[Federal Register Volume 80, Number 207 (Tuesday, October 27, 2015)]
[Notices]
[Pages 65774-65779]
[FR Doc No: 2015-27198]

-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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

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,<PHONE_NUMBER>.

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,

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

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

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.

    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


[Federal Register Volume 85, Number 31 (Friday, February 14, 2020)]
[Rules and Regulations]
[Pages 8472-8475]
[FR Doc No: 2020-02254]

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Parts 281 and 282

[EPA-R04-UST-2019-0310; FRL-10004-27-Region 4]

Georgia: Final Approval and Incorporation by Reference of State
Underground Storage Tank Program Revisions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The Environmental Protection Agency (EPA) is granting the
State of Georgia (Georgia or State) final approval of revisions to its
underground storage tank (UST) program pursuant to the Resource
Conservation and Recovery Act (RCRA). In addition, the EPA is codifying
EPA's approval of Georgia's revised UST program and incorporating by
reference those provisions of the State statutes and regulations that
the EPA has determined meet the requirements for approval. EPA
published a proposed rule on September 16, 2019 and provided for public
comment. No comments were received on the EPA's proposed approval of
Georgia's UST program revisions. No further opportunity for comment
will be provided.

DATES: This final rule is effective February 14, 2020. The
incorporation by reference of certain publications listed in the
regulations is approved by the Director of the Federal Register, as of
February 14, 2020.

ADDRESSES: The EPA has established a docket for this action under
Docket ID No. EPA-R04-UST-2019-0310. All documents in the docket are
listed on the http://www.regulations.gov website. Certain other
material, such as copyrighted material, is not placed on the internet
and will be publicly

available only in hard copy form. Publicly available docket materials
are available electronically through http://www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: Aaryn Jones, RCRA Programs and Cleanup
Branch, Land, Chemicals and Redevelopment Division, U.S. Environmental
Protection Agency, Region 4, Atlanta Federal Center, 61 Forsyth Street
SW, Atlanta, Georgia 30303-8960; Phone number:<PHONE_NUMBER>; email
address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. Approval of Revisions to Georgia's UST Program

A. What changes to Georgia's UST program is EPA approving with this
action?

    On August 8, 2018, in accordance with 40 CFR 281.51(a), Georgia
submitted a complete program revision application (State Application)
seeking approval of changes to its UST program. EPA now makes a final
decision that Georgia's UST program revisions are no less stringent
than the corresponding Federal program. Therefore, the EPA grants
Georgia final approval to operate its UST program with the changes
described in the State Application and as outlined in the proposed rule
published in the September 16, 2019 Federal Register at 84 FR 48573.
Although no comments were received on the EPA's proposed approval of
Georgia's UST program revisions, the EPA noticed an error in the date
of the Georgia statutory and regulatory materials listed in the
proposed regulatory text at 40 CFR 282.60(d)(1)(i). The date of these
materials was improperly listed as August 2018. The EPA has corrected
the date in the final regulatory text to August 2019. The State's
federally-approved and codified UST program as revised pursuant to this
action will remain subject to the EPA's inspection and enforcement
authorities under sections 9005 and 9006 of RCRA subtitle I and other
applicable statutory and regulatory provisions.

II. Codification

A. What is codification?

    Codification is the process of placing citations and references to
a state's statutes and regulations that comprise a state's approved UST
program into the Code of Federal Regulations (CFR). The EPA codifies
its approval of state programs in 40 CFR part 282 and incorporates by
reference state statutes and regulations that the EPA can enforce,
after the approval is final, under sections 9005 and 9006 of RCRA, and
any other applicable statutory provisions. The incorporation by
reference of EPA-approved state programs in the CFR should
substantially enhance the public's ability to discern the status of the
approved state UST program and state requirements that can be federally
enforced. This effort provides clear notice to the public of the scope
of the approved program in each state.

