[Federal Register Volume 80, Number 207 (Tuesday, October 27, 2015)]
[Rules and Regulations]
[Pages 65626-65632]
[FR Doc No: 2015-27197]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2015-N-3472]

Medical Devices; Immunology and Microbiology Devices;
Classification of Autosomal Recessive Carrier Screening Gene Mutation
Detection System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA) has classified an
autosomal recessive carrier screening gene mutation detection system
into class II (special controls). The special controls that apply to
this device are identified in this order and will be part of the
codified language for the autosomal recessive carrier screening gene
mutation detection system classification. The Agency has classified the
device into class II (special controls) in order to provide a
reasonable assurance of safety and effectiveness of the device.

DATES: This order is effective October 27, 2015. The classification was
applicable February 19, 2015.

FOR FURTHER INFORMATION CONTACT: Sunita Shukla, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 4647, Silver Spring, MD 20993-0002,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Background

    In accordance with section 513(f)(1) of the Federal Food, Drug, and
Cosmetic Act (the FD&C Act) (21 U.S.C. 360c(f)(1)), devices that were
not in commercial distribution before May 28, 1976 (the date of
enactment of the Medical Device Amendments of 1976), generally referred
to as postamendments devices, are classified automatically by statute
into class III without any FDA rulemaking process. These devices remain
in class III and require premarket approval, unless and until the
device is classified or reclassified into class I or II, or FDA issues
an order finding the device to be substantially equivalent, in
accordance with section 513(i) of the FD&C Act, to a predicate device
that does not require premarket approval. The Agency determines whether
new devices are substantially equivalent to predicate devices by means
of premarket notification procedures in section 510(k) of the FD&C Act
(21 U.S.C. 360(k)) and part 807 (21 CFR part 807) of the regulations.
    Section 513(f)(2) of the FD&C Act, as amended by section 607 of the
Food and Drug Administration Safety and Innovation Act (Pub. L. 112-
144), provides two procedures by which a person may request FDA to
classify a device under the criteria set forth in section 513(a)(1).
Under the first procedure, the person submits a premarket notification
under section 510(k) of the FD&C Act for a device that has not
previously been classified and, after receiving an order classifying
the device into class III under section 513(f)(1) of the FD&C Act, the
person requests a classification under section 513(f)(2). Under the
second procedure, rather than first submitting a premarket notification
under section 510(k) of the FD&C Act and then a request for
classification under the first procedure, the person determines that
there is no legally marketed device upon which to base a determination
of substantial equivalence and requests a classification under section
513(f)(2) of the FD&C Act. If the person submits a request to classify
the device under this second procedure, FDA may decline to undertake
the classification request if FDA identifies a legally marketed device
that could provide a reasonable basis for review of substantial
equivalence with the device or if FDA determines that the device
submitted is not of ``low-moderate risk'' or that general controls
would be inadequate to control the risks and special controls to
mitigate the risks cannot be developed.
    In response to a request to classify a device under either
procedure provided by section 513(f)(2) of the FD&C Act, FDA will
classify the device by written order within 120 days. This
classification will be the initial classification of the device.
    23andMe, Inc., submitted a direct de novo request for
classification of the 23andMe PGS Carrier Screening Test for Bloom
Syndrome under section 513(f)(2)(A)(ii) of the FD&C Act, based on a
determination that there is no legally marketed device on which to base
a determination of substantial equivalence.
    In accordance with section 513(f)(2) of the FD&C Act, FDA reviewed
the request in order to classify the device under the criteria for
classification set forth in section 513(a)(1) of the FD&C Act. After
review of the information submitted in the de novo request, FDA
classified the device into class II because general controls by
themselves are insufficient to provide reasonable assurance of safety
and effectiveness, and there is sufficient information to establish
special controls to provide reasonable assurance of the safety and
effectiveness of the device for its intended use.
    Therefore, on February 19, 2015, FDA issued an order to the
requestor classifying the device into class II. The classification of
the device will be codified at 21 CFR 866.5940.
    The device is assigned the generic name autosomal recessive carrier
screening gene mutation detection system, and it is identified as 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.

    A gene mutation detection system indicated for the determination of
carrier status by detection of clinically relevant gene mutations
associated with cystic fibrosis is separately classified under 21 CFR
866.5900--Cystic fibrosis transmembrane conductance regulator (CFTR)
gene mutation detection system (class II, special controls), and is
thus not included in the de novo classification.
    FDA has identified the following risks to health associated with
this type of device and the measures required to mitigate these risks
in table 1.

           Table 1--Identified Risks and Required Mitigations
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             Identified risks                   Required mitigations
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Incorrect understanding of the device and   Special controls 1 and 4.
 test system.
Incorrect test results....................  Special controls 2, 3, 5,
                                             and 6.
Incorrect interpretation of test results..  Special controls 1, 3, 4,
                                             and 5.
------------------------------------------------------------------------

    FDA believes that the following special controls, in addition to
the general controls, address these risks to health and provide
reasonable assurance of safety and effectiveness:
    1. If the device is offered over-the-counter, the device
manufacturer must provide information to a potential purchaser or
actual test report recipient about how to obtain access to a board-
certified clinical molecular geneticist or equivalent to assist in pre-
and post-test counseling.
    2. The device must use a collection device that is FDA cleared,
approved, or classified as 510(k) exempt, with an indication for in
vitro diagnostic use in DNA testing.
    3. The device's labeling must include a prominent hyperlink to the
manufacturer's public Web site where the manufacturer shall make the
information identified in this subsection publicly available. The
manufacturer's home page, as well as the primary part of the
manufacturer's Web site that discusses the device, must provide a
prominently placed hyperlink to the Web page containing this
information and must allow unrestricted viewing access. If the device
can be purchased from the Web site or testing using the device can be
ordered from the Web site, the same information must be found on the
Web page for ordering the device or provided in a prominently placed
and publicly accessible hyperlink on the Web page for ordering the
device. 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 information must include:
    a. A detailed device description including:
    i. Gene (or list of the genes if more than one) and variants the
test detects (using standardized nomenclature, Human Genome
Organization (HUGO) nomenclature, and coordinates);
    ii. Scientifically established clinical validity of each variant
detected and reported by the test, which must be well-established in
peer-reviewed journal articles, authoritative summaries of the
literature such as Genetics Home Reference (http://ghr.nlm.nih.gov/),
GeneReviews (http://www.ncbi.nlm.nih.gov/books/NBK1116/), or similar
summaries of valid scientific evidence, and/or professional society
recommendations, including:
    A. Genotype-phenotype information for the reported mutations.
    B. Relevant American College of Medical Genetics (ACMG) or American
Congress of Obstetricians and Gynecologists (ACOG) guideline
recommending testing of the specific gene(s) and variants the test
detects and recommended populations, if available. If not available, a
statement stating that professional guidelines currently do not
recommend testing for this specific gene(s) and variants.
    C. Table of expected prevalence of carrier status in major ethnic
and racial populations and the general population.
    iii. The specimen type (e.g., saliva, whole blood), matrix, and
volume;
    iv. Assay steps and technology used;
    v. Specification of required ancillary reagents, instrumentation,
and equipment;
    vi. Specification of the specimen collection, processing, storage,
and preparation methods;
    vii. Specification of risk mitigation elements and description of
all additional procedures, methods, and practices incorporated into the
directions for use that mitigate risks associated with testing;
    viii. Information pertaining to the probability of test failure
(e.g., failed quality control) based on data from clinical samples,
description of scenarios in which a test can fail (i.e., low sample
volume, low DNA concentration, etc.), how customers will be notified,
and followup actions to be taken; and
    ix. Specification of the criteria for test result interpretation
and reporting.
    b. Information that demonstrates the performance characteristics of
the device, including:
    i. Accuracy (method comparison) of study results for each claimed
specimen type.
    A. Accuracy of the device shall be evaluated with fresh clinical
specimens collected and processed in a manner consistent with the
device's instructions for use. If this is impractical, fresh clinical
samples may be substituted or supplemented with archived clinical
samples. Archived samples shall have been collected previously in
accordance with the device's instructions for use, stored
appropriately, and randomly selected. In some instances, use of
contrived samples or human cell line samples may also be appropriate;
the contrived or human cell line samples shall mimic clinical specimens
as much as is feasible and provide an unbiased evaluation of the
device's accuracy.
    B. Accuracy must be evaluated as compared to bidirectional
sequencing or other methods identified as appropriate by FDA.
Performance criteria for both the comparator method and device must be
predefined and appropriate to the test's intended use. Detailed
appropriate study protocols must be provided.
    C. Information provided shall include the number and type of
specimens, broken down by clinically relevant variants, that were
compared to bidirectional sequencing or other methods identified as
appropriate by FDA. The accuracy, defined as positive percent agreement
(PPA) and negative percent agreement (NPA), must be measured; accuracy
point estimates must be greater than 99 percent (both per reported
variant and overall) and uncertainty of the point estimate must be
presented using the 95 percent confidence interval. Clinical specimens
must include both homozygous wild type and heterozygous genotypes. The
number of clinical specimens for each variant reported that must be
included in the accuracy study must be based on the variant prevalence.
Common variants (greater than 0.1 percent allele frequency in
ethnically relevant population) must have at least 20 unique
heterozygous clinical specimens tested. Rare variants (less than or
equal to 0.1 percent allele frequency in ethnically relevant
population) shall have at least three unique mutant heterozygous
specimens tested. Any no calls (i.e., absence of a result) or invalid
calls (e.g., failed quality control) in the study must be included in
accuracy study results and reported separately. Variants that have a
point estimate for PPA or NPA of less than 99 percent (incorrect test
results as compared to bidirectional sequencing or other methods
identified as appropriate by FDA) must not be incorporated into test

