By Lisa Seachrist
WASHINGTON — As a ban that could remove up to 85 percent of all medicines from the shelves of European pharmacies is about to take effect in 26 days, the U.S. and European Union (EU) met in a Washington summit where the EU's efforts to address the mad cow crisis were highlighted.
At issue for biotechnology and pharmaceutical manufacturers is a measure that would ban the use of all specified risk material (SRM) — brains, spinal cords and eyes from cows, sheep and goats over one year of age, as well as spleens from sheep and goats of any age — in the production of pharmaceutical and biotechnology products, which is set to go into effect Jan. 1, 1998. That measure could effectively ban all bovine-derived gelatin and tallow from these products over a presumed risk of transmitting the prion-based disease bovine spongiform encephalopathy (BSE) to humans.
Despite assurances in a statement released by EU officials Dec. 3 that the ban is being modified to ensure that it won't deprive patients of life-saving medicines, it remains unclear exactly what measures drug manufacturers will be able to take in order to comply with the ban.
"With three weeks before the ban is set to go into effect, we have yet to see a definitive document that tells us what the rules are," said Gillian Woollett, assistant vice president for biologics and biotechnology at the Pharmaceutical Research and Manufacturers of America (PhRMA). "Without the rules, it is virtually impossible for our companies to produce medicines that comply with the ban."
Animal products, particularly bovine-byproducts, are part and parcel of a great number of medicines. Tallow serves as the source for magnesium stearate, which is a component of many pill formulations, and pharmaceutical- grade gelatin is the product of processed bovine bones. Biotechnology products rely on hydrolyzed proteins for cell cultures, and vaccines are produced in a variety of bovine-based nutrient broths, including brain-heart infusion broth.
The EU ban on SRMs in pharmaceuticals arose from a directive by the European Parliament to the European Commission (EC) to adequately address the potential risk of transmitting prion-based diseases from animals to humans.
In March of 1996, approximately 20 British citizens were found to have developed a new variant form of the human prion disease Creutzfeldt-Jakob disease (CJD) that appeared to be related to BSE. In the wake of that news, the EC was criticized for inadequately responding to the potential threat.
Since then, the EC has developed several drafts of the SRM ban. As of October, the ban required countries outside the EU to certify that all of the medicines they produced were free of SRMs. In addition, the ban would go into effect immediately on Jan. 1, meaning that medicines potentially containing SRM would have been ripped from the shelves.
The Dec. 3 statement from the EC indicates that existing medical stocks could remain on the shelves and any medicines approved for marketing in the EU before Jan. 1, 1998, would have until Jan. 1, 1999, to reformulate their medicines to be produced without SRMs. In addition, the requirement for certification has been dropped.
"It is a good thing that the ban is not retroactive," Woollett said. "We are also pleased that manufacturers outside the EU won't be required to have a certification from which EU manufacturers are exempt. However, this statement raises more questions than answers."
Woollett noted that a product approved on Jan. 1, 1998, would have to comply with the ban immediately. In addition, the statement doesn't address what happens to drugs currently in clinical trials in Europe.
"This ban doesn't take into account the time frames associated with pharmaceutical development," Woollett said. "The commission has made it clear that they don't understand how medicines are developed."
The statement also doesn't mention gelatin. It mentions that tallow produced by approved methods won't be banned, but doesn't address the production of gelatin. It notes that all SRM must be removed at the site of slaughter and destroyed, preventing it from becoming a raw material for any use in the EU.
"I presume that the commission assumes that by default all gelatin produced in EU countries will be free from SRM," Woollett said. "But how is a U.S. manufacturer supposed to adhere to this standard? It is counterintuitive to think that a product produced in the U.S., which has never had a case of BSE, should be banned from the EU, where BSE exists."
Potential Health Risks Not Analyzed
In addition, the EC has conducted no risk-benefit analysis to ascertain the financial and public health costs the ban could inflict. A PhRMA-sponsored analysis indicated that the risk of contracting CJD from taking three gelatin capsules a day for a year is one in 100 billion. By comparison, the risk of getting cancer from eating a peanut butter sandwich every day for a year is a million times higher.
In order to assure that patients have access to life-saving medications, the commission permits member countries to exempt drugs from the ban until Dec. 31, 1999, while the companies develop alternatives. Woollett pointed out that the statement offered no definition of "essential medications."
"We appreciate the wiggle room afforded by this provision; but how effective is the ban if member states can arbitrarily exempt medication?" Woollett asked. "None of this is based on science, it is based on politics. But even so, without a firm grasp of the rules, we won't be able to comply with the ban and we certainly won't be able to do it by Jan. 1." *