A controversial area of FDA diagnostics regulation gained renewed attention last week with a citizen petition sent to FDA from clinical laboratories and a speech from FDA Commissioner Margaret Hamburg.

The American Clinical Laboratory Association filed its citizen petition with FDA June 4 reiterating and formalizing its long-held opposition to FDA regulation of laboratory-developed tests. ACLA specifically requested that the agency refrain from issuing planned guidance documents mapping out a regulatory framework for LDTs and that it acknowledge that LDTs are not medical devices as defined by law.

The petition came just two days after Hamburg emphasized FDA plans to regulate at least a subset of the most complex LDTs as a priority during a speech at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. In opposition to the lab industry, manufacturers of lab-test kits strongly support such a move.

ACLA Disputes FDA Authority

LDTs are test services that are performed by the same lab that developed them. They are distinct from in vitro diagnostic test kits that are packaged with instructions and sold to labs across the country, and they are subject to FDA device standards.

Laboratories that offer LDTs are subject to oversight by the Clinical Laboratory Improvement Amendments, under which CMS contractors certify labs to be able to develop and perform complex diagnostic assays. LDTs are also subject to extra requirements by certain states, particularly New York. But FDA has historically not required makers of LDTs to abide by pre-market or post-market requirements mandated for test kits.

In FDA’s view, this has not been for lack of authority, but a result of a long-held practice of enforcement discretion. But the agency says it is ready to start enforcing its regulations in this space as a result of the increasing prevalence of complex, multi-analyte genomic and proteomic assays, and the growing practice of companies that are developing these assays to set up shop as CLIA-certified labs rather than lab-kit manufacturers.

FDA stated more than a year ago that the three draft guidance documents intended to map out an LDT regulatory framework were written and under administrative review, but the documents have yet to see the light of day.

The agency has been moving in this direction for years, and in 2010 it announced specific plans to develop a comprehensive, risk-based regulatory framework for LDTs. (See Also see "FDA Aims To Finalize Framework For Lab-Developed Tests In Near Term" - Medtech Insight, 21 June, 2010..)

The lab industry disputes FDA’s claims of authority, as laid out in ACLA’s petition and in prior arguments from that group and others. The ACLA petition argues that LDTs are not, by law, medical devices because they are not a product or piece of equipment, but are instead “a laboratory’s proprietary procedure for performing the test – essentially its knowledge or know-how.” The group also says that the legislative history of CLIA does not support claims that it was Congress’ intention for LDTs to be regulated by FDA. If gaps are present in current regulations for LDTs, then CLIA should be amended rather than FDA stepping in, ACLA writes.

The citizen petition also argues that FDA regulation would add unnecessary costs and burdens that would detract from public health and would have significant economic repercussions on the U.S. lab industry.

These arguments have been influential in Congress, and opposition from lawmakers has held back FDA efforts.

The agency stated more than a year ago that the three draft guidance documents intended to map out an LDT regulatory framework were written and under administrative review, but the documents have yet to see the light of day. (See Also see "FDA Agrees To Waive User Fees For Reviews Of Lab-Developed Tests" - Medtech Insight, 5 March, 2012..) The FDA Safety and Innovation Act, enacted last summer, requires the agency to provide details of a planned policy to Congress 60 days before issuing a draft or final guidance on establishing a regulatory framework for LDTs.

FDA Framework Efforts Still Alive

But Hamburg’s comments at ASCO signal that the while FDA’s LDT efforts are delayed, they are not dead.

“The risk-based framework we have under development will ensure that diagnostics used in cancer treatment will provide medical professionals with a critical baseline for confidence in the tests they order for their patients,” Hamburg stated. “Our intent in considering what to do about LDTs is to provide for safe and effective diagnostics while promoting innovation and patient access.”

The commissioner specifically referenced the OvaSure ovarian cancer proteomic screening assay, which LabCorp withdrew from the market as a test service in 2008 after FDA warned the company that it required pre-market review. (See Also see "LabCorp Pulls OvaSure, But Charges FDA With Overreaching" - Medtech Insight, 27 October, 2008..)

“Although FDA did not consider OvaSure to be a laboratory-developed test, it was offered as an LDT and thus did not undergo adequate clinical validation before the test was used across the country,” Hamburg said. “Thanks in large part to the involvement of the oncology community, together with FDA, this flawed test was eventually withdrawn from the market, some four months after it had been launched.”

Test-kit manufacturers are anxious for FDA to move forward with the framework, which they believe represents an opportunity for a more level regulatory playing field between their products and LDTs.

It is not clear whether Hamburg’s comments suggest that the three draft guidances (to focus on LDT regulatory oversight; standards for FDA notification and adverse event reporting; and quality system requirements) will be released soon.

An FDA spokeswoman said June 3 that the agency was “not in a place to comment specifically on timing yet.”

Alan Mertz, ACLA’s president, said that the group’s petition was in the works well before Hamburg’s comments at ASCO and that it did not come out of a belief that the framework documents would be released imminently.

“ACLA decided to file a petition several months ago, and work drafting it began in mid-April 2013,” Mertz wrote in an email to “The Gray Sheet.” “ACLA believes that it [is] important to provide all policymakers with a comprehensive piece that lays out the history of LDTs, the value of LDTs to patients and health care, and why LDTs are not medical devices.”

The agency is typically not very quick to react to citizen petitions. For instance, it has yet to definitively respond to a petition filed in 2006 by the Washington Legal Foundation arguing that FDA does not have the authority to regulate LDTs, nor to a 2008 petition filed by Genentech requesting that FDA apply the same standards to LDTs that it does to test kits. (See Also see "Would Expanded Lab-Test Regulation Overstep FDA’s Legal Limits?" - Medtech Insight, 16 March, 2009..)

Test kit manufacturers, meanwhile, are anxious for FDA to move forward with the framework, which they believe represents an opportunity for a more level regulatory playing field between their products and LDTs.

“AdvaMedDx welcomes Commissioner Hamburg’s remarks on the need to pursue a risk-based approach to the regulation of LDTs,” said Andrew Fish, executive director of the group representing kit makers, in a June 3 statement. “These types of tests are increasingly being used to diagnose and guide the treatment of potentially life-threatening conditions, and we believe FDA oversight of all diagnostic tests, regardless of who develops the test, is essential to patient safety.”

[Editor’s note: This story was contributed by “The Gray Sheet,” your source for in-depth coverage of the medical device and diagnostics industry. For more information call 1-800-332-2181. To register for a free trial, click here/ – no credit card needed.]

Lab-Developed Test Regulations In Spotlight With Citizen Petition, Hamburg Speech

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