claims and reports. Accuracy measures generated from clinical specimens
versus contrived samples or cell lines must be presented separately.
Results must be summarized and presented in tabular format, by sample,
and by genotype. Point estimate of PPA should be calculated as the
number of positive results divided by the number of specimens known to
harbor variants (mutations) without ``no calls'' or invalid calls. The
point estimate of NPA should be calculated as the number of negative
results divided by the number of wild type specimens tested without
``no calls'' or invalid calls, for each variant that is being reported.
Point estimates should be calculated along with 95 percent two-sided
confidence intervals.
    D. Information shall be reported on the clinical positive
predictive value (PPV) and negative predictive value (NPV) for carrier
status (and where possible, for each variant) in each population.
Specifically, to calculate PPV and NPV, estimate test coverage (TC) and
the percent of persons with variant(s) included in the device among all
carriers: PPV = (PPA*TC * [pi])/(PPA*TC*[pi] + (1 - NPA) * (1 - [pi]))
and NPV = (NPA*(1 - [pi]))/(NPA*(1 - [pi]) + (1 - PPA*TC) * [pi]) where
PPA and NPA described either in paragraph (3)(b)(i)(D)(1) or in
(3)(b)(i)(D)(2) that follow and [pi] is prevalence of carriers in the
population (pre-test risk to be a carrier for the disease).
    1. For the point estimates of PPA and NPA less than 100 percent,
use the calculated estimates in the PPV and NPV calculations.
    2. Point estimates of 100 percent may have high uncertainty. If
these variants are measured using highly multiplexed technology,
calculate the random error rate for the overall device and incorporate
that rate in the estimation of the PPA and NPA as calculated
previously. Then use these calculated estimates in the PPV and NPV
calculations. This type of accuracy study is helpful in determining
that there is no systematic error in such devices.
    ii. Precision (reproducibility): Precision data must be generated
using multiple instruments and multiple operators, on multiple non-
consecutive days, and using multiple reagent lots. The sample panel
must include specimens with claimed sample type (e.g. saliva samples)
representing different genotypes (i.e., wild type, heterozygous).
Performance criteria must be predefined. A detailed study protocol must
be created in advance of the study and then followed. The ``failed
quality control'' rate must be indicated. It must be clearly documented
whether results were generated from clinical specimens, contrived
samples, or cell lines. The study results shall state, in a tabular
format, the variants tested in the study and the number of replicates
for each variant, and what testing conditions were studied (i.e.,
number of runs, days, instruments, reagent lots, operators, specimens/
type, etc). The study must include all nucleic acid extraction steps
from the claimed specimen type or matrix, unless a separate extraction
study for the claimed sample type is performed. If the device is to be
used at more than one laboratory, different laboratories must be
included in the precision study (and reproducibility must be
evaluated). The percentage of ``no calls'' or invalid calls, if any, in
the study must be provided as a part of the precision (reproducibility)
study results.
    iii. Analytical specificity data: Data must be generated evaluating
the effect on test performance of potential endogenous and exogenous
interfering substances relevant to the specimen type, evaluation of
cross-reactivity of known cross-reactive alleles and pseudogenes, and
assessment of cross-contamination.
    iv. Analytical sensitivity data: Data must be generated
demonstrating the minimum amount of DNA that will enable the test to
perform accurately in 95 percent of runs.
    v. Device stability data: The manufacturer must establish upper and
lower limits of input nucleic acid and sample stability that will
achieve the claimed accuracy and reproducibility. Data supporting such
claims must be described.
    vi. Specimen type and matrix comparison data: Specimen type and
matrix comparison data must be generated if more than one specimen type
or anticoagulant can be tested with the device, including failure rates
for the different specimen types.
    c. If the device is offered over-the-counter, including cases in
which the test results are provided direct-to-consumer, the
manufacturer must conduct a study that assesses user comprehension of
the device's labeling and test process and provide a concise summary of
the results of the study. The following items must be included in the
user study:
    i. The test manufacturer must perform pre- and post-test user
comprehension studies to assess user ability to understand the possible
results of a carrier test and their clinical meaning. The comprehension
test questions must directly evaluate the material being presented to
the user in the test reports.
    ii. The test manufacturer must provide a carrier testing education
module to potential and actual test report recipients. The module must
define terms that are used in the test reports and explain the
significance of carrier status.
    iii. The user study must meet the following criteria:
    A. The study participants must be comprised of a statistically
justified and demographically diverse population (determined using
methods such as quota-based sampling) that is representative of the
intended user population. Furthermore, the users must be comprised of a
diverse range of age and educational levels that have no prior
experience with the test or its manufacturer. These factors shall be
well-defined in the inclusion and exclusion criteria.
    B. All sources of bias (e.g., non-responders) must be predefined
and accounted for in the study results with regard to both responders
and non-responders.
    C. The testing must follow a format where users have limited time
to complete the studies (such as an onsite survey format and a one-time
visit with a cap on the maximum amount of time that a participant has
to complete the tests).
    D. Users must be randomly assigned to study arms. Test reports
given to users must: (1) Define the condition being tested and related
symptoms, (2) explain the intended use and limitations of the test, (3)
explain the relevant ethnicities regarding the variant tested, (4)
explain carrier status and relevance to the user's ethnicity, (5)
provide links to additional information pertaining to situations where
the user is concerned about their test results or would like followup
information as indicated in test labeling). The study shall assess
participants' ability to understand the following comprehension
concepts: The test's limitations, purpose, and results.
    E. Study participants must be untrained, naive to the test subject
of the study, and be provided only the materials that will be available
to them when the test is marketed.
    F. The user comprehension study must meet the predefined primary
endpoint criteria, including a minimum of a 90 percent or greater
overall comprehension rate (i.e. selection of the correct answer) for
each comprehension concept to demonstrate that the education module and
test reports are adequate for over-the-counter use.
    iv. A summary of the user comprehension study must be provided and
include the following:

