Document ID: FDA-2015-N-3455-0001
Agency: fda
Document Type: Notice
Title: Medical Devices; Exemptions From Premarket Notifications; Class II
Devices; Autosomal Recessive Carrier Screening Gene Mutation Detection System; Request for Comments
Posted Date: 2015-10-27T04:00Z

[Federal Register Volume 80, Number 207 (Tuesday, October 27, 2015)]
[Notices]
[Pages 65774-65779]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-27198]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-3455]

Medical Devices; Exemptions From Premarket Notifications; Class 
II Devices; Autosomal Recessive Carrier Screening Gene Mutation 
Detection System; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is announcing its 
intent to exempt from the premarket notification requirements autosomal 
recessive carrier screening gene mutation detection systems, subject to 
certain limitations. These devices are qualitative in vitro molecular 
diagnostic systems used for genotyping of clinically relevant variants 
in genomic deoxyribonucleic acid (DNA) isolated from human specimens 
intended for prescription use or over-the-counter use. These devices 
are intended for autosomal recessive disease carrier screening in 
adults of reproductive age. These devices are not intended for copy 
number variation, cytogenetic, or biochemical testing. FDA is 
publishing this notice in order to obtain comments regarding the 
proposed exemption.

DATES: Submit electronic or written comments by November 27, 2015.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the

[[Page 65775]]

public, submit the comment as a written/paper submission and in the 
manner detailed (see ``Written/Paper Submissions'' and 
``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2015-N-3455 for Medical Devices; Exemptions from Premarket 
Notifications; Class II Devices; Autosomal Recessive Carrier Screening 
Gene Mutation Detection System. Received comments will be placed in the 
docket and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at http://www.regulations.gov or at the Division of 
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION''. The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Steven Tjoe, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 4550, Silver Spring, MD 20993-0002, 301-796-5866.

SUPPLEMENTARY INFORMATION: 

I. Statutory Background

    Section 510(k) of the Federal Food, Drug, and Cosmetic Act (the 
FD&C Act) (21 U.S.C. 360(k)) and the implementing regulations, 21 CFR 
part 807 subpart E, require persons who intend to market a device to 
submit and obtain FDA clearance of a premarket notification (510(k)) 
containing information that allows FDA to determine whether the new 
device is ``substantially equivalent'' within the meaning of section 
513(i) of the FD&C Act (21 U.S.C. 360c(i)) to a legally marketed device 
that does not require premarket approval.
    On November 21, 1997, the President signed into law the FDA 
Modernization Act (FDAMA) (Pub. L. 105-115). Section 206 of FDAMA, in 
part, added a new section 510(m) to the FD&C Act. Section 510(m)(2) of 
the FD&C Act provides that, 1 day after the date of publication of the 
list under section 510(m)(1), FDA may exempt a device on its own 
initiative or upon petition of an interested person, if FDA determines 
that a 510(k) is not necessary to provide reasonable assurance of the 
safety and effectiveness of the device. This section requires FDA to 
publish in the Federal Register a notice of intent to exempt a device, 
or of the petition, and to provide a 30-day comment period. Within 120 
days of publication of this document, FDA must publish in the Federal 
Register its final determination regarding the exemption of the device 
that was the subject of the notice. If FDA fails to respond to a 
petition under this section within 180 days of receiving it, the 
petition shall be deemed granted.

II. Factors FDA May Consider for Exemption

    There are a number of factors FDA may consider to determine whether 
a 510(k) is necessary to provide reasonable assurance of the safety and 
effectiveness of a class II device. These factors are discussed in the 
January 21, 1998, Federal Register notice (63 FR 3142) and subsequently 
in the guidance the Agency issued on February 19, 1998, entitled 
``Procedures for Class II Device Exemptions from Premarket 
Notification, Guidance for Industry and CDRH Staff'' (referred to 
herein as the Class II 510(k) Exemption Guidance) (Ref. 1).