B. What is the history of codification of Georgia's UST program?

    In 1996, the EPA incorporated by reference and codified Georgia's
approved UST program at 40 CFR 282.60 (61 FR 4224, February 5, 1996).
Through this action, the EPA is amending 40 CFR 282.60 to incorporate
by reference and codify Georgia's revised UST program.

C. What codification decisions is the EPA making in this rule?

    In this rule, the EPA is finalizing regulatory text that
incorporates by reference the federally approved Georgia UST program,
including the revisions described in the State Application. In
accordance with the requirements of 1 CFR 51.5, the EPA is
incorporating by reference Georgia's statutes and regulations as
described in the amendments to 40 CFR part 282 set forth below. These
documents are available through https://www.regulations.gov and at the
EPA Region 4 office (see the FOR FURTHER INFORMATION CONTACT section of
this preamble for more information).
    Specifically, in Section 282.60(d)(1)(i), the EPA is incorporating
by reference the Georgia-approved UST program. Section 282.60(d)(1)(ii)
identifies the State's statutes and regulations that are part of the
approved State program, although not incorporated by reference for
enforcement purposes. Section 282.60(d)(2) through (d)(5) reference the
Attorney General's Statement, Demonstration of Adequate Enforcement
Procedures, the Program Description, and the Memorandum of Agreement,
which are part of the State Application and approved as part of the UST
program under subtitle I of RCRA.

D. What is the effect of the EPA's codification of the federally
approved Georgia UST program on enforcement?

    The EPA retains the authority under sections 9003(h), 9005, and
9006 of subtitle I of RCRA, 42 U.S.C. 6991b(h), 6991d, and 6991e, and
other applicable statutory and regulatory provisions, to undertake
corrective action, inspections, and enforcement actions, and to issue
orders in approved states. If the EPA determines it will take such
actions in Georgia, the EPA will rely on federal sanctions, federal
inspection authorities, and other federal procedures rather than the
State analogs. Therefore, the EPA is not incorporating by reference
Georgia's procedural and enforcement authorities, although they are
listed in 40 CFR 282.60(d)(1)(ii).

E. What State provisions are not part of the codification?

    Some provisions of the State's UST program are not part of the
federally approved State program because they are ``broader in scope''
than the federal UST program. 40 CFR 281.12(a)(3)(ii) states that,
where an approved state program has provisions that are broader in
scope than the federal program, those provisions are not a part of the
federally approved program. As a result, State provisions which are
``broader in scope'' than the federal program are not incorporated by
reference for purposes of enforcement in part 282. In addition,
provisions that are external to the State UST program approval
requirements, but included in the State Application, are also being
excluded from incorporation by reference in part 282. For reference and
clarity, 40 CFR 282.60(d)(1)(iii) lists the Georgia statutory and
regulatory provisions which are ``broader in scope'' than the federal
program and external to state UST program approval requirements. These
provisions are, therefore, not part of the approved program that the
EPA is codifying. Although these provisions cannot be enforced by the
EPA, the State will continue to implement and enforce such provisions
under State law.

III. Statutory and Executive Order (E.O.) Reviews

    This final action merely approves and codifies Georgia's revised
UST program requirements pursuant to RCRA section 9004 and does not
impose additional requirements other than those imposed by State law.
For further information on how this action complies with applicable
executive orders and statutory provisions, please see the proposed rule
published in the September 16, 2019 Federal Register at 84 FR 48573.
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the

United States. EPA will submit a report containing this document and
other required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication in the Federal Register. A major rule cannot take effect
until 60 days after it is published in the Federal Register. This
action is not a ``major rule'' as defined by 5 U.S.C. 804(2). This
final action will be effective February 14, 2020.

List of Subjects

40 CFR Part 281

    Environmental protection, Administrative practice and procedure,
Petroleum, Hazardous substances, State program approval, Underground
storage tanks, and Reporting and recordkeeping requirements.

