High-Potency Manufacturing Remains Strong

High-potency manufacturing continues to be an area of investment for pharmaceutical companies and contract service providers. Many companies have recently invested or are planning expansions in API manufacturing and finished product manufacturing.

Patricia Van Arnum

Examining the market

The impetus behind this investment has been the growth in the oncology drug market. In 2010, the global market for oncology drugs was $57.1 billion, according to the IMS Institute for Healthcare Informatics. Market growth was strong; the compound annual growth rate (CAGR) for oncology drugs was 13.2% between 2006–2010. Although growth is expected to slow, due in part to generic-drug incursion, the global oncology drug market is still expected to increase at a CAGR of 5–8% through 2015, and reach between $75 billion and $80 billion, making it the largest single largest therapeutic drug class by value, according to IMS estimates.

API high-potency manufacturing

To keep pace with market potential, several CMOs recently expanded capabilities for high-potency API manufacturing. In October 2011, SAFC was granted SafeBridge certification for its commercial-scale high-potency facility in Verona, Wisconsin. The SafeBridge program assessment focuses on four primary areas: management, hazard identification and evaluation, hazard controls and communication, and education and training. The $30-million facility in Verona opened in 2010 to support Phase III and commercial-scale high-potency API manufacturing. The SafeBridge assessment also included a successful recertification of SAFC's nearby Madison, Wisconsin, high-potency manufacturing facility.

In March 2012, the CMO Aesica opened a new $4.6-million high-potency manufacturing facility for formulated products and confirmed plans to upgrade its API manufacturing facilities to manufacture high-potency APIs at commercial scale. The upgrade will enable Aesica to manufacture SafeBridge Category III API and formulated products from pilot to commercial scale from two of its sites in Europe. The new facilities will produce high-potency APIs in quantities of 1– 200 kg. Further investment in 2013 will equip Aesica to produce batch sizes up to 600 kg.

Lonza invested CHF 24 million ($25 million) to expand its cytotoxic manufacturing capabilities in Visp, Switzerland, by adding multikilogram-scale cytotoxic production for clinical and commercial production. The expansion, announced in May 2011, was scheduled to be completed in the second quarter of 2012. The expansion complements the company's high-potency GMP laboratory suites that operate on a gram scale. In its first-quarter earnings release, the company noted approval for a 250-L high-potency API expansion in Visp.

Helsinn Advanced Synthesis recently reported on its cytotoxic and high-potency manufacturing facilities in Biasca, Switzerland and multiyear expansions. Its capabilities include pilot-scale, small-scale, and commercial-scale capabilities for manufacturing highly potent APIs. It 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 was 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.

Last October, the CMO Saltigo reported it was adding new production capacities for potent APIs at its facility in Redmond, Washington. The expansion, scheduled for completion in early 2012, allows for production and handling of Category III substances up to the kilogram range.

Almac is expanding its manufacturing capacity to more than 30 m³ at its European headquarters in Craigavon, United Kingdom to include reactor vessels with product isolation and drying equipment to allow highly potent API manufacture up to the 600-kg batch size. Almac reported the expansion last October and said the facility will be built, commissioned, and validated in the next two years.

Carbogen Amcis reported earlier this year that its facility in Bubendorf, Switzerland, which includes the manufacture of high-potency APIs, successfully completed a FDA GMP audit for several commercial products and a pre-approval inspection for another program. The audit involved an analysis of all systems, procedures, and processes related to the development, validation, and manufacture of APIs and highly-potent APIs at the Bubendorf site. The site includes R&D capabilities, analytical laboratories, and development and manufacturing units for manufacturing Category III and IV compounds. In January 2012, Carbogen Amcis acquired Creapharm Parenterals, a CDMO specializing in liquid, semisolid, and injectable aseptic dosage forms. The acquisition gives Carbogen formulation, lyophilization and sterile GMP capabilities for drug products, including highly potent products, for preclinical and clinical-trial materials.

In 2011, the biopharmaceutical company OPKO Health acquired FineTech Pharmaceutical, an Israeli company focused on manufacturing high-potency APIs. The acquisition included a facility in Nesher, Israel, for pilot- and commercial-scale production of high-potency APIs.

Finished product manufacturing

Companies also are investing in finished product manufacturing In September 2011, Roche opened a new 17,000-ft² clinical-supply manufacturing facility at its campus in Nutley, New Jersey, for producing dosage forms of highly potent compounds for preclinical safety studies and Phase I and II clinical studies. The clinical dosage forms produced at the facility include tablets, capsules, powders, suspensions, and solutions. The facility has warehouses for components, excipients, APIs, mechanical rooms, and multipurpose isolation suites for manufacturing.

In November 2011, Metrics began offering neat API capsule-filling at its potent and cytotoxic facility in Greenville, North Carolina. The company secured a Capsugel Xcelodose system, a powder microdoser and automated encapsulator that places API directly into capsules with a high level of accuracy. Metrics also installed a custom-built isolation system for the equipment. The company offers dedicated and segregated potent and cytotoxic cGMP manufacturing for Phase I–III projects. It opened a new potent and cytotoxic drug-development facility in 2009 as part of an expansion of the company's Greenville facility.

Earlier this year, Baxter reported that its high-potency manufacturing facilities in Halle and Bielefeld, Germany, received SafeBridge certification. The facilities in Halle and Bielefeld support Baxter's BioPharma Solutions business, a CMO providing contract sterile manufacturing. In November 2011, Baxter's BioPharma Solutions business completed a capacity expansion at the company's cytotoxic contract manufacturing facility in Halle/Westfalen, Germany. The primary component of the expansion was the modular installation of an additional large-scale, commercial lyophilization unit for increasing freeze-drying capacity to support commercial cytotoxic manufacturing capacity. The expansion followed expansions for cytotoxic manufacturing capacity in 2010 and 2006.

The CDMO Pharmaceutics International Inc. began construction of a new 24,000-ft² cGMP aseptic fill–finish manufacturing facility earlier this year. Targeted for completion in the fourth quarter 2012, the new facility will more than double the company's current sterile GMP manufacture capacity. Fill–finish suites will include automated vial and syringe filling, inspection and labeling equipment capable of producing batch sizes of 100,000-plus units. The additional facilities will enable the company to provide preclinical through commercial-scale production and meet the growing demand for fill–finish services for potent compounds and oncology drugs.

The CDMO Penn Pharma is investing €14 million ($22 million) to expand high-potency manufacturing at its facilities in South Wales, United Kingdom by adding a new 15,000-ft² development and commercial manufacturing unit for tablets and capsules. The new production facility is expected to be validated and running by the end of the first quarter 2013.

Pfizer CentreSource has various technologies and capabilities for high-containment oral solid manufacturing, which includes its production facility in Freiburg, Germany. The Freiburg facility was recognized by the International Society for Pharmaceutical Engineers with the 2011 Facility of the Year Award for Sustainability for its Strategic Plant Restructuring and Energy Master Plan project. The Facility of the Years Award recognizes pharmaceutical manufacturing projects that use innovative technologies to enhance quality and reduce costs. The Freiburg facility was recognized for its technologies and automation as part of a sustainability program. Some highlights include a fully automated material-flow system, multipurpose automation systems, paperless order documentation, computer-integrated manufacturing systems, a wood-pellet boiler system for powering air-conditioning systems, and other manufacturing and energy-efficiency practices.

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