III. Proposed Class II Device Exemption

    On February 19, 2015, FDA completed its review of a de novo request 
for classification of the 23andMe Personal Genome Service (PGS) Carrier 
Screening Test for Bloom Syndrome. FDA classified the 23andMe PGS 
Carrier Screening Test for Bloom Syndrome, and substantially equivalent 
devices of this generic type, into class II (special controls) under 
the generic name ``Autosomal recessive carrier screening gene mutation 
detection system.'' This type of device is a qualitative in vitro 
molecular diagnostic system used for genotyping of clinically relevant 
variants in genomic DNA isolated from human specimens intended for 
prescription use or over-the-counter use. The device is intended for 
autosomal recessive disease carrier screening in adults of reproductive 
age. The device is not intended for copy number variation, cytogenetic, 
or biochemical testing. Elsewhere in this issue of the Federal 
Register, FDA is publishing an order to codify the classification of 
the device at 21 CFR 866.5940.
    Based on the analysis described in this document, FDA has 
determined that premarket notification for an autosomal recessive 
carrier screening gene mutation detection system is not necessary for 
assurance of the safety and effectiveness of the device, subject to the 
limitations described in section IV. FDA has assessed the need for 
510(k) clearance for an autosomal recessive carrier screening gene 
mutation detection system against the factors laid out in the Class II 
510(k) Exemption Guidance (Ref. 1) and the January 21, 1998, Federal 
Register notice (63 FR 3142) and has determined that the factors weigh 
in favor of 510(k) exemption, for the following reasons:

A. History of False or Misleading Claims or of Risks Associated With 
Inherent Characteristics of the Device

    FDA has generally considered whether a type of device has had a 
significant history of false or misleading claims or of risks 
associated with inherent characteristics of the device,

[[Page 65776]]

such as device design or materials when determining whether a 510(k) 
exemption is appropriate. Given that autosomal recessive carrier 
screening gene mutation detection systems were initially classified on 
February 19, 2015, under the de novo process, a process by which FDA 
evaluates novel devices anew, FDA has considered other related factors, 
including: (1) The probable frequency, persistence, cause, and 
seriousness of such claims or risks; and (2) mitigations of risk 
provided by the special controls, in combination with general controls.
    To demonstrate clinical validity for this type of test, one must 
define an inheritance pattern of genetic disease and demonstrate the 
appropriate genetic patterns are present in an informative population 
that includes affected persons. 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. Thus, the 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. 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.
    When considering the risks associated with the inherent 
characteristics of tests of this type, FDA has considered the risks of 
both false positive and false negative results, as well as the 
applicable mitigations provided by the special controls, in combination 
with general controls. The probable risks posed by devices of this type 
are generally similar regardless of the genetic carrier condition to be 
detected, as explained in this document.
    Autosomal recessive carrier screening is a type of genetic testing 
performed on people who display no symptoms for a recessive genetic 
disorder but may be at risk for passing it on to their children if they 
are detected to be a carrier. A carrier for a genetic disorder has 
inherited one normal and one abnormal allele for a gene associated with 
a disorder. Autosomal (non-sex chromosome-related) recessive disorders 
require that two abnormal copies of a gene, one inherited from each 
parent, be present in order for the disorder to be manifested. 
Therefore, to have a child with an autosomal recessive disorder, both 
parents must be carriers of an abnormal gene copy. When both parents 
are carriers for the abnormal copy, there is an a priori 1 in 4 chance 
(25 percent) that the child will inherit two abnormal copies of the 