    A. Results regarding reports that are provided for each gene/
variant/ethnicity tested.
    B. Statistical methods used to analyze all data sets.
    C. Completion rate, non-responder rate, and reasons for non-
response/data exclusion, as well as a summary table of comprehension
rates regarding comprehension concepts (purpose of test, test results,
test limitations, ethnicity relevance for the test results, etc.) for
each study report.
    4. Your 21 CFR 809.10 compliant labeling and any test report
generated must include the following warning and limitation statements,
as applicable:
    a. A warning that reads ``The test is intended only for autosomal
recessive carrier screening in adults of reproductive age.''
    b. A 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.
    c. For prescription use tests, the following warnings that read:
    i. ``The results of this test are intended to be interpreted by a
board-certified clinical molecular geneticist or equivalent and should
be used in conjunction with other available laboratory and clinical
information.''
    ii. ``This device is not intended for disease diagnosis, prenatal
testing of fetuses, risk assessment, prognosis or pre-symptomatic
testing, susceptibility testing, or newborn screening.''
    d. For over-the-counter tests, a statement that reads ``This test
is not intended to diagnose a disease, or tell you anything about your
risk for developing a disease in the future. On its own, this test is
also not intended to tell you anything about the health of your fetus,
or your newborn child's risk of developing a particular disease later
on in life.''
    e. For over-the-counter tests, the following warnings that read:
    i. ``This test is not a substitute for visits to a healthcare
provider. It is recommended that you consult with a healthcare provider
if you have any questions or concerns about your results.''
    ii. ``The test does not diagnose any health conditions. Results
should be used along with other clinical information for any medical
purposes.''
    iii. ``The laboratory may not be able to process your sample. The
probability that the laboratory cannot process your saliva sample can
be up to [actual probability percentage].''
    iv. ``Your ethnicity may affect how your genetic health results are
interpreted.''
    f. For a positive result in an over-the-counter test when the
positive predictive value for a specific population is less than 50
percent and more than 5 percent, a warning that reads ``The positive
result you obtained may falsely identify you as a carrier. Consider
genetic counseling and followup testing.''
    g. For a positive result in an over-the-counter test when the
positive predictive value for a specific population is less than 5
percent, a warning that reads ``The positive result you obtained is
very likely to be incorrect due to the rarity of this variant. Consider
genetic counseling and followup testing.''
    5. The testing done to comply with paragraph 3 must show the device
meets or exceeds each of the following performance specifications:
    a. The accuracy must be shown to be equal to or greater than 99
percent for both PPA and NPA. Variants that have a point estimate for
PPA or NPA of less than 99 percent (incorrect test results as compared
to bidirectional sequencing or other methods identified as appropriate
by FDA) must not be incorporated into test claims and reports.
    b. Precision (reproducibility) performance must meet or exceed 99
percent for both positive and negative results.
    c. The user comprehension study must obtain values of 90 percent or
greater user comprehension for each comprehension concept.
    6. The distribution of this device, excluding the collection device
described in paragraph 2, shall be limited to the manufacturer, the
manufacturer's subsidiaries, and laboratories regulated under the
Clinical Laboratory Improvement Amendments.
    Section 510(m) of the FD&C Act provides that FDA may exempt a class
II device from the premarket notification requirements under section
510(k) of the FD&C Act if FDA determines that premarket notification is
not necessary to provide reasonable assurance of the safety and
effectiveness of the device. For this type of device, FDA believes
premarket notification is not necessary to provide reasonable assurance
of the safety and effectiveness of the device type and, therefore, is
planning to exempt the device from the premarket notification
requirements of the FD&C Act. Elsewhere in this issue of the Federal
Register, FDA is publishing a notice of intent to exempt an autosomal
recessive carrier screening gene mutation detection system under
section 510(m) of the FD&C Act. If there are questions about 510(k)
submission prior to finalization of the 510(k) exemption, you should
contact FDA at the number provided in this Final order. Once finalized,
persons who intend to market this device type need not submit a 510(k)
premarket notification containing information on the autosomal
recessive carrier screening gene mutation detection system prior to
marketing the device.

II. Environmental Impact

    The Agency has determined under 21 CFR 25.34(b) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.

III. Paperwork Reduction Act of 1995

    This final administrative order establishes special controls that
refer to previously approved collections of information found in other
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 part 807, subpart E, regarding premarket notification
submissions have been approved under OMB control number 0910-0120, and
the collections of information in 21 CFR parts 801 and 809 regarding
labeling have been approved under OMB control number 0910-0485.

List of Subjects in 21 CFR Part 866

    Biologics, Laboratories, Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner

of Food and Drugs, 21 CFR part 866 is amended as follows:

PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES

0
1. The authority citation for 21 CFR part 866 continues to read as
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

0
2. Add Sec.  866.5940 to subpart F to read as follows:

Sec.  866.5940  Autosomal recessive carrier screening gene mutation
detection system.

    (a) Identification. Autosomal recessive carrier screening gene
mutation detection system 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.
    (b) Classification. Class II (special controls). Autosomal
recessive carrier screening gene mutation detection system must comply
with the following special controls:
    (1) If the device is offered over-the-counter, the device
manufacturer must provide information to a potential purchaser or
actual test report recipient about how to obtain access to a board-
certified clinical molecular geneticist or equivalent to assist in pre-
and post-test counseling.
    (2) The device must use a collection device that is FDA cleared,
approved, or classified as 510(k) exempt, with an indication for in
vitro diagnostic use in DNA testing.
    (3) The device's labeling must include a prominent hyperlink to the
manufacturer's public Web site where the manufacturer shall make the
information identified in this section publicly available. The
manufacturer's home page, as well as the primary part of the
manufacturer's Web site that discusses the device, must provide a
prominently placed hyperlink to the Web page containing this
information and must allow unrestricted viewing access. If the device
can be purchased from the Web site or testing using the device can be
ordered from the Web site, the same information must be found on the
Web page for ordering the device or provided in a prominently placed
and publicly accessible hyperlink on the Web page for ordering the
device. 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 information must include:
    (i) A detailed device description including:
    (A) Gene (or list of the genes if more than one) and variants the
test detects (using standardized nomenclature, Human Genome
Organization (HUGO) nomenclature, and coordinates).
    (B) Scientifically established clinical validity of each variant
detected and reported by the test, which must be well-established in
peer-reviewed journal articles, authoritative summaries of the
literature such as Genetics Home Reference (http://ghr.nlm.nih.gov/),
GeneReviews (http://www.ncbi.nlm.nih.gov/books/NBK1116/), or similar
summaries of valid scientific evidence, and/or professional society
recommendations, including:
    (1) Genotype-phenotype information for the reported mutations.
    (2) Relevant American College of Medical Genetics (ACMG) or
American Congress of Obstetricians and Gynecologists (ACOG) guideline
recommending testing of the specific gene(s) and variants the test
detects and recommended populations, if available. If not available, a
statement stating that professional guidelines currently do not
recommend testing for this specific gene(s) and variants.
    (3) Table of expected prevalence of carrier status in major ethnic
and racial populations and the general population.
    (C) The specimen type (e.g., saliva, whole blood), matrix, and
volume.
    (D) Assay steps and technology used.
    (E) Specification of required ancillary reagents, instrumentation,
and equipment.
    (F) Specification of the specimen collection, processing, storage,
and preparation methods.
    (G) Specification of risk mitigation elements and description of
all additional procedures, methods, and practices incorporated into the
directions for use that mitigate risks associated with testing.
    (H) Information pertaining to the probability of test failure
(e.g., failed quality control) based on data from clinical samples,
description of scenarios in which a test can fail (i.e., low sample
volume, low DNA concentration, etc.), how customers will be notified,
and followup actions to be taken.
    (I) Specification of the criteria for test result interpretation
and reporting.
    (ii) Information that demonstrates the performance characteristics
of the device, including:
    (A) Accuracy (method comparison) of study results for each claimed
specimen type.
    (1) Accuracy of the device shall be evaluated with fresh clinical
specimens collected and processed in a manner consistent with the
device's instructions for use. If this is impractical, fresh clinical
samples may be substituted or supplemented with archived clinical
samples. Archived samples shall have been collected previously in
accordance with the device's instructions for use, stored
appropriately, and randomly selected. In some instances, use of
contrived samples or human cell line samples may also be appropriate;
the contrived or human cell line samples shall mimic clinical specimens
as much as is feasible and provide an unbiased evaluation of the
device's accuracy.
    (2) Accuracy must be evaluated as compared to bidirectional
sequencing or other methods identified as appropriate by FDA.
Performance criteria for both the comparator method and device must be
predefined and appropriate to the test's intended use. Detailed
appropriate study protocols must be provided.
    (3) Information provided shall include the number and type of
specimens, broken down by clinically relevant variants, that were
compared to bidirectional sequencing or other methods identified as
appropriate by FDA. The accuracy, defined as positive percent agreement
(PPA) and negative percent agreement (NPA), must be measured; accuracy
point estimates must be greater than 99 percent (both per reported
variant and overall) and uncertainty of the point estimate must be
presented using the 95 percent confidence interval. Clinical specimens
must include both homozygous wild type and heterozygous genotypes. The
number of clinical specimens for each variant reported that must be
included in the accuracy study must be based on the variant prevalence.
Common variants (greater than 0.1 percent allele frequency in
ethnically relevant population) must have at least 20 unique
heterozygous clinical specimens tested. Rare variants (less than or
equal to 0.1 percent allele frequency in ethnically relevant
population) shall have at least three unique mutant heterozygous
specimens tested. Any no calls (i.e., absence of a result) or invalid
calls (e.g., failed quality control) in the study must be included in
accuracy study results and reported separately. Variants that have a
point estimate for PPA or NPA of less than 99 percent (incorrect test
results as compared to bidirectional sequencing or other methods
identified as appropriate by FDA) must not be incorporated into test

