Inside INFORMEX: Evaluating the Market for Contract API Manufacturing

Contract API manufacturers and fine-chemical producers gathered at Informex, the annual trade show of custom and batch manufacturers, in New Orleans in February. Companies used the show to highlight recent capacity and service expansions as well acquisitions. These investments reflect targeted moves to increase capacity in specialized areas, such as high-potency manufacturing, diversification into non-API areas, such as formulation development, finished product manufacturing, and testing, as well as partnering with other providers to broaden service offerings and capabilities.

Patricia Van Arnum

Capacity expansions

High-potency. Several CMOs highlighted recent expansions in high-potency manufacturing. Aesica opened a new purpose-built $4.6-million high-potency manufacturing facility for the manufacture of formulated products and plans to upgrade its API manufacturing facilities to enable manufacture of high-potency APIs at commercial scale. The upgrade will allow Aesica to manufacture SafeBridge Category 3 APIs and formulated products from pilot to commercial scale from two of its sites in Europe. The new facilities will enable Aesica to manage high-potency API production at quantities from 1–200 kg. Further investment in API manufacturing capability in 2013 will equip Aesica to produce batch sizes up to 600 kg.

Helsinn Advanced Synthesis reported on its cytotoxic and high-potency manufacturing facilities in Biasca, Switzerland, and multiyear expansions in this area. The company's capabilities include pilot-scale, small-scale, and commercial-scale capabilities for manufacturing highly potent APIs. Its cytotoxic capabilities include isolated and dedicated cytotoxic quality control and R&D laboratories, raw-materials and finished-goods warehousing, and finishing and sampling areas. A new laboratory has been constructed exclusively for small-scale cytotoxic production, design of experiment, and initial process development. The company also has pilot-scale, small-scale, and commercial-scale capabilities for manufacturing cytotoxic small molecules.

Evonik recently opened a new laboratory at its site in Hanau, Germany, for highly potent APIs and expanded its cGMP capacity for highly potent APIs on a kilogram scale at its Tippecanoe facility in Lafayette, Indiana. The new laboratory allows Evonik to develop and optimize syntheses for highly potent APIs in Germany. At the US site, Evonik has similar laboratory installations, expanding capacity with a reactor volume for highly potent compounds totaling 170 m³.

Fermion has invested in a new high-potency facility capable of handling OEL Class V compounds. The company added 10 m³ of additional high-potency manufacturing capacity with reactors ranging in volume from 70 L to 1500 L. The construction of this facility began in mid-2011 and the finished plant was scheduled to come on line in March 2012. By the fall of 2012, additional improvements will allow hydrogenation reactions to be undertaken at the facility.

Other expansions. Almac is doubling analytical capacity at its 240,000-ft² North American headquarters in Souderton, Pennsylvania. The facility offers full-service, integrated clinical packaging, drug-supply management, and technology services to pharmaceutical and biotechnology clients. Almac's additional laboratory investment will include polymorph and salt screening and solid-form development. The new facility is also equipped with a bathless dissolution apparatus for comparative dissolution studies.

In addition to API and chemical development services, Almac provides formulation development and solid-dosage manufacturing for clinical-trial materials and commercial manufacturing and related services. The company recently acquired two new pieces of encapsulation equipment for its North American headquarters in Souderton, Pennsylvania: the Bosch GKF 702 capsule filler with integrated KKE 1700 checkweigher. The Bosch cGMP-compliant system is able to produce 42,000 capsules per hour compared to the 2700–4500 output of Almac's current machine in the United States. Further capabilities of the new equipment include powder, pellet, tablet, and placebo fill as well as multifill.

Asymchem Laboratories (Tianjin) reported on the opening its new large-scale manufacturing facility, Jilin Asymchem Laboratories, in Dunhua, Jilin province, China. Phase I completion of Dunhua's manufacturing facility included 5000–20,000 L vessels for cGMP manufacture of raw materials to intermediates. Phase II involved completion of a second module for a total capacity of 532 m³. This site offers manufacturing as a standalone service and also back-integration for internal downstream cGMP targets to be further processed in Asymchem's Tianjin 2 GMP facility. Phase III construction in Dunhua for a GMP API manufacturing plant is on schedule and is expected to be completed later this year.

