As contract manufacturers and pharmaceutical ingredient suppliers gather this week for CPhI Worldwide, the mood is fairly optimistic. Certain key players report healthy gains and expansion plans.

SAFC ups its investment in high-potency manufacturing
SAFC Pharma (St. Louis, MO) is investing $30 million to expand its Madison, Wisconsin, facility, by increasing its capacity to produce commercial-scale high-potency active pharmaceutical ingredients (HPAPIs). The investment includes the purchase of 15 acres of green space in Verona, Wisconsin, near its existing HPAPI production site, where the company will build a new 45,000-ft² manufacturing facility that will house commercial-scale reactors capable of producing HPAPI batch sizes up to 4000 L. Construction of the new plant is expected to be complete by year-end 2009.

The new facility’s design will adhere to Category IV standards. The site will seek “Safebridge” certification upon its completion. The facility will include development laboratories, a 150-L miniprocessing plant and two large-scale CGMP (current good manufacturing practices) manufacturing suites with reactors up to 4000 L. Specially designed quality-control laboratories, a potent-compound packaging area, warehouse and office space, and expansion space, will be featured in the building.

Including this expansion, SAFC has invested more than $75 million in developing its HPAPI manufacturing capabilities in recent years. The company announced a total of $45 million in HPAPI expansions over the past 18 months, including a recently completed $4.5-million extension of its CGMP pilot-plant and kilo-laboratory capacity, and operations have begun at its new biologic-HPAPI conjugation suite in St. Louis. SAFC Pharma has also invested in a major facility in Jerusalem, Israel, for large-scale production of bacterial and fungal fermentation-derived HPAPIs.

In other areas, SAFC is proceeding with a $12-million expansion of its viral-product manufacturing facility in Carlsbad, California. The expansion is scheduled to be operational in the second half of 2009. The new suites will add 8000 ft² of manufacturing space and enable 100-L batch production in stirred-tank bioreactors and 1000-L batch manufacturing in disposable bioreactors. These investments follow a $10-million expansion of commercial-scale API manufacturing and storage capacity at its Arklow, Ireland, and Buchs, Switzerland, facilities, respectively, in 2007.

Dr. Reddy's makes key acquisitions
To build its contract-manufacturing activities, Dr. Reddy's Laboratories (Hyderabad, India) completed two key acquisitions in 2008: Dow Chemical's (Midland, MI) Dowpharma small-molecules business associated with its Mirfield and Cambridge, United Kingdom, sites, as well as BASF's (Ludwigshafen, Germany) manufacturing facility in Shreveport, Louisiana, and related contract-manufacturing business for finished pharmaceuticals. The acquisition of the Dowpharma small-molecules business includes customer contracts, associated products, process technology, intellectual property, trademarks and the transfer of the Mirfield and Cambridge facilities. Dr. Reddy's will also have a nonexclusive license to Dow's "Pfenex" expression technology for biocatalysis development.

The BASF acquisition includes relevant business, customer contracts, related abbreviated new drug applications, new drug applications, trademarks, and the Shreveport facility and related contract-manufacturing activities. It also includes a tolling and supply agreement.

Regis Technologies expands in the US
Regis Technologies (Morton Grove, IL), a contract manufacturer of APIs and provider of separation services, is moving forward with several expansions. The company points to strong growth in supplying clinical trial materials and in its separations services.

Regis expands manufacturing and QC/QA capabilities. Regis plans to invest $10 million to expand its manufacturing facility in Morton Grove, Illinois, by 30,000 ft². The expansion is scheduled to begin in 2009 and will include up to 16 additional reactor bays. The manufacturing expansion is scheduled to be completed by 2011. The company is also currently expanding its quality-control laboratories by 8000 ft². This expansion will allow the QC department to more than double in size to support the manufacturing expansion and will include a nuclear magnetic resonance (NMR) facility. The QC expansion is scheduled to be complete by the end of 2008.

Regis expands separation services. Regis is also expanding its separation services. In early 2007, the company brought its “RegisSEP” supercritical fluid chromatography (SFC) services online. The GMP-approved services provide preparative-scale chiral separations on a gram to multikilogram scale. The SFC services complement the company’s expertise in high-performance liquid chromatography (HPLC) services, which include chiral separations.

In 2007, Regis Technologies introduced two polysaccharide-coated columns for use in SFC and HPLC analyses for chiral separations. The columns are “RegisCell,” which has a (tris-(3,5-dimethylphenyl) carbamoyl cellulose) selector, and “RegisPack,” which has a (tris-(3,5-dimethylphenyl) carbamoyl amylose) selector. “The amylose and cellulose coatings have a different orientation in space (mirror images),” explains Ted Szczerba, technical director of chromatography with Regis, thereby providing subtle differences in the separation of chiral compounds.

