CDMO/CMO Expansion in Parenteral Drug Development and Manufacturing

Contract development and manufacturing organizations (CDMOs) and contract manufacturing organizations (CMOs) have been expanding operations to support the development and manufacturing of parenteral drugs. So what are some key projects?

CDMOs/CMOs have been expanding organically and through acquisitions. DCAT Value Chain Insights takes a look at recent activity.

A roundup of recent activity Several CDMOs and CMOs have announced investments, completed expansions, and/or made acquisitions to expand their capacity and production capabilities for the development and manufacturing of parenteral drugs. A roundup of key activity in 2016 and in 2017 to date is highlighted below.

AB BioTechnologies. AB Technologies (AB) announced a $10.5-million investment in January 2017 to build a new 23,000-square-foot manufacturing facility at its site in Bloomington, Indiana. Construction is scheduled to begin in spring 2017, and the facility, which will include a manufacturing area for formulating, filling, lyophilizing, and packaging drugs for early-phase clinical trial studies, is expected to open in November 2017. AB will add aseptic filling and lyophilizer loading systems, to be installed by the fourth quarter of 2017 and in 2018. The installation will include a gloveless robotic isolator system for aseptic filling and lyophilization of sterile injectable pharmaceuticals. In addition, earlier in October 2016 AB expanded its services to include preclinical manufacturing at its Bloomington site for projects involving small-molecule and large-molecules and projects involving liquid, lyophilized, vial, or syringe delivery formulations.

Alcami. In September 2016, Alcami completed investments in its clinical and commercial manufacturing facility in Charleston, South Carolina and added additional laboratory-scale capabilities to support prefilled syringes at its facility in Wilmington, North Carolina. Investments in the Charleston facility included a small-scale lyophilizer for cycle development studies; a second GMP production line to support sterile manufacturing that more than doubled filling capacity; the installation of a mid-scale lyophilization unit that doubles the site’s lyophilization capacity; and the addition of a third manufacturing shift that further increases capacity and scheduling flexibility. For the Wilmington facility, Alcami invested in semi-automated vacuum stopper equipment to generate prefilled syringe samples that can be used to screen and select components, complete compatibility studies, and conduct developmental stability studies.

AMRI. AMRI added to its capabilities in sterile manufacturing in 2015 with the purchase of Aptuit’s Glasgow, UK business, now Albany Molecular Research (Glasgow) Limited. The Glasgow facility extends the company’s capabilities for sterile injectable drug product pre-formulation, formulation, and clinical-stage manufacturing. The acquisition followed the 2014 acquistion by AMRI of OsoBio, a contract manufacturer of injectable drug products in Albuquerque, New Mexico with key capabilities in liquid fill and lyophilized products, highly potent compounds, cytotoxics, proteins and peptides, monoclonal antibodies, vaccines, liposomal suspensions, and controlled substances.

Ajinomoto Althea. Ajinomoto Althea announced an expansion in March 2016 for its fill and finish capacity at its facility in San Diego, California that was scheduled to come on-line in early June 2016. The expansion included the addition of a second manufacturing shift to increase the number of manufacturing slots for commercial and clinical drug programs. In addition, to support the increase in its parenteral manufacturing capacity, the company invested in additional operational capabilities, more visual inspection suites, automated quality systems, and project management expansion.

Amatsigroup. In January 2017, Amatsigroup, a France-based CDMO, acquired Disposable-Lab, a Martillac, France-based company that specializes in manufacturing sterile clinical batches of drug product in injectable forms. The acquisition expands Amatsigroup’s aseptic manufacturing capabilities and increases its overall capacity for manufacturing parenteral and sterile clinical drug product batches as well as adds to the company’s capability for producing small-scale batches at dosages of approximately one microliter. The acquisition follows an earlier investment in a second manufacturing line at the company’s facility in Idron, France.

CordenPharma. CordenPharma completed an expansion in June 2016 of its sterile manufacturing facility, CordenPharma Caponago, in Monza Brianza, Italy, with the addition a new aseptic filling line for clinical and commercial supply. The additional line provides aseptic filling of liquid and lyophilized vials and pre-filled syringes.

Dalton Pharma Services. Dalton Pharma Services completed a $5-million expansion in sterile filling and active pharmaceutical ingredient (API) manufacturing at its cGMP facility in Toronto in August 2016. The project added three new sterile processing suites, an API manufacturing suite, and a semi-automated powder filling line with scale-up of lyophilization capacity. The expansion also included increased analytical capabilities, increased chemistry capacity, and other facility upgrades.