40 CFR Part 282

    Environmental protection, Administrative practice and procedure,
Petroleum, Hazardous substances, Incorporation by reference, State
program approval, Underground storage tanks, and Reporting and
recordkeeping requirements.

    Authority: This action is issued under the authority of Sections
2002(a), 7004(b), 9004, 9005 and 9006 of the Solid Waste Disposal
Act, as amended, 42 U.S.C. 6912(a), 6974(b), 6991c, 6991d, and
6991e.

Mary S. Walker,
Regional Administrator, Region 4.

    For the reasons set forth in the preamble, EPA is amending 40 CFR
part 282 as follows:

PART 282--APPROVED UNDERGROUND STORAGE TANK PROGRAMS

0
1. The authority citation for part 282 continues to read as follows:

    Authority:  42 U.S.C. 6912, 6991c, 6991d, and 6991e.

0
2. Revise Sec.  282.60 to read as follows:

Sec.  282.60  Georgia State-Administered Program.

    (a) History of the approval of Georgia's Program. The State of
Georgia is approved to administer and enforce an underground storage
tank program in lieu of the federal program under subtitle I of the
Resource Conservation and Recovery Act of 1976 (RCRA), as amended, 42
U.S.C. 6991 et seq. The State's program, as administered by the Georgia
Department of Natural Resources, Environmental Protection Division, was
approved by EPA pursuant to 42 U.S.C. 6991c and part 281 of this
Chapter. EPA approved the Georgia program on May 10, 1991 and it was
effective on July 9, 1991. A subsequent program revision was approved
by EPA and became effective on February 14, 2020.
    (b) Enforcement authority. Georgia has primary responsibility for
administering and enforcing its federally approved underground storage
tank program. However, EPA retains the authority to exercise its
corrective action, inspection, and enforcement authorities under
sections 9003(h), 9005, and 9006 of subtitle I of RCRA, 42 U.S.C.
6991b(h), 6991d, and 6991e, as well as under any other applicable
statutory and regulatory provisions.
    (c) Retention of program approval. To retain program approval,
Georgia must revise its approved program to adopt new changes to the
federal subtitle I program which make it more stringent, in accordance
with section 9004 of RCRA, 42 U.S.C. 6991c, and 40 CFR part 281,
subpart E. If Georgia obtains approval for revised requirements
pursuant to section 9004 of RCRA, 42 U.S.C. 6991c, the newly approved
statutory and regulatory provisions will be added to this subpart and
notice of any change will be published in the Federal Register.
    (d) Final approval. Georgia has final approval for the following
elements of its underground storage tank program originally submitted
to EPA and approved effective July 9, 1991, and the program revisions
approved by EPA effective on February 14, 2020.
    (1) State statutes and regulations--(i) Incorporation by reference.
The Georgia materials cited in this paragraph, and listed in appendix A
to part 282, are incorporated by reference as part of the underground
storage tank program under subtitle I of RCRA, 42 U.S.C. 6991 et seq.
The Director of the Federal Register approves this incorporation by
reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may
