The diagnostic testing business is taking off, moving into genetic testing and more direct-to-consumer (DTC) marketing, and raising red flags all over. Congress is investigating charges that consumer test kits are unreliable or outright fraudulent. FDA is concerned that inaccurate test results could alarm patients or camouflage real health problems. It is looking to regulate these products more aggressively to protect public health, but faces opposition from diagnostic lab operators and marketers of laboratory-developed tests (LDTs). A real concern is that too-heavy regulation could discourage development of new tests vital to personalized medicine. Pharma companies are watching closely to see how these issues may impact drug-diagnostic co-development and medical product marketing.

Jill Wechsler

FDA advised Pathway that its test first must be evaluated and approved for market, and Walgreens cancelled the deal. Soon after, FDA sent similar letters to other leading consumer genetic testing companies—deCODE Genetics, 23andMe, Navigenics, Illumina, and Knome. The firms maintain that FDA review is not appropriate for LDTs, but some have welcomed the move as a way to expand product acceptance and use.

Tricky Rules

A murky, bifurcated regulatory regime for test laboratories makes LDT monitoring a tricky issue. FDA regulates as medical devices the equipment used in test laboratories and certain consumer test kits, such as home pregnancy tests and glucose monitors; the Centers for Medicare and Medicaid Services monitors and certifies test labs under the Clinical Laboratory Improvement Amendments (CLIA) of 1988. FDA has maintained a hands-off approach to LTDs developed and used within labs. However, the proliferation of more complex tests marketed directly to consumers is prompting a new look, particularly at companies using the LTD label to avoid FDA oversight. Moreover, manufacturers of those commercial tests that FDA reviews complain that the LDT loophole creates an unlevel playing field.

These issues were discussed at a two-day FDA public meeting in July on options for LDT regulation. Staffers from CDRH's Office of InVitro Diagnostics (OIVD) summarized FDA's history with LDTs and its efforts to ensure the quality of test components as more complex products have emerged. While the genetic tests marketed a few years ago emphasized "nutritional" analysis and were considered fringe products, DTC genetic tests today claim to predict risk for disease. Elizabeth Mansfield, OIVD director of personalized medicine, noted that LDTs have evolved to be more like commercial diagnostics, and that the public needs greater assurance that the tests are reliable, that design and software is validated, and that the products are safe and effective.

Representatives of clinical laboratories insisted that CLIA provides effective oversight of their operations, and that they don't want that to change. LDT manufacturers agreed that FDA regulation is not needed and warned it would stymie innovation and experimentation. Everyone urged a clear pathway for small volume tests, particularly those that diagnose rare diseases. FDA officials acknowledged that flexibility is needed to spur development of innovative diagnostics for unmet needs, and the importance of achieving balance between ensuring the accuracy and reliability of diagnostics, and encouraging labs to invest in new assays. Diagnostics are the "linchpin of personalized care," Mansfield commented.