Fine-Chemical Companies, CDMOs and CMOs Expand

A review of activity thus far in 2013 shows measured investment by fine- chemical companies, contract manufacturers of APIs and intermediates, CDMOs, and CMOs of finished product manufacturing. High-potency manufacturing continues to be an active area of investment on both the API and finished product side. For CDMOs and CMOs of finished product manufacturing, there have been several partnerships in drug-solubilization as well as investments in lyophilization and sterile manufacturing and aseptic processing.

Fine-chemical companies and contract API manufacturers expand

Among recent developments, Siegfried is proceeding with a new 300-m³ production plant in Nantong, China. The company broke ground for the new facility in July 2013. The plant will begin commercial production in mid-2014 and employ a workforce of about 300 by 2015. Siegfried is also proceeding with the construction of a new 100-m³ chemical plant in Zofingen, Switzerland. The new building will replace several older plants at the Zofingen site that no longer comply with efficiency requirements and generate high maintenance expenses. The two plants in Nantong and Zofingen are based on an identical technical concept to facilitate product transfers from a regulatory and technical perspective. A new administration building also will be erected in Zofingen. The new offices will be ready for occupation in the second half of 2015.

Cedarburg Hauser Pharmaceuticals upgraded its API plant in Grafton, Wisconsin. The upgraded facilities are expected to increase API production by 20–25%. Improvements to the plant include the addition of a 30-ton process chiller, an additional 200-kilowatt backup generator, and an industrial vacuum pump. The company also tripled its filtration capacity through the addition of new, large Aurora filters.

In September 2013, International Chemical Investors Group (ICIG) agreed to acquire Allessa, a manufacturer of fine chemicals intermediates and specialty chemicals, headquartered in Frankfurt with production sites in Frankfurt’s vicinity in Fechenheim, Griesheim, and Hoechst. Allessa has more than 890 employees and an internal training center of more than 70 apprentices employed by the company.

The WeylChem Group, ICIG’s non-GMP fine chemicals platform, operates its plants in Griesheim and Hoechst as well, which also used to belong to the former Hoechst conglomerate, and any future cooperation between Allessa and the WeylChem Group, under one ownership, would result in additional synergies.

Earlier in 2013, ICIG agreed to acquire from the Solvay Group Peptisyntha SA, the Brussels-based custom manufacturer of peptides. Upon closing of the deal, expected this fall, Peptisyntha will become a member of ICIG’s CordenPharma platform as its third site offering peptide manufacturing. Although the US sister company Peptisyntha Inc., located in Torrance, California, is not part of the transaction, certain customer relationships will be assumed by Peptisyntha in Brussels.

Johnson Matthey’s Catalysis and Chiral Technologies business unit is expanding its existing specialty ligand manufacturing capability to include commercial-scale manufacturing up to 100 kg. The expansion is largely focused on the Buchwald ligands from the Massachusetts Institute of Technology.The Buchwald ligands are a class of bulky and electron-rich dialkylbiaryl monophosphine ligands, which are used for the in situ generation of active catalysts. These ligands are used for coupling reactions in the manufacture of both pharmaceuticals and specialty chemicals and are more commonly offered at a research scale for use in the laboratory, according to the company. This is the third recent investment by the company, which has made investments at facilities in Taloja, India, last year and has further expansion underway in Royston, United Kingdom.

In February 2013, Albemarle announced that its fine-chemistry services business approved and began construction on another expansion of its Tyrone, Pennsylvania custom manufacturing facility. The $30-million expansion adds new capacity to the site for custom manufacturing projects, but also improves the infrastructure to allow for future expansions. The expansion follows an earlier expansion that began operation in November 2012. The first increment of new capacity will be operational late in the first quarter of 2014.

Saltigo reported that it successfully passed a FDA inspection for its API production unit in Leverkusen, Germany and all the associated facilities. Also, Saltigo moved its corporate headquarters from Langenfeld to Leverkusen. The relocation of Saltigo’s corporate headquarters is part of a series of moves following the transfer of its parent company, Lanxess, headquarters to Cologne. In Leverkusen, business units and group functions from 11 different office buildings will move into four buildings belonging to Lanxess by the end of January 2014.

In October 2013, DSM opened a new cGMP facility for biopharmaceutical contract manufacturing in Brisbane, Australia. The facility was built in partnership with Biopharmaceuticals Australia with cooperation from the government of Queensland and the Commonwealth of Australia.

Collaborations to enhance capabilities

Companies also are partnering to expand capabilities. Cambridge Major Laboratories, a provider of pharmaceutical API development and manufacturing, and the CDMO/CMO AAIPharma Services agreed to merge in October 2013. Patrick D. Walsh was named as the CEO of the merged company. The combined company forms a supplier of integrated chemistry manufacturing and control (CMC) services, including process chemistry, solid state chemistry, API manufacturing, formulation development, analytical development and testing services, clinical and commercial finished dosage-form manufacturing (oral solid and sterile), and packaging and stability services.

