FDA to scrutinize HPV test linked to false readings

Food and Drug Administration regulators say they will tighten oversight of problematic diagnostic medical tests — including a test used to screen for the virus that causes cervical cancer that was the subject of an investigation by The Arizona Republic this year. That investigation described how laboratories across the country continued to use a test kit, BD SurePath, to screen women for human papillomavirus, or HPV, more than six months after FDA warnings that SurePath can produce false negatives, results that wrongly suggest a woman doesn’t have the virus.

HPV causes nearly all cervical cancers, and a false negative can tell women they are free of HPV when they aren’t, leading to delays in diagnosis and treatment.

But even before the FDA issues the anticipated new requirements, laboratories are challenging the administration’s legal authority to regulate

them. The American Clinical Laboratory Association is petitioning the FDA, arguing that the agency lacks jurisdiction because the tests aren’t medical “devices” under federal law.

However, a leading medical association is backing the FDA’s move.

The dispute focuses on what are called “laboratory-developed tests.” These are tests that don’t have FDA approval. By law, labs can develop their own clinical tests, or use existing tests for non-FDA-approved purposes, so long as each lab conducts a study establishing the test’s accuracy and sensitivity.

One such test involves the off-label use of the BD SurePath kit to screen for HPV. The test is made by Becton Dickinson and Co. of Franklin Lakes, N.J.

As The Republic reported in January, SurePath has FDAapproval for Pap testing, but not for HPV. Some labs switched to another test or restricted their use of SurePath following the FDA’s warning and The Republic’s investigation. But many national laboratories continue to use SurePath to test for HPV, despite the warning — even though national cervical-cancer screening guidelines call for using only FDAapproved tests.

SurePath accounts for about 30 percent of the national Pap/HPV-test market, or about 3 million tests a year, because of its adoption by national chains.

More broadly, the FDA has been raising concerns about laboratory-developed tests as the landscape has changed in recent years, with growing numbers of such tests being developed by national laboratory chains that can roll them out to large numbers of patients around the country.

“There is draft guidance in review with the administration right now, but we don’t have a time frame for when it will come out,” FDA spokeswoman Susan Laine said Tuesday.

However, Adjoa Adofo, a spokeswoman for the laboratory association, noted that the FDA has 90 days to respond to the association’s petition, meaning it must reply by Sept. 3.

Laboratory-developed tests currently are regulated under federal laws known as the Clinical Laboratory Improvement Amendments, or CLIA. They are overseen not by the FDA, but by the Centers for Medicare and Medicaid Services, or CMS.

“We believe that CLIA should continue to regulate laboratories,” Alan Mertz, president of the American Clinical Laboratory Association, said Tuesday. He said the association supports strengthening the CLIA regulation “to make it clear it has oversight over the clinical validity of all laboratory-developed tests.”

As The Republic has reported, federal law doesn’t require labs to provide their validation studies for lab-developed tests to the CMS. That agency outsources its oversight to private organizations such as the College of American Pathologists. The law states that outside auditors “may” review such tests.

Gene Herbek, president-elect of the College of American Pathologists, said in a written response to questions that the college agrees with the FDA proposal to regulate some laboratory-developed tests.

“While we believe oversight for lowand moderate-risk laboratory-developed tests can be strengthened within the existing regulatory framework,” based on the federal CLIA laws, “we also favor requiring that the FDA review all high-risk, laboratory-developed tests.”

Herbek said the college supports a graduated system of review based on a test’s potential risk to patients.

“We view HPV like any laboratory-developed test as regulated by the FDA and CMS,” he said.

As The Republic reported, critics have argued that under the current system, manufacturers can’t give labs guidance on how to use their products for a non-FDA-approved purpose. For competitive reasons, labs don’t share validation studies, and each lab has to come up with its own methods for using the tests.

Mertz argues that the FDA doesn’t have adequate staffing to review even a 10th of the 800 to 1,000 laboratory-developed tests that are created each year.

“The whole CLIA program is paid for by labs; we’re willing to pay more to have better review under the CLIA system,” he said.