obtain copies of the Georgia statutes that are incorporated by
reference in this paragraph from LexisNexis, Attn: Official Code of
Georgia Annotated, 701 East Water Street, Charlottesville, VA 22902-
5389; Phone number: 1-800-833-9844; website: http://sos.ga.gov/index.php/elections/georgia_code_-_lexisnexis. You may obtain copies of
the Georgia regulations that are incorporated by reference in this
paragraph from the Administrative Procedures Division, Office of the
Georgia Secretary of State, 5800 Jonesboro Road, Morrow, Georgia 30260;
Phone number:<PHONE_NUMBER>; website: http://rules.sos.ga.gov/gac/391-3-15. You may inspect all approved material at the EPA Region 4, 61
Forsyth Street SW, Atlanta, Georgia 30303; Phone number: (404) 562-
9900; or the National Archives and Records Administration (NARA). For
information on the availability of the material at NARA, email
<EMAIL_ADDRESS>or go to www.archives.gov/federal-register/cfr/ibr-locations.html.
    (A) ``Georgia Statutory Requirements Applicable to the UST
Program'', dated August 2019.
    (B) ``Georgia Regulatory Requirements Applicable to the UST
Program'', dated August 2019.
    (ii) Legal basis. The EPA evaluated the following statutes and
regulations which provide the legal basis for the State's
implementation of the underground storage tank program, but they are
not being incorporated by reference and do not replace federal
authorities:
    (A) Official Code of Georgia Annotated (2017), Title 12.
``Conservation and Natural Resources,'' Chapter 13, ``Georgia
Underground Storage Tank Act'': Sections 12-13-5; 12-13-6; 12-13-8; 12-
13-11(a) and (f); 12-13-14 through 12-13-17; and 12-13-19 through 12-3-
22.
    (B) Rules and Regulations of the State of Georgia (November 6,
2017), Department 391. ``Rules of the Georgia Department of Natural
Resources,'' Chapter 3, ``Environmental Protection,'' Subject 15,
``Underground Storage Tank Management'': Sections 391-3-15-.01(2) and
391-3-15-.14.
    (iii) Other Provisions not incorporated by reference. The following
specifically identified sections and rules applicable to the Georgia
underground storage tank program that are broader in scope than the
federal program or external to the state UST program approval
requirements are not part of the approved program, and are not
incorporated by reference herein:
    (A) Official Code of Georgia Annotated (2017), Title 12:
``Conservation and Natural Resources,'' Chapter 13, ``Georgia
Underground Storage Tank Act'': Sections 12-13-3(8) and (16); 12-13-7;
12-13-9(d) through (i); 12-13-10; 12-13-11(b) through (e); 12-13-12;
12-13-13(e), and 12-13-18.
    (B) Rules and Regulations of the State of Georgia (November 6,
2017), Department 391: ``Rules of the Georgia Department of Natural
Resources,'' Chapter 3, ``Environmental Protection,'' Subject 15,
``Underground Storage Tank Management'': Sections 391-3-15-.01(1); 391-
3-15-.03(1)(a), (g), (i), and (p) through (r); 391-3-15-.04; 391-3-
15-.05(4); 391-3-15-.09(5) and (7); 391-15-3-.12(3); 391-3-15-.13; and
391-3-15-.15.
    (2) Statement of legal authority. The Attorney General's Statement,
signed by