gene and manifest the specific disease or condition.
    FDA believes that the risks posed by false positives are relatively 
low, and sufficiently mitigated by the applicable special controls, 
including requirements that establish minimum performance 
specifications, without the need for premarket notification. Although 
some autosomal recessive genetic diseases are more common in certain 
ethnic, racial, or geographically-bounded groups, even in these groups 
disease frequencies tend to be low. Most autosomal recessive genetic 
diseases are very rare with frequencies much less than 1 percent in the 
general population, and the respective carrier frequencies are likewise 
low in most populations. For reference, sickle cell trait (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. Persons outside these groups have lower carrier 
frequencies for sickle cell and cystic fibrosis carrier status. Other 
autosomal recessive diseases are rarer and their carrier frequencies 
are correspondingly lower. Carrier screening is only intended to detect 
heterozygotes (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. Further, no conclusion about an individual's future children 
could be made given that the carrier status of the child's second 
parent would need to be known to reach such a conclusion, and even 
where both parents are truly positive the only conclusion that may be 
drawn is that the child has a 25 percent likelihood of manifesting the 
disease. The probability of a couple both receiving false positive 
carrier results from using a device of this type is vastly smaller than 
for a single false positive.
    In this rare scenario, a couple both receiving false positive 
results could lead to the couple choosing not to get married or not to 
have children, or the results could lead to unnecessary fetal testing 
in current or future pregnancies. Fetal testing may consist of 
amniocentesis or chorionic villus sampling (CVS), neither of which is 
risk-free, although other risk factors during pregnancy, including age, 
often warrant such testing regardless of any carrier screening results. 
A false positive result for an individual may also potentially lead to 
adverse psychological effects, particularly if that individual does not 
fully understand the nature of autosomal recessive disorders (i.e., 
that both the mother and father must be carriers in order to have a 25 
percent chance that their child would have the disorder). FDA believes 
that the applicable special controls are sufficient to mitigate such 
risks without the need for premarket review, including: (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.
    Similarly, the applicable special controls, including labeling 
requirements and requirements that establish minimum performance 
specifications, sufficiently mitigate the risks posed by analytical 
false negatives for autosomal recessive carrier status without the need 
for premarket notification. Regardless of analytical accuracy, there 
exists a risk of a clinical false negative result for many carrier 
tests because not all clinically relevant mutations are known or tested 
for; therefore there will be a proportion of carriers who will not be 
detected. The proportion of people who are true carriers who would be 
detected by any test is known as the test's ``coverage.'' For many 
carrier conditions, clinical false negative rate due to ``coverage'' 
less than 100 percent is likely higher than the false negative rate 
from analytical failure or random error of a test. The clinical risks 
associated with false negative results generally occur when only one 
biological parent is tested and experiences a false negative result, 
since in that case it is unlikely the other biological parent will be 
tested. The risk of the false negative would only have consequence in 
the circumstance that the non-tested parent is also a carrier for the 
condition or disorder. In this case, there is a 25 percent chance that 
a future child would inherit the condition or disorder.
    FDA believes that the special controls requiring certain warnings 
in the device labeling are sufficient to mitigate such risk without 
further premarket review. The special controls include requiring a

