What’s New in Biomanufacturing

By Patricia Van Arnum - DCAT Editorial Director

October 14, 2020

What are the latest developments in upstream and downstream bioprocessing? DCAT Value Chain Insights provides a roundup of CDMO/CMO expansions in biomanufacturing and manufacturing for cell and gene therapies.

CDMO/CMO expansions

CDMO/CMOs have been actively investing in new production capacity for biologics and cell and gene therapies. A roundup of recent expansions, announced thus far in 2020, are highlighted below.

Samsung Biologics. In August (August 2020), Samsung Biologics, announced an investment of KWR 2-trillion ($1.7-billion) for a new biomanufacturing plant, the company’s fourth, in Incheon, South Korea, and a second bio complex. The company expects to break ground later this year (2020) for the new biomanufacturing plant and is in negotiations with the authorities of the Incheon Free Economic Zone to purchase additional land for a second bio complex to house a global R&D facility and allow for future biomanufacturing plants.

Upon finalization of the negotiation, the total size of the two investments is expected to be over KWR 2 trillion ($1.7 billion), which would exceed the total amount invested in the company’s other three biomanufacturing plants in Incheon, South Korea. Construction of the plant will begin on an existing site and will add 23.8 million square meters in total floor area, the equivalent to the combined floor area of its existing three plants. The fourth plant would add 256,000 liters of biomanufacturing capacity and would bring the company’s total biomanufacturing capacity to 620,000 liters. Manufacturing activities at the new plant are expected to begin in the second half of 2022.

The land under negotiation for Samsung Biologics’ second bio complex is closely located to the company’s current complex and is slightly larger at 330,000 square meters. Once the terms are finalized, the company says it plans to create an Open Innovation Center to foster biotech companies and build a global R&D facility in addition to securing space for future plants within the new complex.

Fujifilm Diosynth Biotechnologies. In June (June 2020), Fujifilm Corporation announced that it is investing approximately JPY 100 billion ($935 million) in the Denmark site of Fujifilm Diosynth Biotechnologies, its CDMO for biologics and advanced therapies, to double the site's current drug-substance manufacturing capacity and expand its capabilities to include fill–finish and enhance its current assembly, labeling, and packaging services. The investment will expand production lines for bulk drug substances with the addition of six mammalian-cell bioreactors, which would bring the total to 12 x 20,000-liter bioreactors by the fall of 2023. The development will also include the addition of the Denmark site's first fill–finish production line (to be added by the summer of 2023) capable of producing 35 million units per annum for large-scale production. In the spring of 2022, a new packaging line, equipped with facilities to assemble multiple types of auto-injectors as well as automatic labeling, will be added. Fujifilm acquired the facility from Biogen in 2019 for JPY 98 billion ($919 million) to acquire the Denmark site from Biogen.

Additionally, Fujifilm Diosynth Biotechnologies announced in August (August 2020) that it had started construction of a new $55-million, 60,000-square-foot building for an Advanced Therapies Innovation Center in Texas. The new center will house dedicated process development and innovation laboratories to support advanced therapy projects. The building will be part of a 22-acre land parcel acquired by Fujifilm Diosynth Biotechnologies in Bryan-College Station, Texas in June 2020. The laboratories will have BSL-2 capabilities with upstream, downstream, and analytical development technologies. The building will triple the sites' advanced therapies process-development capabilities. The Advanced Therapies Innovation Center is expected to be operational by the fall 2021.

Earlier this month, the company announced that it is adding viral vector process development and manufacturing services at its site in the UK. Viral vector process development laboratories will be on line in the spring of 2021 and will be outfitted with equipment to support upstream (suspension and adherent) processes, downstream processing, and analytical development. The manufacturing capabilities are expected to be available from the autumn 2021 and will support bulk drug-substance production for early-stage clinical trials.

In addition, earlier this year (February 2020), the company announced a $35-million expansion at its College Station, Texas site to add cell-culture and high-throughput manufacturing suites. The expanded facility will house multiple 500-L and 2000-L bioreactors to support the production of gene-therapy products. The expansion is part of a previously announced capital investment of approximately 13 billion yen ($120 million) in the gene therapy field by Fujifilm Corporation. At the time of the announcement in February (February 2020), the company expected the expansion to be completed in the fall of 2020.