the Attorney General on June 12, 2018, though not incorporated by
reference, is referenced as part of the approved underground storage
tank program under subtitle I of RCRA, 42 U.S.C. 6991 et seq.
    (3) Demonstration of procedures for adequate enforcement. The
``Demonstration of Procedures for Adequate Enforcement'' submitted as
part of Georgia's application on August 8, 2018, though not
incorporated by reference, is referenced as part of the approved
underground storage tank program under subtitle I of RCRA, 42 U.S.C.
6991 et seq.
    (4) Program description. The Program Description submitted as part
of Georgia's application on August 8, 2018, though not incorporated by
reference, is referenced as part of the approved underground storage
tank program under subtitle I of RCRA, 42 U.S.C. 6991 et seq.
    (5) Memorandum of Agreement. The Memorandum of Agreement between
EPA Region 4 and the Georgia Environmental Protection Division, signed
by EPA Regional Administrator on October 12, 2018, though not
incorporated by reference, is referenced as part of the approved
underground storage tank program under subtitle I of RCRA, 42 U.S.C.
6991 et seq.

0
3. Appendix A to part 282 is amended by revising the entry for Georgia
to read as follows:

Appendix A to Part 282--State Requirements Incorporated by Reference in
Part 282 of the Code of Federal Regulations

* * * * *

Georgia

    (a) The statutory provisions include: Official Code of Georgia
Annotated (2017), Title 12: ``Conservation and Natural Resources,''
Chapter 13, ``Georgia Underground Storage Tank Act'':
    Section 12-13-1 Short title.
    Section 12-13-2 Public policy.
    Section 12-13-3 Definitions, except (8) and (16).
    Section 12-13-4 Exceptions to chapter.
    Section 12-13-9 Establishing financial responsibility; claims
against the guarantor; Underground Storage Tank Trust Fund, except
(d) through (i).
    Section 12-13-13 Notification by owner of underground storage
tank, except (e).
    (b) The regulatory provisions include: Rules and Regulations of
the State of Georgia (November 6, 2017), Department 391: ``Rules of
the Georgia Department of Natural Resources,'' Chapter 3,
``Environmental Protection,'' Subject 15, ``Underground Storage Tank
Management'':
    Section 391-3-15-.01(3) General Provisions
    Section 391-3-15-.02 UST Exclusions.
    Section 391-3-15-.03 Definitions, except (1)(a), (1)(g), (1)(i),
and (1)(p) through (r).
    Section 391-3-15-.05 UST Systems: Design, Construction,
Installation, and Notification, except (4).
    Section 391-3-15-.06 General Operating Requirements.
    Section 391-3-15-.07 Release Detection.
    Section 391-3-15-.08 Release Reporting, Investigation, and
Confirmation.
    Section 391-3-15-.09 Release Response and Corrective Action for
UST Systems Containing Petroleum, except (5) and (7).
    Section 391-3-15-.10 Release Response and Corrective Action for
UST Systems Containing Hazardous Substances.
    Section 391-3-15-.11 Out-of-Service UST Systems and Closure.
    Section 391-3-15-.12 Underground Storage Tanks Containing
Petroleum; Financial Responsibility Requirements, except (3).
    Section 391-3-15-.16 Operator Training.
    Section 391-3-15-.17 Airport Hydrant Systems and Field
Constructed Tanks.
    (c) Copies of the Georgia statutes that are incorporated by
reference are available from LexisNexis, Attn: Official Code of
Georgia Annotated, 701 East Water Street, Charlottesville, VA 22902-
5389; Phone number: 1-800-833-9844; website: http://sos.ga.gov/index.php/elections/georgia_code_-_lexisnexis. Copies of the Georgia
regulations that are incorporated by reference are available from
the Administrative Procedures Division, Office of the Georgia
Secretary of State, 5800 Jonesboro Road, Morrow, Georgia 30260;
Phone number:<PHONE_NUMBER>; website: http://rules.sos.ga.gov/gac/391-3-15.
* * * * *
[FR Doc. 2020-02254 Filed 2-13-20; 8:45 am]
 BILLING CODE 6560-50-P


[Federal Register: October 20, 2009 (Volume 74, Number 201)]
[Notices]
[Page 53750-53751]
[DOCID:fr20oc09-66]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2009-N-0489]

Agency Information Collection Activities; Proposed Collection;
Comment Request; Recommendations for Clinical Laboratory Improvement
Amendments of 1988 Waiver Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing an
opportunity for public comment on the proposed collection of certain
information by the agency. Under the Paperwork Reduction Act of 1995
(the PRA), Federal agencies are required to publish notice in the
Federal Register concerning each proposed collection of information,
including each proposed extension, of an existing collection of
information and to allow 60 days for public comment in response to the
notice. This notice solicits comments on collections of information
associated with the guidance issued January 30, 2008, and titled
``Recommendations: Clinical Laboratory Improvement Amendments of 1988
(CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic
Devices''.

DATES: Submit written or electronic comments on the collection of
information by December 21, 2009.

ADDRESSES: Submit electronic comments on the collection of information
to http://www.regulations.gov. Submit written comments on the
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. All comments should be identified with the docket
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Denver Presley, Jr., Office of
Information Management (HFA-710), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal
agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes agency requests or requirements that members of
the public submit reports, keep records, or provide information to a
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A))
requires Federal agencies to provide a 60-day notice in the Federal
Register concerning each proposed collection of information, including
each proposed extension of an existing collection of information,
before submitting the collection to OMB for approval. To comply with
this requirement, FDA is publishing notice of the proposed collection
of information set forth in this document.
    With respect to the following collection of information, FDA
invites comments on these topics: (1) Whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.