[[Page 65777]]

warning statement accurately disclosing the genetic coverage of the 
test in lay terms, including, as applicable, information on variants 
not queried by the test, and the proportion of incident disease that is 
not related to the gene(s) tested. For example, where applicable, the 
statement would have to include a warning that the test does not or may 
not detect all genetic variants related to the genetic disease, and 
that the absence of a variant tested does not rule out the presence of 
other genetic variants that may be disease related. Or, where 
applicable, the statement would have to include a warning that the 
basis for the disease for which the genetic carrier status is being 
tested is unknown or believed to be non-heritable in a substantial 
number of people who have the disease, and that a negative test result 
cannot rule out the possibility that any offspring may be affected with 
the disease. The statement would have to include any other warnings 
needed to accurately convey to consumers the degree to which the test 
is informative for carrier status. The labeling special controls as a 
whole help ensure that those individuals for whom the test is conducted 
have the information available to enable them to understand the 
limitations of the test results prior to the test being performed and 
after receiving test results and provide context for the use and 
further interpretation of any results.

B. Well Established Safe and Effective Performance

    FDA has generally considered whether the characteristics of the 
device necessary for its safe and effective performance are well 
established. Given that autosomal recessive carrier screening gene 
mutation detection systems were initially classified on February 19, 
2015, under the de novo process, a process by which FDA evaluates novel 
devices anew, FDA has considered other related factors, including 
whether the performance characteristics that are necessary for the safe 
and effective use of the device are addressed by the special controls, 
in combination with general controls.
    Clinical validity is addressed through the special controls without 
the need for premarket notification. Generally, FDA accepts evidence of 
clinical validity of each variant queried and reported by a test as 
supported by peer-reviewed journal articles, authoritative summaries of 
the literature, and/or professional society recommendations during its 
premarket review. As discussed previously, given the level and nature 
of scientific evidence necessary to establish autosomal recessive 
inheritance patterns and corresponding ease of recognizing false or 
misleading clinical claims for this type of test, clinical validity is 
assured through the special controls requiring that clinical validity 
be scientifically well-established in peer-reviewed journal articles, 
authoritative summaries of the literature, and/or professional society 
recommendations and that evidence supporting such be publicly posted on 
the manufacturer's Web site.
    Moreover, as discussed previously, applicable special controls help 
ensure that individuals for whom the tests are conducted are able to 
understand the testing prior to the test being performed, as well as 
provide context, including limitations, regarding the clinical validity 
of the variants reported. These special controls mitigate the risks 
posed by incorrect test results and the risk that test results are 
interpreted incorrectly or are misleading.
    The special controls for devices of this type require rigorous 
analytical performance metrics and parameters to be met, which is what 
FDA would typically assess in its review of analytical performance in a 
premarket submission. The special control requiring this analytical 
performance information to be posted on the manufacturer's public Web 
site will allow FDA, as well as others, to review this information. 
Together these special controls, described in more detail in this 
document, obviate the need for premarket notification.
     First, the special controls provide a detailed listing of 
the protocol requirements and acceptance criteria for all analytical 
studies (e.g., precision/reproducibility, accuracy, interference, and 
cross-reactivity).
     Second, the special controls define how, in some cases, 
analyses must be performed and presented to the person from whom the 
tests are conducted.
     Third, a very high level of accuracy is prescribed in the 
special controls.
     Fourth, the special controls also require that devices of 
this type only use collection devices that are FDA cleared, FDA 
approved, or classified as 510(k) exempt, with an indication for in 
vitro diagnostic use in DNA testing. The use of a lawfully marketed 
collection device intended for such use provides assurances regarding 
the safety and effectiveness of that component of the device, which in 
turn helps to assure the safety and effectiveness of the device as a 
whole.
     Fifth, the special controls limit the distribution of 
devices of this type, excluding the collection device, to the 
manufacturer, manufacturer's subsidiaries, and laboratories subject to 
regulation under the Clinical Laboratory Improvement Amendments. This 
limitation mitigates risk through lowering the probability of 
inaccurate test results by ensuring that testing is performed by 
qualified individuals and in a manner that provides greater assurance 
of quality of the testing process.
     Sixth, specific statements regarding the probability of 
test failure and a description of scenarios in which a test can fail 
are prescribed in the special controls.
     Lastly, the special controls require warnings in the 
labeling to help ensure that persons for whom the tests are conducted 
and users are able to understand the testing prior to the test being 
performed, as well as provide context, including limitations, regarding 
the analytical validity of the variants reported.
    Taken together, these special controls mitigate the risks through 
lowering the probability of inaccurate test results and increasing the 
likelihood of user understanding regarding test limitations and 
performance. FDA believes that given the unique characteristics of an 
autosomal recessive carrier screening gene mutation detection system, 
including that both a mother and father must be carriers in order to 
have a 25 percent chance that their child would have the disorder, 
these special controls reasonably assure that a legally marketed device 
of this type will have the characteristics necessary for its safe and 
effective performance without the need for premarket notification.

C. Anticipated Changes in the Device That Could Affect Safety and 
Effectiveness Are Readily Detectable by Users or Would Not Materially 
Increase Risk

    The special controls, in combination with the general controls, 
assure that anticipated changes in the device that could affect safety 
and effectiveness will either be readily detectable by users or not 
materially increase risk.
    As discussed previously, the special controls include a detailed 
outline of clinical and analytical performance information that must be 
generated or obtained and posted on the manufacturer's Web site. Such 
special controls provide details on how analytical testing must be 
performed and provide certain performance criteria that the analytical 
testing must demonstrate have been met. Any changes to the device that 
could significantly affect safety or effectiveness would require new 
data or information in support of such changes, which would also have 
to be posted on

[[Page 65778]]

the manufacturer's Web site. The types of permissible changes are 
limited by the limitations of exemption at Sec.  866.9 (21 CFR 866.9), 
as discussed in this document.

D. Changes to the Device Would Not Result in a Change in Classification

    Subject to the applicable requirements under the special controls, 
in combination with general controls, changes to a device of this type 
would not be likely to result in a change in the device's 
classification. FDA also considered, in proposing to exempt these 
devices, that these devices would be subject to the limitations 
described in section IV.

