[Federal Register Volume 83, Number 108 (Tuesday, June 5, 2018)]
[Rules and Regulations]
[Pages 25910-25915]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-11879]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 862, 866, 876, 880, and 884
[Docket No. FDA-2017-N-1129]
Medical Devices; Exemptions From Premarket Notification: Class II
Devices
AGENCY: Food and Drug Administration, HHS.
ACTION: Final order.
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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
publishing an order to exempt a list of class II devices from premarket
notification (510(k)) requirements, subject to certain limitations.
This exemption from 510(k), subject to certain limitations, is
immediately in effect for the listed class II devices. This exemption
will decrease regulatory burdens on the medical device industry and
will eliminate private costs and expenditures required to comply with
certain Federal regulations. FDA is also amending the codified language
for the listed class II devices to reflect this final determination.
FDA is publishing this order in accordance with the section of the
Federal Food, Drug, and Cosmetic Act (FD&C Act) permitting the
exemption of a device from the requirement to submit a 510(k).
DATES: This order is effective June 5, 2018.
FOR FURTHER INFORMATION CONTACT: Scott McFarland, Center for Devices
and
[[Page 25911]]
Radiological Health (CDRH), Food and Drug Administration, 10903 New
Hampshire Ave, Bldg. 66, Rm. 4676, Silver Spring, MD 20993-0002, 301-
796-6217.
SUPPLEMENTARY INFORMATION:
I. Statutory Background
Section 510(k) of 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 new device to submit and obtain 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 December 13, 2016, the 21st Century Cures Act (Cures Act) (Pub.
L. 114-255) was signed into law. Section 3054 of the Cures Act amended
section 510(m) of the FD&C Act. As amended, section 510(m)(2) provides
that, 1 calendar day after the date of publication of the final list
under section 510(1)(B), FDA may exempt a class II device from the
requirement to submit a report under section 510(k) of the FD&C Act,
upon its own initiative or a 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 provide a 60-calendar-day
comment period. Within 120 days of publication of such notice, FDA
shall publish an order in the Federal Register that sets forth its
final determination regarding the exemption of the device that was the
subject of the notice.
II. Criteria 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'' (``Class II 510(k)
Exemption Guidance''). That guidance can be obtained through the
internet at https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM080199.pdf or by
sending an email request to [email protected] to receive a copy
of the document. Please use the document number 159 to identify the
guidance you are requesting.
Accordingly, FDA generally considers the following factors to
determine whether premarket notification is necessary for class II
devices: (1) The device does not have a significant history of false or
misleading claims or of risks associated with inherent characteristics
of the device; (2) characteristics of the device necessary for its safe
and effective performance are well established; (3) changes in the
device that could affect safety and effectiveness will either (a) be
readily detectable by users by visual examination or other means such
as routine testing, before causing harm, or (b) not materially increase
the risk of injury, incorrect diagnosis, or ineffective treatment; and
(4) any changes to the device would not be likely to result in a change
in the device's classification. FDA may also consider that, even when
exempting devices, these devices would still be subject to the
limitations on exemptions.
III. Comments on the Proposed Exemption and FDA Response
In the Federal Register of November 7, 2017 (82 FR 51633), FDA
published a notice (``November 2017 notice'') announcing its intent to
exempt, upon its own initiative, certain class II devices listed in
table 1 from 510(k) requirements, subject to certain limitations, and
provided opportunity for interested persons to submit comments by
January 8, 2018. After reviewing comments received, FDA is now
providing its final determination on exempting the certain class II
devices listed in table 1 from 510(k) requirements, subject to certain
limitations as identified in this order. FDA is also amending the
codified language for the classification regulations for the certain
class II devices listed in table 1 to reflect this final determination.
Persons with pending 510(k) submissions for devices that are now exempt
from 510(k), subject to the limitations, should withdraw their
submissions.
In response to the November 2017 notice announcing FDA's intent to
exempt those device types from 510(k) requirements, FDA received a
submission from one commenter--a professional organization--opposing an
exemption from 510(k) for the genetic health risk assessment test
device type.
To make it easier to identify comments and our responses, the word
``Comment'' appears in parentheses before the comment's description,
and the word ``Response'' in parentheses precedes the response.
Specific issues raised by the comment and the Agency's response
follows.
