Big Pharma Manufacturing Update: Biologics on the Rise

By Patricia Van Arnum - DCAT Editorial Director

June 8, 2016

Expansions in biologics manufacturing continue to dominate the capital expenditures of the pharmaceutical majors. So what are the leading projects announced, underway, or recently completed? DCAT Value Chain Insights (VCI) examines key projects.

Although the pharmaceutical industry as a whole has experienced a period of manufacturing rationalization, biologics manufacturing continues to be an active area of investment. With recent large investments by Bristol-Myers Squibb, AstraZeneca, and Boehringer Ingelheim to name a few, biomanufacturing expansions are on an upward trajectory. A look inside the major projects and what is on the horizon.

BMS, BI, AstraZeneca, and Shire lead the way
Bristol-Myers Squibb. Bristol-Myers Squibb is proceeding with another large-scale biomanufacturing project, this time in Ireland following the company's $750-million investment for a new biologics bulk manufacturing facility in Devens, Massachusetts. Bristol-Myers Squibb's plans to open a new EUR 900 million ($1.02 billion) large-scale biologics manufacturing facility in Cruiserath, County Dublin, near Blanchardstown that will produce multiple therapies for the company's growing immuno-oncology portfolio. The manufacturing facility is estimated to be operational in 2019.

Earlier this year, Bristol-Myers Squibb completed a major expansion at its Devens facility. The $280- million project added two new buildings to the 89-acre Devens campus: a Biologics Development Building for designing processes for the early production of investigational medicines, and a Clinical Manufacturing Building where investigational medicines will be produced to support clinical trials. Both are new capabilities for Devens, a site that had previously focused solely on large-scale, bulk biologics manufacturing.

The expansion increases the site's workforce, with approximately 200 new jobs having been added at the project's initial completion rising to approximately 350 jobs over time. The two new buildings also add approximately 200,000 square feet to a site now comprised of eight major buildings in a 600,000 square-foot complex. Furthermore, the buildings add to the major investment the company has made at Devens, a former military base. When combined with the company's initial $750 million investment to build the facility, the expansion project brings the company's total investment at the site to more than $1 billion.

Boehringer Ingelheim. In December 2015, Boehringer Ingelheim announced an approximate EUR 500 million ($568 million) investment for a new large-scale biopharmaceutical production facility for active ingredients manufactured using cell cultures at its site in Vienna, Austria. In Vienna, Boehringer Ingelheim has up to now produced pharmaceutical active ingredients using microorganisms; over the next few years, cell culture technology will also be transferred there. The new production plant will go into operation by 2021.The company already has two large-scale facilities in Biberach, Germany used for market launch and cell-culture-based manufacture of biopharmaceuticals. Biberach will remain Boehringer Ingelheim's largest European cell culture and global launch site for biopharmaceutical products.

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.

Shire. Shire announced earlier this year that it plans to expand its global biotechnology manufacturing capacity over the next four years by investing $400 million in Ireland. The company will create a biologics manufacturing campus, which it expects will lead to the creation of approximately 400 permanent jobs on a 120-acre site at Piercetown, County Meath. Construction of the new site will begin in mid-2016 with the site expected to be operational by mid-2019.

Shire's current manufacturing facilities are in Cambridge and Lexington Massachusetts. The Cambridge site also includes warehouse facilities. The Lexington site also includes laboratories, warehousing, and distribution operations. The company also has a warehousing and distribution facility in Florence, Kentucky, a warehousing facility in North Reading, Massachusetts, and laboratory and office space in Sao Paulo, Brazil.

Shire will also be adding to is manufacturing network following its $32 billion acquisition of Baxalta, which was completed earlier this month. Baxalta's global headquarters are located in a 260,000 square foot facility in Bannockburn, Illinois, and the company manufactures its products in more than 10 manufacturing facilities. Baxalta is expanding its manufacturing facility in Krems, Austria, for production of hematology products. The expansion project is expected to be completed in 2018. The company is also building a manufacturing facility near Covington, Georgia, to support the growth of its plasma-based products. The timeline on the project spans several years with commercial production scheduled to begin in 2018.

