Marketing of Laboratory Tests to Consumers: Is a Practitioner Order Enough to Avoid FDA Enforcement?

Danielle Sloane, Esq., Bass, Berry & Sims	Courtney Ginn, Esq., Bass, Berry & Sims

Laboratory developed tests (LDTs) are tests designed, manufactured, and used within a single laboratory. Historically, the FDA opted not to regulate LDTs, which were originally relatively simple laboratory tests. As technology has progressed, however, LDTs have become increasingly complex and sophisticated in the ability to diagnosis and influence decision-making; simultaneously, consumers have become more sophisticated and hands-on in their approach to health care.

Together, these trends mean that laboratories are seeking to differentiate themselves in a competitive market by marketing their LDTs directly to consumers, but what is the impact of marketing on a laboratory’s ability to remain within the FDA’s historic exception for LDTs? The FDA has recently intensified its enforcement against laboratory companies that market LDTs directly to consumers. As evidenced by a number of FDA warning letters, it is clear that the FDA deems any test marketed and sold directly to consumers as no longer qualifying for the historic LDT exception, necessitating instead the appropriate level of FDA approval. But the FDA warning letters and recent commentary seem to be expanding beyond tests sold directly to consumers, to tests that are marketed to consumers and ordered by qualified physicians. It seems likely, however, the FDA may be focusing on situations in which the ordering practitioner is affiliated with the laboratory rather than truly independent.

FDA’S REGULATION FRAMEWORK FOR LDTs The FDA is the federal agency with the primary regulatory authority over laboratory tests sold directly to consumers (“DTC tests”). The FDA regulates DTC tests as in vitro diagnostic medical devices, a category that includes any products intended for use in the collection, preparation, and examination of specimens taken from the human body.¹ Like other medical devices, these in vitro diagnostic products are subject to premarket and postmarket controls, including appropriate FDA approval prior to being marketed and sold in the United States.

LDTs have historically fallen within an “enforcement discretion” exception to the FDA’s regulation of in vitro diagnostic products. When the FDA first began regulating medical devices under the Medical Device Amendments in the 1970s, the FDA declined to enforce applicable regulatory requirements for LDTs.² This was due in large part to the fact that LDTs were relatively simple lab tests and generally available on a limited basis, which the FDA concluded were sufficiently safeguarded by the CLIA program. Accordingly, LDTs generally have not been subject to premarket and postmarket controls applicable to other medical devices.

As LDTs have become more advanced and more widely available, however, concerns over the validity and safety of the tests have resurfaced. Specifically, the FDA has taken the position that some modern LDTs have attributes not present in 1976 that create potential increased risk for patients, including tests that are (i) manufactured with components that are not legally marketed for clinical use; (ii) offered beyond local populations and manufactured in high volume; (iii) used widely to screen for common diseases rather than rare diseases; (iv) used to direct critical treatment decisions; and (v) highly complex.³

The increased risks that accompany some modern LDTs exposed a perceived gap in regulatory oversight of LDTs. After years of rumblings, on Oct. 3, 2014, the FDA issued a Draft Framework for regulating LDTs.⁴ The Draft Framework proposes a risk-based approach to regulating LDTs, similar to the classification used for medical devices, which would be implemented over about 10 years. The FDA would continue to exercise its enforcement discretion against low-risk LDTs while requiring premarket review for moderate and high risk LDTs. Since release of the Draft Guidance, the FDA has been bombarded with industry commentary, held stakeholder meetings,⁵ issued case studies in support of its position that regulation is necessary,⁶ and presented before Congress.⁷ A final guidance document is expected sometime in 2016. In addition, the FDA is exploring regulatory alternatives for genetic testing in relation to President Obama’s “Precision Medicine Initiative.”