In addition, the company is investing JPY 9 billion ($83 million) to expand microbial production capacity, which will triple its current capacity of microbial production at its site in Billingham, UK. The expansion is scheduled to be operational after 2022. The expansion will include a new production line equipped with 2 x 2000-L fermenters and a modular purification suite. The utilities at the facility will be upgraded to accommodate for high-volume production. The company also announced in March (March 2020) that it began construction of a new BioCampus at its Billingham, UK site to include a 42,000-square-foot purpose-built office accommodation and visitor center in addition to making ready the land for potential expansion that could include additional research and development laboratories and new manufacturing facilities.

In addition, in February (February 2020), the company began construction of a new 31,778-square-foot addition at its site in North Carolina for the expansion of its cell-culture and microbial manufacturing trains through the addition of new recover and purification suites. The North Carolina site will increase its cell-culture manufacturing capacity by approximately 25% and microbial capacity by approximately 50%. A new receiving warehouse is also included in the project. The company expects that the increased production capacity will be ready for cGMP manufacture by mid-2021.

Catalent. Last month (September 2020), Catalent announced that it is investing $130 million to add five additional Phase III through commercial-scale manufacturing suites to its gene-therapy campus in Harmans, Maryland. The Catalent Gene Therapy campus in Harmans consists of two facilities that, when completed, will house a total of 15 gene-therapy suites each designed to accommodate multiple bioreactors for commercial supply. The first facility on the campus was recently approved by the US Food and Drug Administration for commercial manufacturing and is expected to have all 10 cGMP suites qualified and operational by the first quarter of 2021.The five new cGMP suites will be located in an adjacent building on the Harmans campus and are anticipated to be operational in the first half of 2022. The second Harmans building will also offer cold-storage warehousing and additional office space. The campus is one of Catalent’s five gene-therapy locations in Maryland and houses multiple cGMP manufacturing suites with pre-seed, bioreactor, and downstream rooms, together with fill–finish, testing, warehousing, supply chain, and central services capabilities. Catalent gained the facilities as part of its $1.2-billion acquisition in 2019 of Paragon Bioservices, a contract provider of viral vector development and manufacturing services for gene therapies.

In addition, in February (February 2020), Catalent added to its capabilities in cell therapies with the completion of its $315-million acquisition of MaSTherCell Global, a CDMO based in Gosselies, Belgium and Houston, Texas. MaSTherCell has a 25,000-square-foot facility in Gosselies, Belgium that provides clinical development and manufacturing services for cell and gene therapies. Construction is in progress for a dedicated 60,000-square-foot adjacent commercial-scale production and fill–finish facility, which is scheduled to open in the fall of 2021. As part of the overall transaction, Catalent also acquired a 32,000-square-foot US facility in Houston, Texas, which, upon completion of validation activities, will focus on development-scale projects. In addition, a commercial manufacturing site, which will mirror the facility in Belgium, is in the preliminary planning stages with sites in Texas being identified.

Lonza. In August (August 2020), Lonza announced an expansion to the company’s microbial manufacturing facility in Visp, Switzerland to provide mid-scale commercial manufacturing to multiple customers, including the French pharmaceutical company, Servier. Servier and Lonza recently signed a long-term extension to their manufacturing agreement for Servier’s L-asparaginase, a drug to treat acute lymphoblastic leukemia, and produced by Lonza since 2009. The new facility, which is under construction, will be the sixth to be housed in Lonza’s new biopark in Visp, Switzerland. The new mid-scale (3,000 L) microbial facility will use existing central utilities and labs and will complement the existing small-scale (1,000 L) and large-scale (15,000 L) assets in Visp. The facility is expected to be operational in the second half of 2022, and Lonza expects to add 100 new staff to its existing microbial team.

Lonza is also proceeding with a new biomanufacturing facility in China. The company provided an update earlier this year (2020) for a new 17,000-square-meter mammalian biologics development and manufacturing facility in Sino-Singapore Guangzhou Knowledge City, an industrial park in Guangzhou, China. The facility is the product of a three-way agreement between Lonza, GE Healthcare (now Cytiva following the completion of the $21.4-billion acquisition by Danaher of GE Healthcare Life Sciences in March 2020), and the Guangzhou Development District (GDD), which was signed in 2018, and under which Cytiva and the GDD built and Lonza bought and will operate the facility. As reported earlier this year (April 2020), Lonza expects to begin operational qualification activities of the plant later in 2020 and to begin laboratory and manufacturing operations for new CDMO projects in early 2021.