Other investments

AbbVie. In 2014, AbbVie announced it will invest $320 million to establish operations in Singapore for small-molecule and biologics active drug substance manufacturing. The completed facility will provide manufacturing capacity for emerging compounds within AbbVie's oncology and immunology pipeline to serve markets globally. The investment will establish the first manufacturing presence in Asia by AbbVie. AbbVie anticipates the new facility will be fully operational by 2019. Also, in 2014, Abbvie expanded its manufacturing facility in Sligo, Ireland. The expansion provides increased manufacturing capacity for the company's existing product portfolio as well as new therapies within the company's pipeline.

Amgen In November 2014, Amgen announced that it had completed construction of its $200 million biomanufacturing facility in Tuas Biomedical Park in Singapore to expand its manufacturing capability for monoclonal antibodies. The facility is designed to manufacture both clinical and commercial products.Built in less than two years, the biomanufacturing facility was completed in half the time required for conventional biomanufacturing single-use plants. It uses 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, according to the company. 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 for another facility where it will make carfilzomib, the small-molecule active ingredient for Kyprolis, an anti-cancer drug.

Novartis. Novartis is proceeding with a major biomanufacturing investment. In 2012, the company announced the planned construction of a new biotechnology production site in Singapore with a planned investment of more than $700 million. The new facility will focus on drug substance manufacturing based on cell culture technology. Ground was broken in February 2013, and construction was completed in the third quarter of 2015 for Phase One of the project, according to the company's 2015 annual filing. The company expects Phase One of this project to be operational in 2017 and Phase Two in 2019. It will be co-located with the company's 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. Through December 31, 2015, the total amount paid and committed to be paid on this project was $452 million.

Roche. Over the past several years, Roche has announced investments of more than CHF 2 billion ($2.1 billion) in its biologics manufacturing capacity. Roche is proceeding with several expansions across sites in Penzberg (Germany), Basel (Switzerland) as well as Vacaville and Oceanside (California). The additional Vacaville capacity was scheduled to be operational in the first quarter of 2016. At the Oceanside site, Roche is investing approximately CHF 120 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 was scheduled 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 ($417 million). 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) and is planned to be operational in August 2016.

Sanofi. In 2014, Sanofi launched a platform dedicated to biologics to develop synergies between Pharmaceuticals, Sanofi Pasteur, Sanofi Genzyme and the company's Biotherapeutics activities. This platform is helping the company extend its footprint in biotechnologies by adopting a multi-disciplinary approach and improving capacity utilization and leveraging its expertise in the production of biologics, from active ingredient through to integrated manufacturing, including both the medicine itself and associated medical devices. Three dedicated biotechnology sites have been developed: Paris/Lyon (France), Frankfurt (Germany) and Boston (United States).

Additionally, in the Sanofi Genzyme industrial network, which is predominantly located in the United States, major investments are underway. The site at Allston (Massachusetts) has initiated a major investment program in connection with the implementation of its compliance remediation workplan, which was approved by the US Food and Drug Administration in January 2012.

In vaccines, Sanofi Pasteur's industrial operations are in an investment phase, which includes a new dedicated dengue fever vaccine facility at Neuville (France), which began production in 2015. Also in 2015, Sanofi Pasteur inaugurated a new building at Marcy L'Étoile (France), dedicated mainly to production of the Hemophilus influenza type b (Hib) vaccine. In May 2016, Sanofi Pasteur began commercial manufacturing at a new vaccines production facility of its affiliate, Shantha Biotechnics Private Limited, located in the Special Economic Zone Muppireddipalli near Hyderabad, India. Construction of the 19,000 square-meter facility began in 2010, and the site is now ready for operations post approval from the Indian regulatory authorities and the World Health Organization. The new filling facility will be used for producing vaccines against multiple diseases starting with Shan5, pediatric pentavalent vaccine.

In January 2015, Sanofi entered into a strategic agreement with Boehringer Ingelheim for the manufacture of therapeutic monoclonal antibodies 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 monoclonal antibodies. 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 monoclonal antibodies for global market supply.