Washington Editor

WASHINGTON - An FDA proposal to restrict certain cow-derived components of drugs, biologics and medical devices to lessen the risk of mad cow disease is having an effect on at least one sector of the industry, companies making thrombin products to promote clotting. But the agency's plan certainly could affect a wider swath of drugmakers.

The proposed policy is designed to keep medical products free of prions, the infectious proteins thought to cause bovine spongiform encephalopathy (BSE), or mad cow disease. It's the latest in a series of BSE safeguards that would bar material that harbors the highest concentrations of the fatal agent in infected cattle; already the FDA prohibits the use of certain cattle material in human food, including dietary supplements, and cosmetics.

The new rule would cover therapeutic products intended for use in humans and ruminant animals like cattle and sheep.

Currently available stand-alone thrombins, all of which come from cows, have been used for more than 30 years to control blood loss in a variety of surgical settings. Bovine-derived thrombin, an enzyme already tagged with a black-box warning because of its association with adverse immune responses, is used in nearly 1 million surgeries each year in the U.S., according to some estimates.

In the wake of last week's FDA announcement, investors have taken note of a couple of biotech companies that are making alternative-source, stand-alone thrombins. Share values have ticked upward for Omrix Biopharmaceuticals Inc., which is developing a human plasma-derived thrombin, and ZymoGenetics Inc., which is developing a recombinant human thrombin. New York-based Omrix's stock (NASDAQ:OMRI) tacked on $1.08 to close at $33.45 last Friday, the day after the agency news came out, while shares in Seattle-based ZymoGenetics (NASDAQ:ZGEN) traded up $1.28 on the same day to $16.30.

Both companies have filed for FDA approval of their products, and are awaiting word on whether the agency will accept their submissions for review. Neither representatives from Omrix nor ZymoGenetics returned calls seeking comment on the FDA proposal's impact on their products.

A spokesman for the Biotechnology Industry Organization said the rule likely would affect traditional pharmaceuticals more so than biologic products, though he noted that current industry practices aren't yet fully known as member companies still are being polled about the broad influence the new regulation could have. However, he conceded that products made through in vitro cell growth systems that employ bovine serum albumin could be impacted by these restrictions.

Indeed, an FDA document noted that many biological products are manufactured with or use cattle-derived material because it provides necessary nutrients for cell growth. For example, microorganisms used in manufacturing vaccines typically are grown under controlled conditions in media that may contain bovine material. Other animal-derived products used for manufacturing vaccines include amino acids, glycerol, detergents, gelatin, enzymes and blood. Also, cows' skeletal muscle is used to prepare broths used in certain complex media.

In addition, the agency said cattle-derived materials such as fetal calf serum, insulin, aprotinin and enzymes often are used in cell culture techniques to manufacture hematological, cell and gene-therapy products.

Beyond thrombins, other drugs that could be impacted by these restrictions include the anticoagulant heparin, which is made from cow lungs, and hyaluronic acid. Also, some pharmaceutical products contain cow-derived gelatin or magnesium stereate - the former in drug capsules and the latter in product filler.

The proposed restrictions extend to cow parts that include fetal calf serum, if appropriate procedures have not been followed to prevent its contamination with materials prohibited by the proposed rule. That includes the brain, skull, eyes and spinal cords from cows 30 months and older; the tonsils and a portion of the small intestines from all cattle, regardless of their age or health; any material from those that cannot walk; any material from cows not inspected and passed for human consumption; tallow that contains more than 0.15 percent insoluble impurities if the fat is derived from materials prohibited by the proposed rule; and mechanically separated beef.

FDA officials declined to comment, but according to the agency's press release, the proposal also would mandate new record-keeping requirements for medical products that are manufactured from or otherwise contain cow material, to ensure that companies comply with these prohibitions. Interested parties have until March 13 to respond to the proposed rule.