Remarks at the American Clinical Laboratory Association Annual Meeting March 6, 2018

Speech | In Person

• Speech by: Scott Gottlieb, M.D.

Remarks by Scott Gottlieb, M.D.
Commissioner of Food and Drugs
American Clinical Laboratory Association annual meeting
Washington, D.C.

(Remarks as prepared for delivery)

Thank you for having me here today.

It’s a pleasure to speak with a group that’s done so much to support laboratory services. And whose members are working every day not only to deliver those critical services; but to also innovative ways that can benefit our entire health care system.

As you all know, some of the most exciting innovations in health care today are happening in clinical laboratories.

We’re seeing innovations that hold the promise of less invasive testing, earlier and more reliable diagnoses, more focused treatment -- and ultimately, better patient outcomes.

For example, there are tests today that can provide cancer diagnostic information by analyzing tumor DNA in a blood sample. This is information that, in the past, could be obtained only through tissue biopsies. These tests – sometimes called “liquid biopsies” – could make it possible to identify patients with specific cancerous mutations in much less invasive ways.

Today, we’re also seeing diagnostics based on next generation sequencing, or NGS, which have the potential to detect a high number of genetic mutations with a single run of the test.

Given their detection capabilities, such tests can have broad uses in patient care. This innovative technology has enormous potential to help patients learn more about their diseases and better inform their health care decisions. We’re just beginning to develop the full utility of these kinds of advances.

In many respects, innovations like these are just as important as the development of new drug treatments and cures.

And I know many of you are proud of the work you do to deliver quality, reliable, in vitro diagnostic tests and test services.

As test developers innovate and the market evolves, we also need to make sure that our regulations are keeping pace.

At FDA we’re working hard to make sure that as inventive new tests come to us for review, we have the right tools to evaluate cutting-edge technologies. And we have the right processes in place so we can do our job of reviewing for clinical and analytical validity when we’re asked to; so important new diagnostic tools are more quickly adopted into clinical practice.

FDA has recently adopted new approaches to its review of diagnostics.  These new policies recognize that we have unique opportunities to reform and innovate as we consider the right role for FDA with respect to laboratory-developed tests.

As I’ve said before, I believe comprehensive legislation is the right way to address these issues. 

Meanwhile, over the past few years, we’ve seen more and more LDTs coming forward and seeking FDA review.

One obvious reason is that a test that receives FDA marketing authorization has met important standards for analytical and clinical validity. And these test developers want patients and providers to know that.  

But let me tell you what else I think is going on.

Over the past few years, FDA’s device center has proposed changes to the premarket review of diagnostics that are better tailored to review of LDTs; making the process more efficient.

A key one is the pre-cert pilot.

Although you’ve probably heard me talk about pre-cert in relation to digital health; you should know that the concept was first used to review DTC genetic health risk tests.

In the setting of these DTC tests, we realized that if we had enough confidence in the quality of a lab’s underlying system, we could exempt from premarket review many individual tests that met pre-specified standards. And we could better leverage post-market data to make our processes more efficient.

The pre-cert approach to laboratory tests is just one way that changes to our device program can improve the regulatory experience for test developers who come forward and pursue FDA review, and for the FDA reviewers.  We’re seeing increasing interactions and inquiries about the path to FDA approval. And our staff is working hard to address the unique concerns of the lab community as they pursue FDA review of their tests.

In the current fiscal year alone, several more LDT developers have come forward with premarket submissions to the agency. And we’ve also received more than a dozen pre-submission requests.

That’s not all we’ve done.

I want to highlight two other important advances in our approach to diagnostics review that I believe show FDA stands ready to promote innovation in the LDT space. The first is qualification of New York State Department of Health as a third party reviewer. The second is the agency’s flexible, modern approach to review of next generation sequencing or NGS.