(Comment) The commenter recommended FDA not exempt one-time FDA
reviewed genetic health risk assessment system devices from the 510(k)
requirement because there would be insufficient oversight to ensure the
analytical and clinical validity of these tests, consumers would be
misled regarding which tests FDA has affirmed are scientifically valid,
and concerns that, if one-time FDA reviewed genetic health risk
assessment system devices were exempted, consumers would not be assured
of being adequately informed about test quality. The commenter believed
it is not possible to assess the analytical and clinical validity of
all genetic health risks a company might offer by conducting a one-time
review of its `assessment system', as proposed by FDA. Such oversight,
it is argued, will only allow FDA to assess the analytical and clinical
validity, and `mitigate the risks of false negatives and positives',
for tests initially proposed by the company during this one-time
review. The commenter believed that it does not appear that there will
be assessment of the analytical or clinical validity of subsequent
tests offered, nor any assessment of the risks to the consumer of an
incorrect result. This commenter believed that FDA's proposal to exempt
one-time FDA reviewed genetic health risk assessment system devices
will not prevent scientifically invalid tests from being marketed to
the public and lacks a comprehensive assessment. Further, the commenter
argued that, after undergoing the one-time FDA review for genetic
health risk assessment tests, companies would be able to market
subsequent tests to the public as part of the same system and declare
that the tests meet FDA's standards. Such tests would not be held to
any specific standards of analytical or clinical validity. The public
would likely assume (and purveyors would likely advertise) that FDA had
reviewed and approved such tests as valid even though they had not been
reviewed by the Agency. The commenter also argued that there is a vast
range of quality (i.e., scientific merit) of direct-to-consumer (DTC)
genetic health risk assessment tests on the market. The commenter
argued that the market's current mixing of entertainment tests, which
make claims unsubstantiated by the scientific literature, with those
tests which have a clinical utility, are clinically valid, and can be
supported by current scientific
[[Page 25912]]
literature, is particularly confusing for the average consumer.
(Response) We agree that the concerns raised above are important.
These concerns were considered during our review and development of the
initial classification regulation for genetic health risk assessment
system devices and in our consideration of whether to exempt one-time
FDA reviewed genetic health risk assessment system devices from the
510(k) requirement. We believe these concerns have been addressed and
accounted for in our determination that the 510(k) requirement is not
necessary to provide a reasonable assurance of safety and effectiveness
for these devices. We outline our rationale below.
Consumer understanding of genetic risk is clearly an important
issue that was considered extensively by FDA in the context of genetic
health risk assessment system devices. This issue was balanced with the
increasing desire from the public to learn more about one's own genetic
makeup and how it affects genetic risk for health conditions. To ensure
that the tests and test reports are presented to the lay consumer in a
manner that is understandable, we employed several requirements.
Consumer understanding of the tests and associated test reports is
assured by user comprehension study requirements, specific labeling
requirements for these over-the-counter (OTC) tests, and general
requirements for devices. The special labeling requirements for these
devices under Sec. 866.5950(b) (21 CFR 866.5950(b)) include providing
information on the manufacturer's website about frequently asked
questions, available professional guidelines, and how to obtain access
to a genetic counselor.
A. User Comprehension Study
A user comprehension study is required under Sec.
866.5950(b)(3)(iii)(M). The required user comprehension study must
assess comprehension of the test process and results by potential users
of the test with pre- and post-test user comprehension studies. This
study must be conducted on a statistically sufficient sample size of
non-trained individuals who represent the demographics of the United
States as well as a diverse range of age and educational levels. The
study must include directly evaluating a representative sample of the
material being presented to the user during use of the test. The test
that is given to the participants must be informed by a physician and/
or genetic counselor that identifies the appropriate general and
variant-specific concepts contained within the material being tested in
the user comprehension study to ensure that all relevant concepts are
incorporated in the study as well as having included the definition of
the target condition being tested and related symptoms, explain the
intended use and limitations of the test, explain the relevant
ethnicities in regard to the variant tested, explain genetic health
risks and relevance to the user's ethnicity, and assess participants'
ability to understand the following comprehension concepts: The test's
limitations, purpose, appropriate action, test results, and other
factors that may have an impact on the test results. The outcome of
this study has to meet rigorous standards, including meeting 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. In addition, 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).
