Parenteral Drugs: CDMOs/CMOs Expand

CDMOs/CMOs are proceeding with expansions and advancing technology in parenteral drug development and manufacturing. DCAT Value Chain Insights rounds up the latest developments announced in 2020 and 2021 to date.

CDMOs/CMOs expand

Driven by increased demand resulting from continued gains in biologic-based drug development and commercialization and COVID-19 and non-COVID-19 projects, CDMOs/CMOs are expanding drug-product development and manufacturing for parenteral drugs. Highlights of key expansion activity, announced in 2020 and 2021 to date (as of February 1, 2021), are outlined below.

Catalent. In 2020, Catalent announced plans to invest $50 million to install an additional high-speed vial filling line at its facility in Bloomington, Indiana. The new line is expected to be operational by April 2021 and will add capacity to support clinical programs and commercial launches at the site. It will provide sufficient capacity to produce up to 80 million vials annually under barrier isolator technology and a peristaltic pump filling mechanism under GMP.

This marks the third major investment in the last two years at the Bloomington site. By the end of 2021, the site will have high-speed filling capacity across three vial lines, two syringe lines, and a flexible line capable of filling vials, syringes, or cartridges. The facility has expertise in sterile formulation, drug-substance development and manufacturing, and drug-product fill-finish capacity, including primary and secondary packaging. In April 2020, the company completed a $14-million expansion at its Bloomington, Indiana facility to increase biologics packaging capabilities and capacity. The expansion added 15,000 square feet of packaging infrastructure to the biologics and sterile manufacturing site, including five new packaging suites and a new quality control laboratory.

In addition, in July (July 2020), Catalent announced plans to invest $30 million at its facility in Limoges, France to create a European center of excellence for clinical biologics, formulation development, and drug-product fill–finish services. The expansion was scheduled to begin in September 2020 with completion anticipated in 2022. Catalent says it plans to gradually hire approximately 80 additional employees to support the center.

Thermo Fisher Scientific. In December (December 2020), Thermo Fisher Scientific announced it will further expand its footprint in North America and Europe for sterile drug-product development and commercial manufacturing. The company is currently expanding the following sites: Greenville, North Carolina; Swindon, UK; and Ferentino and Monza, Italy. These investments will add 15 development and commercial production lines as well as support a range of services, including live virus, aseptic liquid, and lyophilized vial filling. These projects are expected to be completed over the next two years (as reported on December 9, 2020). In addition to expansions in North America and Europe, the company recently announced projects in Asia-Pacific, including a new sterile manufacturing facility in Singapore and a new integrated biologics and sterile drug development and manufacturing site in Hangzhou, China.

Baxter BioPharma Solutions. In November (November 2020), Baxter BioPharma Solutions announced plans to invest $50 million to expand its sterile fill–finish manufacturing facilities in Bloomington, Indiana. The planned expansion of existing facility infrastructure includes construction of a new 25,000-square-foot warehouse, a new filling line for flexible plastic containers, a high-speed automated syringe fill line, and a new high-speed automated visual inspection line. Construction is currently underway and is expected to be completed in 2021. Contract product manufacturing in the expanded facilities is expected to begin in 2022.

Vetter. Vetter, a CDMO of aseptic filling and packaging, invested approximately EUR 50 million ($60 million) in a new company headquarters in Ravensburg, Germany and moved into the headquarters last summer (summer 2020). The company’s previous company headquarters in Ravensburg was re-purposed as a training and education center. Other recent investments include a new combination building for manual optical inspection and secondary packaging at the Ravensburg Vetter Süd / Vetter Secondary Packaging location. In 2021, the company plans to commission a new cleanroom for filling syringes at one of its sites in Ravensburg (Schützenstrasse location). Vetter has also secured an adjacent plot of land for another production building at the site. In 2020, the company acquired a clinical production facility in Rankweil, Austria and plans to open the facility in the second half of 2021. The new site expands the company’s European footprint and is a counterpart to its existing US clinical manufacturing site near Chicago. The new site in Austria will provide early clinical development to support for Phase I and Phase II projects. After the recent implementation of a system for automatic optical control at its center for visual inspection and logistics in Ravensburg, the company is planning to purchase three additional machines.

