoxetine), and "Zyprexa" (olanzapine).
Wyeth. Wyeth is investing EUR 24 million ($33 million) to add 6000 m2 of laboratory space for process-development and R&D facilities at its Grange Castle biopharmaceutical campus in Dublin, Ireland, according to the Irish Development Agency. Wyeth opened the $2-billion biotechnology drug-production facility in Grange Castle in 2005. The facility performs drug fermentation, sterile fill-and-finish, and process development. In 2006, Wyeth added a manufacturing suite at its biopharmaceutical manufacturing facility in Andover, Massachusetts. The company also has significant, ongoing capital projects to support additional manufacturing capacity and new products at its facilities in Sanford, North Carolina, and Puerto Rico, according to its annual report.
Bristol-Myers Squibb. BMS broke ground in May 2007 for its $750-million, large-scale, multiproduct, bulk-biologics 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 Lonza Biologics, Inc. (Basel, Switzerland) and Celltrion, Inc. (Incheon, Korea).
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.
BMS continues to pursue its goal of achieving a $500-million cost reduction by 2007 and an additional $100-million cost reduction by 2008. The cost reductions are companywide and include technical operations.
Amgen. 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 timelines 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 investing more than $1 billion to build a new bulk-protein manufacturing facility in Juncos, Puerto Rico, for "Neupogen" (filgrastim), "Neulasta" (pegfilgrastim), Epogen, and Aranesp. The company also will construct a new formulation, fill, and finish facility.
Abbott. In April 2007, Abbott opened a $450-million, 330,000-ft2 biologics manufacturing facility in Barceloneta, Puerto Rico, to support the long-term supply of its biologic agent, "Humira" (adalimumab).
Boehringer Ingelheim. Boehringer Inghelheim (BI) is investing EUR 170 million ($229 million) in its chemical-production facilities in Petersburg, Virginia, and Fornovo, Italy. The company also is doubling capacity for "Respimat" (dabigatran) at its facility in Dortmouth, Germany. The expansion is scheduled to be completed in 2009. In 2006, BI invested EUR 50 million ($68 million) for a new pharmaceutical R&D facility in Biberach, Germany. BI is investing more than EUR 50 million to expand its Cleveland, Ohio, facility. The expansion will include new laboratories and office buildings. In addition, the company is expanding its LogiPack Center packaging facility in Ingelheim, Germany.
Bayer Schering Pharma. Bayer Schering Pharma AG, formed from the Bayer Group's acquisition of Schering AG, is proceeding with an integration plan that will result in annual savings of EUR 700 million ($951 million) from 2009. Bayer announced in 2006 that the integration of the two companies will result in 6100 job cuts.
Schering-Plough. As part of a global manufacturing streamlining effort, Schering-Plough phased out and closed its pharmaceutical manufacturing facility in Manati, Puerto Rico, at the end of 2006 and reduced the workforce in facilities in Las Piedras, Puerto Rico, and Kenilworth, New Jersey. About 1000 employees were eliminated. Also, Schering-Plough invested $38 million in its pharmaceutical-sciences center in Kenilworth and plans to invest an additional $260 million during the next three years.
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