Evonik. Evonik, a specialty chemicals company, announced in November 2016 an expansion of its production facilities in Birmingham, Alabama and Darmstadt, Germany to create additional capacity for producing biodegradable polymers used to manufacture controlled-release formulations for parenteral drug delivery and bioresorbable medical devices. The expansion at its Birmingham site involves construction of a new building adjacent to Evonik’s existing facility at that site, with commissioning of the new building slated for late 2018. In addition to increased production capacity, the project will add new production cleanrooms and a laboratory for polymer contract research projects. The capacity in Darmstadt was scheduled to be increased at the end of 2016 with the opening of a new production line. In addition to these expansions, Evonik closed on a previously announced acquisition of Transferra Nanosciences in August 2016, a CDMO specializing in liposomal drug-delivery systems, to further support its parenteral drug-delivery capabilities.

Grifols. Grifols, a Barcelona, Spain-headquartered healthcare company specializing in plasma-derived proteins and contract manufacturer of sterile solutions, recently has made investments in sterile manufacturing technology with the installation of a fourth form/fill/ seal (FFS) line in its manufacturing site in Murcia, Spain. The addition of the new FFS line will increase the company’s flexible bag manufacturing capacity by 30%. The new line can operate using the standard Grifols connector and can also manufacture bags with one or two tubes.

The new line will be operational in 2017 once validations have been completed and approved by Spanish health authorities. Grifols is also waiting for US Food and Drug Administration approval for the new FFS line as part of the company’s plan to expand sales of parenteral solutions in new markets. The Murcia facility has also been fitted with a new high-capacity autoclave and a new conditioning line to handle the increased production. Another production line is scheduled to be completed in the company’s Parets del Vallés facility in Barcelona, in the first half of 2018.

Lonza. In November 2016, Lonza opened a new 1,300-square-meter facility with pharmaceutical drug product services laboratories in Basel, Switzerland, which will focus initially on formulation development, drug product analytical development, and quality control. The new facility, announced in February 2016, is part of Lonza’s expansion into drug product development and manufacturing services, which, as part that announcement, reflects a focus on parenteral dosage forms, including products for injection and infusion for intravenous, subcutaneous, intraocular, and other routes of parenteral administration. The new facility’s services include options for monoclonal antibodies, other biologics, drug conjugates, peptides, and small molecules that require a parenteral dosage form and will provide the following services: particle testing, container-closure integrity testing, and detection of trace impurities in pharmaceutical products, such as extractables and leachables from plastics used in manufacturing. Also as part of its strategy to offer drug product services, Lonza announced in December 2016 that it will acquire Capsugel, a contract provider of dosage forms, for $5.5 billion, which is expected to close in 2017. With the acquisition, Lonza would gain oral dosage delivery technologies, including hard-capsule technologies.

Lubrizol LifeSciences. The Lubrizol Corporation’s LifeSciences division announced in April 2016 that is adding commercial drug product manufacturing capacity with a new facility at its Particle Sciences site in Bethlehem, Pennsylvania, which is expected to be completed in the third quarter of 2017. The new 18,000 square-foot facility will include both sterile and non-sterile space with complete lyophilization and filling operations and will be tailored for nano-milling and other complex processes.

Nitto Denko Avecia. In October 2016, Nitto Denko Avecia, a provider of development and manufacturing services for nucleic acid-based drug substances, formed a new CDMO, Nitto Avecia Pharma Services, which offers parenteral drug manufacturing that was created from Nitto’s acquisitions of Avrio Biopharmaceuticals and Irvine Pharmaceutical Services in 2016. The Avrio acquisition provided Nitto Denko with cGMP parenteral contract manufacturing capabilities that complement its oligonucleotide drug substance services while the Irvine acquisition added analytical capabilities.

Pfizer CentreOne. Pfizer CentreOne, a CMO within Pfizer, completed expansion of its fill-finish services at its Kalamazoo, Michigan site in February 2017. The facility now provides vial-filling of sterile suspensions along with vial-filling of small molecules and biologics. In addition to small molecules and biologics, Pfizer CentreOne’s Kalamazoo facility includes sterile suspensions, potent and controlled substances, aqueous and oil-based formulations, lyophilization, vials in 1-mL to 100-mL sizes, bulk formulation ranging from less than 1 liter to 1,600 liters, and technical transfer. The CMO, formed by the union of Pfizer CentreSource and Hospira One 2 One, a sterile-injectables CMO, upon Pfizer’s $17-billion acquisition of Hospira in 2015, focuses on API synthesis, sterile injectables fill-finish, and highly potent solids.