From our experience with user comprehension studies, the Agency
believes that meeting or exceeding these user comprehension study
requirements ensures that the materials presented to the user are
adequate for OTC use. The information the test provider must provide on
its website includes a summary table of comprehension rates regarding
comprehension concepts (e.g., purpose of test, test results, test
limitations, ethnicity relevance for the test results, etc.) for each
study report.
B. Frequently Asked Questions
The manufacturer's website must have a frequently asked questions
section in the summary and technical information sections under Sec.
866.5950(b)(3)(ii)(C)(3) and (b)(3)(iii)(L)(3). For the frequently
asked questions sections, information must be included that is specific
for each variant/disease pair that is reported and scientifically valid
and supported by corresponding publications. Further information must
be included that explains the health condition/disease being tested,
the purpose of the test, the information the test will and will not
provide, the relevance of race and ethnicity on the test results,
information about the population to which the variants in the test is
most applicable, the meaning of the result(s), other risks factors that
contribute to disease, appropriate followup procedures, how the results
of the test may affect the user's family, including children, and links
to resources that provide additional information.
C. Resources
Likely the test labeling information provided by the test
manufacturer will not be the sole source of information that the
consumer is seeking or even requires. For this reason, there are
requirements under Sec. 866.5950(b)(3)(ii)(C)(2) and (b)(3)(iii)(L)(2)
that the manufacturer of the test provide a pre-purchase page in the
summary and technical information sections that includes information
regarding professional guidelines for testing specific genes and
variants. Similar information must be provided in the frequently asked
questions section found in the summary and technical information
sections on the manufacturer's website, under Sec.
866.5950(b)(3)(ii)(C)(3) and (b)(3)(iii)(L)(3). These frequently asked
questions sections must include a statement about the current
professional guidelines for testing these specific gene(s) and
variant(s) and, if guidelines do not exist for certain genes or
variants being tested for, then this information must be provided as
well. Further, to facilitate more personalized support, under Sec.
866.5950(b)(1)(i)(E), test manufacturers are required to provide
information in the Sec. 809.10 (21 CFR 809.10) compliant labeling and
any pre-purchase page and test report generated regarding how a user
obtains access to a genetic counselor, board-certified clinical
molecular geneticist, or equivalent healthcare professional regarding
the results of a user's test.
D. Genetic Health Risk Assessment System Tests
The tests that fall under the genetic health risk assessment system
regulation are identified in the regulation in Sec. 866.5950(a) as a
qualitative in vitro molecular diagnostic system used for detecting
variants in genomic deoxyribonucleic acid (DNA) isolated from human
specimens that will provide information to users about their genetic
risk of developing a disease to inform lifestyle choices and/or
conversations with a healthcare professional. This assessment system is
for OTC use. This device does not determine the person's overall risk
of developing a disease.
The limitations that are most important for lay users to know about
the intended use of these tests that fall under this device type are
conveyed via the limiting statements required, under Sec.
866.5950(b)(1)(i), to be provided on the Sec. 809.10 compliant
labeling and any pre-purchase page and test report generated. One of
these limiting statements must explain that this test is
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not intended to diagnose a disease, tell you anything about your
current state of health, or be used to make medical decisions,
including whether or not you should take a medication or how much of a
medication you should take. The limitations that are most important for
healthcare professionals to know about the intended use of tests that
fall under this device type are, under Sec. 866.5950(b)(1)(ii),
required to be provided in the Sec. 809.10 labeling and any test
report generated. These limitations include that the test is intended
to provide users with their genetic information to inform lifestyle
decisions and conversations with their doctor or other healthcare
professional and that any diagnostic or treatment decisions should be
based on testing and/or other information that a healthcare
professional determines to be appropriate for a patient.
E. Rigorous Validation Requirements
FDA believes the analytical validation requirements are
sufficiently detailed in the special controls under Sec.
866.5950(b)(3)(iii)(J) that test providers will have no difficulty in
appropriately following these requirements. A high accuracy requirement
is necessary for tests that are provided under this regulation and
accuracy point estimates for all variants is required to be 99 percent
or higher under Sec. 866.5950(b)(3)(iii)(J)(1)(vii) or else they
cannot be claimed or reported. Once FDA has reviewed one test that
demonstrates this level of accuracy, then the test provider has
demonstrated an ability to meet the accuracy requirements for
additional similar tests offered.