Recommendations for Clinical Laboratory Improvement Amendments of 1988
Waiver Applications--21 CFR Section 493 (OMB Control Number 0910-
0598)--Extension

    Congress passed the Clinical Laboratory Improvements Amendment
(CLIA) (Public Law 100-578) in 1988 to establish quality standards for
all laboratory testing. The purpose was to ensure the accuracy,
reliability, and timeliness of patient test results regardless of where
the test took place. CLIA requires that clinical laboratories obtain a
certificate from the Secretary of Health and Human Services (the
Secretary), before accepting materials derived from the human body for
laboratory tests (42 U.S.C. 263a(b)). Laboratories that perform only
tests that are ``simple'' and that have an ``insignificant risk of an
erroneous result'' may obtain a certificate of waiver (42 U.S.C.
263a(c)(2)). The Secretary has delegated to FDA the authority to
determine whether particular tests (waived tests) are ``simple'' and
have ``an insignificant risk of an erroneous result'' under CLIA (69 FR
22849, April 27, 2004). This

guidance document describes recommendations for device manufacturers
submitting to FDA an application for determination that a cleared or
approved device meets this CLIA standard (CLIA waiver application).
    The guidance recommends that CLIA waiver applications include a
description of the features of the device that make it ``simple''; a
report describing a hazard analysis that identifies potential sources
of error, including a summary of the design and results of flex studies
and conclusions drawn from the flex studies; a description of fail-safe
and failure alert mechanisms and a description of the studies
validating these mechanisms; a description of clinical tests that
demonstrate the accuracy of the test in the hands of intended
operators; and statistical analyses of clinical study results. Only new
information collections not already approved are included in the
estimate in the following table. Quick reference instructions are a
short version of the instructions that are written in simple language
and that can be posted.
    FDA estimates the burden of this collection as follows:

                                                     Table 1.--Estimated Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                 No. of       Annual Frequency  of   Total Annual      Hours per                        Operating and
              21 CFR Section                  Respondents           Response           Responses       Response       Total Hours     Maintenance Costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
493.15(a) and (b)                                         40                     1              40             780          31,200               $50,200
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs associated with this collection of information.

                                                   Table 2.--Estimated Annual Recordkeeping Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                 No. of         Annual Frequency     Total Annual      Hours per                        Operating and
              21 CFR Section                 Recordkeepers      per Recordkeeping       Records         Record        Total Hours     Maintenance Costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
493.15(a) and (b)                                         40                     1              40           2,800         112,000               $16,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs associated with this collection of information.

    The total number of reporting and recordkeeping hours is 143,200
hours. FDA bases the burden on an agency analysis of premarket
submissions with clinical trials similar to the waived laboratory
tests. Based on previous years' experience with CLIA waiver
applications, FDA expects 40 manufacturers to submit one CLIA waiver
application per year. The time required to prepare and submit a waiver
application, including the time needed to assemble supporting data,
averages 780 hours per waiver application for a total of 31,200 hours
for reporting. Based on previous years experience with CLIA waiver
applications, FDA expects that each manufacturer will spend 2,800 hours
creating and maintaining the record for a total of 112,000 hours.
    The total operating and maintenance cost associated with the waiver
application is estimated at $66,200. The cost consists of specimen
collection for the clinical study (estimated $23,500); laboratory
supplies, reference testing and study oversight (estimated $26,700);
shipping and office supplies (estimated $6,000); and educational
materials, including quick reference instructions (estimated $10,000).
    This guidance also refers to previously approved collections of
information found in FDA regulations. The collections of information in
21 CFR part 801 and Sec.  809.10 have been approved under OMB control
number 0910-0485 and the collections of information in 21 CFR part 803
have been approved under OMB control number 0910-0437.

