The FDA 510(k): Bringing a New Genetic Test Directly to Consumers (Part 1)

So, you’ve developed a genetic test that you’d like to sell directly to the public in the U.S.—from a regulatory perspective, what do you need to know? To start, some genetic tests require U.S. Food & Drug Administration (FDA) review before being marketed direct-to-consumers (DTC), while others do not—we’ll get into that below. For those that do, the most common review pathway is called the FDA 510(k) or Premarket Notification, named after Section 510(k) of the Food, Drug and Cosmetic Act.

It’s a predicate-driven process

Genetic testing companies that want to market their test (usually online) directly to consumers, rather than through (or mediated by) a healthcare provider, must notify the FDA of their intent to do so in advance by submitting a 510(k). The FDA will want to know that your genetic test is basically the same (i.e.: as safe and effective) as another DTC genetic test already on the market (i.e.: the “predicate”). 

The goal is to have your DTC product cleared by the FDA. The semantics are important here; an FDA 510(k) clearance is not an approval; it is an authorization to take your DTC genetic test (DTCGT) to market.

If your genetic test is novel and there is no predicate, your test can pave a new regulatory path. To do this, companies submit a De Novo Classification Request; read on to learn more about the De Novo process. Helix recently went through this with their first-to-market whole exome sequencing laboratory platform. (21 CFR 866.6000, DEN190035)

FDA oversight of medical devices

DTCGTs are in vitro diagnostics (IVDs), as they involve sending a human sample (usually saliva or cheek cells collected at home) to a DNA testing lab for analysis. DTCGTs that can impact a person’s health care are regulated by the FDA as medical devices.

Part of the FDA’s mission is to protect public health by ensuring the safety and efficacy of medical devices.

Medical devices include everything from an elastic bandage to an implantable pacemaker, so to ensure appropriate safeguards are applied to each device, the FDA uses a risk classification system to guide the regulatory pathway.

• Class I devices are considered low risk (e.g.: tongue depressor); most are exempt from the regulatory process (i.e.: do not need 510(k) clearance) and are subject to general controls.
• Class II devices are considered moderate risk (e.g.: pregnancy test kit); most require 510(k) clearance to go to market and are subject to both general and special controls. 
• Class III devices are considered high risk (e.g.: defibrillator). These require the highest level of scrutiny and are regulated through a rigorous premarket approval (PMA) process.

All brand new devices, where there is nothing like it out there, are automatically considered Class III ​​– it’s the default classification. But, of course, most devices are not actually high risk. Manufacturers can ask the FDA to consider reclassifying their new device from Class III to a more appropriate risk class (Class I or II) in a De Novo Classification Request. If the request is successful, a new classification regulation is established, a CFR (Code of Federal Regulations Title 21) code is generated, and the newly authorized device can serve as a predicate for others. 

General vs. special controls

All medical devices are subject to general controls, which are standard regulatory requirements set forth by the FDA. Special controls are specific measures, unique to each classification regulation, to ensure the device is safe and effective for its intended use. Special controls are meant to mitigate the risk(s) brought on by Class II devices. 

For example, one special control in the Genetic Health Risk regulation is the required use of an FDA-cleared sample collection device, like the Oragene Dx saliva kit. This special control ensures safe and effective saliva collection.

So, which genetic tests need FDA 510(k) clearance?

When it comes to DTCGTs, non-medical tests, such as ancestry testing, trait testing, and general wellness DNA tests, currently do not require FDA premarket review. According to a recent guidance document, the FDA does not review low risk wellness products, and while not specifically mentioned, many have extended this to include DTCGT wellness products. 

If you want to sell a product that is intended to promote a healthy lifestyle and does not have any potential medical implications for the user, you do not need the go ahead from the FDA.

Carrier screening tests (for the purpose of family planning) pose a relatively low risk to the health of the user, so they do not require FDA premarket clearance, but they do need to comply with the special controls outlined in the carrier screening regulation (21 CFR 866.5940) as the results can be used to inform medical choices. 

DTCGTs which can impact a person’s medical care, such as cancer predisposition tests, genetic health risk tests, or pharmacogenetic tests are regulated as Class II medical devices and must be reviewed by the FDA to determine the validity of test claims. 

These regulations include:

• Genetic Health Risk (GHR) Tests (21 CFR 866.5950):

• Pharmacogenetics Tests (21 CFR 862.3364):

• Cancer Predisposition Tests (CFR 21 866.6090):

What do they actually review in the FDA 510(k)?

In a 510(k) for DTCGTs, the FDA will evaluate several criteria, including analytical validity (i.e.: accuracy and reliability of your genetic test), clinical validity (i.e.: your test’s ability to measure and predict impacts on health), and transparency and precision of your test claims.

The FDA will assess how well your test materials (e.g.: your genetic test report and related materials) can be understood by a consumer without the involvement of a healthcare provider. This is done by conducting a user comprehension study. 

Now that you know some 510(k) basics, keep an eye out for our next post, which reviews some quick practical tips on how to get started on FDA user experience studies, Part 2 of this two-part series.