Genetic testing garners lawmaker’s attention

WASHINGTON D.C.—Targeted toward preventing the U.S. Food andDrug Administration (FDA) from revving up its regulation oflaboratory-developed genetic tests, U.S. Rep. Michael C. Burgess (R-Texas) hasintroduced legislation aimed at blocking what he believes is overzealousgovernmental bureaucracy to the detriment of the multibillion-dollar healthcarebusiness, pharma profits and patients.

Burgess introduced H.R. 3207 on Oct. 14. Four days later,the bill was referred to the House Subcommittee on Health, where it remained asthis issue went to press.

The bill would allow a test developer to claim that alaboratory diagnostic test (LDT) is a "companion diagnostic test" intended tobe used for "specifying the use of a drug or biological product for therapeuticpurposes," and thus falls under the Centers for Medicare & MedicaidServices (CMS) for review, rather than the FDA.

According to the FDA, the purpose of genetic tests includespredicting risk of disease, screening newborns, directing clinical management,identifying carriers and establishing prenatal or clinical diagnoses orprognoses in individuals, families or populations. More than 350 U.S.laboratories have listed themselves on a voluntary website that providesinformation about laboratories offering genetic tests, but there may be as manyas 700 laboratories offering such tests. The FDA is working on releasing aseries of guidelines to lay out its regulatory plan for LDTs.

H.R. 3207 would expand the CMS' regulatory authority bygranting it the ability to assess whether marketed LDTs are "clinically valid"or can accurately measure or predict disease. Currently, under the ClinicalLaboratory Improvement Amendments (CLIA), the CMS can only certify that testsperformed in a lab are "analytically valid," or can measure the analytes orsubstances that they were developed to measure.

The bill would also mandate that the agency overseedirect-to-consumer testing firms that work with external labs to analyzecustomer saliva samples and deliver genetic test results to consumers withoutthe involvement of a doctor.

Burgess starting working on the legislation in 2007,believing that increased FDA scrutiny would be "far too restrictive," he tells ddn. Many tests are developed in the lab, and "anunintended consequence will be the difficulty in getting through the process ina timely manner … and costly delays would cause the U.S. to lose itscompetitive edge," he says.

On Dec. 5, 2008, Genentech filed a citizen petition to theFDA stating that given the "recent proliferation" of lab-developed tests making"unsubstantiated and … inaccurate or misleading claims," it is critical for theFDA to regulate all such tests and to "provide much needed clarity" over itsregulatory plan.

Genentech urged the agency to regulate all in-vitro diagnostic tests that guide therapeutic decisions,including tests that help clinicians decide to give a patient a certain drug.

"Given the potential risks to patient safety associated withuse of diagnostic tests that make unsubstantiated claims intended to guidespecific drug or biologic therapeutic decision-making, it is imperative thatthe FDA exercise its regulatory authority consistently," the citizen petitionstates.

Genentech has support from Johns Hopkins' Genetics andPublic Policy Center, but other diagnostic labs have thrown their support toBurgess, who emphasizes the economic and health-related effects of waiting forFDA approval.

"Genetic tests have the potential to identify risk factorseven before a patient gets sick and can help tailor treatments to eachpatient's unique needs," Burgess says. "Adding additional and duplicative FDAregulations to industries that are not under the agency's jurisdiction willfurther burden an overstretched institution that cannot currently process theirsubstantial backlog due to their own regulations being a hindrance."

Burgess' bill "will provide clear regulatory certainty,foster innovation, save American jobs and ensure patients have access to thebreakthrough medical products of tomorrow," the congressman says.

But Genentech says things have changed, and the FDA has tokeep up with the times. First, the number and type of lab-developed tests havegrown significantly in recent years, its petition states. Lab testshistorically have been more focused on rare diseases or conditions, but nowaddress more "serious and life-threatening" circumstances, the company argues.In addition, the so-called "home-brew" tests are also moving towardpersonalized medicine, Genentech contends.

Efforts to design drug therapies to individual patientsbased on their genetic characteristics have become more popular, too, Genentechsays, with 10 percent of all FDA-approved drugs containing some pharmacogenomicinformation in the labeling.

For example, before Genentech's breast cancer drug Herceptin(trastuzumab) can be prescribed, patients must be tested and exhibit anoverexpression of the HER-2 protein. There are a number of FDA-cleared testkits and lab-developed tests used for this purpose, Genentech states in itspetition.

The CMS regulates lab practices and protocols under CLIA,and conducts periodic sample testing and inspections. But for tests that helpguide therapy, "it is critical that they are accurate, reliable and clinicallyvalid," Genentech states, adding CLIA validation is not enough.

CLIA "is intended to ensure the quality of conditions underwhich the tests are performed, not the safety and effectiveness of the teststhemselves," the Genetics and Public Policy Center stated in its Dec. 15, 2008comments supporting the citizen petition.

The FDA's "current failure to regulate these genetic[lab-developed tests] threatens public health, creates serious inequities inthe marketplace that disincentivize innovation and impedes the success of personalizedmedicine," the Genetics and Public Policy Center wrote in its public comments.

The regulatory pathway of a test should depend on whatclaims are made about it, not where the test is produced, Genentech argues. Thecompany's petition calls on the FDA to establish, through rulemaking, standardsfor the development of diagnostic tests that guide therapeutic decisions, andto explain what information test makers must submit to FDA prior to marketing.

The FDA should also take immediate action to remove from themarket tests that make clinical claims without strong scientific evidence,Genentech says.

The line has been blurred over time between lab-developedtests used as part of a lab testing service, regulated by CMS under the CLIAprogram, and commercial test kits made by manufacturers and regulated by theFDA, the citizen petition states.

Siding with Burgess, the American Clinical LaboratoryAssociation (ACLA) called the Genentech petition "ill-informed."

Many clinical laboratory testing companies are concernedwith Genentech's call for all laboratory tests to be regulated, CombiMatrixMolecular Diagnostics CEO Mansoor Mohammed has stated.

CombiMatrix, Monogram Biosciences and Genzyme were all namedin Genentech's petition as examples of firms that market tests with clinicalclaims not vetted by the FDA.In response, the companies argue that FDA review is not theonly way to establish the clinical validity of a product.