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Patricia Van Arnum was executive editor of Pharmaceutical Technology.
Despite overall manufacturing rationalization in the pharmaceutical/biopharmaceutical industry, the large pharmaceutical companies continue to invest in biologic-based manufacturing. The author provides an update in recent investment activity among the pharmaceutical majors in biologic-drug substance, vaccine, and parenteral drug manufacturing.
Alfred Pasieka/Getty Images; Dan WardRestructuring and manufacturing rationalization have been the order of the day for the large bio/pharmaceutical companies during the past several years. Small-molecule and solid-dosage operations have been the largest target for such cost cutting, but there are bright spots on the manufacturing investments. Several Big Pharma companies are investing in biologic drug-substance, vaccine, and parenteral drug finished product manufacturing.
Bristol-Myers Squibb. Bristol-Myers Squibb is investing approximately $250 million to expand its large-scale biologics manufacturing facility in Devens, Massachusetts. The expansion will introduce biologics development and clinical-trial manufacturing capabilities to the site while adding approximately 350 employees to the Devens workforce over time. The Devens site is home to the company’s large-scale bulk biologic manufacturing facility. Construction of the Devens site was completed in 2009. It represented the company’s largest single capital investment ($750 million) and provided Bristol-Myers Squibb with large-scale bulk biologics production capacity. In May 2012, the company received FDA approval to manufacture its arthritis drug Orencia (abatacept) at the Devens facility.
The new $250-million investment will be used to construct two new buildings on the 89-acre Devens campus: one building for process development and one for clinical manufacturing. Together, the two buildings will add approximately 200,000 ft2 of laboratory and office space to the Devens site, which is now comprised of six major buildings in a 400,000-ft2 complex. Work on the expansion is expected to begin in late 2013 and be completed in 2015. In the interim, Bristol-Myers Squibb has leased 30,000 ft2 of laboratory space in nearby Hopkinton, Massachusetts, to begin moving some biologics process-development functions closer to Devens during construction. The company intends to maintain this space until construction is completed.
Novartis. In the fourth quarter of 2012, Novartis announced the planned construction of a new biotechnology production site in Singapore with an investment valued at more than $500 million. The new facility will focus on drug- substance manufacturing based on cell-culture technology. Construction will begin in 2013, and the site is expected to be fully operational in 2016. It will be colocated with the company’s pharmaceutical production site in Tuas, Singapore. In the future, Novartis expects its Singapore site to be a technological competence center for both biotechnology and pharmaceutical manufacturing.
In December 2012, Novartis acquired a 16,000-m2 FDA-approved manufacturing facility in Morris Plains, New Jersey from the biopharmaceutical company Dendreon for $43 million. Novartis purchased all fixed assets at the site, including all equipment, machinery, utilities, and cell- therapy-related plant infrastructure. The land and building will continue to be leased from a third party. The facility, and certain former Dendreon personnel that were retained will support clinical and commercial production of potential new products and therapies that emerge from the Novartis–University of Pennsylvania (Penn) collaboration announced in August 2012. These drugs include CTL019, a drug in Phase I/11 development for treating certain blood cancers. Under the Novartis–Penn pact, the parties will research, develop, and commercialize targeted chimeric antigen receptor immunotherapies for the treatment of cancers as well as build on the Penn campus in Philadelphia the Center for Advanced Cellular Therapies, which will be dedicated to developing and manufacturing adoptive T-cell immunotherapies.
Novartis also is proceeding with a multiyear vaccine-production project. In 2008, its Vaccines and Diagnostics Division broke ground on a new rabies and tick-borne encephalitis $330-million manufacturing facility in Marburg, Germany. Construction is complete and the facility is in the process of executing the necessary validation activities with regulatory approvals for products planned for 2013.
In 2009, Novartis opened a new cell culture-based influenza vaccine-manufacturing site in Holly Springs, North Carolina. As of Dec. 31, 2012, the total amount spent on the project was $426 million, net of grants reimbursed by the US government. The total investment in this new facility is expected to be at least $900 million, partly supported by grants from the US government and prior investments in influenza cell-culture technologies at the Novartis vaccines site in Marburg, Germany.
The company is also proceeding with the building of a new $475-million vaccine-manufacturing facility in Recife, Brazil. The manufacturing plant is part of Novartis vaccines’ strategy to enter the Brazilian market and is aligned with the government’s goal to become self-sufficient in vaccines. The technical start-up of the facility is planned for approximately 2015.