claims and reports. Accuracy measures generated from clinical specimens
versus contrived samples or cell lines must be presented separately.
Results must be summarized and presented in tabular format, by sample
and by genotype. Point estimate of PPA should be calculated as the
number of positive results divided by the number of specimens known to
harbor variants (mutations) without ``no calls'' or invalid calls. The
point estimate of NPA should be calculated as the number of negative
results divided by the number of wild type specimens tested without
``no calls'' or invalid calls, for each variant that is being reported.
Point estimates should be calculated along with 95 percent two-sided
confidence intervals.
    (4) Information shall be reported on the clinical positive
predictive value (PPV) and negative predictive value (NPV) for carrier
status (and where possible, for each variant) in each population.
Specifically, to calculate PPV and NPV, estimate test coverage (TC) and
the percent of persons with variant(s) included in the device among all
carriers: PPV = (PPA * TC * [pi])/(PPA * TC * [pi] + (1 - NPA) * (1 -
[pi])) and NPV = (NPA * (1 - [pi]))/(NPA *(1 - [pi]) + (1 - PPA*TC) *
[pi]) where PPA and NPA described either in paragraph
(b)(3)(ii)(A)(4)(i) or in paragraph (b)(3)(ii)(A)(4)(ii) of this
section and [pi] is prevalence of carriers in the population (pre-test
risk to be a carrier for the disease).
    (i) For the point estimates of PPA and NPA less than 100 percent,
use the calculated estimates in the PPV and NPV calculations.
    (ii) Point estimates of 100 percent may have high uncertainty. If
these variants are measured using highly multiplexed technology,
calculate the random error rate for the overall device and incorporate
that rate in the estimation of the PPA and NPA as calculated
previously. Then use these calculated estimates in the PPV and NPV
calculations. This type of accuracy study is helpful in determining
that there is no systematic error in such devices.
    (B) Precision (reproducibility): Precision data must be generated
using multiple instruments and multiple operators, on multiple non-
consecutive days, and using multiple reagent lots. The sample panel
must include specimens with claimed sample type (e.g. saliva samples)
representing different genotypes (i.e., wild type, heterozygous).
Performance criteria must be predefined. A detailed study protocol must
be created in advance of the study and then followed. The ``failed
quality control'' rate must be indicated. It must be clearly documented
whether results were generated from clinical specimens, contrived
samples, or cell lines. The study results shall state, in a tabular
format, the variants tested in the study and the number of replicates
for each variant, and what testing conditions were studied (i.e.,
number of runs, days, instruments, reagent lots, operators, specimens/
type, etc). The study must include all nucleic acid extraction steps
from the claimed specimen type or matrix, unless a separate extraction
study for the claimed sample type is performed. If the device is to be
used at more than one laboratory, different laboratories must be
included in the precision study (and reproducibility must be
evaluated). The percentage of ``no calls'' or invalid calls, if any, in
the study must be provided as a part of the precision (reproducibility)
study results.
    (C) Analytical specificity data: Data must be generated evaluating
the effect on test performance of potential endogenous and exogenous
interfering substances relevant to the specimen type, evaluation of
cross-reactivity of known cross-reactive alleles and pseudogenes, and
assessment of cross-contamination.
    (D) Analytical sensitivity data: Data must be generated
demonstrating the minimum amount of DNA that will enable the test to
perform accurately in 95 percent of runs.
    (E) Device stability data: The manufacturer must establish upper
and lower limits of input nucleic acid and sample stability that will
achieve the claimed accuracy and reproducibility. Data supporting such
claims must be described.
    (F) Specimen type and matrix comparison data: Specimen type and
matrix comparison data must be generated if more than one specimen type
or anticoagulant can be tested with the device, including failure rates
for the different specimen types.
    (iii) If the device is offered over-the-counter, including cases in
which the test results are provided direct-to-consumer, the
manufacturer must conduct a study that assesses user comprehension of
the device's labeling and test process and provide a concise summary of
the results of the study. The following items must be included in the
user study:
    (A) The test manufacturer must perform pre- and post-test user
comprehension studies to assess user ability to understand the possible
results of a carrier test and their clinical meaning. The comprehension
test questions must directly evaluate the material being presented to
the user in the test reports.
    (B) The test manufacturer must provide a carrier testing education
module to potential and actual test report recipients. The module must
define terms that are used in the test reports and explain the
significance of carrier status.
    (C) The user study must meet the following criteria:
    (1) The study participants must be comprised of a statistically
justified and demographically diverse population (determined using
methods such as quota-based sampling) that is representative of the
intended user population. Furthermore, the users must be comprised of a
diverse range of age and educational levels that have no prior
experience with the test or its manufacturer. These factors shall be
well-defined in the inclusion and exclusion criteria.
    (2) All sources of bias (e.g., non-responders) must be predefined
and accounted for in the study results with regard to both responders
and non-responders.
    (3) The testing must follow a format where users have limited time
to complete the studies (such as an onsite survey format and a one-time
visit with a cap on the maximum amount of time that a participant has
to complete the tests).
    (4) Users must be randomly assigned to study arms. Test reports
given to users must: Define the condition being tested and related
symptoms; explain the intended use and limitations of the test; explain
the relevant ethnicities regarding the variant tested; explain carrier
status and relevance to the user's ethnicity; and provide links to
additional information pertaining to situations where the user is
concerned about their test results or would like followup information
as indicated in test labeling. The study shall assess participants'
ability to understand the following comprehension concepts: The test's
limitations, purpose, and results.
    (5) Study participants must be untrained, naive to the test subject
of the study, and be provided only the materials that will be available
to them when the test is marketed.
    (6) The user comprehension study must meet the predefined primary
endpoint criteria, including a minimum of a 90 percent or greater
overall comprehension rate (i.e. selection of the correct answer) for
each comprehension concept to demonstrate that the education module and
test reports are adequate for over-the-counter use.

    (D) A summary of the user comprehension study must be provided and
include the following:
    (1) Results regarding reports that are provided for each gene/
variant/ethnicity tested.
    (2) Statistical methods used to analyze all data sets.
    (3) Completion rate, non-responder rate, and reasons for non-
response/data exclusion, as well as a summary table of comprehension
rates regarding comprehension concepts (purpose of test, test results,
test limitations, ethnicity relevance for the test results, etc.) for
each study report.
    (4) Your 21 CFR 809.10 compliant labeling and any test report
generated must include the following warning and limitation statements,
as applicable:
    (i) A warning that reads ``The test is intended only for autosomal
recessive carrier screening in adults of reproductive age.''
    (ii) A 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.
    (iii) For prescription use tests, the following warnings that read:
    (A) ``The results of this test are intended to be interpreted by a
board-certified clinical molecular geneticist or equivalent and should
be used in conjunction with other available laboratory and clinical
information.''
    (B) ``This device is not intended for disease diagnosis, prenatal
testing of fetuses, risk assessment, prognosis or pre-symptomatic
testing, susceptibility testing, or newborn screening.''
    (iv) For over-the-counter tests, a statement that reads ``This test
is not intended to diagnose a disease, or tell you anything about your
risk for developing a disease in the future. On its own, this test is
also not intended to tell you anything about the health of your fetus,
or your newborn child's risk of developing a particular disease later
on in life.''
    (v) For over-the-counter tests, the following warnings that read:
    (A) ``This test is not a substitute for visits to a healthcare
provider. It is recommended that you consult with a healthcare provider
if you have any questions or concerns about your results.''
    (B) ``The test does not diagnose any health conditions. Results
should be used along with other clinical information for any medical
purposes.''
    (C) ``The laboratory may not be able to process your sample. The
probability that the laboratory cannot process your saliva sample can
be up to [actual probability percentage].''
    (D) ``Your ethnicity may affect how your genetic health results are
interpreted.''
    (vi) For a positive result in an over-the-counter test when the
positive predictive value for a specific population is less than 50
percent and more than 5 percent, a warning that reads ``The positive
result you obtained may falsely identify you as a carrier. Consider
genetic counseling and followup testing.''
    (vii) For a positive result in an over-the-counter test when the
positive predictive value for a specific population is less than 5
percent, a warning that reads ``The positive result you obtained is
very likely to be incorrect due to the rarity of this variant. Consider
genetic counseling and followup testing.''
    (5) The testing done to comply with paragraph (b)(3) of this
section must show the device meets or exceeds each of the following
performance specifications:
    (i) The accuracy must be shown to be equal to or greater than 99
percent for both PPA and NPA. Variants that have a point estimate for
PPA or NPA of less than 99 percent (incorrect test results as compared
to bidirectional sequencing or other methods identified as appropriate
by FDA) must not be incorporated into test claims and reports.
    (ii) Precision (reproducibility) performance must meet or exceed 99
percent for both positive and negative results.
    (iii) The user comprehension study must obtain values of 90 percent
or greater user comprehension for each comprehension concept.
    (6) The distribution of this device, excluding the collection
device described in paragraph (b)(2) of this section, shall be limited
to the manufacturer, the manufacturer's subsidiaries, and laboratories
regulated under the Clinical Laboratory Improvement Amendments.

