FDA approves first nucleic acid test

Mark A. Desorbo

Rockville, MD—The U.S. Food and Drug Administration (FDA) has approved the first nucleic acid test (NAT) systems for screening donor plasma, a landmark move that aims at ensuring the safety of blood protein-derived products by providing faster detection of HIV- and hepatitis C- viruses.

While virus inactivation is a required step in the manufacturing of all U.S. licensed plasma derivatives, removal of potentially infectious donations through screening adds a safeguard by limiting the amount of contamination that the manufacturing process must clear.

“It will help increase the safety profile of our plasma products for the patients who use them and will allow for earlier

notification of plasma donors with reactive test results,” says Edward Colton, president and chief executive of Alpha Therapeutics Corp., a Los Angeles-based developer of plasma-derived biopharmaceutical products that helped formulate the NAT systems.

Alpha's algorithmic programming was combined with polymerase chain reaction (PCR) tests that were developed by the National Genetics Institute (NGI; Los Angeles). Together, Alpha and NGI obtained a patent for the “efficient algorithm method” for blood-borne infectious agent screening.

“We developed the PCR test and Alpha developed the algorithms,” says Pamela Sherry, senior vice president of investor and public relations for Laboratory Corp. of America (Burlington, NC), NGI's parent company. “This is the only test we'll have to use when we screen plasma pools. Before, we had to run a P-24 antibody test along with tests for HIV and hepatitis. The NAT test systems eliminates that cost and enhances safety to the population.”

The technology, she explains, allows detection of very small amounts of genetic material by massively amplifying gene fragments. The approved test systems permit highly sensitive detection of RNA from HIV, type 1, the HIV variant that is responsible for the vast majority of AIDS cases in the United States, and hepatitis C in test pools of 512 plasma samples obtained from multiple donors.

“Using this test allows us to find out which donations are problematic so we can single them out,” Sherry says.

According to the FDA, the use of pooled plasma samples for testing makes use of the NAT system cost-effective. However, if a test pool is positive for either virus, the individual donation that is suspected of containing a virus can be identified and not used for further manufacturing, and the donor can be deferred and notified.

The agency also indicates that donors of blood and plasma are tested for antibodies to hepatitis C, HIV as well as HIV-1 antigens, which are proteins of the viruses.

“However, there is still a 'window period' during which a donor can be infected, but have negative screening tests. With the use of NAT for hepatitis C, the 'window period' for detection is reduced by 57 days, from an average of 82 days to 25 days,” an FDA report indicates. “For HIV-1, the average window period with antibody tests is 22 days. Antigen testing cuts the window period to approximately 16 days and NAT further reduces this period to 12 days.”

In the clinical trials that supported FDA approvals, a total of 342,729 donations from approximately 48,000 donors collected at 33 plasma-pheresis centers were tested for HIV-1 and hepatitis C. The NAT systems detected a number of HIV and hepatitis infections that would have been missed by previously licensed test methods, confirming the effectiveness of these systems. Additionally, use of the NAT system for HIV will allow Alpha to discontinue antigen testing, although antibody testing will still be done on all plasma donations.

NAT and PCR tests had long been considered experimental, but since 1997 the FDA has encouraged the investigation of the technology in hopes of improving the safety of plasma derivatives and further reducing the risk of an infectious unit of blood being transfused.

The approval came on the heels of Deerfield, IL-based Baxter International Inc.'s voluntary recall of a therapy used to treat burn victims and patients in shock after a PCR test revealed a rare form of the AIDS virus in the plasma used to make the product. [See “Drug recalled for possible HIV-contamination,” CleanRooms, September 2001, p. 1].


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