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Patricia Van Arnum was executive editor of Pharmaceutical Technology.
Contract API manufacturers proceed with select investment in capacity and service additions.
Informex, the exhibition of custom and batch manufacturers, which was held in February in Anaheim, California, provided an opportunity to review recent activity in the fine-chemicals and contract API market. In examining developments from 2012 and 2013 to date, companies are proceeding with select investments to expand manufacturing capacity and enhance service capabilities. High-potency manufacturing continues to be an active area of investment among CMOs, and several CMOs also are expanding overall manufacturing capacity.
Lonza, the bellwether of the contract API manufacturing sector, proceeded with several expansions in its small-molecule custom-manufacturing business in 2012. Earlier this year, Lonza reported that its custom manufacturing and bioscience sectors will be regrouped into one pharmaceutical market segments group.In 2012, Lonza completed the first two build-out phases of its large-scale multipurpose cGMP API plant in Nansha, China, following FDA approval of several customer projects in late 2011. Also, the company successfully brought on line a small-scale manufacturing train and a GMP kilo-laboratory in Nansha. The company’s large-scale antibody drug conjugates project in Visp, Switzerland was finalized on schedule, and the plant received FDA approval in the third quarter of 2012. A second expansion phase has started and will be finalized toward the end of the first half of 2014. Five additional high-potency API (HPAPI) laboratories in Visp, with capabilities for cytotoxic substances, are operational and utilized, and new investment in additional cytotoxic API manufacturing capacity in Visp was started up in 2012. Lonza also increased peptide-manufacturing capabilities at its site in Braine, Belgium.
Other companies are proceeding with investments and alliances to build HPAPI capabilities. In 2012, Carbogen Amcis and ADC Biotechnology formed a partnership to provide customers with development and manufacturing services for antibody drug conjugates. ADC Bio will provide access to proprietary solid-phase immobilization technologies for conjugation and long-term storage of antibody drug conjugates. Carbogen Amcis will focus on small- to large-scale GMP supply and on the formulation of antibody drug conjugates.
In October 2012, Fujifilm Diosynth Biotechnologies formed a strategic alliance with Piramal for antibody drug conjugate production, whereby the two companies will offer contract development and manufacture of antibody drug conjugates. Piramal offers antibody drug conjugate production at its site in Grangemouth, Scotland. In 2012, Fujifilm also expanded its cGMP manufacturing facilities at its sites in Research Triangle Park, North Carolina and Billingham, United Kingdom. Novasep announced in 2012 a $3.9-million (EUR 3 million) investment to expand its HPAPI manufacturing capabilities at its facility in Le Mans, France. The plant expansion was scheduled to be fully operational by the beginning of 2013.
In addition to its HPAPI capacity expansion, Novasep is investing EUR 30 million ($39 million) to build a chromatography plant for the large-volume production of commercial APIs. The plant is being built on Novasep’s existing site in Mourenx, France and is expected to be operational and validated in 2014 . The new plant will contain Varicol continuous chromatography systems with 1200-mm diameter columns operated at up to 70 bars.
Several companies have announced overall manufacturing capacity additions. For example, Albemarle is expanding its manufacturing facility in Tyrone, Pennsylvania. The $30-million expansion builds on an earlier expansion that began operations in November 2012, which will result in an eventual 40% increase in reactor capacity for the company’s custom-manufacturing business. The first increment of new capacity will be operational late in the first quarter of 2014.
In February 2013, PharmaZell added an additional manufacturing site to its European manufacturing network. The company acquired a manufacturing site in Liestal, Switzerland previously operated by AbbVie (formerly Abbott). Abbott’s pharmaceutical business was spun off in a separate company, AbbVie, in January 2013. The Liestal site consists of multipurpose manufacturing equipment with 150 m3 of reactor volume with drying and milling capacity, packaging cleanrooms, a pilot plant, quality-control laboratories, and warehouses for manufacturing small-molecule, large-volume APIs.
