Washington Editor

WASHINGTON - The FDA last week proposed new guidelines intended to clarify the agency's regulatory authority over genetically engineered animals and its requirements and recommendations for drugs, devices and food derived from such animals.

Genetic engineering—the process in which recombinant DNA technology is used to introduce new characteristics or traits into organisms - has been widely used in agriculture to make crops resistant to certain pests or herbicides or with improved nutritional qualities, regulators noted.

In medicine, genetic engineering is used to develop microbes that produce drugs and other therapeutic products for use in humans, and in food, the process is used to produce microorganisms that aid in baking, brewing and cheese-making, the FDA said.

Regulators stressed that genetically engineered animals are not clones—genetic copies of the animals from which they are produced.

Many kinds of genetically engineered animals are in development but none have been approved by the FDA for marketing in the U.S.

Such animals can be classified in groups based on their intended use, regulators explained. For example, biopharm animals are those that have undergone genetic engineering to produce particular substances, such as human insulin, for pharmaceutical use. Research animals may be engineered to make them more susceptible to particular diseases, such as cancer.

Food use animals are engineered to provide healthier meat, such as pigs that contain healthy omega-3 fatty acids at levels comparable to those in fish, regulators explained.

The draft guidelines, which are open for public comment until Nov. 18, are not legally binding or enforceable as with regulations, the FDA noted.

Rather, the guidelines provide advice to industry about how best to comply with statutory or regulatory requirements.

The FDA said its existing statutory authorities under the new animal drug provisions of the Food, Drug and Cosmetic Act and current rules are sufficient to regulate genetically engineered animals.

While the FDA's Center for Veterinary Medicine will be responsible for overseeing biopharm animals, the final pharmaceutical will be reviewed by either the Center for Drug Evaluation and Research or the Center for Biologics Evaluation and Research, the agency said.

Genetically engineered mice in research laboratories are not covered by the FDA's guidance, but instead remain under the National Institutes of Health's guidelines for recombinant DNA research, regulators said.

"Genetically engineered animals hold great promise for improving human medicine, agriculture, the environment and the production of new materials," said Randall Lutter, deputy commissioner for policy at the FDA. The agency, he said, has "long been involved" in the scientific evaluation of such animals.

"Through genetic engineering animals can produce pharmaceutical proteins and replacement tissues in their milk, eggs, and blood, which can be used in the treatment of human diseases such as cancer, heart attacks, hemophilia, rheumatoid arthritis, pandemic flu, malaria and small pox," said Barbara Glenn, the Biotechnology Industry Organization's managing director of animal biotechnology.

In addition, she noted, research also is being conducted to produce transplant organs in pigs that may be a source of organs for humans.

Giuliani to Fight Ranbaxy's Import Ban

After the FDA last week said it was banning imports of drugs made at two plants owned by Indian drugmaker Ranbaxy Laboratories Ltd, the firm hired former New York Mayor Rudolf Giuliani to help fight its case.

The FDA said Ranbaxy had repeatedly failed to fix problems at two plants in Dewas and Paonta Sahib, India. Therefore, regulators said they issued an alert to U.S. Customs officials to detain 30 generic drugs made at the plants, which include gabapentin, cephalexin and zidovudine, a drug designated under the President's Emergency Program for AIDS Relief (PEPFAR) program.

Because Ranbaxy is the sole supplier of the antiviral drug ganciclovir, the FDA said it would not "generally" detain shipments into the U.S. of that drug.

Douglas Throckmorton, deputy director of the FDA's Center for Drug Evaluation and Research, stressed that the agency had no concerns so far about any drugs from the plants that currently are on U.S. pharmacy shelves and had no evidence that Ranbaxy has shipped defective products.

"This is a preventive action taken to protect the quality of the drugs used each day by millions of Americans by ensuring that the process used to make the drugs adheres to the FDA standards for quality manufacturing," Throckmorton told reporters during a media briefing.

A spokeswoman for the agency told BioWorld Today that U.S. regulators had analyzed about 80 samples of finished drugs from the two Ranbaxy plants and found that "all samples met their applicable specifications."

Regulators said until the firm addresses its manufacturing plant deficiencies, the drugs from the two plants would remain on the import alert and the agency would not approve any of Ranbaxy's other drug applications.

Ranbaxy, meanwhile, has hired New York-based Giuliani Partners LLC at an undisclosed fee. "Ranbaxy is committed to a swift resolution to address these issues and to continuing to supply the global marketplace with safe and effective pharmaceuticals," the firm said in a statement.

The India-based company also is the subject of an investigation by the Justice Department for possible fraud and other improprieties in the firm's applications to sell drugs in the U.S.

Rep. John Dingell (D-Mich.), chairman of the House Energy and Commerce Committee, Thursday said he was expanding an ongoing investigation into whether the FDA knowingly allowed drugs suspected of being fraudulently approved and manufactured in violation of good manufacturing practices to be sold in the U.S. to include Ranbaxy's PEPFAR drugs. "It is important that the recipients of PEPFAR drugs know the FDA has done everything it should be doing to ensure the safety and effectiveness of these life-saving medications," Dingell said.

PEPFAR drugs are supplied to developing nations to treat HIV/AIDS and are granted expedited reviews by the FDA. However, the drugs cannot be granted approval for marketing in the U.S.