IV. Limitations of Exemption

    FDA's proposal to grant an exemption from the premarket 
notification for an autosomal recessive carrier screening gene mutation 
detection system applies only to those devices that have existing or 
reasonably foreseeable characteristics of commercially distributed 
devices within that generic type, or, in the case of in vitro 
diagnostic devices, for which a misdiagnosis, as a result of using the 
device, would not be associated with high morbidity or mortality. FDA 
proposes that a manufacturer of an autosomal recessive carrier 
screening gene mutation detection system would still be required to 
submit a premarket notification to FDA before introducing a device or 
delivering it for introduction into commercial distribution when the 
device meets any of the conditions described in Sec.  866.9, except 
Sec.  866.9(c)(2) to the extent it may include an autosomal recessive 
carrier screening gene mutation detection system.
    FDA added the limitation of exemption from section 510(k) of the 
FD&C Act for in vitro devices intended for use in screening or 
diagnosis of familial or acquired genetic disorders, including inborn 
errors of metabolism (codified at Sec.  866.9(c)(2)) by notice in the 
Federal Register of January 21, 1998 (63 FR 3142), when FDA exempted 62 
types of class II devices from section 510(k) under section 510(m)(1). 
When FDA later made this limitation of exemption applicable to certain 
class I devices in 2000, FDA explained that FDA intended that devices 
used in connection with either familial or acquired genetic disorders 
be subject to premarket notification requirements because misdiagnosis 
of either of these disorders would be associated with high morbidity or 
mortality (65 FR 2296 at 2299). This category of in vitro diagnostic 
devices is much broader than autosomal recessive carrier screening gene 
mutation detection, if such a use is included in this category at all. 
To the extent such a use is included in Sec.  866.9(c)(2), FDA is 
proposing that this limitation not apply to the exemption of autosomal 
recessive carrier screening gene mutation detection systems from 
section 510(k) of the FD&C Act for the reasons that follow.
    First, autosomal recessive carrier screening gene mutation 
detection present very different risks from other tests covered by 
Sec.  866.9(c)(2), such as tests for screening or diagnosis of genetic 
disorders in the individuals being tested, as opposed to their 
offspring. As discussed in detail previously, because carrier screening 
is only intended to detect heterozygotes (carriers), false positive 
results would suggest that a person was a carrier of a mutation, but 
would not contain information that could lead to conclusions of disease 
for the tested person. Further, no conclusion about an individual's 
future children could be made given that the carrier status of the 
child's second parent would need to be known to reach such a 
conclusion, and even where both parents are truly positive the only 
conclusion that may be drawn is that the child has a 25 percent 
likelihood of manifesting the disease. The probability of a both 
parents receiving false positive carrier results from using a device of 
this type is vastly smaller than for a single false positive result.
    Second, based on FDA's increased understanding of genetic testing 
and the risks posed by devices of this type, FDA was able to develop 
special controls to mitigate the risks of false positive and false 
negative results, as detailed in section III. For example, the special 
controls requiring demonstration of both analytical and clinical 
validity, posting of this information on the manufacturer's Web site, 
consumer comprehension studies, information regarding genetic 
counseling, and warnings regarding the meaning, context, and 
limitations of results all reduce the likelihood of false results and 
of the harms that such may cause. As a result, the risk of false 
results, as mitigated by the special controls, in combination with 
general controls, for such device would not be associated with high 
morbidity or mortality, and FDA is proposing that the limitation of 
exemption in Sec.  866.9(c)(2) not apply to devices of this type to the 
extent the limitation includes autosomal recessive carrier screening 
gene mutation detection.
    FDA proposes that an autosomal recessive carrier screening gene 
mutation detection system is not exempt from the premarket notification 
requirement if such device: (1) 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; or (2) operates using a different 
fundamental scientific technology than that used by a legally marketed 
device in that generic type; 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; or (3) is an 
in vitro device that is intended: for use in the diagnosis, monitoring 
or screening of neoplastic diseases with the exception of 
immunohistochemical devices; for measuring an analyte which serves as a 
surrogate marker for screening, diagnosis, or monitoring of life 
threatening diseases, such as acquired immune deficiency syndrome 
(AIDS), chronic or active hepatitis, tuberculosis, or myocardial 
infarction, or to monitor therapy; 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 (point of care).
    When a device falls within or ``trips'' any of these limitations, 
510(k) clearance is required prior to marketing. Following a 
determination by FDA, through the premarket notification process, that 
such a device is substantially equivalent to a legally marketed device 
in the 510(k)-exempt generic type under 21 CFR 866.5940, and compliance 
with the special controls, future devices with the same indications and 
technological characteristics would be exempt from premarket 
notification. If you have questions regarding whether your device's 
indication for use constitutes a different intended use requiring 
510(k) submission, you may contact the Division of Chemistry and 
Toxicology Devices in the Office of In Vitro Diagnostics and 
Radiological Health to request a review of your indication for use and 
any relevant literature.