    Dated: October 20, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-27197 Filed 10-26-15; 8:45 am]
BILLING CODE 4164-01-P


[Federal Register Volume 77, Number 108 (Tuesday, June 5, 2012)]
[Rules and Regulations]
[Pages 33089-33094]
[FR Doc No: 2012-13404]

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DEPARTMENT OF HOMELAND SECURITY

Coast Guard

33 CFR Parts 100 and 165

[Docket Number USCG-2012-0174]
RIN 1625-AA00, AA08, AA11

OPSAIL 2012 Virginia, Port of Hampton Roads, VA

AGENCY: Coast Guard, DHS.

ACTION: Temporary final rule.

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SUMMARY: The Coast Guard is establishing temporary regulations in the
Port of Hampton Roads, Virginia for Operation Sail (OPSAIL) 2012
Virginia activities. This regulation is necessary to provide for the
safety of life on navigable waters before, during, and after OPSAIL
2012 Virginia events. This action is intended to restrict vessel
traffic movement in portions of Chesapeake Bay, Hampton Roads, the
James River and Elizabeth River.

DATES: This rule is effective from June 6, 2012 to June 12, 2012.

ADDRESSES: Documents mentioned in this preamble are part of docket
[USCG-2012-0174]. To view documents mentioned in this preamble as being
available in the docket, go to 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 rulemaking. You may also
visit the Docket Management Facility in Room W12-140 on the ground
floor of the Department of Transportation West Building, 1200 New
Jersey Avenue SE., Washington, DC 20590, between 9 a.m. and 5 p.m.,
Monday through Friday, except Federal holidays.

FOR FURTHER INFORMATION CONTACT: If you have questions on this rule,
call or email Dennis Sens, Prevention Division, Fifth Coast Guard
District;<PHONE_NUMBER>, email<EMAIL_ADDRESS>If you have
questions on viewing or submitting material to the docket, call Renee
V. Wright, Program Manager, Docket Operations, telephone (202) 366-
9826.

SUPPLEMENTARY INFORMATION:

Table of Acronyms

DHS Department of Homeland Security
FR Federal Register
NPRM Notice of Proposed Rulemaking

A. Regulatory History and Information

    On April 3, 2012, we published a notice of proposed rulemaking
(NPRM) entitled ``OPSAIL 2012 Virginia, Port of Hampton Roads, VA'' in
the Federal Register (77 FR 19957). We received no comments on the
proposed rule. No public meeting was requested, and none was held.
    Under 5 U.S.C. 553(d)(3), the Coast Guard finds that good cause
exists for making this rule effective less than 30 days after
publication in the Federal Register. Due to the need for immediate
action, the restriction of vessel traffic is necessary to protect life,
property and the environment; therefore, a 30-day notice is
impracticable. Delaying the effective date would be contrary to the
regulations intended objectives of protecting persons and vessels, and
enhancing public and maritime safety.

B. Basis and Purpose

    The legal basis for the rule is the Coast Guard's authority to
establish

special local regulations, regulated navigation areas, and other
limited access areas: 33 U.S.C. 1231; 33 U.S.C. 1233; 46 U.S.C. chapter
701, 3306, 3703; 50 U.S.C. 191, 195; 33 CFR 1.05-1, 6.04-1, 6.04-6,
160.5; Public Law 107-295, 116 Stat. 2064; Department of Homeland
Security Delegation No. 0170.1.
    Operation Sail, Inc. is sponsoring OPSAIL 2012 Virginia in the Port
of Hampton Roads. Planned events include the scheduled arrival of U.S.
and foreign naval vessels, public vessels, tall ships and other vessels
on June 6, 2012 and June 8, 2012; the scheduled departure of those
vessels on June 12, 2012; and three fireworks displays on June 9, 2012
with a rain date of June 10, 2012.
    The Coast Guard anticipates a large spectator fleet for these
events. Vessel operators should expect significant congestion along the
OPSAIL parade route and viewing areas for fireworks displays.
    The purpose of these regulations is to promote maritime safety and
protect participants and the boating public in the Port of Hampton
Roads immediately prior to, during, and after the scheduled events. The
regulations provide clear passage and a safety buffer around
participating vessels along the parade route while they are in transit,
enhancing safety of participant and spectator vessels. The regulations
also establish areas where vessels shall proceed at the minimum speed
necessary that minimizes wake along the parade route and temporarily
modifies use of existing anchorages for the benefit of participants and
spectators. These regulations provide a safety buffer around the
planned fireworks displays. The regulations will impact the movement of
all vessels operating in the specified areas of the Port of Hampton
Roads.
    The Coast Guard will establish safety zones as a part of these
regulations to safeguard dignitaries and certain vessels participating
in the event. The Coast Guard will implement and enforce safety zones
as specified in this regulation. The details of the safety zones
outlined in this regulation will be announced separately via Local
Notice to Mariners, Safety Voice Broadcasts, and by other public media
outlets.
    Vessel operators are reminded that Norfolk Naval Base will be
strictly enforcing the existing restricted area defined at 33 CFR
334.300 during all OPSAIL events.
    All vessel operators and passengers are reminded that vessels
carrying passengers for hire or that have been chartered and are
carrying passengers may have to comply with certain additional rules
and regulations beyond the safety equipment requirements for all
pleasure craft. When a vessel is not being used exclusively for
pleasure, but rather is engaged in carrying passengers for hire or has
been chartered and is carrying the requisite number of passengers, the
vessel operator must possess an appropriate license and the vessel may
be subject to inspection. The definition of the term ``passenger for
hire'' is found in 46 U.S.C. 2101(21a). In general, it means any
passenger who has contributed any consideration (monetary or otherwise)
either directly or indirectly for carriage onboard the vessel. The
definition of the term ``passenger'' is found in 46 U.S.C. 2101(21). It
varies depending on the type of vessel, but generally means individuals
carried aboard vessels except for certain specified individuals engaged
in the operation of the vessel or the business of the owner/charterer.
The law provides for substantial penalties for any violation of
applicable license and inspection requirements. If you have any
questions concerning the application of the above law to your
particular case, you should contact the Coast Guard at the address
listed in ADDRESSES for additional information.
    Vessel operators are reminded they must have sufficient facilities
on board their vessels to retain all garbage and untreated sewage.
Discharge of either into any waters of the United States is strictly
forbidden. Violators may be assessed civil penalties up to $40,000 or
face criminal prosecution.
    We recommend that vessel operators visiting the Port of Hampton
Roads for this event obtain up to date editions of the following charts
of the area: NOS. 12222, 12245, 12253, and 12254 to avoid anchoring
within a charted cable or pipeline area. With the arrival of OPSAIL
2012 Virginia participants and spectator vessels in the Port of Hampton
Roads for this event, it will be necessary to curtail normal port
operations to some extent. Interference will be kept to the minimum
considered necessary to ensure the safety of life on the navigable
waters immediately before, during, and after the scheduled events.

C. Discussion of Comments, Changes and the Final Rule

    The Coast Guard did not receive comments in response to the notice
of proposed rulemaking (NPRM) published in the Federal Register.
Accordingly, the Coast Guard is establishing special local regulations
and safety zones on the specified navigable waters listed in this
regulation.

D. Regulatory Analyses

    We developed this rule after considering numerous statutes and
executive orders related to rulemaking. Below we summarize our analyses
based on these statutes or executive orders.

1. Regulatory Planning and Review

    This rule is not a significant regulatory action under section 3(f)
of Executive Order 12866, Regulatory Planning and Review, as
supplemented by Executive Order 13563, Improving Regulation and
Regulatory Review, and does not require an assessment of potential
costs and benefits under section 6(a)(3) of Executive Order 12866 or
under section 1 of Executive Order 13563. The Office of Management and
Budget has not reviewed it under those Orders. The primary impact of
these regulations will be on vessels desiring to transit the affected
waterways during OPSAIL 2012 Virginia vessels arrival beginning on June
6, 2012, June 8, 2012, their departure ending on June 12, 2012 and
during the fireworks display on June 9, 2012. Although these
regulations prevent traffic from transiting a portion of the Chesapeake
Bay, Thimble Shoals Channel, Hampton Roads, James River and Elizabeth
River during these events, that restriction is limited in duration,
affects only a limited area, and will be well publicized to allow
mariners to make alternative plans for transiting the affected area.
Moreover, the magnitude of the event itself will limit or prevent
transit of the waterway. These regulations are designed to ensure such
transit is conducted in a safe and orderly manner.