FDA’S REGULATION OF DTC TESTING In the meantime, the FDA continues to target laboratories that market their LDT products to consumers. Traditionally, laboratory marketing was directed at qualified practitioners (e.g., physicians, nurse practitioners, etc.). Because of competitive pressures (and perhaps taking inspiration from pharmaceutical manufacturers), laboratories have identified consumers as a worthwhile marketing demographic, even if the LDT requires a physician order. Is marketing an LDT itself problematic in the eyes of the FDA? Or, is it the combination of marketing and allowing consumers to order directly (absent an order from a qualified professional)—or maybe something in between? Considering laboratories have long had websites touting their lab and testing, one would think it is the latter—the removal of a qualified practitioner from the process—and not simply the marketing of LDTs that would trigger enforcement. In April 2015, “[a]n F.D.A. spokeswoman said that if doctors place orders, testing companies that operate their own laboratories do not need F.D.A. approval to offer their tests.”⁸ And, until recently, that concept was supported by the pattern of FDA enforcement and commentary.

The FDA’s disapproval of marketing and selling LDTs directly to consumers was made clear in 2013 when the FDA issued a scathing warning letter to Google-backed 23andMe, Inc. regarding the sale of its saliva collection kit and personal genome service for reporting on, among other things, 254 diseases and conditions, in violation of the Federal Food, Drug and Cosmetic Act (the “FD&C Act”). As part of that letter, the FDA directed 23andMe to immediately stop marketing its personal genome service until it received authorization from the FDA.⁹ More than a year later, 23andMe made news again when the FDA approved 23andMe to market a specific test to consumers for one disease, Bloom Syndrome, a rare inherited disorder. This FDA approval was extremely narrow in comparison to 23andMe’s original personal genome service.¹⁰ In conjunction with this approval, the FDA classified autosomal recessive carrier screening tests as a Class II medical device requiring premarket notice (or 510(k) review). The FDA stated that “in many circumstances it is not necessary for consumers to go through a licensed practitioner to have direct access to their personal genetic information” and stated this was the “least burdensome regulatory path” for these types of tests—though notably expects those tests to have gone through FDA 510(k) review.¹¹

Recent FDA enforcement activity reaffirms the FDA’s disapproval of laboratories marketing LDTs (i.e., tests without PMA or 510(k) clearance) to consumers. In late 2015 and early 2016, the FDA issued five warning letters to companies engaging in DTC marketing of LDTs. In several of these letters, it appears the FDA may be going beyond situations in which the consumer can order the test directly to also regulate situations in which the practitioner signing the order is affiliated with the laboratory.

On Sept. 21, 2015, the FDA issued a warning letter to Pathway Genomics, Inc. addressing the marketing of a non-invasive blood test intended for use as a screening tool for the early detection of up to 10 different cancer types in high risk populations. The FDA stated that the “high risk test” was a medical device that required approval and expressed concern that the company’s current promotional materials “may harm the public health.”¹² According to Pathway’s current website, the test kit is shipped directly to patients, but the test must be ordered by a physician.¹³ Upon selecting the “patient” identifier on the company’s website, the viewer receives the following message: “All Pathway tests must be ordered by a licensed and registered physician or other qualified health care provider.”¹⁴ It is unclear, however, whether the company was requiring a qualified practitioner order at the time it received the letter.

On Nov. 2, 2015, the FDA issued a letter to DNA-Cardiocheck, Inc., which notes that the company is “currently marketing a direct-to-consumer test” that “appears to meet the definition of a device,” and concluded that the test was a medical device.¹⁵ An archived webpage indicates that the test was available for purchase on Walgreens’s website.¹⁶

The same day, the FDA also issued a warning letter to DNA4Life. DNA4Life’s warning letter was related to its direct-to-consumer marketing of its Pharmacogenetic Report, which is “intended to predict how patients will respond to more than 120 of the most commonly prescribed medications.”¹⁷ The FDA concluded that this test was a medical device requiring a clearance number.¹⁸ According to DNA4Life’s website, the test does not appear to require a physician order.¹⁹ Patients are, however, asked to promise to share the results with their physician by clicking a box in the checkout process. In addition, the company’s privacy policy “urges [buyers] to seek the advice of your physician or other health care provider if you have questions or concerns arising from your genetic information.”²⁰