Earlier this year, DSM Pharmaceutical Products signed a collaboration agreement with Chemtrix in the field of continuous flow chemistry. The collaboration is intended to provide equipment, development, and manufacturing services to the pharmaceutical industry. Also, Almac completed its knowledge-transfer partnership with Queens University Belfast, which was intended to develop, improve, and embed bioprocesses to facilitate the delivery of products for its biocatalysis business. The overall partnership aim was to allow technology transfer of fermentation and molecular/microbiology expertise from Queens University to Almac. Almac met the specific partnership objectives by not only sharing a program of work with academics at Queens, but also by attending training courses organized through University College London and embedding key learning back into the company.

In February 2013, AMRI and Codexis formed a SMARTSOURCING partnership. The collaboration will provide opportunities to combine the two companies’ capabilities and technologies for specific customer projects. Under the nonexclusive, two-year agreement, the companies will align their respective strengths to identify and implement new and improved manufacturing routes for select APIs with Codexis contributing directed evolution technology that enables enzyme discovery and optimization with AMRI’s process development and manufacturing capabilities, including using AMRI’s proprietary microbial strains.

Investment in high-potency manufacturing

Several companies are expanding capabilities in high-potency manufacturing, including antibody-drug conjugates (ADCs). For example, Sigma-Aldrich's custom-manufacturing services business unit, SAFC Commercial is expanding two of its manufacturing facilities in the United State: The company is investing in commercial-scale manufacturing capacity for ADCs at its facility in St. Louis, Missouri and is expanding its high-potency API (HPAPI) manufacturing and storage capacity at its facility in Verona, Wisconsin. Additional commercial-scale manufacturing capacity has also been designed to accommodate future growth in demand for ADC production.

Carbogen Amcis is investing $4 million to expand its cleanroom clinical-supply facility at its Bubendorf, Switzerland. The Bubendorf facility features a new 100-m² ADC cleanroom suite for the development and production of ADC clinical material under cGMP and contains Grade D and Grade C areas to allow aseptic and safe handling of highly potent material at occupational exposure limit values (OELs) below 1 µg/m³ at 8-hour time weighted average (8h-TWA). In 2012, Carbogen Amcis and ADC Biotechnology (ADC Bio) partnered for ADC development and manufacturing services.

In January 2013, Lonza announced plans to invest CHF 14 million ($15 million) to expand ADC manufacturing capacity at its site in Visp, Switzerland. The expansion of the ADC facility will double the company's existing large-scale manufacturing capacity in Visp. The expansion is expected to be completed in the second quarter of 2014.

In October 2012, Fujifilm Diosynth Biotechnologies formed a strategic alliance with Piramal for ADC production, whereby the two parties will offer contract development and manufacture of ADCs. Piramal offers ADC production at its site in Grangemouth, Scotland. Piramal recently invested $2.5 million at is Grangemouth site to upgrade one of its ADC manufacturing sites from clinical phase to commercial grade. The upgrade gives Piramal two commercial grade ADC suites at the Grangemouth facility while retaining clinical phase manufacturing capacity in other suites on site.

Investment in formulation development and finished product manufacturing

Dow Chemical and Cambrex have opened a new facility for Dow’s hydroxypropyl methylcellulose acetate succinate (HPMCAS) for drug solubility enhancement at Cambrex’s site in Karlskoga, Sweden. The Cambrex Karlskoga expansion began in early 2013. The facility completion and start of the HPMCAS product validation is part of the solubilization partnership between Dow and Bend Research, announced in October 2012. Beginning in 2014, Dow will be able to commercially supply solubility enabling excipients.

Colorcon and Evonik have formed a cooperation agreement for the market promotion and technical support of the Acryl-EZE aqueous acrylic enteric system. The Acryl-EZE system, used for the application of an enteric film coating for oral solid dosage forms, was originally codeveloped by the two companies. It combines Evonik’s enteric polymer, EUDRAGIT L 100-55, with a fully or partially formulated coating system from Colorcon. Prior to this new cooperation agreement, the product was produced, distributed, marketed, and supported solely by Colorcon to the pharmaceutical industry. From now on, customers with enteric coating projects will have access to nine technology centers of Evonik and twenty technical services laboratories of Colorcon globally.

The Controlled Release Alliance between Colorcon and Dow Pharma and Food Solutions has introduced new grades of flowing METHOCEL Premium Cellulose Ethers for direct compression and dry-granulation applications. METHOCEL DC2 is the latest addition to cellulose ethers manufactured by Dow. It is designed to enhance material flow from the blender to the tablet press through a proprietary technology to change the fibrous morphology of traditional METHOCEL materials to a more spherical shape to form an easy-flowing powder.

