Biopure Corp. filed a biologics license application with the FDA for its oxygen-carrying blood treatment, Hemopure, with the entire electronic filing taking up 14.5 gigabytes.

That filing amounts to "several hundred thousand pages," said Douglas Sayles, director of corporate communications for Cambridge, Mass.-based Biopure. The company is asking for approval to market the product for the treatment of the symptoms of acute anemia in adult patients undergoing orthopedic surgery. The product is designed to eliminate, delay or reduce the need for red blood cells in those patients, the company said.

"The application includes preclinical information," Sayles said. "Over the past 18 years, we have conducted or sponsored more than 180 preclinical animal and laboratory studies."

The FDA has 60 days from Wednesday's filing to respond to Biopure as to whether or not it agrees to review the application.

Each unit of Hemopure consists of 30 grams of hemoglobin that has been extracted from bovine red blood cells, ultra-purified, chemically cross-linked and formulated in 250 millimeters of balanced salt solution.

"It can be used as an alternative to red blood cell transfusion, but it does have different physiology and clinical characteristics," Sayles said, explaining that people often refer to Hemopure as simply a "blood substitute," which is incorrect.

Biopure also completed two Phase III trials, one of which served as the basis for the product's approval for marketing in South Africa in 2001 for patients undergoing surgery. The company has contracted South Africa-based health care provider Network Healthcare Holdings Ltd. and Community Healthcare Holdings Ltd. to exclusively market and distribute the product in sub-Saharan Africa. Those companies have formed a joint subsidiary. (See BioWorld Today, April 11, 2001.)

Biopure owns the rights in the rest of the world, but is seeking a partner for the European market, Sayles said.

The second pivotal Phase III trial was conducted in patients undergoing elective orthopedic surgery in the U.S., and that study met primary safety and efficacy endpoints. (See BioWorld Today, Aug. 28, 2001.)

At the time of the U.S. pivotal Phase III trial conclusion, Biopure said it planned to file the BLA before the end of 2001. However, Sayles said the company met with the FDA last fall, when Biopure was told that it would need to take some additional steps.

"The FDA told us they wanted us to validate our manufacturing plant at expanded capacity before they would review the BLA," Sayles said, noting that it had been validated at existing capacity.

The changes were "mostly utility upgrades," Sayles said, and the plant, located in Cambridge next to its corporate headquarters, was closed before reopening in May to demonstrate that it could support a worldwide launch. The plant is validated to produce 75,000 units per year, he said. However, the company has plans for a new plant in Sumter, S.C., that would have the capacity to produce 500,000 units per year.

"When we talk about commercialization of this product, we look at it as a world market," Sayles said.

The U.S. market is an important one both from the standpoint of generating revenue and securing credibility for the product, even though it's only about 18 percent to 20 percent of the worldwide market. Those numbers were determined based on the fact that the U.S. provides about that percentage of blood units for the world, Sayles said.

"The risk-benefit of blood is even greater outside the U.S., where there may not be as sophisticated blood-banking facilities," Sayles said.

For example, medical professionals encouraged the company to seek approval in South Africa first due to the high incidence of HIV, hepatitis and malaria in the population there, Sayles said. Biopure is now educating physicians in South Africa about Hemopure, with plans for a January launch.

"During the past year, we have provided about 1,700 units to our South African distributor free of charge," Sayles said.

And even though the official launch is not planned in that country until January, Sayles said Biopure would record some revenue from product sales in South Africa during the fourth quarter of this year.

Biopure's stock (NASDAQ:BPUR) rose 6 cents Thursday to close at $7.09.