Corden Pharma. In 2020, CordenPharma advanced an approximate EUR 30-million ($36-million) multi-year investment at its CordenPharma Caponago injectable drug-product facility in Italy. The investment is part of a three-phase capital-expenditure program to add aseptic fill–finish commercial-scale capacity and expanded R&D capabilities at the company’s injectables drug-product facility in Caponago, Italy.

Phase 1 of the expansion program (completed in 2015) saw the introduction of aseptic fill–finish capability with the construction and qualification of a clinical/development plant. Phase 2a of the program (completed in 2018) saw the construction of an aseptic prefilled syringe and cartridge line, which has undergone regulatory approvals in the US and European Union. Phase 2b further saw the expansion of aseptic processing capabilities with the construction of a second filling line dedicated solely to vial production. Construction was completed, and the line received approval by the US Food and Drug Administration in 2019, with further approval by the Italian Medicines Agency (AIFA) for liquid vials in 2020. A lyophilized drug-product vial line was completed at the end of 2020, with validation during mid-2021 and regulatory approvals expected in late 2021.

Under a parallel Phase 3 of the expansion (overlapping Phases 2a and 2b), a dedicated R&D laboratory was constructed and is now operational and was fully approved as of early 2020.

Ajinomoto Bio-Pharma Services. Ajinomoto Bio-Pharma Services, a CDMO of small- and large-molecule active pharmaceutical ingredients (APIs) and drug products, is proceeding with the addition of a new multi-purpose filling line at its site in San Diego, California to provide the company a 50% increase in its aseptic fill–finish capacity. The new line will be able to process ready-to-use syringes, vials, and cartridges. Construction began in 2019, and the company started site-acceptance testing and validation work in 2020, with the new line slated to become fully operational in the summer 2021.

Carbogen Amcis. Carbogen Amcis, a Bubendorf, Switzerland-based CDMO of APIs and drug products, is building a new facility in Riom, France, for the development and manufacture of parenteral drug products. The facility will allow for the handling of complex formulations, including a range of different types of APIs, including highly potent compounds, and supply clinical batches up to Phase III and small-scale commercial projects. There will be two automated lines: the first one for both liquid filling plus lyophilization and the second one dedicated to liquid forms. In addition, development and analytical laboratories will be incorporated to support customer projects. Construction of the facility began in January 2021, and operations are scheduled to begin during the first quarter of 2023.

Fareva. In 2020, Fareva completed the acquisition of two sterile-manufacturing sites in Idron, France and Saint Julien-en-Genevois, France from Pierre-Fabre Group. The Idron, France site has 200 employees and is dedicated to the manufacture of sterile injectable forms (pre-filled syringes and lyophilized and liquid-filled vials). The facility has 10 commercial lines and a pilot plant that is slated to be operational in 2022. The core business of the site is to handle highly potent and biologics entities. The site in Saint Julien-en-Genevois, France manufactures monoclonal antibodies and conjugated monoclonal antibodies with high potent actives. Last November (November 2020), Fareva announced negotiations with Merck & Co. and Novartis to acquire two sterile-manufacturing sites in Mirabel, France and Unterach, Austria, respectively.

BSP Pharmaceuticals. BSP Pharmaceuticals, an Italian CDMO based in Latina, south of Rome, which provides clinical and commercial products as bio-conjugated drug substances and drug products as injectable and oral solids, is expanding. BSP developed a strategic plan to include seven sterile manufacturing suites with fully contained technology (closed restricted access barrier systems) and/or isolators that allow the management of high potent and cytotoxic products with occupational exposure limits less than 10 ng/m3 to provide annual capacity of approximately 25 million units.

Three BDS (drug substance) manufacturing suites for bio-conjugated products and liposomal formulations have been developed, and starting from 2012, will provide an integrated supply chain (drug substance and drug product), including drug-product manufacturing and testing for antibody drug conjugates and nanotechnologies (liposomal formulations). Two additional BDS manufacturing suites will be available between 2021 and 2022 for large-scale batch size (+6 kg monoclonal antibody) to provide total annual capacity of 1,250 kg. New development labs are available starting from 2021 as well as new space for quality control labs.

In addition to anticancer products, BSP is investing in a new plant to handle immuno-oncology drugs (monoclonal antibodies, checkpoint inhibitors, and synthetic vaccines), immunotherapy drugs, and other innovative products. The new facility will have fully contained technology and also will be available for non-cytotoxic drug products (small and large molecules) starting from 2021 (12.7 million annual capacity). The facility will be completed by the end of 2023 with six filling lines and an overall annual capacity of 44.5 million units.