The New York State accreditation means that labs whose tests have been approved by the NY Health Department – including laboratories with advanced NGS-based tumor profiling tests – do not need to submit separate applications to FDA. Instead, they can choose to request that their NY State application, and the state’s review memorandum and recommendation be shared with FDA for possible 510(k) clearance.

The third-party accreditation program is designed to reduce the burden on test developers and streamline the regulatory assessment of eligible innovative products. Going forward, we hope that additional accredited, third-party reviewers will become eligible to conduct reviews; and make recommendations to FDA, and provide even more options to test developers.

On the NGS front, we’re developing several policies designed specifically to improve the development and review of advanced NGS technologies. To take one example, we recently provided public information describing the three-tiered approach that FDA is taking to our review of NGS oncopanel tests in order to minimize the burden on developers.

Under this approach, we’re communicating with developers about the flexibility they have in developing analytical and clinical evidence to support marketing authorization, depending on the type of claim being made.

The evidence to support a companion diagnostic can be different from the evidence to support tests that identify cancer mutations with evidence of clinical significance. And this can be different than the evidence needed to support tests that identify cancer mutations with only potential clinical significance.

By communicating clearly, we hope to enable less burdensome review and better-informed development programs.

We’ll also be providing other information soon to help NGS developers, including final guidance on FDA’s broader, and more flexible regulatory approach to all NGS tests.

We’re developing policies that will permit more tests to be exempt from the burdens of premarket review. For some tests, we may be able to establish initial controls that provide a reasonable assurance of analytical and clinical validity.

We’re also looking into new, innovative approaches to demonstrating analytical and clinical validity.

For example, a developer may be able to demonstrate analytical validity by showing that its test conforms to FDA-recognized standards – perhaps including standards established by the scientific community or standards development organizations.

And, to help us implement this approach, while making sure it keeps current with the science, we plan to qualify third party databases that could be used to help establish clinical validity.

For next generation sequencing, in particular, this could include our adoption of ClinGen as a reference database. This is a database maintained by NIH that aggregates information about genomic variation and its relationship to human health. Under this approach, a new NGS test can rely on a reference database to help demonstrate clinical validity.

We're closely following all the work in this space and leave the door open to other databases, in addition to ClinGen, to qualify.

As we continue these efforts, we hope to work with a collaborative community of stakeholders. This will include developers, clinicians, and patients. All who could help us assess the evolving science and make recommendations about clinical validity. Assessments that could be used to support FDA premarket review, or to avoid premarket review altogether.

To facilitate these policies, and better protect the public health, we’re continuing to look for innovative ways and new pipelines of data to better understand LDT performance.

This includes investigating the use of real world evidence. It also includes our efforts to advance the utility of technologies such as biosensors, machine learning and artificial intelligence.

We’re starting to see tangible benefits from these changes. Last November we authorized the marketing of two NGS-based LDTs for which developers came forward and requested FDA review. These tests are capable of detecting hundreds of genetic mutations by testing a single solid tumor, and thus differ from many other cancer diagnostics, which are designed to detect just one cancer biomarker for use with a single drug.

As a result, they’re powerful tools that can generate important new information to help guide treatment options for cancer patients. One of these tests also can be used as a companion diagnostic to identify patients who may benefit from specific FDA-approved treatments for a range of cancers. It can detect mutations for which the use of different FDA-approved treatments would be appropriate; to guide treatment decisions.

These are significant advances than can improve medical outcomes for patients. They have the potential to reduce health care costs. And streamline care. To help make sure that patients have access to valid tests based on this technology, we’re adopting new approaches to work individually with developers to use the least burdensome approach to reviewing their tests.

Let me come back to NGS to provide some more detail on these efforts. In approving one NGS-based test last November; we leveraged two policy efforts – FDA’s Breakthrough Device Program and Parallel Review with CMS – to expedite access.

Through the combined impact of these two policies, the test developer was able to secure FDA approval, as well as an immediate proposed Medicare coverage determination, within six months of the FDA receiving the product application.