Piramal Pharma Solutions. Piramal Pharma Solutions announced two investments in 2016: a $25-million investment in August 2016 to expand its sterile drug development and manufacturing facilities in Lexington, Kentucky and a $10-million investment in February 2016 to expand its Coldstream Laboratories subsidiary, a CDMO focused on the development and manufacturing of sterile injectable products that Piramal acquired in 2015 for approximately $31 million. The $25-million expansion will add capacity for commercial aseptic manufacturing by increasing vial-filling capability and lyophilization capacity as well as upgrading associated facilities and utilities. This expansion will be conducted in two phases: Phase I, which increases vial-filling capabilities by more than five-fold by adding a new manufacturing suite with a high-speed vial-filling machine and a new isolator-based vial filler; and Phase II, which adds two lyophilizers that will be integrated with a new filler line in the added manufacturing suite, providing dedicated capacity for both potent and non-potent products.

Recipharm. In 2016, Recipharm made two acquisitions and two investments in parenteral drug manufacturing. The two acquisitions were a SEK 824-million ($91-million) acquisition of a majority stake (74%) in Nitin Lifesciences Limited, an Indian sterile CMO, which Recipharm completed in April 2016, and a SEK 640-million ($71-million) acquisition of Mitim Srl, an Italian CDMO that specializes in filling injectable beta lactam products, which Recipharm completed in February 2016. The Nitin acquisition gives Recipharm three manufacturing facilities for small-volume parenterals in Karnal and Paonta Sahib, India, and the Mitim acquisition gives Recipharm a manufacturing site in Brescia, Italy with six production lines and a product portfolio of beta lactams in dry sterile powder for injectable solutions, tablets, and oral suspensions as well as injectable sterile solutions, oral solids and liquids, and semi-solids.

Recipharm’s two investments included an EUR 18-million ($19-million) investment announced in July 2016 to expand its blow/fill/seal (BFS) capacity at its facility in Kaysersberg, France, a sterile facility specializing in BFS technology for sterile liquids, and an EUR 3.7-million ($3.9-million) investment announced in August 2016 to expand its lyophilization capacity at its facility in Masate, Italy, which specializes in aseptic manufacturing and filling of parenterals and offers lyophilization capabilities in both vials and ampules. The investment in the Kaysersberg facility includes the addition of a new BFS high-speed filling and packaging line for a total of eight lines and plans for further additions of three more filling lines over the coming years to increase BFS capacity by 50% and that would more than double the size of the facility from 2,000 square meters to 4,150 square meters. For the Masate facility, the investment introduces a new lyophilizer for vials that increases capacity by approximately 20%.

Rentschler Biotechnologie. Rentschler Biotechnologie, which specializes in biologics drug substance development and manufacturing, formed a strategic alliance in February 2017 with Leukocare, a German drug formulation company focused on protein therapeutics, to add parenteral drug product services, making Leukocare its specialized technology partner and the exclusive formulation developer for Rentschler’s biopharmaceuticals business. Rentschler in return will have access to Leukocare´s patented stabilizing and protecting solutions formulation technologies and gains a 10% stake in Leukocare.

Vetter. Vetter announced two investments to expand its fill-finish and aseptic processing operations: an approximately $320-million investment over a more than 10-year period at its site in Des Plaines, Illinois, announced in July 2016, and an approximately EUR 70-million ($74-million) investment, announced in March 2016, for its site in Ravensburg, Germany. The $320-million investment funds construction of a new 1,138,237 square-foot facility on an 18-acre site in Des Plaines that would focus on supplying commercial drugs. The EUR 70-million ($74-million) investment in its Germany site is funding the construction of a new seven-story, 8,000-square-meter (86,000-square-foot) building, which is scheduled for completion in the first quarter of 2018 and to begin operations in early 2019. The new facility will contain the site’s central material preparation and will include a cleanroom with media systems dedicated to filling bulk syringes and that will be compatible for the filling of sensitive drugs such as biologics and ophthalmics.

Xellia Pharmaceuticals. Xellia Pharmaceuticals, a Danish specialty pharmaceutical company focused on anti-infective treatments, expects to start production of sterile, anti-infective injectable products at its facilities in Cleveland, Ohio during 2018 after the US Food and Drug Administration (FDA) cleared the company’s Cleveland facilities in November 2016 for Xelia to begin drug product packaging and distribution at the site. With the FDA clearance, the company can initiate certain commercial activities that involve labelling, secondary packaging, and distribution of drug products manufactured at other sites. Xellia Cleveland will operate alongside the company’s existing sterile injectables production plants in Raleigh, North Carolina and Copenhagen, Denmark.

Editor’s note: this article has been updated to include news development from Grifols.

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