Similarly, a Nov. 4, 2015 warning letter to Interleukin Genetics notes that the company was marketing unapproved genetic tests intended to identify individuals with a genetic predisposition for increased risk for diabetes, heart attack, and obesity, which “appear to meet the definition of devices.”²¹ The FDA noted that Interleukin Genetics had previously claimed the tests as LDTs, but that “at the present time, your firm is offering these tests under a [DTC] model.” According to its website, it appears that Interleukin sends sample collection kits directly to consumers with no physician order necessary, although the company offers consumers the option to speak with a “licensed, board-certified genetic professional.”²²

Most recently, Sure Genomics received an FDA warning letter on Feb. 16, 2016, stating that the company was marketing a test “which is intended to catch saliva samples for DNA sequencing and reporting of patient information such as disease risks and likelihood of drug reactions.”²³ As with the warning letters issued in 2015, the FDA concluded that the SureDNA test met the definition of a device as defined in section 201(h) of the FD&C Act. A press release on the company’s website describing the process states that “Users register online for a collection kit to mail-in a saliva sample— testing is physician prescribed....”²⁴

The requirement of a physician order should place laboratory tests within the FDA’s LDT exception at least until the FDA issues final guidance on regulating LDTs. And yet, it appears that some of the FDA enforcement efforts have involved companies that required qualified practitioner orders, leaving us to question where the line between an LDT and a DTC test lies. Our guess is the answer may depend on the relationship between the laboratory and the physician.

The FDA has signaled as much in recent commentary. In a recent interview by GenomeWeb, Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Device Evaluation for the FDA, said that the FDA is looking into DTC models “that rely on ordering of the test either by the physician that is incorporated into the company or that somehow has a relationship not with the patient but with the company.”²⁵ This shift in focus suggests that marketing LDTs ordered by unaffiliated, independent practices should continue to fall within the LDT category, but affiliated physician orders may shift a test to a DTC test. As a result, in addition to considering fraud and abuse laws when entering into physician relationships, laboratories may need to consider if those relationships impact their FDA compliance.

Danielle M. Sloane is a Member at the firm, Bass, Berry & Sims PLC, 150 Third Ave. South, Ste. 2800, Nashville, TN 37201 and is available at (615) 742-7763; dsloane@ bassberry.com.

Courtney Ginn is an Associate at Bass, Berry & Sims PLC, 150 Third Ave. South, Ste. 2800, Nashville, TN 37201 and is available at (615) 742-7741; cginn@bassberry.com.

