Challenging the FDA: A History Lesson for DTC Genetics

Last week the FDA sent letters to five personal genomics companies alleging that the companies are manufacturing and selling medical devices without appropriate FDA review. The FDA’s decision to substantially increase its regulatory oversight of some of the most prominent direct-to-consumer (DTC) genetic service providers has met with a mixed reaction. Supporters of the move argue that these DTC products are medical in nature and require more stringent regulatory controls. Critics, including at least one of the companies receiving a letter (23andMe), fault the FDA for adopting a paternalistic stance to personal genetic information and imposing unnecessary regulatory controls.

What’s Next for DTC? In last week’s post, we outlined several possible responses available to DTC genetics companies, including (1) pulling products from market, (2) agreeing to comply with FDA regulatory requirements, (3) modifying products to avoid FDA oversight or (4) challenging the FDA’s regulatory authority over DTC genetic testing products. We also noted the possibility that the FDA’s decision to look more closely at DTC genetic tests could presage increased scrutiny of the genetic testing industry more broadly, including the many tests currently offered without FDA clearance or approval as laboratory developed tests (LDTs).

With the personal genomics landscape shifting seemingly on a daily basis, what should we expect to happen next? Will the FDA follow up last week’s letters with letters to additional personal genomics companies, continuing its current policy of case-by-case regulation? Will it announce some form of industry-wide guidance? Will one of last week’s lucky recipients reveal its response to the FDA? Will we hear more from the Congressional committee investigating DTC genetic testing, which sent out its own letters nearly a month ago, then followed those up yesterday with another letter to 23andMe?

While we wait to see what tomorrow will bring, those interested in forecasting future chapters in the ongoing DTC regulatory saga are advised to take a look back at the FDA’s most recent attempt to shape the regulation of genetic testing.

A Complex Debate. Four years ago the FDA touched off a similar regulatory controversy when it ratcheted up its oversight of a specific type of high-complexity LDT: the in vitro diagnostic multivariate index assay or IVDMIA. On January 23, 2006, in a letter that bears remarkably similarities to the one sent just last month by the FDA to Pathway Genomics, the FDA invited Genomic Health, Inc. to discuss with the agency the regulatory status of its Onco type DX test, a complex genetic test designed to predict cancer recurrence in certain breast cancer patients. The FDA’s letter to Genomic Health was followed in September 2006 by draft guidance (pdf) announcing the FDA’s intent to regulate the entire class of genetic tests it deemed to be IVDMIAs.

The FDA’s initial proposal to regulate IVDMIAs was criticized as being vague, overly broad and unduly burdensome for genetic testing laboratories. The intense criticism resulted in the FDA’s publication of a revised guidance document in July of 2007 (pdf). That guidance was no less immune to criticism, and resulted in the FDA placing the proposed regulatory change on the back burner. Although the FDA has periodically indicated that IVDMIA guidance is still on the table, including earlier this year, it has now been nearly three full years since the FDA last took a meaningful public step in the direction of regulating IVDMIAs. (And, as described in Genomic Health’s most recent 10-Q (pdf), the Onco type DX test remains free from FDA regulation, at least for the moment.)

Why IVDMIA Matters. The history of FDA’s attempt to regulate IVDMIAs matters because it is almost certain to inform the FDA’s current attempt to regulate DTC genetic tests, as well as any attempts by the DTC genetic testing industry to resist that regulation. Most DTC genetic tests have long been considered, just like IVDMIAs, to be LDTs subject to the FDA’s enforcement discretion. In its letters to 23andMe, Knome and deCODE, however, the FDA argued that these tests do not qualify as LDTs because they are “not developed by and used in a single laboratory.” Even if that distinction holds, and DTC genetic tests are not determined to be LDTs, there is plenty to learn from the FDA’s experience with IVDMIAs.

Challenging the FDA’s Authority. Of particular interest are two petitions filed with the FDA concerning the agency’s proposal to regulate IVDMIAs, and its broader authority to regulate LDTs as medical devices. The first petition, filed by the Washington Legal Foundation (WLF) in 2006 (pdf), shortly after the FDA’s initial IVDMIA guidance was proposed, challenges the FDA’s legal authority to regulate LDTs (including IVDMIAs) and argues that the FDA’s approach of case-by-case regulation and informal agency guidance violated the agency’s responsibilities under the Administrative Procedure Act (APA). The WLF petition builds on a similar petition filed by the law firm of Hyman, Phelps & McNamara, P.C. (HPM) in 1992 (pdf) which challenged the FDA’s original assertion that it possessed the authority to regulate LDTs, even as it noted that it intended to exercise enforcement discretion and refrain from LDT regulation at that time.

The HPM petition, which was finally denied by the FDA nearly six years later, and the WLF petition are countered by a 2008 petition filed by biotechnology company Genentech, Inc. (pdf). Genentech’s petition argues that not only does the FDA have sufficient legal authority to regulate LDTs, but that given the potential risks to patient safety the agency should regulate all genetic tests, including all LDTs, rather than limiting its regulatory oversight to IVDMIAs.

If the FDA’s recent attempt to regulate certain DTC genetic testing products is challenged – whether by one of the five companies the FDA singled out or by some other third party – it is likely that many of the same arguments appearing in the HPM, WLF and Genentech petitions will reappear. In particular, questions about FDA’s authority to regulate these products, especially its ability to do so without undertaking notice and comment rulemaking pursuant to the FDA, are almost certain to play a prominent role. (As Kirell Lakhman of The Sample reported earlier this year, the need for APA-compliant rulemaking may be the reason that FDA’s proposed IVDMIA guidance remains on hold.)

While we can predict with some confidence what a challenge to the FDA’s authority to regulate DTC genetic tests might look like, it is far more difficult to predict whether such a challenge will ever actually be brought, let alone succeed. Such a regulatory challenge would be time-consuming and expensive – for both the challenger and for the agency – and, should it proceed into the courtroom, would be stepping into the relatively uncharted territory of consumer genetic testing.

A fight that entails such considerable expense and uncertainty is not one that any DTC genetic testing company will be eager to initiate. Still, for the companies and investors most directly threatened by the FDA’s recent activities, the history of the LDT/IVDMIA debate – and especially the regulatory silence that has followed – may be impossible to ignore.