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FDA Proposes to Exempt Some Genetic Screening Systems from Premarket Requirements

Posted 26 October 2015 | By Zachary Brennan 

FDA Proposes to Exempt Some Genetic Screening Systems from Premarket Requirements

The US Food and Drug Administration (FDA) has decided to look into exempting from premarket requirements some genetic screening systems that can test parents for specific conditions they could possibly pass down to their children.

The possible exemption of the autosomal recessive carrier screening gene mutation detection systems, which are Class II devices, would help companies bring to market systems that can test parents for specific genetic conditions, such as cystic fibrosis, sickle cell disease and Tay-Sachs disease, which they could potentially pass down to their children.

FDA notes that the exemption may come because the screening is only intended to detect carriers, "so false positive results would only suggest that a person was a carrier of a mutation, and would not contain information that could lead to conclusions of disease for the tested person."


Under current law, FDA may exempt a device if the agency determines that a 510(k) application is not necessary to provide reasonable assurance of the safety and effectiveness of a device.

As for autosomal recessive carrier screening gene mutation detection systems, FDA says the "nature and level of scientific evidence necessary to establish autosomal recessive inheritance patterns makes it easily discernable whether such evidence establishes clinical validity or not."

In addition, with new special controls requiring that clinical validity be scientifically established and that evidence supporting such must be publicly posted on the manufacturer's Web site "render the probability of false or misleading claims for autosomal recessive inheritance very low," FDA says.

The agency also points to its recent classification of the 23andMe PGS Carrier Screening Test for Bloom Syndrome as such an example of a screening system.

Low Frequency

And although some autosomal recessive genetic diseases are more common in certain ethnic, racial, or geographically-bounded groups, FDA notes that even in these groups, the number of such diseases tends to be low.

For example, a carrier of sickle cell mutation, which has one of the highest known carrier frequencies, is estimated to occur in about 1 of 13 African Americans, and cystic fibrosis carrier status is estimated to occur in about 1 of 25 Caucasians.

"Clinical validity must be well-established in peer reviewed journal articles, authoritative summaries of the literature, and/or professional society recommendations. If there is no professional guideline recommending testing of a certain gene or variant in the indicated population, the manufacturer's Web site must warn that no such recommendation currently exists," FDA notes.

FDA also says it believes that its special controls will be sufficient to mitigate potential risks for parents, such a psychological distress, without the need for premarket review from FDA.

Those special controls include: (1) The requirement for over-the-counter test manufacturers to provide users information about how to obtain access to the counseling services of a board-certified clinical molecular geneticist or equivalent, and (2) labeling and comprehension study requirements to help ensure that users are able to understand the limitations and context of the testing prior to ordering.

In addition, labeling requirements and requirements that establish minimum performance specifications, according to FDA, will "sufficiently mitigate the risks posed by analytical false negatives for autosomal recessive carrier status without the need for premarket notification."


FDA also notes that not all autosomal recessive carrier screening gene mutation detection systems will be exempt from the premarket notification requirement, particularly if such a device:

  • Has an intended use that is different from the intended use of a legally marketed device in that generic type; e.g., the device is intended for a different medical purpose, or the device is intended for lay use where the former intended use was by health care professionals only;
  • Operates using a different fundamental scientific technology than what's used by an already marketed device; e.g., a surgical instrument cuts tissue with a laser beam rather than with a sharpened metal blade, or an in vitro diagnostic device detects or identifies infectious agents by using a DNA probe or nucleic acid hybridization or amplification technology rather than culture or immunoassay technology;
  • Is an in vitro device intended for the diagnosis, monitoring or screening of neoplastic diseases with the exception of immunohistochemical devices; or for measuring an analyte which serves as a surrogate marker for screening, diagnosis, or monitoring of life threatening diseases or to monitor therapy; or for assessing the risk of cardiovascular diseases; for use in diabetes management; for identifying or inferring the identity of a microorganism directly from clinical material; for detection of antibodies to microorganisms other than immunoglobulin G (IgG) and IgG assays when the results are not qualitative, or are used to determine immunity, or the assay is intended for use in matrices other than serum or plasma; for noninvasive testing; or for near-patient testing.

Katherine Donigan, PhD, of FDA's Office of IVDs and Radiological Health explained Monday at RAPS' Regulatory Convergence that the exemption will be published in the Federal Register on Tuesday.  Industry and other interested parties have 30 days to comment on the proposal, and FDA has 120 days to make a final decision on the exemption.


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