Capsugel’s Dosage Form Solutions business unit will upgrade and expand three of its manufacturing facilities in the United States and Europe. The multimillion-dollar investments broaden the company’s global capabilities to handle hormonal as well as high-potent compounds for soft gelatin and liquid-fill hard capsules. The expansions are part of the implementation of its Lipidex technology platform, which was launched in June 2013.

In October 2013, the CDMO Aenova Group agreed to acquire the CDMO Haupt Pharma. Financial terms were not disclosed, and the deal is expected to close at the end of 2013. The merger will add areas such as sterile manufacturing and the production of special active ingredients, including hormones, antibiotics and cytostatics, to Aenova’s existing range of solid, semisolid, and liquid dosage forms. The Aenova Group’s existing production network will increase from eight to 21 sites. In addition to new production facilities in Germany (Berlin, Brackenheim, Münster, Gronau, Regensburg, and Wolfratshausen) and in Europe, Aenova will also acquire its first site in Asia (Japan). The number of employees will increase from 2500 to more than 4000.

The CDMO Aesica plans opening a new inhalation Lead Technical Center by the end of 2014. Aesica also extended its aseptic capabilities at its site in Nottingham, the United Kingdom with the acquisition of new prefilled-syringes manufacturing equipment capable of processing 5000 units/batch. This latest addition is undergoing validation via process simulation, and validation is expected to be completed by January 2014.

Aesica is expanding its aseptic capabilities at its site in Nottingham, United Kingdom with new prefilled syringes manufacturing equipment capable of processing 5000 units/batch. The equipment is currently undergoing validation through process simulation trials. The company’s total investment is more than £500,000 ($797,395), and completion of the validation process is expected to be completed by January 2014. The company’s new equipment also enables production of other product forms, such as pen and cartridge syringes and nasal devices. Over the next three years, Aesica is targeting production of 900,000 units and is in advanced discussions with one company for the scale-up of a clinical trial product for which a joint validation is pending.

Almac reported several recent developments. In January 2013, Almac completed the doubling of its pharmaceutical development service capabilities with the opening of a new dedicated non-GMP facility and two analytical laboratories at its UK headquarters. In parallel to the new non-GMP facility, Almac doubled its analytical capacity with new analytical laboratories for processing large sample sets that result from non-GMP process development work for clients who seek to better understand their processes in line with the principles of quality by design. Additionally, in response to increased demand for preclinical and early-phase clinical GMP supply, Almac added to its pharmaceutical development offering with an investment in additional Xcelodose technology, which provides the capability to dose potent APIs directly into capsules. Also, Novozymes Biopharma, part of Novozymes, has formed a new collaboration with Almac to provide a combined service for drug-development applications in the field of drug targeting and pharmacokinetic improvements. The collaboration will combined Almac’s manufacturing assets and protein conjugation capability to link Novozymes’ Recombumin Flex technology to peptide and small-molecule drugs. Collaborations with commercial partners have already begun and will continue to expand in early 2014.

IDT Biologika, a producer of proprietary and third-party biopharmaceuticals and viral and bacterial vaccines, and Oncotec Pharma Produktion announced investments for increasing their respective production capacities. IDT will invest an additional EUR 40 million ($55 million) in its vaccine and parenteral sterile fill-and-finish capacities in syringes, vials, lyophilization and packaging at its BioPharmaPark, located in Dessau-Roβlau. Among the upgrades are serialization and anticounterfeiting capabilities. In September 2013, IDT started up its new production capacity dedicated to sterile parenteral drug products, including vaccines and biologics, having completed an expansion project announced in 2011. Capacity to manufacture vial-based products in liquid and lyophilized form will increase to 60 million units per year. Oncotec Pharma Produktion, a pharmaceutical manufacturing partner of aseptically produced cytostatic drug products, recently announced an EUR 30-million ($41-million) investment to expand sterile parenteral oncology drug manufacturing capacity within IDT’s BioPharmaPark. The expansion projects are expected to be completed in 2016.

Vetter is investing more than $100 million across its production sites in Germany and the United States to expand and upgrade its facilities to expand filling capacity. Two new filling lines are currently being designed for Vetter's Ravensburg South facility in Germany. The new lines will fill liquid cartridges and vials and will add to the production site’s current lines, one of which is a syringe line that was launched in the spring of 2013. At Vetter’s US clinical manufacturing facility in Chicago, a third filling line for prefilled syringes is nearing completion. Expected to be operational in 2014, the new clinical line will have a maximum batch size of 30,000.