Process Improvements Boost Steroid Production

Forbes Medi-Tech has discovered two improvements that will lower the cost of producing therapeutic corticosteroids while improving the yield and purity of these materials. The first development involves more pure, less costly starting materials, while the second (for which a patent is pending) covers improved fermentation technology.

Synthetic corticosteroid production typically begins with phytosterols (plant steroids) derived from soybeans. These raw materials, which are extracted in low yield, contain the familiar A-B-C-D ring structure of the corticosteroids, cholesterol, and other active materials. The phytosterols are chemically converted to androstenedione (AD) and adrostadienendione (ADD), which are then subjected to oxidative fermentation to generate the steroids.

The tall oil source yields relatively large quantities of AD and ADD precursurs, as well as a second group of phytosterols used to make cholesterol-lowering drugs and food additives. Target products include off-patent steroids, of which Forbes Medi-Tech is working on ten. These include estrogen, progesterone, and cortisone; higher-value steroids such as sex hormones and contraceptive agents are in the planning stage.

"Although soybean-derived materials are not expensive as pharmaceutical intermediates go, the price of soybeans does fluctuate," says Maurice Bouchet, a consultant with Forbes Medi-Tech. "Our new process uses tall oil soap, a waste product of the pulp and paper industry. This steroid source is essentially free, is at least as pure as the soybean-derived material, and we never have to worry about the supply."

Forbes has scaled up the fermentation to 1,000 liters, which is low by production standards but will be upgraded shortly. "Even at that level," Bouchet told Pharmaceutical Online, "the purity of our starting materials is such that we can actually produce reasonable quantities of product."

The U.S. market for AD and ADD as steroid precursors is about $1 billion, with the finished products valued at $4 billion. Cholesterol-lowering prescription drugs is an $8 billion market, but Forbes Medi-Tech estimates the potential market for cholesterol-lowering food additives at $10 billion.

Forbes' extraction and fermentation process has caught the eye of at least one major pharmaceutical firm. On January 28, 1998, the company signed an agreement with Novartis (Basel, Switzerland), involving Forbes' plant-based sterol composition for lowering cholesterol. Under the agreement, Novartis paid Forbes a lump sum fee for the exclusive option to a worldwide license to use or sub-license FCP for use in nutritional products and food additives.

By Angelo DePalma

For more information: Don Lay, Forbes Medi-Tech, 1066 West Hastings St., Suite 2000, Vancouver, BC, Canada V6E 3X2. Tel: 604-689-5899.