Thermo Fisher Scientific. Last month (September 2020), Thermo Fisher Scientific reported that it had opened a new Bioprocessing Collaboration Center in St. Louis, Missouri, where multiple Thermo Fisher businesses will jointly develop bioprocessing products, workflows, and services. The center is adjacent to the company's biologics manufacturing facility, which recently doubled production capacity with a $50-million expansion. In addition, the company announced in March (March 2020) plans to open a new cell-therapy development and manufacturing collaboration center in Princeton, New Jersey to combine pharma services and biosciences expertise from across the broader Thermo Fisher network. A new cell-therapy facility will come on line at the same location later this year (2020). Following its $1.7-billion acquisition of Brammer Bio, a cell- and gene-therapy CDMO in 2019, Thermo Fisher also expanded its viral vector development and manufacturing capabilities by opening a new site in Lexington, Massachusetts and expanding sites in Cambridge, Massachusetts and Alachua, Florida.

AGC Biologics. Earlier this year (2020), AGC Biologics reported that it had purchased a commercial manufacturing facility, formerly owned by AstraZeneca, in Boulder, Colorado for additional and larger-scale biopharmaceutical production capacity. The facility is expected to begin full-scale operations and manufacturing by April 2021. The facility houses two 20,000-liter (total volume) stainless-steel mammalian-cell bioreactors. The site also has more than 20 acres to allow for future expansions, including space for up to four more 20,000-liter bioreactors. In addition to this facility acquisition, AGC Biologics is completing facility expansion projects in 2020 and early 2021 at its facilities in Seattle, Copenhagen and Chiba, Japan.

In addition, AGC Biologics reported in July (July 2020) an investment of EUR 1 million ($1.1 million) to expand its pDNA Center of Excellence in Heidelberg, Germany for process development and manufacturing of plasmid DNA (pDNA). The investment in a laboratory build-out includes an increase of lab area, additional staffing, and equipment to support high-throughput techniques and quality-by-design processes.

WuXi Biologics. In June (June 2020), WuXi Biologics, a contract biologics manufacturer, signed a 10-year lease for a clinical manufacturing facility in Cranbury, New Jersey. The new clinical manufacturing facility will consist of 6,000-L bioreactors, process development, and quality control labs and supporting functions. The 66,000-square-foot facility is expected to become operational in late 2020. The news follows WuXi Biologics’ purchase of land to build a new 107,000-square-foot clinical and commercial manufacturing facility in Worcester, Massachusetts.

Merck KGaA’s CDMO business. In April (April 2020), Merck KGaA announced plans to invest EUR 100-million ($108-million) for a second commercial viral vector and gene-therapy manufacturing facility in Carlsbad, California for the CDMO service offerings of its life-science business. The new facility is expected to open next year (2021). Merck KGaA gained the first and current Carlsbad site through its $17-billion acquisition of Sigma-Aldrich in 2015, which included Sigma Aldrich’s custom manufacturing business, SAFC, including the viral-product manufacturing facility in Carlsbad. The new, 140,000-square-foot manufacturing facility will support viral and gene-therapy production at the 1,000-liter scale. The Carlsbad site now has 16 modular viral bulk manufacturing cleanroom suites with single-use equipment and two fill–finish suites for gene therapy, viral vaccine, and immunotherapy products. The expansion will add 11 suites, bringing the total to 27, used in various steps of manufacturing.

Abzena. Abzena, a contract manufacturer of biologics and antibody drug conjugates, reported this month (October 2020) that it had invested $60 million in a new facility in San Diego, California for late-phase and commercial manufacturing. The new facility is approximately 50,000 square feet and houses a 7,400-square-foot process-development laboratory and two new manufacturing cleanrooms at the 500-L and 2,000-L scale using single-use bioreactors. The facility also houses a GMP warehouse and analytical development and quality control laboratories. It provides Phase I to commercial manufacturing for biologics projects. The new facility in San Diego mirrors the company’s bioconjugation facility in Bristol, Pennsylvania, which supports bioconjugation from Phase I into commercial manufacturing.