2. Impact on Small Entities

    The Regulatory Flexibility Act of 1980 (RFA), 5 U.S.C. 601-612, as
amended, requires federal agencies to consider the potential impact of
regulations on small entities during rulemaking. The Coast Guard
received no comments from the Small Business Administration on this
rule. The Coast Guard certifies under 5 U.S.C. 605(b) that this rule
will not have a significant economic impact on a substantial number of
small entities.
    (1) This rule would affect the following entities, some of which
might be small entities: the owners or operators of vessels intending
to transit or anchor in portions of the Chesapeake Bay, Thimble Shoals
Channel, Hampton Roads, James River and Elizabeth River, in Virginia
during various time periods on June 6, June 8, June 9 and June 12,
2012. The regulations would not have a significant impact on a
substantial number of small entities for the

following reasons: the restrictions are limited in duration, affect
only limited areas, and will be well publicized to allow mariners to
make alternative plans for transiting the affected areas.
    (2) The special local regulations, regulated navigation areas and
safety zones specified in this regulation will not have a significant
economic impact on a substantial number of small entities for the
following reasons. The regulated areas would be activated, and thus
subject to enforcement, for only the minimum time necessary to provide
clear passage and a safety buffer around participating vessels along
the parade route while they are in transit, enhancing safety of
participant and spectator vessels. Although the safety zone would apply
to the entire width of the river, traffic may be allowed to pass
through the zone with the permission of the Captain of the Port. Before
the activation of regulated areas or safety zones, we would issue
maritime advisories widely available to users of the affected waterway.

3. Assistance for Small Entities

    Under section 213(a) of the Small Business Regulatory Enforcement
Fairness Act of 1996 (Pub. L. 104-121), we want to assist small
entities in understanding this rule. If the rule would affect your
small business, organization, or governmental jurisdiction and you have
questions concerning its provisions or options for compliance, please
contact the person listed in the FOR FURTHER INFORMATION CONTACT,
above.
    Small businesses may send comments on the actions of Federal
employees who enforce, or otherwise determine compliance with, Federal
regulations to the Small Business and Agriculture Regulatory
Enforcement Ombudsman and the Regional Small Business Regulatory
Fairness Boards. The Ombudsman evaluates these actions annually and
rates each agency's responsiveness to small business. If you wish to
comment on actions by employees of the Coast Guard, call 1-888-REG-FAIR
(1-888-734-3247). The Coast Guard will not retaliate against small
entities that question or complain about this rule or any policy or
action of the Coast Guard.

4. Collection of Information

    This rule will not call for a new collection of information under
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

5. Federalism

    A rule has implications for federalism under Executive Order 13132,
Federalism, if it has a substantial direct effect on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government. We have analyzed this rule under that Order and determined
that this rule does not have implications for federalism.

6. Protest Activities

    The Coast Guard respects the First Amendment rights of protesters.
Protesters are asked to contact the person listed in the FOR FURTHER
INFORMATION CONTACT section to coordinate protest activities so that
your message can be received without jeopardizing the safety or
security of people, places or vessels.

7. Unfunded Mandates Reform Act

    The Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-1538)
requires Federal agencies to assess the effects of their discretionary
regulatory actions. In particular, the Act addresses actions that may
result in the expenditure by a State, local, or tribal government, in
the aggregate, or by the private sector of $100,000,000 (adjusted for
inflation) or more in any one year. Though this rule will not result in
such an expenditure, we do discuss the effects of this rule elsewhere
in this preamble.

8. Taking of Private Property

    This rule will not cause a taking of private property or otherwise
have taking implications under Executive Order 12630, Governmental
Actions and Interference with Constitutionally Protected Property
Rights.

9. Civil Justice Reform

    This rule meets applicable standards in sections 3(a) and 3(b)(2)
of Executive Order 12988, Civil Justice Reform, to minimize litigation,
eliminate ambiguity, and reduce burden.

10. Protection of Children

    We have analyzed this rule under Executive Order 13045, Protection
of Children from Environmental Health Risks and Safety Risks. This rule
is not an economically significant rule and does not create an
environmental risk to health or risk to safety that may
disproportionately affect children.

11. Indian Tribal Governments

    This rule does not have tribal implications under Executive Order
13175, Consultation and Coordination with Indian Tribal Governments,
because it does not have a substantial direct effect on one or more
Indian tribes, on the relationship between the Federal Government and
Indian tribes, or on the distribution of power and responsibilities
between the Federal Government and Indian tribes.

12. Energy Effects

    This action is not a ``significant energy action'' under Executive
Order 13211, Actions Concerning Regulations That Significantly Affect
Energy Supply, Distribution, or Use.

13. Technical Standards

    This rule does not use technical standards. Therefore, we did not
consider the use of voluntary consensus standards.

14. Environment

    We have analyzed this rule under Department of Homeland Security
Management Directive 023-01 and Commandant Instruction M16475.lD, which
guide the Coast Guard in complying with the National Environmental
Policy Act of 1969 (NEPA) (42 U.S.C. 4321-4370f), and have determined
that this action is one of a category of actions that do not
individually or cumulatively have a significant effect on the human
environment. This rule involves implementation of regulations at 33 CFR
part 100 and part 165 that apply to organized marine events on the
navigable waters of the United States that may impact on the safety or
other interest of waterway users and shore side activities in the event
area. These regulations are necessary to provide for the safety of the
general public and event participants from potential hazards associated
with movement of vessels near the event area. This rule involves
establishing special local regulations and safety zones issued in
conjunction with a OPSAIL 2012 Virginia a marine event.
    This rule is categorically excluded, under figure 2-1, paragraph
(34)(g), of the Instruction. This rule involves establishing temporary
safety zones. An environmental analysis checklist and a categorical
exclusion determination are available in the docket where indicated
under ADDRESSES.
    Additionally, this rule involves establishing special local
regulations issued in conjunction with a marine event, as described in
figure 2-1, paragraph (34)(h), of the Instruction. Under figure 2-1,
paragraph (34)(h), of the Instruction, an environmental analysis
checklist and categorical exclusion determination are not required for
this rule.
    We seek any comments or information that may lead to the discovery
of a

significant environmental impact from this rule.

List of Subjects

33 CFR Part 100

    Marine safety, Navigation (water), Reporting and recordkeeping
requirements, Waterways.

33 CFR Part 165

    Harbors, Marine safety, Navigation (water), Reporting and
recordkeeping requirements, Security measures, Waterways.

    For the reasons discussed in the preamble, the Coast Guard amends
33 CFR part 100 and 165 as follows:

PART 100--SAFETY OF LIFE ON NAVIGABLE WATERS

0
1. The authority citation for part 100 continues to read as follows:

    Authority: 33 U.S.C. 1233.

0
2. Add a temporary Sec.  100.35T-05-0174 to read as follows:

Sec.  100.35T-05-0174  Special Local Regulations; OPSAIL 2012 Virginia,
Port of Hampton Roads, VA.

