February 6, 2009 dates the FDA announcement of a new class of drugs made in living organisms altered by scientists as producers instead of chemical factories. ATryn signifies USA's first approval for a biological product made by genetically engineered (GE) animals. A therapeutic protein, ATryn, is derived from the milk of goats that have been genetically altered by introducing a segment of DNA (called a recombinant DNA or rDNA construct) into their genes for the animal to produce human antithrombin in its milk.

Antithrombin (AT) is a protein that helps to keep blood from clotting in the veins and arteries of an healthy individual. Atryn is thus an anticoagulant approved in USA for the prevention of blood clots in patients with a rare disease known as hereditary AT deficiency.

ATryn was approved in 2006 by the European Medicines Agency for use in preventing clotting conditions during surgical procedures in patients with hereditary AT deficiency. The FDA approval appears to be wider in application. The manufacturer of ATryn, GTC Biotherapeutics, Inc., received approvals from these two FDA centers:

(1) The Center for Biologics Evaluation and Research (CBER) approved the human biologic based on its safety and efficacy. "This product offers an important new treatment option for patients with hereditary antithrombin deficiency, preventing life-threatening clots that otherwise frequently occur during high risk situations," explained Jesse Goodman, M.D., M.P.H., CBER director.

(2) The Center for Veterinary Medicine (CVM) approved the rDNA construct in the goats that produce ATryn. “We have looked carefully at seven generations of these GE goats; all of them are healthy and we haven't seen any adverse effects from the rDNA construct or its expression. I am pleased that this approval makes possible another source of an important human medication,” said Bernadette Dunham, D.V.M., Ph.D., CVM director.

On the other hand, the General Acounting Office (GAO) designated in January 2009 the FDA oversight of medical products as one of the three new high risk areas in the United States Government. New laws, the complexity of items submitted to FDA for approval, and the globalization of the medical products industry were identified to be challenging FDA’s ability to guarantee the safety and effectiveness of drugs, biologics, and medical devices. Furthermore, GAO is on the record that: 

FDA needs to improve the data it uses to manage the foreign drug inspection program, do more inspections of foreign establishments that manufacture drugs or medical devices, more systemically review the claims made in drug advertising and promotional material, and ensure that drug sponsors accurately report clinical trial results.

Hence, it is fair to say that the approval of ATryn was not necessarily given under the new GAO guidelines to be yet implemented. Consumer groups can use the GAO process to bring closer examination of the FDA's policy on all genetically engineered foods and the risk posed by genetically engineered animals on the environment.

It is noteworthy that almost one-quarter of biologic therapies approved in USA and Europe since 1995 have had safety issues in the decade following their approval. Although the animal source is not genetically altered to make these drugs, they are derived from biological sources, including antibodies, enzymes, and hormones. Since 1982, when the first biologic treatment, recombinant insulin, was approved in USA, more than 250 biologics have come to the pharmaceutical market, amounting to about one-quarter of all new drugs approved by the European Union and USA.

Because hereditary AT deficiency occurs in a small population (roughly 1 in 5,000 people in USA), the FDA gave ATryn an orphan drug designation. The orphan drug designation system promotes the development of medications for patients with a rare disease or condition. 

From FDA: Genetically Engineered Animals

Diagram showing how new traits can be introduced into animals. Here’s how it works for animals engineered to produce a human pharmaceutical.

New traits can be introduced into animals. Here's how it works for animals engineered to produce a human pharmaceutical.

1. Generation of the rDNA Construct

A. Milk Protein Promoter DNA: allows for expression only in goat mammary glands.

B. Therapeutic Protein Gene: encodes a protein known to treat disease in people.

C. Terminator Sequence: assures that only the gene of interest is controlled by A.

D. Other DNA Sequences: helps with the introduction of the new combination DNA strand

2. The rDNA construct is created by combining A, B, C and D.

3. This new DNA strand is then introduced by any of a number of methods into an animal cell, such as an egg, that is then used to produce a genetically engineered animal.

4. The first genetically engineered goat is produced.

5. The offspring of the first genetically engineered goats, referred to as production animals, are milked. The milk is transferred to a purification facility.

6. The drug to be used to treat human disease is purified from the goat's milk.

For More Information:

For FDA publications about the technology of GE animals and the FDA's regulation of them, visit www.fda.gov/cvm/GEAnimals.htm

FDA Issues Final Guidance on Regulation of Genetically Engineered Animals

FDA Releases Draft Guidance on Regulation of Genetically Engineered Animals