Arranta Bio. Arranta Bio, a CDMO focused on live therapeutic products and the human microbiome, reported last month (September 2020) the mechanical completion of GMP suites at its new $100-million manufacturing facility in Watertown, Massachusetts. Arranta is investing more than $100 million in 2020 to establish a multi-product, commercial-ready manufacturing facility that will supply live biotherapeutic products (LBPs) to microbiome innovator companies. Arranta is also expanding process development and GMP capacity at its early-clinical supply facility in Gainesville, Florida.

Arranta Bio was established in 2019 and was founded by Mark Bamforth, founder and former CEO of Brammer Bio, a CDMO focusing on cell and gene therapies, which Thermo Fisher Scientific acquired for $1.7 billion in 2019. He is also the founder and former CEO of Gallus BioPharmaceuticals, a St. Louis, Missouri-based biologics CDMO, which was acquired by Patheon in 2014 and that subsequently became part of Thermo Fisher with Thermo Fisher’s $7.2-billion acquisition of Patheon in 2017. Later in 2019, Arranta Bio acquired Captozyme, a CDMO of process development and clinical contract manufacturing for microbiome companies.

Wacker. Wacker, a Munich, Germany-based chemical company, announced in July (July 2020) that it is investing in its production facilities for biologics, LMPs (live microbial products), and vaccines at its Amsterdam site. Projects include the construction of a new fermentation line with a volume of 1,500 liters as well as the setting up of new cleanroom structures in the 270-liter fermentation line. The investment price is a mid-double-digit million-euro amount. Existing cleanrooms are to be renovated and re-equipped with equipment. Among other improvements, new utility supplies are planned, such as water for injection. These measures will contribute to preparing the plant to produce new classes of actives, such as pDNA and mRNA-based vaccines.

Sekisui Diagnostics. Sekisui Diagnostics, a provider of enzymes and a biologics CDMO, plans to invest £14.4 million ($19 million) in its biopharma CDMO business to expand microbial capacity at its existing site in Maidstone, Kent, UK. The expansion is scheduled to be completed by the second half of 2022. The facility expansion and upgrades will allow for drug-substance contract manufacturing on a clinical scale. The new microbial fermentation and purification suites will accommodate production scales up to 1,000 L to complement existing capabilities that range from 20 L to 5,000 L. The planned expansion follows the investment of $1.9 million in a new Bioprocess Innovation Center, which was completed in October 2019. Previously part of Genzyme Corporation, Sekisui Diagnostics’ enzyme business launched its microbial biopharma CDMO service offering in 2017.

Hitachi Chemical Advanced Therapeutics Solutions/Minaris. Hitachi Chemical Advanced Therapeutics Solutions (HCATS), a cell-therapy CDMO and a subsidiary of Hitachi Chemical Co., Ltd. representing Hitachi Chemical’s Regenerative Medicine Business Sector in North America, opened a new cell- and gene-therapy manufacturing facility in Allendale, New Jersey in February (February 2020). The new facility more than doubles HCATS’ existing manufacturing capacity in New Jersey. Hitachi Chemical has operations in North America (Allendale, New Jersey and Mountain View, California), Europe (Munich, Germany), and Japan (Yokohama). Last month (September 2020), the regenerative medicine business of Hitachi Chemical, adopted the name, Minaris Regenerative Medicine, for its CDMO business.

Oxford Biomedica. Oxford Biomedica, a developer of cell and gene therapies and a contract manufacturer, reported earlier this month (October 2020) that the UK Medicines and Healthcare products Regulatory Agency (MHRA) issued a certificate of GMP compliance for the fourth GMP manufacturing suite within the company’s new Oxbox manufacturing facility in Oxford, UK. Oxbox is Oxford Biomedica’s new 7,800-m2 commercial manufacturing center. Phase I of Oxbox is 4,200 m2 of developed area consisting of six GMP manufacturing suites: four for viral vector production and two for fill–finish, along with warehousing, cold-chain facilities, and support laboratories. Construction and commissioning of Phase I was completed at the end of 2019. This approval by the MHRA follows the initial approval of the first two Oxbox suites in May 2020 and the subsequent approval of the third suite in September 2020.

