LDTs


How to Improve Lab Tests in the Absence of FDA Regulation?

Rubbing shoulders at molecular medicine conferences these days one senses a sigh of relief when you talk about laboratory developed tests (LDTs). With the FDA’s decision to put regulation on hold coupled with the expected confirmation of Scott Gottlieb as FDA commissioner, those in the lab testing business seem to be confidently settling back to the status quo. And those who were arguing that all we need is a “beefed up” CLIA to hold labs to better testing standards don’t appear to be motivated to do so anymore.

Several questions arise when it comes to LDTs. First of all, if regulation was truly important for enabling this revolution we call precision medicine, then why couldn’t the Obama administration get it issued? In other words, is the status quo so bad? Secondly, without the FDA even threatening to regulate, will we see the “beefed up” CLIA that many labs argued is the best way forward? Without the stick of the FDA, is the carrot gone too?

Russell Garlick is the CSO of SeraCare, a private company that has worked to improve clinical laboratory standards for over thirty years. The company recently added a new business unit for precision medicine diagnostics, and Russell was brave enough to come on today and address these questions.

As for the status quo being good enough, Russell isn't happy.

“Many of the organizations undertaking clinical trials to recruit oncology patients have lost confidence because LDTs in one geography of the United States don’t perform the same as in other parts of the United States,” he says.

Russell has worked many years with labs on IVDs--the already regulated group of diagnostic tests. He sounds disappointed that the FDA has dropped their focus on LDTs, but is hopeful that existing organizations, such as the College of American Pathologists, or even private companies such as SeraCare might step in and seize an opportunity to improve things.

“There’s a lot of status quo. And frankly it’s a little bit disappointing,” he says, “because the laboratories can benefit from [improved standards]. It’s that inertia to do something new and different."

With FDA Guidance on LDTs Still Not Out, What Are Labs Doing?

As we get closer to the election and the end of 2016, the debate over LDT regulation has gone quiet. At this time last year, there was one hearing after another, first in the Senate, then in the House. The FDA’s Jeffrey Shuren was called before congress and drilled over the nuances of the guidance as well as asked when it would be released. He said, in the first half of 2016.

Though there has been no guidance released, the FDA has continued sending letters out to individual labs, requesting certain LDTs be approved before the labs market them. In March of this year, the FDA put a couple labs and two Texas hospitals on notice that were marketing “high risk” unregulated diagnostics. This surprised many in the laboratory community. These tests were diagnostics to detect the Zika virus, and any delay could negatively impact public health. The FDA told the labs they expected them to submit a request for emergency authorization (EUA).

So what are labs across the country doing? What are they supposed to be doing? Are they shying away from developing new LDTs? Are they proactively working to develop 'clinical validity’ for their tests, something they haven’t had to do under CLIA (the current regulatory statue for labs), but would be required to pursue by the FDA?

Some lab directors, such as today’s guest, say they haven’t changed a thing and are in “wait and see” mode. John Longshore is the Director of Molecular Pathology for the Carolinas Pathology Group and Carolinas HeathCare System, an integrated health network with more than 40 hospitals. He’s optimistic that laboratories are being heard on Capitol Hill and that it won't come down to FDA guidance. Referring to a recent Senate HELP meeting in September 2016 on the topic of LDTs, he says he's confident "that we will have regulation through congressional legislation rather than FDA guidance.”

The debate continues . .

Do Alternate Proposals to Regulate LDTs Stand a Chance?

As the FDA works away on final guidance for regulating LDTs, various professional groups unhappy with the course of the FDA have put together and hurried their own proposals up to Captiol Hill. The Diagnostic Testing Working Group (DTWG) has had their proposal drafted into legislation which has already been revised once in the House Energy and Commerce Committeee, while proposals from the College of American Pathologists (CAP) and the Association of Molecular Pathology (AMP) have been presented to both the Senate and the House. Various other groups, including the American Medical Association (AMA) and the American College of Medical Genetics (ACMG), have either signed on in support of one of these proposals or are independently lobbying Congress as well.

What chance do these organizations have at persuading Congress to step in and change the course of LDT regulation?

Here to help us parse through these options and get a sense of congressional reception is Scott McGoohan, the new Director of Science and Regulatory Affairs at BIO. Scott says that all of the proposals fit into “three buckets:”

First, there’s the guidance that the FDA is working on which will bring regulatory oversight to thousands of tests which heretofore have not been regulated.

Second, there’s the CAP and AMP proposals which call for the modernization of CLIA which will include increased oversight of laboratory developed tests. These proposals reserve a small set of high risk tests for FDA oversight.

And third, there’s the DTWG who are hoping to get Congress to establish a new center at the FDA for all in vitro diagnostics.

One thing is for sure, says Scott. Whichever proposal wins out, “the general sense is that there will be a change coming with increased regulatory standards for laboratory developed tests.”

Scott joins BIO at a very busy time in Washington for biotech policy. The House has passed the 21st Century Cures Initiative and the Senate Help Committee is doing active work on their health innovation agenda.

“It is an incredible time [in Washington] and an incredible opportunity for transformative regulatory change,” says Scott.

Certainly not all regulatory change is transformative, as Scott reminds at the conclusion of today's show with a story about a crazy bill in Wisconsin.

Still Unhappy with FDA’s Plan to Regulate LDTs, Professional Lab Groups Go Direct to the Senate

It's no secret that America's molecular testing laboratories by and large are worried that the FDA's plan to regulate laboratory developed tests, or LDTs, will severely harm patients. Now they have a new proposal which they are taking directly to Capitol Hill.