    Dated: October 9, 2009.
David Horowitz,
Assistant Commissioner for Policy.
[FR Doc. E9-25177 Filed 10-19-09; 8:45 am]

BILLING CODE 4160-01-S


[Federal Register Volume 81, Number 233 (Monday, December 5, 2016)]
[Rules and Regulations]
[Pages 87454-87455]
[FR Doc No: 2016-29049]

-----------------------------------------------------------------------

DEPARTMENT OF HOMELAND SECURITY

Coast Guard

33 CFR Part 117

[Docket No. USCG-2016-1007]

Drawbridge Operation Regulation; Atlantic Intracoastal Waterway
(Albemarle and Chesapeake Canal), Chesapeake, VA

AGENCY: Coast Guard, DHS.

ACTION: Notice of deviation from drawbridge regulation.

-----------------------------------------------------------------------

SUMMARY: The Coast Guard has issued a temporary deviation from the
operating schedule that governs the S168 (Battlefield Blvd. S/SR 168
BUS) Bridge across the Albemarle & Chesapeake Canal, mile 12.0,
Atlantic Intracoastal Waterway, Chesapeake (Great Bridge), VA. The
deviation is necessary to accommodate the 32nd Annual Chesapeake Rotary
Christmas Parade. This deviation allows the bridge to remain in the
closed-to-navigation position.

DATES: The deviation is effective from 4:00 p.m. to 10:00 p.m.,
December 3, 2016.

ADDRESSES: The docket for this deviation, [USCG-2016-1007] is available
at http://www.regulations.gov. Type the docket number in the ``SEARCH''
box and click ``SEARCH''. Click on Open Docket Folder on the line
associated with this deviation.

FOR FURTHER INFORMATION CONTACT: If you have questions on this
temporary deviation, call or email Mr. Martin Bridges, Bridge
Administration Branch Fifth District, Coast Guard, telephone 757-398-
6422, email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:  The City of Chesapeake, who owns the S168
(Battlefield Blvd. S/SR 168 BUS) Bridge across the Albemarle &
Chesapeake Canal, mile 12.0, Atlantic Intracoastal Waterway, Chesapeake
(Great Bridge), VA, has requested a temporary deviation from the
current operating regulations set out in 33 CFR 117.997(g) to
facilitate the 32nd Annual Chesapeake Rotary Christmas Parade.
    Under this temporary deviation, the bridge will remain in the
closed-to-navigation position from 4:00 p.m. to 6:00 p.m. and from 8:00
p.m. to 10:00 p.m., on December 3, 2016. The closure has been requested
to ensure the safety of the increased volume of cars and spectators
that will be participating in the 32nd Annual Chesapeake Rotary
Christmas Parade. The bridge is a single bascule bridge and has a
vertical clearance in the closed-to-navigation position of 8 feet above
mean high water.
    The Atlantic Intracoastal Waterway (Albemarle and Chesapeake Canal)
is used by a variety of vessels including recreational, tug and barge,
fishing vessels, and small commercial vessels. The Coast Guard has
carefully considered the nature and volume of vessel traffic on the
waterway in publishing this temporary deviation.
    Vessels able to pass through the bridge in the closed- position may
do so at any time. The bridge will open in case of an emergency and
there is no immediate alternate route for vessels to pass. The Coast
Guard will also inform the users of the waterway through our Local
Notice and Broadcast Notices to Mariners of the change in operating
schedule for the bridge so that vessel operators can arrange their
transits to minimize any impact caused by the temporary deviation.
    In accordance with 33 CFR 117.35(e), the drawbridge must return to
its regular operating schedule immediately at the end of the effective
period of this temporary deviation. This deviation from the operating
regulations is authorized under 33 CFR 117.35.