The Discovery Laboratories. In January (January 2020), The Discovery Laboratories, a provider of cGMP manufacturing, turnkey laboratory solutions, materials, and office space for building life-sciences and technology companies, and Deerfield Management Company, an investment firm, launched The Center for Breakthrough Medicines, a CDMO and specialty investment company with a planned investment of $1.1-billion for a cell- and gene-therapy manufacturing facility in King of Prussia, Pennsylvania. At the time of the announcement in January (January 2020), the companies said that the new CDMO business will provide preclinical through commercial manufacturing of cell and gene therapies and component raw materials as well as process development, plasmid DNA, viral vectors, cell banking, cell processing, and support testing capabilities. Renovations were underway to construct a total of 86 suites for plasmid, viral vector production, universal cell processing, cGMP testing, process development and cell-banking.

Bionova Scientific. Bionova Scientific, a Fremont, California-based biologics CDMO, reported in July (July 2020) that it had initiated construction of a new biologics manufacturing facility in Fremont. Construction is scheduled to be completed in approximately 10 months (as reported on July 9, 2020), with commissioning scheduled for the third quarter of 2021. The 36,000-square-foot-facility will use single-use technologies for all core unit operations and is designed to accommodate two 2,000-L mammalian cell-culture trains for producing clinical and commercial bulk drug substance.

Luina Bio. Luina Bio, a Brisbane, Australia-based biologics CDMO, is expanding bacterial and yeast development and manufacturing capacity for microbiome and recombinant protein projects. The company plans to open an additional small-scale (30 L) manufacturing suite in late 2020. This expansion will be followed by the opening of four additional development laboratories in late 2020 to allow projects from early development to a volume of 500 L for microbiome and recombinant protein projects. Luina also plans to commission a new 10,000-m2 late-phase clinical and commercial production facility in late 2021. The new facility will have up to five production lines in parallel to allow for multiple-strain live biotherapeutics projects. Luina’s largest reactor (2,000 L) will allow it to deliver live biotherapeutics volumes compatible with the commercial needs of those companies that have single-strain projects.

Polpharma Biologics. Polpharma Biologics, a Gdańsk, Poland-based biologics CDMO, reported in July (July 2020) that an expansion of its facility in Warsaw is in the final stages of completion. The expansion will add four single-use bioreactor trains offering drug-substance manufacturing at 500-L to 2,000-L scales and will be ready for clinical and commercial supply in 2021. The site has been designed for further capacity expansion with space for a further six 2,000-L bioreactors. In addition, the company integrated its site in Utrecht, Netherlands site, acquired from Bioceros, a biologics CDMO in 2016, and Bioceros’ cell-line development services into Polpharma’s existing biologics development and manufacturing offering and has retired the Bioceros name.

ChemPartner. ChemPartner, a CRO/CDMO, opened a new biomanufacturing facility in Qidong, China outside of Shanghai earlier this year. The 67,000-m2-campus includes a laboratory center with a 5,000-m2 animal facility, administration building, and biologics production plant. The biologics production plant was scheduled to start operation in August 2020. The 13,000-m2 Phase I biologics production plant can accommodate up to eight 2,000-L and three 500-L single-use bioreactors as well as a vial aseptic-filling and freeze-drying line. It also has analytical facilities to support method development and product-release testing.

Univercells. In May (May 2020), Univercells, a technology company specializing in bioprocessing, launched Univercells Technologies, a new subsidiary and brand of the company focused on the development and commercialization of intensified, automated biomanufacturing technologies for the cell- and gene-therapy market. The new subsidiary will apply Univercells' proprietary scale-X bioreactor portfolio, which provides upstream processing of viral products, and its NevoLine biomanufacturing platform for viral products, such as viral vaccines, gene therapies, and oncolytic viruses.

In addition, earlier this year (2020), Univercells launched Exothera, a viral vector CDMO targeting cell- and gene-therapy and vaccine developers, in a refurbished 161,000-square-foot facility in Jumet, Belgium. The GMP areas at Jumet will contain Exothera’s CDMO activities and ongoing Univercells vaccine development and manufacturing initiatives, with capacity for rapid response programs, such as COVID-19 vaccine projects.