Acquisitions and partnerships

Some contract API manufacturers also recently expanded to support biopharmaceutical development and manufacturing. For example, SAFC reported on its recent $350-million acquisition of BioReliance, a provider of global biopharmaceutical testing services, from Avista Capital Partners. BioReliance provides biologic, specialized toxicology, and animal-health testing to pharmaceutical, biopharmaceutical, diagnostics, and other life-science companies.

BioReliance employs more than 650 people and is headquartered in Rockville, Maryland, with additional operations in Glasgow and Stirling, Scotland, and sales offices in Tokyo, Japan, and Bangalore, India. The acquisition complements SAFC's industrial media position, and its CompoZr zinc finger nuclease technology is synergistic with BioReliance's toxicology and animal-health services operations for the development of new assays, cell lines, and animal models, according to the company.

Carbogen Amcis recently acquired Creapharm Parenterals, a subsidiary of France-based Creapharm Group and a CDMO specializing in liquid, semisolid, and injectable aseptic dosage forms. Creapharm Parenterals employs 16 specialists and operates a GMP manufacturing site in Riom, France.

Solvias and RohnerChem reported on their partnership for custom research and manufacturing services, which was announced in October 2011. The preferred but nonexclusive partnership provides services from route scouting to commercial manufacturing. Solvias brings expertise in chemical, analytical and solid-state development, and RohnerChem brings experience in scale-up and commercial-scale custom synthesis of complex, small-molecule fine chemicals and APIs.

Key capabilities from Solvias include high-throughput screening methods, which have been used in asymmetric homogeneous catalysis, CX-couplings, racemate resolutions, carbonylations, hydroformylations, biocatalysis development, and various other transformations. Solvias' solid-state development group also is equipped to assist in developing crystallization processes, perform polymorphism studies, and provide guidance in the development of the best solid form for an API. After process optimization, which can be performed either at Solvias' or at RohnerChem's kilo laboratories, commercial quantities can be manufactured at RohnerChem facilities.

In January, evocatal, a biocatalysis provider, and RohnerChem formed a strategic partnership in biocatalysis with evocatal providing its biocatalysis experitse and RohnerChem manufacturing expertise.

Service expansions

BASF has opened an industrial biotechnology and microbiology research center in Tarrytown, New York. The company uses biotechnological methods to produce products such as vitamins, enzymes, pharmaceutical intermediates, and specialties for the personal care, food and feed industries. One focus of the research laboratory work is to develop more efficient and resource-conserving production processes. The use of metabolic engineering, or the targeted modification of metabolism, is used to enhance the efficiency of the microorganisms used in these production processes. The laboratory also will be used to develop bacterial biofilms.

DSM reported on InnoSyn, a route-scouting service that supports R&D as well as implementation of economical and scalable routes. The service offering includes consulting, route scouting, biocatalyst/catalyst screening, prefeasibility studies, full feasibility studies, mini-plant campaigns, and support in transfer and implementation. Various technical packages are provided for biocatalysis, homogeneous catalysis, organic chemistry and process R&D and continuous chemistry (i.e., microreactor technology).

Neuland Laboratories, a contract manufacturer of APIs, intermediates, and peptides, launched a new mobile app version of its GuarD project-management system. GuarD was developed to support customers' participation in project planning and real-time tracking. GuarD uses the principles of critical-chain project management, which emphasizes resource availability and flexibility to maintain project timelines. GuarD allows for a detailed project plan that is viewable in an online template to provide a customer progress of its project, information on the latest task updates, expected time of completion, and other information important to the project.

Patricia Van Arnum is a executive editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, pvanarnum@advanstar.com.