In 2012, Almac expanded its API manufacturing facility at its European headquarters in Craigavon, United Kingdom, with a scheduled completion for the end of 2012. The upgrade included installation of two 1000-L reactors and a pressure-filter dryer, which allows production of GMP APIs up to 150-kg batches.
In September 2012, Cambridge Major Laboratories (CML) reported that it is expanding its large-scale API manufacturing facility in Germantown, Wisconsin. The expansion comes three years after commissioning the new site. The expansion includes additional reactor capacity and isolation equipment as well as additional investments in engineering controls. Also, in 2012, Cedarburg Hauser Pharmaceuticals expanded its capacity at its Wisconsin-based API manufacturing plant and made additional upgrades for improving safety and GMP systems.
Other companies are making targeted investment in select manufacturing activities. In 2012, Dr. Reddy’s Custom Pharmaceutical Services expanded its activated mPEG manufacturing capabilities at is facility in Mirfield, United Kingdom. SAFC, part of Sigma-Aldrich, is expanding its operations in Scotland by investing in the development of a new powder-manufacturing facility at its Irvine site. SAFC’s new facility in Irvine is its second powder manufacturing facility, which will support SAFC’s risk-management program, which provides an internal back-up supplier for its customers. The new facility will be used to serve customers across Europe.
Almac and DSM Pharmaceutical Products recently reported the successful transfer of enzymes for enzyme screening, process development and scale-up as part of the companies’ agreement in biocatalysis, which was announced in October 2012. The agreement grants both companies access to their enzyme platform technologies and services for the manufacturing of APIs. The collaboration also enables Almac to offer its customers a preferred partner for large-scale production. In February 2013, DSM Pharmaceutical Products signed an agreement with Chemtrix, a supplier of flow-chemistry equipment and services, for providing equipment, development and manufacturing services to the pharmaceutical industry. Chemtrix specializes in ready-to-use laboratory and kilo-scale microreactors as well as reactor and process design for industrial reactors. DSM provides drug-synthesis route development, scale-up, and implementation of continuous-flow processes for manufacturing. DSM has FDA approval for using microreactors for making a pharmaceutical product at commercial scale under cGMP at its facility in Linz, Austria, where its dedicated commercial-scale installation is located. The DSM–Chemtrix collaboration will initially offer an industrial flow process-development package for customized scalable flow-chemistry solutions. The package covers all phases of process design, scanning chemistries, chemistry development, route scouting, equipment design, and scale-up for fully continuous or integrated processes.
Ajinomoto plans to invest approximately JPY 1.3 billion ($13.9 million) to double production capacity for amino acids for use in pharmaceuticals and foods at its subsidiary Shanghai Ajinomoto Amino Acid in Shanghai. The expansion is scheduled to come on line in October 2013. Ajinomoto estimates the current global market for amino acids for pharmaceuticals and foods at 30,000 tons, and with growth in emerging markets, expects demand to rise to 45,000 tons by 2020. Several fine-chemical producers and contract API producers also recently announced activity in support of finished product manufacturing. For example, earlier this year, Ajinomoto agreed to acquire Althea Technologies, a San Diego-based contract provider of fill–finish services. Aesica and the CDMO EmulTech are partnering on the commercial development of ET4ME, an emulsion technology for product formulation. ET4ME is a microencapsulation technology that uses a microfluidic process to create a measurable microparticulate suspension. The technology can be used for small molecules and biologics.
Cambrex agreed to contract manufacture Dow Chemical’s hydroxypropyl methylcellulose acetate succinate, an excipient provided by Dow as part of a solubilization partnership that Dow and Bend Research formed in 2012 under which Dow is commercially supplying solubility-enabling excipients. Cambrex has begun construction of the new facility at Cambrex’s site in Karlskoga Sweden with commercial product availability set for year end 2013. In another development, ScinoPharm and Foresee Pharmaceuticals agreed to form a joint venture to develop a series of peptide injectable drugs, with the first being a leuprolide injectable drug product, by which leuprolide will be formulated in a proprietary controlled-release drug delivery system originally developed by Foresee and transferred to the joint venture. ScinoPharm is investing $3.6 million for a minority ownership in the new company.