Investing in High-Potency Manufacturing

Market demand for cytotoxic drugs is leading CMOs to expand their API manufacturing and formulation services.
Nov 02, 2007
Volume 31, Issue 11

Reflecting strong pipeline potential and growth in the oncology drug market, contract manufacturers of active pharmaceutical ingredients (APIs) and formulation services are investing in high-potency manufacturing.

Cytotoxic drugs, prostaglandins, opiates, and certain hormones may be classified as potent compounds. Cytotoxic compounds (see sidebar, "Inside the cytotoxic drug market") represent a portion of the oncology drug market. Global sales of oncology drugs were $34.6 billion in 2006, according to IMS Health. These sales represented 5.7% of the global market and were second in market share only to lipid regulators, which held 5.8% of the global market in 2006. In 2006, global sales of oncology drugs rose 20.5%, making this class of drugs the strongest-performing therapeutic class. The growth in oncology drugs far surpassed the average growth (10.7%) of the top 10 therapeutic classes, according to IMS.

Patricia Van Arnum
The pipeline potential of oncology products is strong. Overall, at the end of 2006, there were a total of 2075 molecules in development, including 95 oncology products in Phase III clinical trials or preapproval stage, according to IMS. Other industry estimates show that 25% of all emerging new chemical entities are highly potent substances, and 60% of these are novel, highly targeted small molecules.

Expanding API manufacturing

Highly potent compounds
To meet demand for highly potent compounds, contract manufacturing organizations (CMOs) are expanding. SAFC (St. Louis, MO) is planning to build a new current good manufacturing practices (CGMP) suite for potent API conjugation at its St. Louis manufacturing campus. The new suite will enable the conjugation of highly potent APIs to a variety of targeted delivery molecules, including monoclonal antibodies. The new 600-ft2 conjugation suite is expected to be operational in late 2007 and will seek "SafeBridge" certification (see sidebar, "Certification for high-potency manufacturing"). The suite will accommodate early-stage clinical supplies of potent conjugated APIs and be able to expand production into commercial scale.

Inside the cytotoxic drug market
This investment follows SAFC's recently announced plans to add assets in the United States and Israel for high-potency API manufacturing. These plans include a $4.5-million expansion to introduce additional CGMP pilot-plant and kilo-laboratory capacity at its Madison, Wisconsin, facility. The facility underwent a $12-million, 38,000-ft2 expansion program that was completed in 2006.

SAFC is also investing $29 million to expand fermentation capacity at its facility in Jerusalem, Israel. The expansion is scheduled for completion in 2009. The enhancement will allow for process development and CGMP manufacturing for large-scale, high-potency, toxic or hazardous drug substances. The 50,000-ft2 high-potency fermentation expansion will focus production on secondary metabolites (antibiotic-like molecules), cytotoxins, and large-molecule proteins. A 30,000-ft2 area of the new facility was designed to be compliant with Biosafety Level 2 thus, enabling manipulation of human pathogens. Site capabilities include 1000- and 4000-L tank capacities for bacterial and fungal fermentation.

The $4.5-million expansion in Madison will add an additional CGMP pilot- plant and kilo-laboratory capacity and is scheduled to be commissioned in early 2008. The investment also includes the addition of X-ray powder diffraction (XRPD) analytical equipment for advanced solid-form testing to provide on-site CGMP and XRPD analysis of potent compounds. The capacity expansion includes the addition of two 400-L CGMP pilot-plant reactors and two 100-L CGMP portable jacketed reactors into a 1200-ft2 large-scale kilo laboratory. The addition will enable large-scale chromatography for process purification.

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