To regulate, or not to regulate--that has been the question with LDTs, or laboratory developed tests.
Last Thursday, July 31, the FDA gave their answer when they notified Congress that in the next 60 days draft guidance on LDTs would be given. The bell has been rung. The other foot has dropped. The “Anticipated Details” can be seen here.
Regulation has been an important topic here at Mendelspod. Later this week, we’ve booked an interview with Liz Mansfield from the FDA to explain their recent move, and just how she expects it to play out. In the meantime, I’ve reached out to, or followed, some of the guests we’ve had on the show who have argued both for and against the regulation of LDTs.
In her blog on Thursday, “FDA Releases the Kraken”, Mya Thomae, CEO of the regulatory consultancy, Myraqa (recently acquired by Illumina), admits she had become quite pessimistic that the guidance would ever make its way into the light. After the FDA sent 23andMe a letter last November, Mya told me on the program that she’d become hesitant about the issue because she “lost several bets on when the FDA will regulate LDTs.”
“I was a naysayer on this recently and FDA has shown my pessimism to be premature. And I'm very happy to be wrong this time. . . . I’m still working through the document, but at first and second read, it appears FDA has had ample time to prepare themselves for the arguments against regulating LDTs. Those opposed to regulation will need to step up their game.” Mya writes.
It’s been common gossip in the industry that the FDA had the guidance written up for some time, awaiting the go ahead from the Obama administration. Just last month, five Democratic senators wrote a letter to the Office of Management and Budget urging that the guidance be released.
The folks at Roche have long been calling for the FDA to increase regulations of LDTs and thereby create a “more level playing field” in the industry. Roche has spent big time resources gaining FDA approval for their tests only to be challenged in the market with LDTs that are not standardized and have not undergone a similar level of analytical and clinical validation.
Walter Koch is VP of Research at Roche Molecular Systems and has argued for more regulation here at Mendelspod. I expected to find Walter with an open bottle of Champagne on Thursday, but instead found him cautious.
“I expect there will be some resistance to this,” he said with characteristic understatement.
When we talked, he was about halfway through the inch thick stack of guidance. Walter says the path is anything but straight forward. The action plan outlined in the guidance would take nearly a decade to fully implement. The FDA says they’ll be moving forward based on risk, but won’t even have the definitions for the three classes of risk for 18 months after the guidance is finalized.
Why wasn’t Walter more ebullient about the fact that labs around the country won’t be able to offer high risk tests, such as HER2 and BRAF without FDA approval?
“We're happy to see some movement on this. But it’s very complicated,” Walter said. He doubts that labs which offer LDTs competing with FDA approved tests will stop offering them until forced to do so.
Furthermore, there is still much up in the air about how the FDA should handle panels, or groups of tests, let alone a whole genome test.
“What about the Foundation Medicine test?” he wondered aloud.
Foundation Medicine’s Foundation One test has become popular with oncologists because rather than test one marker at a time, such as the KRAS gene, the test analyzes 200 of the most common molecular abnormalities in tumor samples and can help doctors in choosing treatment.
In his post announcing the FDA action, Forbes writer, Matthew Herper, felt the news significant enough to warn Illumina investors to “watch closely, as its machines are now used by virtually all players who are doing this type of work.”
Illumina declined comment.
The complexity of the task ahead for the FDA has been pointed out by those opposed to regulation of LDTs. We recently featured a geneticist from ARUP Laboratories in Salt Lake City and president of AMP, or the Association for Molecular Pathology, Elaine Lyon, on the program where she argued that, actually, what her lab offers is more of a service than tests and should be called LDPs, or Laboratory Developed Processes, not LDTs.
I reached out to Elaine on Thursday and she wrote back the following:
“If the proposed guidance stands, it certainly has the potential to limit the access of medically necessary procedures which is why AMP is talking with the FDA to educate them on the distinction between LDPs and in vitro diagnostics, which are tests manufactured and shipped to customer laboratories.”
As for how this action by the FDA might impact their business at ARUP, Elaine told me that the affect is unknown yet, “but it could limit the number of new or improved tests that we develop and offer. It may also be a disincentive to improve an FDA cleared assay (i.e. perform off-label) for our patient population.”
Another group not happy about the new guidance is ACLA, or the American Clinical Laboratory Association. Their president, Alan Mertz, has been on the program arguing that LDTs are regulated by CLIA and this is sufficient. In a statement released within hours of the FDA’s notice, Alan wrote:
“To the extent that stakeholders have concerns about possible regulatory gaps under CLIA, ACLA has long supported enhancing the CLIA regulatory framework, rather than impose an additional layer of regulation based upon a different statute designed for manufactured products rather than laboratory testing.”
There will be much more written over the coming weeks as more attorneys and experts parse their way through the documents. I heard one industry executive on Friday say that he was waiting for a translation of the guidance from his attorney, but was happy the FDA had “chosen not to include DTC testing.”
However, the language in the guidance on DTCs is not that clear. In a post at the Genomics Law Report, Jennifer Wagner takes issue with DTC comment in the document after pointing out that it was buried in a footnote. It reads:
“FDA generally does not exercise enforcement discretion for direct-to-consumer (DTC) tests regardless of whether they meet the definition of an LDT provided in this guidance. Therefore, the enforcement policies in this guidance do not apply to DTC tests, and the FDA’s usual enforcement policies apply to DTC tests."
Jennifer reminds us that “exercise enforcement discretion” is FDA jargon for choosing not to regulate something that the FDA has authority to regulate.
“So the FDA is saying here--hold on for a jarring double negative--that it does not choose not to regulate DTC tests, and that consequently, DTC tests fall under “usual enforcement policies”? The FDA asserting authority over DTC tests and reconsidering its enforcement discretion is one thing, but rewriting the regulatory history is quite another,” she writes.
Finally, I chatted with Cliff Reid, the CEO of Complete Genomics, which is now owned by the Chinese genomics powerhouse, BGI. As a guest here at Mendelspod Cliff has asserted that genomic medicine could very well take off overseas before it does in the U.S. FedEx and the internet are available everywhere around the world, he points out, and it’s very easy to order tests abroad.
“The FDA must be careful here. In today’s global economy, by over regulating, the FDA might end up deregulating,” he said.
It’s an ongoing story, and one we will be covering closely. Congress went on recess beginning August 1 (was guidance released the day before the recess on purpose?) until after Labor Day. Support and resistance to the guidance are expected to fall roughly down political lines with Democrats favoring and Republicans opposed.
Stay tuned for our interview with Liz Mansfield later this week. And please send in your own comments to the news via email or the comment section below.