Sanofi. As part of its growth strategy in diabetes, Sanofi’s Frankfurt, Germany site, its principal manufacturing center for Sanofi diabetes products, is being equipped with a new aseptic processing area that uses isolator technology to significantly improve the aseptic-filling process. This investment will be operational in 2016. The Sanofi diabetes industrial network also is expanding its manufacturing footprint in emerging markets, both in Russia and in China (Beijing), where a new facility that was inaugurated in 2012 has begun assembly and packaging of SoloSTAR, the prefilled injection system for Lantus (insulin glargine). Also, during 2012, Sanofi’s Ankleshwar Pharma site in Gujarat State, India, handled packaging and quality control through to release the first commercial batches of AllSTAR, the company’s insulin pen specifically intended for the India market.
Its Frankfurt site is one of three dedicated biotechnology hubs that Sanofi is developing in Europe. In 2012, its facility in Vitry-sur-Seine, its biggest integrated cell-culture facility, produced the first technical batches of aflibercept, the API in the company’s anticancer drug Zaltrap. Its facility in Lyon Gerland, France, is a new world center dedicated to the production of thymoglobulin, a drug to prevent and treat transplant rejection. During 2012, teams at Lyon prepared a dossier for the healthcare authorities as part of the process of transferring production to this site.
In the United States, Sanofi, through its subsidiary Genzyme, has major investments underway, including at its Framingham, Massachusetts biologics site, which was approved by FDA and EMA in 2012 for the manufacture of Fabrazyme (agalsidase beta) to treat Fabry disease. Its site at Allston, Massachusetts has initiated a major investment program in connection with the implementation of its compliance-remediation workplan, approved by FDA in January 2012. In 2012, Sanofi’s Genzyme acquired the Bayer Healthcare facility in Lynnwood, Washington, which specializes in the manufacture of Leukine (sargramostim).
On the vaccine side, Sanofi Pasteur, the company’s vaccine arm, is undergoing a major investment phase, which includes a new dedicated dengue fever vaccine facility in Neuville, France, which is scheduled to produce its first batches in 2014. Two new, dedicated influenza vaccine-manufacturing facilities are in the start-up phase. Sanofi’s facility in Shenzhen, China is currently testing its production processes, and its facility in Ocoyoacac, Mexico was approved by Mexican regulatory authorities at the start of 2012 and began production in time for the Mexican influenza vaccination program in September 2012. In response to observations made by FDA during routine inspections conducted in 2012 at its facility in Toronto and Marcy l’Etoile, France, Sanofi Pasteur initiated a compliance program to addres quality issues that had been identified.
Roche. Roche is investing CHF 240 million ($257 million) at its facility in Penzberg, Germany to expand raw-material manufacturing for its Elecsy immunoassays, to be completed by the end of 2014, as well as to increase compounding, filling, and lyophilization capacity, which is planned for 2016. At its sites in Basel and Kaiseraugst, Switzerland Roche is investing approximately CHF 230 million ($246 million). Three projects were completed in 2012: a new pharmaceutical quality control and assurance building, expansion of cold-chain storage capacity, and a filling line upgrade for Herceptin (trastuzumab) subcutaneous formulation. The company is also expanding capacity to increase capacity for high-potency drugs.
GlaxoSmithKline. GlaxoSmithKline (GSK) announced plans to invest more than £500 million ($798 million) in the UK across its manufacturing sites, which included selecting Ulverston in Cumbria as the location for the first new GSK manufacturing facility to be built in the UK in almost 40 years. The company also will invest in sites in Montrose and Irvine, Scotland. GSK’s announcement followed plans by the UK government to implement a “patent box” to encourage investment in R&D and related manufacturing in the UK by introducing a lower rate of corporation tax on profits generated from UK-owned intellectual property. Following a feasibility study conducted through 2011, GSK said it will locate a new £350 million ($559 million) biopharmaceutical manufacturing facility in Ulverston, Cumbria. Detailed planning and design of the new facility is underway with an anticipated start date for construction of 2014–2015, dependent on portfolio timing and obtaining necessary planning and related consents. Once construction starts, it is likely to take at least six years before the plant is fully operational.
Eli Lilly. In 2012, Eli Lilly reported that it is investing EUR 330 million ($430 million) in a new biopharmaceuticals facility at its Kinsale campus in Cork, Ireland.