"These columns provide enantiomeric separations of a wide range of racemate classes, rather than for the separation of a specific group of chiral compounds,” he says. “Therefore, both columns can serve as a starting point for developing a chiral separation method.” 

Regis positions in the US. In evaluating the health of the outsourcing market on an industry level, Scott Mohler, a sales and project manager with Regis Technologies, sees a similar performance in 2008 as in 2007. “Although more large pharmaceutical companies are outsourcing manufacturing, this appears to be offset by a decrease in outsourcing by smaller companies.”

Shifting geographic patterns of outsourcing activity represent an important change, a situation attenuated by for example, the high-profile case of contaminated heparin.  “Driven by the cost differential, many large pharmaceutical companies began outsourcing their drug-substance manufacturing over five years ago, mostly to companies in China and India,” says Mohler. “But we have begun to see strong indicators that some outsourcing services have begun to shift from China to the US.”

On an industry-wide level, several factors are favorably affecting US suppliers. “The weakness of the US dollar is changing the competitive nature of the outsourcing market,” says Mohler. “The cost differential of outsourcing to Asian companies is not as large as it was several years ago,” he says. “In addition, with several quality issues that surfaced this past year, quality has become a major issue. Quality and compliance concerns require increased surveillance and attention to the supply stream to make sure end products have integrity and quality, all of which increase cost and concern. Pharmaceutical companies are looking for partners with a pristine quality and compliance track record and find reassurance in the fact that FDA makes more frequent and more thorough investigations of US manufacturers.”

He adds that US suppliers also benefit from other logistical issues such as a lack of import delays or rejections when a product is manufactured in the US, the advantages of working in common time zones, and fewer travel requirements.

Other mid-sized players expand
Earlier this year, AMRI (Albany, NY) opened its first in vitro biology laboratory in Singapore and completed a 10,000-ft² laboratory expansion for medicinal-chemistry discovery services, more than doubling the capacity of its Science Park III facility. The in vitro biology group will test compounds synthesized by AMRI's Singapore-based medicinal-chemistry teams to provide potency data using cell-based or biochemical assays. AMRI anticipates hiring roughly 70 additional chemists and biologists to staff the Singapore facility during the next three years.

These moves complement AMRI's recent activity in Asia. In 2007, the company acquired the assets of Ariane Orgachem, in Aurangabad, and Ferico Laboratories, in Navi Mumbai, India, giving the company two API and intermediates facilities in the country. AMRI also acquired additional land for expansion and plans to invest approximately $15 million to increase and upgrade manufacturing capabilities during the next several years.

Cambridge Major Laboratories (Germantown, WI) is expanding its large-scale API manufacturing with a new 120,000-ft² manufacturing facility. The facility is designed for multiple GMP manufacturing suites capable of producing multiton quantities of APIs. The facility will initially feature six manufacturing suites with reactors as large as 2000 gallons. The facility will have complete isolation and containment, several vessels for hydrogenation and cryogenic reactions, and the potential to accommodate additional manufacturing suites to the 4000-gallon scale. Completion is scheduled for August 2009.

Carbogen Amcis's (Bubendorf, Switzerland) Indian subsidiary, Carbogen Amcis India, plans to open a high-potency facility in Bavla, India. The facility will be located on the Bavla site of its parent company, Dishman Pharmaceuticals and Chemicals (Ahmedabad, India). The facility's design and operation is modeled after Carbogen Amcis's high-potency operations at its Bubendorf, facilities. The facility is expected to be operational by the first quarter of 2009.

Carbogen Amcis is part of Dishman Pharmaceuticals and Chemicals. Dishman acquired Carbogen Amcis in 2006 as part of a broader strategy to increase its global presence by acquiring Western fine-chemicals and pharmaceutical assets. In 2007, Dishman acquired Solvay Pharmaceuticals's (Brussels) fine-chemicals and vitamin businesses for an undisclosed sum. The deal included Solvay's Veenendal, The Netherlands, facilities, as well as the intellectual property rights for fine chemicals, vitamin D, and vitamin D analogues. In 2006, Dishman acquired I03S, a company specializing in ozone chemistry. In 2005, it acquired the UK-based contract research company Synprotec.

Earlier this year, Hovione (Loures, Portugal) purchased a 75% stake in China's Hisyn Pharmaceutical. The acquisition includes development laboratories in Shanghai and a 22,000-m² API plant. Hovione's relationship with Hisyn started with the supply of intermediates, but this facility will now produce two of Hovione’s largest volume products, according to the company.