Biologics manufacturing is an active area of investment by the large pharmaceutical companies. DCAT Value Chain Insights examines key manufacturing projects for production of recombinant proteins and monoclonal antibodies.

The pharmaceutical industry has undergone manufacturing rationalization over the past several years in chemical active pharmaceutical ingredient (API) and solid-dosage manufacturing as companies aligned their manufacturing networks to product demand. Biologics manufacturing, however, has been an active area of investment, with several announced and completed projects, including projects from Bristol-Myers Squibb, AstraZeneca, Amgen, Sanofi, and Roche. 

A roundup of activity
So what are some key projects? Chief among them are plans announced by Bristol-Myers Squibb in November 2014 to construct a new biologics manufacturing facility in Cruiserath, County Dublin, Ireland, which will produce multiple therapies for the company’s biologics portfolio. The 30,000-square meter project will house six 15,000-liter bioreactors and a purification area as well as office and laboratory space. The plant will be built on the grounds of the company’s existing bulk pharmaceutical manufacturing plant. Bristol-Myers Squibb’s board of directors has approved initial funding that will support the first phase of the project. The full cost of the facility, expected to be finalized in the second half of 2015, is anticipated to be comparable to the approximately $900-million investment to construct and operationalize the company’s biologics manufacturing facility in Devens, Massachusetts, which represented the company’s largest single capital investment at the time. Approximately 350 to 400 scientists, engineers, bioprocess operators, quality specialists, and other skilled professionals are expected to work at the Irish facility when construction is completed, and the construction program is expected to create about 1,000 jobs. The completion of the facility, including commissioning and validation, is anticipated to take approximately four years and is estimated to be operational in 2019.

AstraZeneca. In November 2014, AstraZeneca announced plans to expand its biologics manufacturing center in Frederick, Maryland. The more than $200-million project will increase production capacity at the facility to support AstraZeneca’s maturing pipeline and to meet future demand for its biologics portfolio, which currently represent nearly 50% of AstraZeneca’s overall pipeline, according to the company. AstraZeneca’s Frederick biologics manufacturing center is a US Food and Drug Administration (FDA) licensed, large-scale cell-culture production facility with administrative, production, warehouse, laboratory and utility space. The expansion project is expected to be complete in mid-2017, will add approximately 40,000 additional square feet of manufacturing, laboratory, and administrative space. The expansion is also expected to bring a total of 300 new jobs to the site. AstraZeneca’s Frederick manufacturing center is the largest biologics manufacturing facility within the company’s global network and portfolio of assets and provides cell culture manufacturing. The site currently produces a pediatric medication as well as other investigational biologic products.

Amgen. In November 2014, Amgen announced that it had completed construction of its $200 million biomanufacturing facility in Tuas Biomedical Park in Singapore.The facility will initially focus on expanding Amgen’s manufacturing capability for monoclonal antibodies. The facility will be capable of manufacturing both clinical and commercial products. Built in less than two years, the biomanufacturing facility was completed in half the time required for conventional biomanufacturing plants. It uses single-use bioreactors, disposable plastic containers, continuous purification processing, and real-time quality analysis. It has flexible, modular design that can be replicated in future facilities. The biomanufacturing facility is expected to have the same annual output as a conventional facility but in a single building that will use less energy and water and have lower solid waste and emission levels. The company estimates that enhanced bulk production capabilities at the new plant, when compared to conventional alternatives, represents at one-quarter of the capital costs, one-third of the operating expense, and twice the speed. The company estimates these new capabilities will result in an estimated cost reduction of 60% or more per gram of protein. Amgen also announced it will continue building at its Tuas site in Singapore and for another facility where it will make carfilzomib, the active ingredient for Kyprolis, an anti-cancer drug.

Sanofi In January 2015, Sanofi entered into a strategic agreement with Boehringer Ingelheim for the manufacture of therapeutic monoclonal antibodies (mAbs) to reinforce Sanofi’s manufacturing capacity to support upcoming product launches. Sanofi said that 72% of its research and development projects are in biologics, nearly half of which are mAbs. Boehringer Ingelheim’s cell-culture operations will provide contract manufacturing capacities to support the production of Sanofi’s biologics pipeline. Under the agreement, Sanofi will have access to Boehringer Ingelheim’s capabilities in Biberach an der Riss, Germany to transfer and manufacture therapeutic mAbs for global market supply.

In another investment, Shantha Biotechnics, a Sanofi company, laid the foundation for a new production facility to manufacture Insuman, human insulin product from Sanofi’s range of diabetes treatments. Sanofi will make an investment of INR 460 crores in this insulin facility, which is located in Muppireddipalli (Telangana), India. This will be Sanofi’s second plant aside from the company’s existing Insuman manufacturing plant in Frankfurt. The construction of the 13,400 square-meter building is underway with the site expected to be fully operational by 2019. While Sanofi’s Frankfurt facility will continue to manufacture the human insulin, Insuman, the new facility will contribute toward addressing local demand. Shantha is a fully integrated biotechnology company involved in R&D, manufacturing, and marketing. It was acquired by Sanofi in 2009.

Sanofi also is developing three dedicated biotech hubs in Europe at Frankfurt (Germany); Vitry-sur-Seine (France), Sanofi’s biggest integrated cell culture facility, which in 2013 completed a production campaign of aflibercept (the active ingredient of Zaltrap) as well as launching production of a new product; and Lyon Gerland (France), a new world center dedicated to production of thymoglobulin for the prevention and treatment of transplant rejection. In  2009, Sanofi began construction of a new vaccine manufacturing center at its  Neuville-sur-Saône site in France. The EUR 300 million ($334 million) investment over the 2009-2011 period replaced the chemicals activity on the site, which was discontinued at the end of 2013, by vaccine production from 2014 onwards.

Roche. Roche is proceeding with several expansions for its global production network for biologic medicines. Manufacture will be extended across sites in Penzberg (Germany), Basel (Switzerland) as well as Vacaville and Oceanside (California). Activities to re-open the previously idled drug substance production unit in Vacaville are on track and will further increase Roche’s biologic manufacturing capacity. The company will invest about CHF 250 million ($260 million). The additional Vacaville capacity is expected to be operational in the first quarter of 2016. At the Oceanside site, Roche is investing approximately CHF120 million ($125 million) into a second purification line to further increase its manufacturing flexibility. This will enable the site to process two products simultaneously. The expansion is expected to be operational by the first quarter 2016, according to the company’s 2014 annual filing.

At its manufacturing site in Penzberg, Germany, Roche is expanding its biologics capabilities and is investing a total of CHF 400 million ($415 million) over the next several years. This expansion project will be operational in 2018. In Basel, Switzerland, Roche has begun the construction of a production center for antibody–drug conjugates (ADCs). The new ADC facility will support the manufacturing of Kadcyla, the company’s ADC for the treatment of breast cancer, as well as future ADCs. This new center will cost approximately CHF 190 million ($198 million) investment and is planned to be operational in August 2016.

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 over $500 million. The new facility will focus on drug substance manufacturing based on cell culture technology. Groundbreaking happened in February 2013, and construction is underway. The site is expected to be operational in 2016. It will be co-located with the pharmaceutical production site based in Tuas, Singapore. In the future, Singapore is expected to be a technological competence center for both biotechnology and pharmaceutical manufacturing at Novartis.