[[Page 65779]]

    Based on FDA's review of current scientific literature, FDA would 
not consider the determination of carrier status by detection of 
clinically relevant gene mutations associated with the diseases and 
conditions listed in Table 1 to constitute a different intended use 
from that of a legally marketed device in the generic type 21 CFR 
866.5940 for purposes of Sec.  866.9(a). Thus such uses would be 
510(k)-exempt once there is compliance with special controls. A gene 
mutation detection system indicated for the determination of carrier 
status by detection of clinically relevant gene mutations associated 
with Cystic Fibrosis is not 510(k)-exempt since it is a class II device 
subject to premarket notification and special controls under 21 CFR 
866.5900--Cystic fibrosis transmembrane conductance regulator (CFTR) 
gene mutation detection system.

                                 Table 1
------------------------------------------------------------------------
 
-------------------------------------------------------------------------
Beta Thalassemia
Bloom Syndrome
Canavan Disease
Congenital Disorder of Glycosylation Type 1a (PMM2-CDG)
Autosomal Recessive Connexin 26-Nonsyndromic Hearing Loss
D-Bifunctional Protein Deficiency
Dihydrolipoamide Dehydrogenase Deficiency
Familial Dysautonomia
Familial Mediterranean Fever
Fanconi Anemia Group C
Gaucher Disease
Glycogen Storage Disease Type 1 (1a and 1b)
Gracile Syndrome
Hereditary Fructose Intolerance
Junctional Epidermolysis Bullosa (LAMB3-related)
Leigh Syndrome, French Canadian Type (LSFC)
Autosomal Recessive Limb-girdle Muscular Dystrophy
Maple Syrup Urine Disease
Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency
Mucolipidosis IV
Autosomal Recessive Neuronal Ceroid Lipofuscinosis (CLN5-related)
Autosomal Recessive Neuronal Ceroid Lipofuscinosis (PPT1-related)
Niemann-Pick Disease--Type A
Nijmegen Breakage Syndrome
Pendred Syndrome
Phenylketonuria
Autosomal Recessive Polycystic Kidney Disease
Primary Hyperoxaluria Type 2 (PH2)
Rhizomelic Chondrodysplasia Punctata Type 1 (RCDP1)
Salla Disease
Sickle Cell Anemia
Sj[ouml]gren-Larsson Syndrome
Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)
Spinal Muscular Atrophy
Tay Sachs Disease
Tyrosinemia Type I
Usher Syndrome Type 1F
Usher Syndrome Type III
Zellweger Syndrome Spectrum
------------------------------------------------------------------------

    Exemption from the requirement of premarket notification does not 
exempt a device from other applicable regulatory controls under the 
FD&C Act, including the applicable general and special controls. 
Indeed, FDA's decision to propose 510(k) exemption for these devices is 
based, in part, on the special controls, in combination with general 
controls, providing sufficiently rigorous mitigations for the risks 
identified for this generic type.
    Subject to the limitations described previously, FDA has determined 
that the requirement of premarket notification is not necessary to 
assure the safety and effectiveness of an autosomal recessive carrier 
screening gene mutation detection system. Accordingly, FDA is 
announcing its intent to exempt from the premarket notification 
requirements autosomal recessive carrier screening gene mutation 
detection systems, subject to the limitations described previously. FDA 
is publishing this notice in order to obtain comments regarding the 
proposed exemption.

V. Paperwork Reduction Act of 1995

    This notice refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collections of information in 21 CFR part 807, subpart, E have been 
approved under OMB control number 0910-0120 and the collections of 
information in 21 CFR parts 801 and 809 have been approved under OMB 
control number 0910-0485.

VI. Reference

    The following reference is on display in the Division of Dockets 
Management (see ADDRESSES) and is available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; it is also 
available electronically at http://www.regulations.gov. FDA has 
verified the Web site address, as of the date this document publishes 
in the Federal Register, but Web sites are subject to change over time.

    1. ``Procedures for Class II Device Exemptions from Premarket 
Notification, Guidance for Industry and CDRH Staff,'' February 1998, 
available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM080199.pdf.

    Dated: October 20, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-27198 Filed 10-26-15; 8:45 am]
BILLING CODE 4164-01-P