Grand River Aseptic Manufacturing. Grand River Aseptic Manufacturing (GRAM), a Grand Rapids, Michigan-based provider of sterile-manufacturing services, announced in June (June 2020) that it had completed a $60-million expansion project with the opening of a large-scale fill–finish facility in Grand Rapids, Michigan. The new facility is part of GRAM’s current campus and is the company’s third fill–finish facility. With the opening of the large-scale fill–finish facility, GRAM more than tripled its existing footprint in Grand Rapids. The company later announced it had invested in additional syringe and vial equipment. The equipment is scheduled for delivery during the first quarter of 2022. The Bausch+Ströbel filler with SKAN isolator is a duplicate of GRAM’s current vial filler that reached production in September 2020. The duplication will allow experts to qualify the equipment and reach production. Additionally, the VarioSys syringe and vial filler system provides the flexibility to increase production capacity with the option to dedicate complete modules to individual drug products. GRAM added nearly 100 new employees in 2020 and says it will continue to grow as equipment and facilities expand.

Recipharm. Recipharm, a CDMO of APIs and drug products, announced in 2020 it had invested EUR 2.6 million ($3 million) for additional manufacturing capacity at its facility in Kaysersberg, France. The Kaysersberg facility is one of the company’s sterile manufacturing facilities. It specializes in producing sterile liquids, including eye-care products and ear drops. In 2020, Recipharm completed its £505 million ($629 million) acquisition of Consort Medical, a CDMO of APIs, drug products, and drug devices. Consort Medical was the parent company of Bespak, a CDMO of drug devices, which includes auto-injectors, and Aesica, a CDMO of APIs and drug products, including fill–finish services.

Alcami. In January 2020), Alcami, a CDMO of drug products, acquired TriPharm Services, a new CDMO formed in 2019 that announced plans for a new manufacturing center for sterile fill–finish services near Research Triangle Park, North Carolina. Alcami’s acquisition of TriPharm followed Alcami’s $17-million expansion of its sterile fill–finish facility in Charleston, South Carolina. TriPharm’s facility adds to Alcami’s existing sterile fill–finish business by adding new prefilled-syringe capabilities and isolator technology as well as sterile fill–finish and lyophilization capacity. Phase I of the manufacturing facility was scheduled to to be completed in the fourth quarter of 2020 to bring the first two filling suites on line.

Evonik. In 2020, Evonik announced the qualification of an advanced aseptic filling line for complex parenteral drug products at its Birmingham, Alabama facility. The VarioSys line, which was designed by Bausch+Ströbel, can aseptically fill powder, liquid, suspension, or combination forms into vials for clinical or commercial batch sizes. The line is suitable for highly potent, personalized, or sensitive drug products as well as for some specialized vaccines, which are often designed for systemic or localized delivery of small molecules, peptides, proteins, and nucleic acids.

LSNE Contract Manufacturing. Earlier this year (2021), LSNE Contract Manufacturing, a CDMO of fill–finish and lyophilization services, expanded its vial-filling and lyophilization capacity with the addition of a new automated aseptic fill line. The new aseptic fill line will be housed in an existing ISO-5 cleanroom suite at its facility in Bedford, New Hampshire.

Samsung Biologics. Samsung Biologics announced plans in 2020 to expand its drug-product capability for aseptic filling by building a flexible filling line and adding two additional lyophilizer units. The filling line is expected to begin operations in the second half of 2021, and the expanded lyophilization line will become operational in the first half of 2022. Through this expansion, Samsung Biologics will add small-scale cartridge- and syringe-filling to its drug-product offerings and increase its total lyophilization capacity by 246% of current capacity.

PCI Pharma Services. PCI Pharma Services, a CDMO and contract provider of packaging services, announced in 2020 that it had completed an expansion of its new Biotech Packaging Center of Excellence in Philadelphia, Pennsylvania and announced an expansion of packaging operations in Ireland for biologics and injectable drug products. The new center is the company’s new US biologics flagship site. Additionally, PCI is planning to expand its biotech packaging capabilities at its operations in Ireland to complement existing capabilities in the UK and Germany. The expansions include increasing high-speed automatic syringe assembly and labeling, vial labeling and cartoning, auto-injector assembly, and a build-out of existing cold-storage capabilities and manufacturing suites.

