On February 19, 2015, the U.S. Food and Drug Administration (FDA or the Agency) authorized for marketing 23andMe’s Bloom Syndrome carrier test, a direct-to-consumer genetic test to determine whether a healthy person has a variant in a gene that could lead to their offspring inheriting the serious disorder.[1] The test is intended only for postnatal carrier screening in adults of reproductive age, and the results should be used in conjunction with other available laboratory and clinical information for any medical purposes.

In addition to issuing its authorization, the Agency also announced that it will classify carrier screening tests as Class II, and intends to exempt such products from FDA’s premarket review. The Agency will issue a notice that announces its intentions regarding carrier screening tests, as well as provide a 30-day period for public comment. According to Alberto Gutierrez, Ph.D., Director of the Office of In Vitro Diagnostics and Radiological Health, the proposed administrative action reflects the Agency’s belief 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.” While this position matches the Agency’s stated intent to create “the least burdensome regulatory path for autosomal recessive carrier screening tests,” it will be interesting to see how FDA defines any proposed limitations on the exemptions for carrier testing, and whether such limitations will expand upon the general limitations found in 21 C.F.R § 864.9.

Carrier tests for genetic disorders differ from other genetic testing in that a person displays no symptoms for the genetic disorder being tested; rather these tests are meant to inform the person of a potential risk for passing the subject genetic disorder on to their offspring. Presently, FDA does not intend to limit who may use these tests. However, the product’s labeling will need to clearly explain to consumers what the results might mean for a prospective parent. The results of such tests will also need to be conveyed in a format that can be easily understood by a lay user. In addition, if the product is sold over-the-counter, the Agency will require 23andMe to include in its labeling, information about how consumers can access a board-certified clinical molecular geneticist (or equivalent) to assist in pre- and post-test counseling. The product requirements described above are reflective of, but also go beyond, the recommendations found in FDA’s Guidance Design Considerations for Devices Intended for Home Use (Nov. 24, 2014).[2]

23andMe supplied 4 studies to support its marketing application: 2 laboratory studies (123 samples and 105 samples) to assess the test’s accuracy in detecting Bloom Syndrome carrier status; 1 usability study (295 participants) to demonstrate that consumers could understand the test instructions and procedures; and 1 user study (302 randomly recruited participants reflecting the U.S. population) to demonstrate the test instructions and results were easy to follow and understand.

Previously, FDA issued a warning letter[3] (dated November 22, 2013) to 23andMe for marketing its Saliva Collection Kit and Personal Genome Service without marketing clearance or approval from the Agency. In its warning letter, FDA noted that the company’s website advertised “‘health reports on 254 diseases and conditions’ including categories such as ‘carrier status,’ ‘health risks,’ and ‘drug response,’ and specifically as a ‘first step in prevention’ that enables users to ‘take steps toward mitigating serious diseases’ such as diabetes, coronary heart disease, and breast cancer.” FDA further noted that most of the proposed uses had not been previously classified and thus would require premarket approval or de novo classification. Though the company submitted two 510(k) notifications in 2012, both submissions were later treated as withdrawn due to the company’s failure to respond to the Agency’s request for additional information. Shortly after receiving FDA’s warning letter, 23andMe posted on its website that it was suspending health-related genetic tests.

It should be noted that 23andMe’s recently authorized Bloom Syndrome carrier test is only for identifying carrier status of a single-rare genetic disorder, thus presenting a lower risk to user safety. In contrast, and of particular concern to the Agency at the time it issued the warning letter to 23andMe, was the company’s Personal Genome Service that claimed to assess a user’s BRCA-related genetic risk and drug responses. These intended uses exposed users to heightened risk due the potential for false-positives and false-negatives, whereby the false result might encourage the user to enter into a drastic treatment plan, or forgo critical diagnostic or necessary treatment measures. Genetic testing that entails such heightened risks to users will almost certainly be subject to a comparably heightened regulatory burden.

Summary

FDA’s decision to exempt carrier screening testing from premarket review indicates the Agency’s flexibility concerning “low risk” personal genome services. Based on the Agency’s press release authorizing 23andMe to market its Bloom Syndrome carrier test, and its 2013 warning letter to the company, factors that will likely affect the regulatory pathway of future personal genetic services include:

  • Risk to the user in the event of a false-positive or false-negative result
  • Risk to the user for foregoing, or engaging in, diagnostic or treatment options based on a false test result
  • Status to be identified (e.g. carrier status, drug response, health risk)
  • Purpose of the genetic testing (prevention or mitigation of a disease versus informational)
  • Prevalence of the genetic disorder
  • Risk to the user associated with the genetic disorder
  • Probability of a false test result
  • Likelihood that risks associated with a personal genetic service can be mitigated by:
    • clear and understandable labeling,
    • information on how to access board-certified clinical molecular geneticist or equivalent, and
    • limiting the device to prescription use only.