The outbreak of the novel coronavirus has increased scrutiny of how diagnostic devices are regulated in the US. Two new legislative proposals would enact very different reforms. AgencyIQ explains what’s at stake and how the proposals would work.
Executive IQ Brief
- How Things Work Now: Laboratory Developed Tests (LDTs) have traditionally not been subject to FDA premarket review requirements and are instead overseen by CMS through its authority under the Clinical Laboratory Improvement Act (CLIA). This is because traditionally, LDTs were developed and used within a single laboratory or healthcare delivery site. As a result, LDTs face lower regulatory barriers to market than other types of In Vitro Diagnostics (IVDs) and pay smaller regulatory fees. However, in case of a designated public health emergency (like the COVID-19 outbreak) even LDTs are required to submit authorization requests to the FDA.
- What’s New: With the outbreak of the novel coronavirus, all eyes are now on the FDA and life sciences industry. There are two new legislative proposals in Congress that would update regulatory product policy. The VALID Act, from a bipartisan coalition, would create a new regulatory framework for all diagnostics, including both IVDs and LDTs. The VITAL Act, from Senator Rand Paul (R-KY), would exempt LDTs from regulatory oversight even in the case of a public health emergency.
- What’s Next: The difficulties with establishing widespread testing for COVID-19, the administration, industry, and the American public are questioning the adequacy of diagnostic regulation. The challenges highlighted by the outbreak are likely to face increased scrutiny from lawmakers in the coming months.
Statutorily, medical devices are defined as: “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other related article, including any component, part, or accessory, which is:
- recognized in the official National Formulary, or the US Pharmacopeia, or any supplement to them;
- intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals….”
In vitro diagnostics (IVDs) are tests that are conducted on samples that have been taken from the human body (such as tissue, blood or sputum) to detect disease or other conditions. Increasingly, these products are also being used to identify which therapies (“personalized medicine”) will work best for specific patients. IVDs that are developed by device or diagnostic manufacturers and distributed for sale on a widespread basis are regulated as medical devices.
However, since the 1970s the FDA has chosen not to enforce these regulatory requirements for a subset of IVDs known as laboratory developed tests (LDTs). This practice is known as “enforcement discretion.”
LDTs have traditionally been developed and used within a single clinical laboratory, and are generally not subject to review by the FDA. Although the FDA has expressed interest in ending the enforcement discretion policy as LDTs become more complex and widely available, pushback from the industry and a lack of clear statutory authority have hindered these efforts.
Exceptions to the policy
There are a few situations in which the FDA will enforce regulatory requirements for LDTs.
For example, the FDA has held that certain LDTs that represent higher risk than “home brewed” tests used for a single patient are subject to oversight by the agency, such as pharmacogenomic tests or direct-to-consumer products.
Additionally, the FDA considers all diagnostic products developed to treat a condition that has been identified as a public health emergency (PHE) as subject to regulatory oversight—even if that product is an LDT. Because the presence of a PHE inherently raises the risk of a diagnostic or treatment for all stakeholders, all LDTs intended to diagnose an emergency condition are considered high risk. For example, a poor-quality diagnostic test could raise the prospects of a person thinking they are sick with seasonal influenza, when in reality they have a pandemic strain of coronavirus.
As the FDA explains, “because [LDTs] historically were relatively simple and available on a limited basis, FDA generally has not enforced premarket review and other legal requirements. However, LDTs for which an HHS EUA declaration justifies a need (and that potentially meet the EUA criteria) present a higher risk.”
When the Secretary of the US Department of Health and Human Services (HHS) declares a PHE, HHS may also authorize the FDA to issue Emergency Use Authorizations (EUAs). An EUA allows a manufacturer to distribute certain products to respond to the PHE without first obtaining full approval as a safe and effective product.
In the case of a PHE and EUA declaration, clinical laboratories developing LDTs are required to submit an EUA request for their diagnostic—even if they wouldn’t have been subject to regulatory review in the absence of an emergency.
As the US has sought to confront an outbreak of a novel coronavirus, COVID-19, front-line responders have been struggling to obtain diagnostic tools with which to diagnose patients suspects of having COVID-19.
The FDA was authorized to issue EUAs by the HHS Secretary on February 4, and has since issued several EUAs to diagnostic companies. However, the rollout of these tests has been slow, and the CDC’s diagnostic test – the first to receive authorization from the FDA – was plagued by problems with its accuracy.
To increase capacity, the FDA therefore altered its policy to allow the widespread use of LDTs under specific circumstances. On February 29th, the FDA issued guidance intended to encourage clinical laboratories to submit EUAs for their laboratory developed diagnostics.