Roger Klein is the Medical Director of Molecular Oncology at the Cleveland Clinic. He’s also serving as the spokesperson for the Association for Molecular Pathology (AMP) on the controversial topic of regulating LDTs.

Several weeks ago Roger was in Washington arguing before the Senate’s HELP Committee presenting them a newly drafted proposal that he, AMP and other professional groups feel to be a better solution to regulating LDTs. Currently the FDA is on a path to issue their final guidance for LDTs in a way that treats these lab tests as medical devices.

Klein and the professional lab groups are highly concerned that the FDA’s proposed regulation will be too restrictive and will curtail an industry just as it is blooming. Their proposal: to beef up the existing CLIA regulation so that it includes determining a test’s clinical validity. So far, CLIA has been concerned only with the analytical validity of a test.

But wait a minute, haven't we heard these arguments before? Roger explains in today’s interview that his proposal before the Senate is much more complete than what they had in January.

Myriad Settlements Mark End of an Era: Antoinette Konski on Gene Patents

This past month one of the most successful genetic testing companies, Myriad Genetics, has been settling one gene patent case after another. Also, the FDA has been attempting to regulate some very complicated lab testing. So we figured we better talk to a lawyer about the devil in the details. We’ve chosen Antoinette Konski of the law firm, Foley and Lardner.

Antoinette agrees that the Myriad settlements indicate the end of an era with gene patents. So how is she advising her life science clients in securing IP?

Antoinette is also interested in the regulation of diagnostics. What does she have to say of the FDA’s recent move on LDTs, particularly with regard to next-gen sequencing tests?

January 2015: This Month in Biotech with Theral Timpson

January 2015

In our new show format, host Theral Timpson engages three guests in some lively discussion about January's hottest biotech news.

Guests:

FDA Will Take Time to Digest Comments on LDT Guidance, Says Liz Mansfield

We’re very pleased to have Liz Mansfield of the FDA on the program to finish up our current Special Report on LDTs Series. Liz is part of the team at the FDA working on the new guidance for the regulation of LDTs, and she was at the recent meeting the FDA held to receive community feedback.

Today we get into some of the details of that feedback. Did Liz and the FDA hear any new issues that they had not already considered? What about the BRAF testing that was mentioned in the meeting? Is there a risk that patients will lose access to some important tests?

In a recent interview in this series, Amy Miller of the Personalized Medicine Coalition urged the FDA to push out their timeline for guidance. In this very open and candid interview, Liz responds that there is no set date for final guidance. “We will take the time it requires to go through them [community comments], analyze them, and decide what we need to do in response and finalize the guidance,” she says. "There is no rush to do that."

Podcast sponsored by: This Month in Biotech - Coming January 30th!

Future of Personalized Medicine at Stake, says Amy Miller of PMC about LDT Regulation

Amy Miller is the Executive Vice President for the Personalized Medicine Coalition (PMC) and joins us in our Special Report on LDTs Series. Though the PMC does not have a position on whether the FDA should regulate LDTs, Amy says that the stakes could not be higher.

“We see the future of personalized medicine is at stake. We urge the FDA to get this right the first time so that personalized medicine can continue to improve the quality of care that patients currently have access to,” she says at the outset of today’s interview.

Amy and her organization represent stakeholders from every side of the current debate on LDT regulation. They hear from industry, payers, providers, and labs. Amy is asking the FDA to step back, take time to respond to the recent community feedback conference, and publish supplementals that will provide more clarity to the guidance, such as how risk will be determined. Amy and the PMC would also like to see the FDA “harmonize” their language with that of CLIA, the current system in place for lab regulation.

“I absolutely think the timeline has to be pushed out,” she says. “The community needs another crack at that framework."

Current Version of LDT Draft Guidance Means Much Fewer and Lower Quality Tests for Patients, Says Elaine Lyon of ARUP

Guest:

Elaine Lyon, Former President, AMP; Medical Director of Molecular Genetics, ARUP Laboratories Bio and Contact Info

Listen (4:37) What is at stake here?

Listen (6:16) Is your message being heard?

Listen (8:03) Current guidance would shut down two thirds of current tests

Listen (2:33) What would be the best outcome with guidance?

Today we begin a Special Report on LDTs Series. LDTs, or Laboratory Developed Tests, have been used in healthcare for years to aid in diagnosis and treatment of illness. In the age of genomics, the number of these tests has boomed and become ever more complex. It was not until last year that the FDA, who had long been suggesting it, put out the first version of a draft guidance, or terms of regulation for LDTs. Implementation is expected to take about ten years.

Last week the FDA held a community feedback workshop at the NIH and heard from dozens of stakeholders from around the country. Today we’re joined by one of the speakers at the workshop, Elaine Lyon, the Medical Director of Molecular Genetics at ARUP Laboratories. Elaine was the President of AMP or Association of Molecular Pathologists for 2014.

Elaine joined us on the program last year just before the FDA issued the guidance to make the argument that actually what her lab performs are LDPs or Laboratory Developed Processes and not tests. Because they are processes that require a medical professional, this service is more akin to the practice of medicine and therefore not to be regulated by the FDA, she believes.

Nonetheless, guidance has been issued, and it looks like it will go forward. Elaine and other stakeholders around the community have given their input. Will they be heard? What is Elaine’s best hope for an outcome that will work for laboratories across the country and satisfy the FDA?

Stay tuned for interviews with Liz Mansfield of the FDA and the feedback of other stakeholders in this ongoing series.



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