    (a) Definitions. (1) Captain of the Port Representative means any
U.S. Coast Guard commissioned, warrant or petty officer who has been
authorized by the Captain of the Port, Hampton Roads, Virginia to act
on their behalf.
    (2) Official Patrol Vessel includes all U.S. Coast Guard, public,
state, county or local law enforcement vessels assigned and/or approved
by the Captain of the Port, Hampton Roads, Virginia.
    (3) Parades of Sail Vessel include all vessels participating in
OPSAIL 2012 Virginia under the auspices of the U.S. Department of
Homeland Security Application for Marine Event, Form CG-4423, for
OPSAIL 2012 Virginia activities in the Port of Hampton Roads, Virginia
approved by the Captain of the Port, Hampton Roads.
    (4) Parade of Sail arrivals is the movement of Parades of Sail
vessels in orderly succession as they navigate designated routes in the
Port of Hampton Roads, Virginia while inbound to the Port of Hampton
Roads, Virginia on June 6, 2012 and June 8, 2012.
    (5) Parade of Sail departure is the movement of Parades of Sail
vessels in orderly succession as they navigate designated departure
routes from the Port of Hampton Roads, Virginia to Baltimore, Maryland
on June 12, 2012.
    (6) Spectator Vessel includes any vessel, commercial or
recreational, being used for pleasure or carrying passenger that is in
the Port of Hampton Roads to observe part or all of the OPSAIL 2012
Virginia events.
    (7) Large Spectator Vessel includes any spectator vessel 60 feet or
greater in length with a passenger capacity of 50 persons or greater.
    (8) Vessel Traffic Control Point means a designated point which
vessel traffic may not proceed past in either inbound or outbound
direction without permission of the Captain of the Port.
    (b) Regulated Areas. The following Vessel Traffic Control Points
are established as special local regulations during OPSAIL 2012
Virginia in the Port of Hampton Roads, Virginia. All coordinates
reference Datum NAS 1983:
    (1) Elizabeth River, Western Branch along a line drawn across the
Elizabeth River, Western Branch, at the West Norfolk Bridge, located at
36[deg]51'31'' N 076[deg]20'54'' W thence to 36[deg]51'16'' N
076[deg]20'38'' W.
    (2) Elizabeth River, Eastern Branch along a line drawn across the
Elizabeth River, Eastern Branch, at the Berkley Bridge, located at
36[deg]50'33'' N 076[deg]17'11'' W thence to 36[deg]50'27'' N
076[deg]17'12'' W.
    (3) Elizabeth River, Southern Branch along a line drawn across the
Elizabeth River, Southern Branch, at the Jordan Bridge, located at
36[deg]48'29'' N 076[deg]17'30'' W thence to 36[deg]48'32'' N
076[deg]17'17'' W.
    (4) James River along a line drawn across the James River at the
Monitor-Merrimac Bridge/Tunnel, located at 36[deg]57'32'' N
076[deg]24'36'' W thence to 36[deg]56'54'' N 076[deg]24'18'' W.
    (5) Chesapeake Bay, Hampton Roads, Hampton Bar, along a line drawn
from the Old Point Comfort Light (LLNR 9380) to Fort Wool Light (LLNR
9385), located at 37[deg]00'03'' N 076[deg]18'24'' W thence to
36[deg]59'14'' N 076[deg]18'10'' W.
    (6) Elizabeth River along a line drawn from Elizabeth River Channel
Lighted Buoy 20 (LLNR 9620) to Lafayette River Channel Light 2 (LLNR
10660), located at 36[deg]53'33'' N 076[deg]20'15'' W thence to
36[deg]53'36'' N 076[deg]19'27'' W.
    (7) Elizabeth River along a line drawn from Elizabeth River Channel
Lighted Buoy 29 (LLNR 9715) to Elizabeth River Channel Lighted Buoy 30
(LLNR 9735), located at 36[deg]52'13'' N 076[deg]19'44'' W thence to
36[deg]52'02'' N 076[deg]19'41'' W.
    (8) Elizabeth River along a line drawn from Elizabeth River Channel
Lighted Buoy 36 (LLNR 9900), located at 36[deg]50'49.7'' N
076[deg]17'58.7'' W thence to the southeast corner of Hospital Point,
approximate position latitude 36[deg]50'51'' N, longitude
076[deg]18'09'' W.
    (9) Elizabeth River, Southern Branch along a line drawn across the
Elizabeth River, Southern Branch, at the Downtown Tunnel, located at
36[deg]49'57.3'' N 076[deg]17'44.5'' W thence to 36[deg]50'00.3'' N
076[deg]17'35.4'' W.
    (c) Notification. (1) Coast Guard Captain of the Port will notify
the public of the enforcement of these safety zones by all appropriate
means to affect the widest publicity among the affected segments of the
public. Publication in the Local Notice to Mariners, marine information
broadcasts, and facsimile broadcasts may be made for these events,
beginning 24 to 48 hours before the event is scheduled to begin, to
notify the public.
    (2) Contact Information. Questions about safety zones and related
events should be addressed to the Coast Guard Captain of the Port.
Contact Coast Guard Sector Hampton Roads--Captain of the Port Zone,
Norfolk, Virginia:<PHONE_NUMBER>.
    (d) Special Local Regulations. (1) Except for persons or vessels
authorized by the Coast Guard Patrol Commander, no person or vessel may
enter or remain in the regulated area.
    (2) The operator of any vessel in the regulated area shall:
    (i) Stop the vessel immediately when directed to do so by an
Official Patrol.
    (ii) Proceed as directed by any official patrol.
    (iii) The operator of any vessel shall proceed at the minimum speed
necessary to maintain a safe course that minimizes wake in or near the
regulated area.
    (e) Enforcement Period. This regulation will be enforced on June 6,
8, 9, and 12, 2012.

PART 165--REGULATED NAVIGATION AREAS AND LIMITED ACCESS AREAS

0
3. The authority citation for part 165 continues to read as follows:

     Authority: 33 U.S.C. 1231; 46 U.S.C. chapter 701, 3306, 3703;
50 U.S.C. 191, 195; 33 CFR 1.05-1, 6.04-1, 6.04-6, 160.5; Pub. L.
107-295, 116 Stat. 2064; Department of Homeland Security Delegation
No. 0170.1.

0
4. Add a temporary Sec.  165.T05-0174 to read as follows:

Sec.  165.T05-0174  Chesapeake Bay entrance and Hampton Roads, VA and
adjacent waters--Regulated Navigation Area.

    (a) Regulations in this temporary section are supplemental to the
regulations in 33 CFR 165.501. All coordinates listed reference Datum
NAD 1983.
    (b) Definitions. In this section:
    (1) Official Patrol Vessel includes all U.S. Coast Guard, public,
state, county or local law enforcement vessels assigned and/or approved
by the Captain of the Port, Hampton Roads, Virginia.