WuXi Biologics. In April (April 2020), WuXi Biologics, a contract biologics manufacturer, completed the acquisition of a drug-product manufacturing plant of Bayer’s in Leverkusen, Germany. WuXi Biologics took over the plant operations, purchased plant equipment, and signed a long-term building lease contract. Equipped with a drug-product filling line, the plant will provide sterile filling and freeze-drying services of up to 10 million vials per year.

Bushu Pharmaceuticals. Bushu Pharmaceuticals, a Saitama, Japan-based CMO of injectables and solid-dosage products, announced in August 2020 a five-year capital program of $100 million to expand its footprint, capacity and portfolio of services. Bushu is nearing completion of a 3,900-square-meter cold-chain warehouse facility at its plant in Misato, north of Tokyo. The new facility was scheduled to be commissioned and validated in September 2020 for storage of temperature-controlled sterile drugs and biologics for the Japanese market. The inspection capacity will be expanded to 12 stations for prefilled syringes, and seven stations each for liquid vials and for lyophilized vials. Of the 26 inspection stations, 23 will be supported by cameras. In addition to the new warehouse and inspection capacity, Bushu has also funded the addition of eight new packaging lines, including one prefilled packaging line and a new water-for-injection line to support its sterile manufacturing filling suite. Bushu is also upgrading its production automation systems and its laboratory information management system.

Incog BioPharma Services. Incog BioPharma Services, a new CDMO of injectable drug products, is investing approximately $60 million to construct and equip its first manufacturing facility and global headquarters in Fishers, Indiana. The company planned to break ground for the 60,000-square-foot facility in December 2020 with the target of being fully operational in the first half of 2022. It plans to add more than 65 team members over the next two years (as reported in October 2020) and continue ramping up hiring as customer demand increases. Hiring will begin in early 2021 for positions in engineering, manufacturing sciences, quality assurance, human resources, project management, and business development. In all, the company plans to create up to 150 new jobs by the end of 2024.

Berkshire Sterile Manufacturing. Berkshire Sterile Manufacturing, a Lee, Massachusetts-based fill–finish contract manufacturer for injectable medications, reported in June (June 2020) that it had secured $16.5 million in financing to expand its operations in Lee, including for an additional robotic line for producing sterile drug products in vials, syringes, and cartridges. The company also plans to install a new pharmaceutical-grade water system, add additional testing capabilities in its microbiology and analytical labs, expand its warehouse, and double the size of its cleanrooms. The expansion is expected to be fully operational by early 2022.

Integrity Bio. Integrity Bio, a Thousand Oaks, California-based CDMO, reported in June (June 2020) the validation of its second fill–finish manufacturing line, which more than doubles the company’s manufacturing capacity.

Argonaut Manufacturing Services. Avid Bioservices, a biologics CDMO, and Argonaut Manufacturing Services, a CDMO, formed a co-marketing agreement in July 2020 to provide an integrated manufacturing service to include services for process development, drug-substance manufacturing, and drug-product manufacturing. The companies will offer Avid’s process development and drug-substance manufacturing services in tandem with Argonaut’s parenteral drug-product fill-finish services to support parenteral drug products in clinical studies. Argonaut launched aseptic vial-filling services earlier in 2020.

August Bioservices. August Bioservices, a Nashville, Tennessee-headquartered CDMO (formerly PMI Biopharma Solutions), announced an investment of $64.7 million to expand its sterile manufacturing operations. The investment will allow the company to expand services within its current facility and to build a 60,000-square-foot commercial manufacturing facility in Nashville. The first phase of the project, which is slated to be completed in late 2021, will expand the company’s existing Nashville facility by adding technologies such as lyophilization and terminal sterilization to its existing fill–finish manufacturing capabilities. The second phase of the project involves the construction of a new drug development and manufacturing facility that will feature multiple high-speed production lines for commercial-scale production across an array of sterile injectables containers, including vials, IV bags, and prefilled syringes.

Leukocare Leukocare AG, a Martinsried/Munich, Germany-based company specializing in formulation development for biologics, viral vectors, and vaccines, reported earlier this year (2021) the beginning of operations in the US, with the opening of its development laboratories and offices in Milford, Massachusetts. The offices and laboratories are located at the Milford premises of Rentschler Biopharma, a CDMO for biopharmaceuticals. Leukocare and Rentschler Biopharma have had a strategic alliance since 2017.

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