    Dated: November 29, 2016.
Hal R. Pitts,
Bridge Program Manager, Fifth Coast Guard District.
[FR Doc. 2016-29049 Filed 12-2-16; 8:45 am]
 BILLING CODE 9110-04-P


[Federal Register Volume 79, Number 85 (Friday, May 2, 2014)]
[Notices]
[Page 25129]
[FR Doc No: 2014-10095]

-----------------------------------------------------------------------

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Project No. 4296-010]

Wave Hydro, LLC; Northline Energy, LLC; Notice of Transfer of
Exemption

    1. By letter filed March 26, 2014, Northline Energy, LLC informed
the Commission that the exemption from licensing for the Seneca
Hydroelectric Project, FERC No. 4296, originally issued February 17,
1982,\1\ has been transferred to Northline Energy, LLC. The project is
located on the Seneca River in Onondaga County, New York. The transfer
of an exemption does not require Commission approval.
---------------------------------------------------------------------------

    \1\ 18 FERC ] 62,227, Order Granting Exemption from Licensing of
a Small Hydroelectric Project of 5 Megawatts or Less.
---------------------------------------------------------------------------

    2. Northline Energy, LLC, located at 15 School Lane, P.O. Box 656,
Au Sable Forks, NY 12912, is now the exemptee of the Seneca
Hydroelectric Project, FERC No. 4296.

    Dated: April 28, 2014.
Kimberly D. Bose,
Secretary.
[FR Doc. 2014-10095 Filed 5-1-14; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register Volume 79, Number 123 (Thursday, June 26, 2014)]
[Rules and Regulations]
[Page 36220]
[FR Doc No: 2014-14868]

-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 52

[EPA-R05-OAR-2014-0274; FRL-9912-57-Region 5]

Approval and Promulgation of Air Quality Implementation Plans;
Illinois; Revision to the Chicago 8-Hour Ozone Maintenance Plan

AGENCY: Environmental Protection Agency (EPA).

ACTION: Withdrawal of direct final rule.

-----------------------------------------------------------------------

SUMMARY: Due to the receipt of an adverse comment, EPA is withdrawing
the May 22, 2014, direct final rule approving a revision to the
Illinois State Implementation Plan (SIP). EPA will address the comment
in a subsequent final action based upon the proposed rulemaking action,
also published on May 22, 2014. EPA will not institute a second comment
period on this action.

DATES: The direct final rule published at 79 FR 29324 on May 22, 2014,
is withdrawn effective June 26, 2014.

FOR FURTHER INFORMATION CONTACT: Michael Leslie, Environmental
Engineer, Control Strategies Section, Air Programs Branch (AR-18J),
Environmental Protection Agency, Region 5, 77 West Jackson Boulevard,
Chicago, Illinois 60604,<PHONE_NUMBER><EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: EPA is withdrawing the May 22, 2014 (79 FR
29324), direct final rule approving a revision to the 1997 8-hour ozone
maintenance plan for the Illinois portion of the Chicago-Gary-Lake
County, Illinois-Indiana area. In the direct final rule, EPA stated
that if adverse comments were received by June 23, 2014, the rule would
be withdrawn and not take effect. On May 26, 2014, EPA received a
comment, which it interprets as adverse and, therefore, EPA is
withdrawing the direct final rule. EPA will address the comment in a
subsequent final action based upon the proposed rulemaking action, also
published on May 22, 2014 (79 FR 29395). EPA will not institute a
second comment period on this action.

List of Subjects in 40 CFR Part 52

    Environmental protection, Air pollution control, Incorporation by
reference, Oxides of nitrogen, Ozone, Volatile organic compounds.

    Authority: 42 U.S.C. 7401 et seq.

    Dated: June 10, 2014.
Susan Hedman,
Regional Administrator, Region 5.

PART 52--APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS

0
Accordingly, the amendment to 40 CFR 52.726 published in the Federal
Register on May 22, 2014 (79 FR 29324) on page 29327 is withdrawn
effective June 26, 2014.

[FR Doc. 2014-14868 Filed 6-25-14; 8:45 am]
BILLING CODE 6560-50-P