Cautious Times for Fine-Chemical Producers and Contract API Manufacturers

As fine-chemical producers, contract manufacturers, and pharmaceutical companies gather this month for Informex, being held Feb. 19-22 in Anaheim, California, custom manufacturers face improving conditions. Certain CMOs report improving business conditions in 2012, and although overall capacity expansions are few, CMOs continue to invest in specialized technological capabilities, such as high-potency API (HPAPI manufacturing).  

Company activity
Lonza, a bellwether in the custom-manufacturing arena, reported improvements in this business in 2012 following a weak 2011. In 2012, Lonza reported that it strengthened its chemical manufacturing product pipeline in all clinical phases to more than 350 active projects and its manufacturing capacity utilization to above 75%. The improvement reflects a recovery from 2011, when the business unit recovered from various product delays and project cancellations. In 2013, the chemical manufacturing business will be part of the company’s “Visp Challenge,” a program initiated in 2011 to improve the efficiency and economic viability of its Visp, Switzerland, manufacturing site, the largest site in Lonza’s manufacturing network.

On the expansion side, Lonza reported on the first two build-out phases of its large-scale multpurpose cGMP API plant in Nansha, China, following FDA approval of several customer projects in late 2011. Also, a new cGMP kilo-laboratory in Nansha and an additional small-scale manufacturing train were successfully brought on line. The company’s large-scale antibody drug conjugates project in Visp 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 HPAPI labs 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, according to the company. Lonza also increased peptide-manufacturing capabilities at it site in Braine, Belgium.

On the biologics manufacturing side, Lonza raised its mid- and large-scale asset utilization in 2012, which included a new facility in Singapore, to above 70% with its mammalian and microbial services and manufacturing offerings increasing to more than 340 active projects. Some key highlights in 2012 included the new Singapore facility successfully performing its first validation campaigns for multiple customers and approval by FDA in the fourth quarter of 2012. Expansion of the laboratories and manufacturing suites at its Slough, United Kingdom, is on track. The company’s Hopkinton, Massachusetts, site is fully operational, manufacturing multiple early-phase products for various customers following recent quality-control problems. Lonza reported that in cooperation with FDA and customers, the Hopkinton site made significant progress with its quality systems and equipment performance, and the company expects the lifting of the FDA Warning Letter ban in 2013 after a final FDA inspection. The harmonization programs for all mid- and large-scale mammalian manufacturing facilities are continuing. These programs enable its facilities to provide capacity from 20 to 20 000 liters.

Other companies are proceeding with investments and alliances to build HPAPI capabilities. In 2012, Carbogen Amcis and ADC Biotechnology announced 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, and Carbogen Amcis will focus on small- to large-scale GMP supply and on the formulation of antibody drug conjugate. In October 2012, Fujifilm Diosynth Biotechnologies formed a strategic alliance with Piramal for antibody drug conjugate production, whereby the two parties will offer contract development and manufacture of ADCs. Piramal offers antibody drug conjugate production at its site in Grangemouth, Scotland. Fujifilm recently announced an expansion of 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 highly potent API manufacturing capabilities at its Le Mans, France, facility. The plant expansion is expected to be fully operational by the beginning of 2013. The new Le Mans facility adds to Novasep’s strategy for total synthesis of antibody drug conjugates.

Other companies are proceeding with investment or recently made investments in 2012. Almac expanded its API manufacturing facility at its European Headquarters in Craigavon, United Kingdom, with a scheduled completion for end of 2012. This upgrade includes installation of two 1000-L reactors and a pressure-filter dryer, which allows production of GMP APIs up to 150-kg batch. Cambridge Major Laboratories (CML) is planning an expansion of its large-scale API manufacturing facility in Germantown, Wisconsin. The expansion comes three years after commissioning the new site. The expansion will include additional reactor capacity as well as isolation equipment. Alongside capacity additions, CML has made additional investments in engineering controls to ensure the sustainability of the business. Cedarburg Hauser Pharmaceuticals expanded the capacity of its Wisconsin-based API manufacturing plant as a result of an increased demand for contract manufacturing of commercial APIs as well as additional upgrades for improving safety and GMP systems. Dr. Reddy’s eports expansion in the areas of activated mPEG manufacturing and in the development and manufacture of APIs for use in preclinical through to commercial development at its manufacturing facility in Mirfield, United Kingdom. Also,in addition to its HPAPI capacity expansion, Novasep is investing EUR 30 million ($39 million) to build a chromatography plant for the production of large volumes of commercial APIs. The plant will be built on Novasep’s existing site in Mourenx, France, and is expected to be operational and validated within 18 months. The new plant will contain Varicol continuous chromatography systems with 1200-mm diameter columns operated at up to 70 bars. SAFC, part of Sigma-Aldrich, is expanding its operations in Scotland by investing in the development of a new powder-manufacturing facility on its Irvine site. SAFC’s new facility in Irvine is its second powder manufacturing facility, which will support SAFC’s risk-management program, providing an internal back-up supplier for its customers. The new facility will be used to service customers across Europe.