To make this happen, we worked closely with the developer to help it enter FDA’s new Breakthrough Devices Program.  The Breakthrough Devices program builds on FDA’s Expedited Access Pathway Program, which was established in 2015 and codified and expanded in 2016 under the Cures Act. This program is available to developers of certain devices, including tests that provide more effective diagnosis for life threatening or irreversibly debilitating diseases; and for which there are no approved or cleared alternatives, or in situations where the test offers significant advantages over existing alternatives.

In these cases, FDA staff works closely with product developers in this program to provide guidance on efficient development and to help expedite evidence generation and the agency’s review.

In addition, our relatively new Parallel Review program offered a further opportunity to accelerate patient access.

For diagnostics submitted under this program, FDA and CMS concurrently review for marketing authorization and coverage to help reduce the time between the two agencies’ decisions.

The two agencies also work with sponsors during the development process to provide guidance on the evidence they will need to develop to support the agencies’ separate decisions.

By reducing, or even eliminating, the lag between approval and coverage decisions, more patients will hopefully see the benefits of innovative new diagnostics on a faster timeline.

As we modernize to better accommodate the review of these and similar new technologies, we’re driven in part by the need to adapt to changes in the market. In the 1970s, when Congress first authorized FDA to regulate IVDs as devices, only a small subset was laboratory-developed tests.

Back then, LDTs were relatively simple tests that were often used for patients in the same institution that was delivering health care to them. In that market, there was less of a need for FDA oversight. So FDA generally didn’t enforce the requirements applicable to in vitro diagnostics to the LDTs. This includes the pre-market review requirements.

The landscape now is far different. LDTs are not a mom-and-pop industry anymore. Some of the most sophisticated, innovative, and important tests on the market today are LDTs.

And they’re often available to large, nationwide populations.

As I’ve described, the LDTs we’re seeing today are used to diagnose common and serious medical conditions, including heart disease, cancers, and a range of genetic diseases.

We know LDTs are being used to guide therapies for these and other conditions; and others are used to predict the risk that an individual patient will develop a particular disease.

These are remarkable developments that are bringing improvements to many people. And these clinical advances often reflect significant scientific breakthroughs.

In view of these developments, we must continue to ask ourselves — how do we adapt payment schemes, regulations, enforcement policies that were designed for the technologies and market of the 1970s for today’s innovations?

I think FDA is on the right path, using the regulatory tools I’ve described today; and by continuing to push the agency to be more efficient, while maintaining its mission to protect patients.

Marketing authorization by FDA provides assurance to patients, providers, payors, and the marketplace; that a new test is reliably valid -- both clinically and analytically.

Tests that haven’t been properly validated present serious risks. Faulty tests can generate false negatives that can lead people to delay or even forego appropriate medical treatment. Or false positives that can cause people to believe that they are suffering from serious diseases or conditions when in fact they are not.

A test with a greater assurance of validity may have advantages both in clinical adoption and gaining coverage by payers.

Finally, in all of this work, we’re making sure that the approach we take is complementary to, and not duplicative of, the work of other regulators, particularly CMS’s work under the Clinical Laboratory Improvement Amendments or CLIA.

FDA and CMS have separate and well-defined roles. Whereas CMS is focused on setting laboratory standards and overseeing laboratory accreditation, inspection, and certification; FDA regulates and reviews the tests themselves.

It’s key we understand and continue to act upon that distinction; to avoid recreating the wheel and imposing unnecessary burdens, and to best leverage existing work and oversight.

Through all of these efforts, FDA is building and executing a modern regulatory framework for diagnostics that enables us to keep up with rapidly developing scientific advances and perform our public health mission in the most efficient ways.

We need to make sure that patients can access accurate, reliable, and clinically meaningful advanced diagnostics as quickly as possible. And as we move forward, the input and collaboration of the developer community will be essential.

I look forward to our continued partnership. Thank you.