    (2) Parade of Sail Vessel includes all vessels participating in
OPSAIL 2012 Virginia under the auspices of the U.S. Department of
Homeland Security Application for Marine Event, CG-4423, for the OPSAIL
2012 Virginia activities in the Port of Hampton Roads, Virginia
approved by the Captain of the Port, Hampton Roads.
    (3) Parade of Sail Arrivals is the movement of Parades of Sail
vessels in orderly succession as they navigate designated routes in the
Port of Hampton Roads, Virginia while inbound to the Port of Hampton
Roads, Virginia on June 6, 2012 and June 8, 2012.
    (4) Parade of Sail Departure is the movement of Parades of Sail
vessels in orderly succession as they navigate designated departure
routes from the Port of Hampton Roads, Virginia to Baltimore, Maryland
on June 12, 2012.
    (5) Spectator Vessel includes any vessel, commercial or
recreational, being used for pleasure or carrying passenger that is in
the Port of Hampton Roads to observe part or all of the OPSAIL 2012
Virginia events.
    (6) Large Spectator Vessel includes any Spectator Vessel 60 feet or
greater in length with a passenger capacity of 50 persons or greater.
    (7) Vessel Traffic Control Point means a designated point which
vessel traffic may not proceed past in either inbound or outbound
direction without permission of the Captain of the Port.
    (c) Vessels participating in OPSAIL 2012 Virginia Parades of Sail
are exempt from the regulations of Sec.  165.501(d)(4).
    (d) Regulated Navigation Area for OPSAIL 2012 Virginia. During
parades of sail, after firework displays, and any other time deemed
necessary for safety and security by the Captain of the Port, Hampton
Roads, vessels shall operate at the minimum speed required to maintain
steerage and shall avoid creating a wake when operating within the
Regulated Navigation Area, as defined in this regulation. During the
enforcement period a regulated navigation area will be established for
spectator vessel anchorage. Spectator vessel anchoring will preempt use
of these areas by other vessels.
    (1) Chesapeake Bay near Thimble Shoals channel, all waters bounded
by a line connecting the following points latitude 36[deg]59'59.2'' N
Longitude 76[deg]13'45.8'' W, thence to latitude 36[deg]59'08.7'' N
longitude 76[deg]10'32.6'' W, thence to 36[deg]58'13.5'' longitude N
76[deg]10'50.6'' W, thence to latitude 36[deg]59'02.5'' N longitude
76[deg]14'08.9'' W, thence to point of origin.
    (2) Hampton Roads, Hampton Bar, all waters bounded by a line
connecting the following points latitude 36[deg]59'25.5'' N longitude
76[deg]20'05.8'' W, thence to latitude 36[deg]59'52.1'' N longitude
76[deg]19'10.8'' W, thence to latitude 36[deg]59'25.7'' N longitude
76[deg]18'47.3'' W, thence to latitude 36[deg]58'49.6'' N longitude
76[deg]19'32.6'' W, thence to point of origin.
    (3) Newport News Middle Ground, all waters bounded by a line
connecting the following points latitude 36[deg]57'56.4'' N longitude
76[deg]20'30.5'' W, thence to latitude 36[deg]57'08.5'' N longitude
76[deg]20'31.0'' W, thence to latitude 36[deg]56'48.8'' N longitude
76[deg]20'22.5'' W, thence to latitude 36[deg]56'45.0'' N longitude
76[deg]20'32.0'' W, thence to latitude 36[deg]56'45.0'' N longitude
76[deg]21'37.7'' W, thence to latitude 36[deg]57'14.1'' N longitude
76[deg]23'29.1'' W, thence to latitude 36[deg]57'28.1'' N longitude
76[deg]21'11.7'' W, thence to point of origin.
    (e) Regulated areas. The following locations are a moving safety
zone:
    (1) All waters within 500 yards of any OPSAIL 2012 vessel which is
greater than 100 feet in length, while operating in the navigable
waters of the Chesapeake Bay or its tributaries, south of the Maryland-
Virginia border and north of latitude 36[deg]55'00'' N. Vessels must
operate at minimum speed within 100 yards of any OPSAIL 2012 vessel and
proceed as directed by the official patrol commander.
    (2) All waters within 100 yards of any OPSAIL 2012 vessel which is
greater than 100 feet in length overall, while operating in the
navigable waters of the Chesapeake Bay or its tributaries, south of the
Maryland-Virginia border and north of latitude 36[deg]55'00'' N.
Vessels shall not approach within 100 yards of any OPSAIL vessel. If a
vessel needs to pass within 100 yards of an OPSAIL 2012 vessel in order
to ensure safe passage in accordance with the Navigation Rules, the
vessel must contact the Coast Guard patrol commander on VHF-FM marine
band radio channel 13 (165.65MHz) or channel 16 (156.8 MHz).
    (f) Safety Zone. The following areas are safety zones. OPSAIL
Parade of Sail Route Segments. Regulated waters enclosed by the
following lines:
    (1) Segment One. All waters bounded by a line connecting the
Chesapeake Bay Entrance Lighted Whistle Buoy CH (LLNR 405) to Thimble
Shoal Channel Lighted Bell Buoy 1TS (LLNR 9205), thence to Thimble
Shoal Channel Lighted Bell Buoy 9 (LLNR 9255), thence to Thimble Shoal
Channel Lighted Bell Buoy 10 (LLNR 9260), thence to Thimble Shoal
Channel Lighted Buoy 2 (LLNR 9210), thence to the beginning.
    (2) Segment Two. All waters bounded by a line connecting Thimble
Shoal Channel Lighted Bell Buoy 9 (LLNR 9255), thence to Thimble Shoal
Channel Lighted Gong Buoy 17 (LLNR 9295), thence to Fort Wool Light
(LLNR 9385), thence to Old Point Comfort Light (LLNR 9380), thence to
Thimble Shoal Channel Lighted Buoy 22 (LLNR 9320), thence to Thimble
Shoal Channel Lighted Buoy 18 (LLNR 9300), thence to Thimble Shoal
Channel Lighted Buoy 10 (LLNR 9260), thence to the beginning.
    (3) Segment Three. All waters bounded by a line connecting Fort
Wool Light (LLNR 9385), thence to Elizabeth River Channel Lighted Buoy
1ER (LLNR 9445), thence to Elizabeth River Channel Lighted Bell Buoy 3
(LLNR 9465), thence to Elizabeth River Channel Lighted Gong Buoy 5
(LLNR 9470), thence to Elizabeth River Channel Lighted Buoy 7 (LLNR
9475), thence to Elizabeth River Channel Lighted Buoy 9 (LLNR 9515),
thence to Elizabeth River Channel Lighted Buoy 11 (LLNR 9525), thence
to Elizabeth River Channel Lighted Buoy 15 (LLNR 9545), thence to
Elizabeth River Channel Lighted Gong Buoy 17 (LLNR 9595), thence to
Elizabeth River Channel Lighted Buoy 19 (LLNR 9605), thence to
Lafayette River Channel Light 2 (LLNR 10660), thence to Elizabeth River
Channel Lighted Buoy 20 (LLNR 9620), thence to Elizabeth River Channel
Lighted Buoy 18 (LLNR 9600), thence to Elizabeth River Channel Lighted
Buoy 14 (LLNR 9540), thence to Elizabeth River Channel Lighted Buoy 12
(LLNR 9530), thence to Elizabeth River Channel Lighted Bell Buoy 10
(LLNR 9520), thence to Elizabeth River Channel Lighted Buoy 8 (LLNR
9500), thence to Newport News Channel Lighted Buoy 2 (LLNR 10840),
thence to Old Point Comfort Light (LLNR 9380), thence to the beginning.
    (4) Segment Four. All waters bounded by a line connecting Elizabeth
River Channel Lighted Buoy 20 (LLNR 9620), thence to Elizabeth River
U.S. Navy Deperming Range Sound Signal (LLNR 9725), thence to Elizabeth
River Channel Lighted Buoy 30 (LLNR 9735), thence to Elizabeth River
Channel Lighted Buoy 32 (LLNR 9840), thence to Elizabeth River Channel
Lighted Buoy 36 (LLNR 9900), thence following the shoreline to the
western terminus of the Jordan Bridge, thence to the eastern terminus
of the Jordan Bridge shoreline, thence following the shoreline to the
southern terminus of the Berkley Bridge, thence to the northern
terminus of the Berkley Bridge, thence following the shoreline to
Elizabeth River Channel Lighted Buoy 33 (LLNR 9850), thence to

Elizabeth River Channel Buoy 31 (LLNR 9835), thence to Elizabeth River
Channel Lighted Buoy 29 (LLNR 9715), thence to Elizabeth River Channel
Lighted Buoy 25 (LLNR 9710), thence to Elizabeth River Channel Lighted
Buoy 21 (LLNR 9625), thence to Lafayette River Channel Light 2 (LLNR
10660), thence to the beginning.
    (g) Regulated Area. The following area is a safety zone. Fireworks
Display Safety Zone: Regulated waters enclosed by the following lines:
All waters bounded by a line connecting Elizabeth River Channel Lighted
Buoy 20 (LLNR 9620), thence to Elizabeth River U.S. Navy Deperming
Range Sound Signal (LLNR 9725), thence to Elizabeth River Channel
Lighted Buoy 30 (LLNR 9735), thence to Elizabeth River Channel Lighted
Buoy 32 (LLNR 9840), thence to Elizabeth River Channel Lighted Buoy 36
(LLNR 9900), thence following the shoreline to the western terminus of
the Jordan Bridge, thence to the eastern terminus of the Jordan Bridge
shoreline, thence following the shoreline to the southern terminus of
the Berkley Bridge, thence to the northern terminus of the Berkley
Bridge, thence following the shoreline to Elizabeth River Channel
Lighted Buoy 33 (LLNR 9850), thence to Elizabeth River Channel Buoy 31
(LLNR 9835), thence to Elizabeth River Channel Lighted Buoy 29 (LLNR
9715), thence to Elizabeth River Channel Lighted Buoy 25 (LLNR 9710),
thence to Elizabeth River Channel Lighted Buoy 21 (LLNR 9625), thence
to Lafayette River Channel Light 2 (LLNR 10660), thence to the
beginning.
    (h) Notification. (1) Coast Guard Captain of the Port will notify
the public of the enforcement of these safety zones by all appropriate
means to affect the widest publicity among the affected segments of the
public. Publication in the Local Notice to Mariners, marine information
broadcasts, and facsimile broadcasts may be made for these events,
beginning 24 to 48 hours before the event is scheduled to begin, to
notify the public.
    (2) Contact Information. Questions about safety zones and related
events should be addressed to the Coast Guard Captain of the Port.
Contact Coast Guard Sector Hampton Roads--Captain of the Port Zone,
Norfolk, Virginia:<PHONE_NUMBER>.
    (i) Regulations: (1) In accordance with the general regulations in
Sec.  165.23 of this part, entry into these zones is prohibited unless
authorized by the Captain of the Port, Hampton Roads or his designated
representatives.
    (2) The operator of any vessel in the immediate vicinity of this
safety zone shall:
    (i) Stop the vessel immediately upon being directed to do so by any
commissioned, warrant or petty officer on shore or on board a vessel
that is displaying a U.S. Coast Guard Ensign.
    (ii) Proceed as directed by any commissioned, warrant or petty
officer on shore or on board a vessel that is displaying a U.S. Coast
Guard Ensign.
    (3) The Captain of the Port, Hampton Roads can be reached through
the Sector Duty Officer at Sector Hampton Roads in Portsmouth, Virginia
at telephone Number<PHONE_NUMBER>.
    (4) The Coast Guard Representatives enforcing the safety zone can
be contacted on VHF-FM marine band radio channel 13 (165.65MHz) or
channel 16 (156.8 MHz).
    (j) Enforcement Period. This regulation will be enforced June 6, 8,
9, and 12, 2012.

    Dated: May 17, 2012.
Steven H. Ratti,
Rear Admiral, U.S. Coast Guard, Commander, Fifth Coast Guard District.
[FR Doc. 2012-13404 Filed 6-4-12; 8:45 am]
BILLING CODE 9110-04-P