End Notes

(1)  21 C.F.R. § 809.3.
(2) Of course, this enforcement abstention assumes that the FDA has authority to regulate LDTs as medical devices in the first place. See, e.g., “Laboratory Testing Services, As the Practice
of Medicine, Cannot be Regulated as Medical Devices,”Paul D. Clement & Laurence H. Tribe, available at http://www.acla. com/wp-content/uploads/2015/01/Tribe-Clement-White- Paper-1-6-15.pdf.
(3) FDA,“Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)”at 8, issued October 3, 2014.
(4) Id.
(5) See e.g., FDA Public Workshop – Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs), January 8-9, 2015. http://www.fda.gov/MedicalDevices/NewsEvents/ WorkshopsConferences/ucm423537.htm.
(6) FDA,“The Public Health Evidence for FDA Oversight of Laboratory Developed Tests: 20 Case Studies”(Nov. 16, 2015) available at http://www.fda.gov/downloads/AboutFDA/Re- portsManualsForms/Reports/UCM472777.pdf.
(7) Jeffrey Shuren, Director of CDRH, FDA“Examining the Regula- tion of Diagnostic Tests and Laboratory Operations”before the
U.S. House, Energy and Commerce, Subcommittee on Health (Nov. 17, 2015) available at http://www.fda.gov/NewsEvents/ Testimony/ucm473922.htm.
(8) Andrew Pollack,“New Genetic Tests for Breast Cancer Hold Promise,”The New York Times (Apr. 21, 2015) available at http:// www.nytimes.com/2015/04/21/business/more-accurate-af- fordable-tests-for-detecting-breast-cancer-genes.html?_r=1.
(9) FDAWarning Letter, 23andMe, Inc. (Nov. 22, 2013) available at http://www.fda.gov/ICECI/EnforcementActions/Warn- ingLetters/2013/ucm376296.htm.
(10) FDA News Release: FDA permits marketing of first di- rect-to-consumer genetic carrier test for Bloom syndrome (Feb. 19, 2015; modified Feb. 23, 2015) available at http://
www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ UCM435003.
(11) Id.
(12) FDAWarning Letter, Pathway Genomics (Sept. 21, 2015), available at http://www.fda.gov/downloads/MedicalDevices/ ResourcesforYou/Industry/UCM464092.pdf.
(13) “Request a Test Kit”, available at https://www.pathway.com/ request-a-kit/ (last visited Feb. 22, 2016).
(14) Id.
(15) FDAWarning Letter, Cardiocheck, Inc. (Nov. 2, 2015), available at http://www.fda.gov/downloads/MedicalDevices/ ResourcesforYou/Industry/UCM471784.pdf.
(16) https://web.archive.org/web/20140517060903/http:// dnaidcheck.com/ (last visited Feb. 22, 2016). Although the DNA-CardioCheck test is no longer available for purchase, the
company is still offering its DNA-IDCheck (a paternity/maternity test) for purchase on the Walgreens website without a physi- cian order. See http://www.dnaidcheck.com/ (last visited Feb. 22, 2016); http://www.walgreens.com/store/c/dna-id-check- dna-sample-collection-kit-fatherhood/motherhood-confirma- tion/ID=prod1107920-product (last visited Feb. 22, 2016).
(17) FDAWarning Letter, DNA4Life (Nov. 2, 2013) available at http://www.fda.gov/downloads/MedicalDevices/Resourcesfo- rYou/Industry/UCM471785.pdf.
(18)  FDAWarning Letter, DNA4Life (Nov. 2, 2013).
(19) “How It Works”available at https://dna4life.com/how-it- works/ (last visited Feb. 22, 2016).
(20)  https://dna4life.com/checkout/ (last visited Feb. 22, 2016);
https://dna4life.com/privacy-policy/ (last visited Feb. 22, 2016).
(21) November 4, 2015 Warning Letter, available at http://www. fda.gov/downloads/MedicalDevices/ResourcesforYou/Indus- try/UCM471788.pdf.
(22) “How Does DNATesting Work”available at http://www. inherenthealth.com/the-process.aspx (last visited Feb. 22, 2016; Inherent Health is the brand name of genetic tests that Interleukin Genetics).
(23) FDAWarning Letter, Sure Genomics, Inc. (Feb. 16, 2016) available at http://www.fda.gov/downloads/MedicalDevices/ ResourcesforYou/Industry/UCM486449.pdf.
(24) “Sure Genomics Introduces First Full DNA Sequence to Consumers Delivered on an Interactive Easy to Comprehend Platform”http:// www.suregenomics.com/press/ (last visited Feb. 22, 2016).
(25) Turna Ray, GenomeWeb: Q&A: FDA’s Gutierrez, Mansfield Discuss Regulatory Efforts in 2015; Set 2016 Expectations (Jan. 13, 2016) available at https://www.genomeweb.com/molec- ular-diagnostics/qa-fdas-gutierrez-mansfield-discuss-regu- latory-efforts-2015-set-2016-0. See also GenomeWeb: Sure Genomics Gets FDA Letter (Feb 18, 2018) available at https:// www.genomeweb.com/molecular-diagnostics/sure-genom- ics-gets-fda-letter.