Under the guidance, the FDA said it would allow COVID-19 testing to be performed in CLIA-certified laboratories before the agency grants an EUA—as long as the laboratory pursues an EUA within 15 days of first using the device. It also outlined the steps that labs should take to validate their test.
Testing rates for COVID-19 are still catching up to the spread of the virus as of this week.
Mounting frustration from the Trump administration, lawmakers and the American public about the low testing rates and slow roll-out of available tests means the FDA’s diagnostic regulatory policies are under increased scrutiny.
Diagnostic regulation was underway even before the outbreak
Even before the outbreak, Congress had been considering reforms to the way in which FDA regulates IVDs and LDTs.
After several false starts in recent years, a new iteration of the Verifying Leading-edge IVCT Diagnostics (VALID) Act was introduced by a bipartisan, bicameral coalition of lawmakers in February. That legislation, developed in consultation with both the FDA and the diagnostics industry, would create an entirely new regulatory framework for IVDs and LDTs, rebranding them as In Vitro Clinical Tests (IVCTs).
Regulators and industry have long raised questions about whether the medical device framework, which is currently the pathways under which diagnostics are regulated, is suitable for diagnostic products. Under VALID, IVCTs would be removed from that pathway and a new risk-based pathway specifically for diagnostic products would be created.
Senator Rand Paul (R-KY) introduced a new bill to fully exempt all LDTs from FDA oversight, even in the case of an emergency, on March 17.
The Verified Innovative Testing in American Laboratories (VITAL) Actwould specifically affirm that all regulatory authority for LDTs and lab-developed testing procedures belongs to the Centers for Medicare and Medicaid Services under the Clinical Laboratory Improvement Amendments (CLIA), which is how the tests are now generally overseen. However, CMS doesn’t review the tests for validity, and instead focuses on the operating procedures of the clinical laboratories in which they are developed.
According to Senator Paul, requiring LDTs to submit EUAs in the case of emergency creates barriers to accessing diagnostics quickly.
“Undue regulation of laboratory-developed testing procedures may hamper the medical management and public health response to infectious disease outbreaks and pandemics, leading to delays in access to testing and the ability to meet needed capacity to stem community spread,” Paul said in a statement.
The legislation would not alter how IVDs are currently regulated, meaning that they would remain within the scope of the medical device pathways. If enacted, the bill would fully exempt LDTs from the EUA process, allowing clinical laboratories to develop and use their own home-brewed tests in case of a PHE.
The bill also includes a “Sense of the Senate” provision, or an affirmation of an idea, that the federal government should work to “preserve the ability of the laboratory community to provide surge capacity” in the case of emergency, and take additional action to strengthen the Laboratory Response Networks.
Additionally, Senator Paul’s proposal would direct HHS to convene a meeting on updating clinical laboratory certification policy under CLIAwithin 90 days of its passage and report policy options to Congress within 180 days.
While neither the VALID Act nor VITAL Act proposals are likely to be enacted or have an impact on the ongoing outbreak, the dueling legislative proposals address a common question: How should diagnostics and tests be regulated?
Some regulatory experts have stated that diagnostics shouldn’t be regulated under the device framework, as a pathway developed for products like surgical gloves, knee replacements and surgical tools doesn’t work well for things like immunoassays and next generation sequencing (NGS) tools, which may be more platform-based.
The diagnostics industry has expressed its preference for greater regulation over LDTs, or at least a consistent approach to regulation between IVDs and LDTs.
AdvaMed, a trade organization representing the medical device and diagnostics industry, has historically taken the position that increased LDT regulation is imperative to protect both traditional diagnostic manufacturers and patient safety as LDTs become more complex and widely distributed. Additionally, the risk-based framework and new approval standards proposed under VALID align more with the use and efficacy standards for diagnostic products, according to Precision for Medicine’s Karen Richardson. If all that was accomplished under VALID was to reform IVD regulation, “that would be a win,” she told AgencyIQ in an interview soon after the release of the VALID Act, even if LDT regulation remained unchanged.
On the other hand, clinical laboratories have resisted new regulatory burdens on their industry. Because LDTs are often personalized for specific patients and used in low volumes, the industry has stated that requiring increased federal oversight of these products is both an interference in the practice of medicine and could pose risks to complex patients who need individualized solutions.
In the meantime, the FDA is working to increase flexibility for diagnostics and testing manufacturers, though it’s not clear how long that flexibility will last.