F. Four Important Limitations on the Scope of the Classification
Regulation
FDA agrees that there are four important express limitations to the
types of tests that can be offered under this classification regulation
even when these special controls are met. Tests cannot be offered under
this classification regulation that are indicated for prenatal testing;
predisposition for cancer where the result of the test may lead to
prophylactic screening, confirmatory procedures, or treatments that may
incur morbidity or mortality to the patient; assessing the presence of
genetic variants that impact the metabolism, exposure, response, risk
of adverse events, dosing, or mechanisms of prescription or OTC
medications; or assessing the presence of deterministic autosomal
dominant variants.
G. False or Misleading Claims
It is a prohibited act for devices to have labeling that is false
or misleading in any particular manner, and thus FDA would deem such
device to be misbranded under section 502(a) of the FD&C Act (21 U.S.C.
352(a)). This prohibition would include prohibiting the manufacturer of
a genetic health risk assessment test device from falsely or
misleadingly representing a test as having been part of an original FDA
cleared device when it was added subsequently to FDA clearance. This
prohibition would also include falsely or misleadingly representing the
analytical or clinical validity of one of its tests. In addition, under
section 502(c) of the FD&C Act, it is a prohibited act and thus FDA
would deem a device to be misbranded if any information required on the
labeling of a device by FDA by or under the FD&C Act is not placed
prominently thereon with such conspicuousness and in such terms, as to
render it likely to be read and understood by the ordinary individual
under customary conditions of purchase and use. Thus, a genetic health
risk assessment test device for which a manufacturer later modified the
formerly compliant labeling to make the labeling such that the labeling
was not likely to be read and understood by the ordinary individual
under customary conditions of purchase and use would be a misbranded
device.
H. Conclusion
In summary, all tests that are marketed under this classification
regulation must meet the general controls and the special controls that
are specified in the regulation. Ability of a manufacturer to meet
these special controls is demonstrated during the one-time review. Even
after the one-time review, the general controls and special controls
must continue to be met, including for all tests added or modified
after the one-time review of a manufacturer's device.
IV. Limitations on Exemptions
FDA has determined that 510(k) is not necessary to assure the
safety and effectiveness of the class II devices listed in table 1.
This determination is based, in part, on the Agency's knowledge of the
device, including past experience and relevant reports or studies on
device performance (as appropriate), the applicability of general and
special controls, and the Agency's ability to limit an exemption.
A. General Limitations of Exemptions
FDA's exemption from 510(k) for class II devices listed in table 1
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. A manufacturer of a listed
device is still required to submit a 510(k) 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. Sec.
862.9 to 892.9 (21 CFR 862.9 to 21 CFR 892.9).
B. Partial Limitations of Exemptions
In addition to the general limitations, FDA may also partially
limit an exemption from 510(k) requirements to specific devices within
a listed device type when initial Agency assessment determines that the
factors laid out in the Class II 510(k) Exemption Guidance do not weigh
in favor of exemption for all devices in a particular group. In such
situations where a partial exemption limitation has been identified,
FDA has determined that premarket notification is necessary to provide
a reasonable assurance of safety and effectiveness for these devices.
In table 1, for example, FDA is listing the exemption of the genetic
health risk assessment system, but limits the exemption to such devices
that have received a first-time FDA marketing authorization (e.g.,
510(k) clearance) for the genetic health risk assessment system (a
``one-time FDA reviewed genetic health risk assessment system''). FDA
has determined that a one-time FDA review (e.g., premarket
notification) of a genetic health risk assessment system is necessary
to provide reasonable assurance of the safety and effectiveness of the
device. FDA has determined that a one-time FDA review of a genetic
health risk assessment system is necessary to mitigate the risk of
false negatives and false positives by ensuring that certain
information be submitted to FDA to allow the Agency to assess the
safety and effectiveness of the devices as well as to ensure the
devices perform to acceptable standards.
Exemption from the requirement of 510(k) does not exempt a device
from other applicable regulatory controls under the FD&C Act, including
the applicable general and special controls. This exemption from
510(k), subject to the limitations described above, is immediately in
effect for the device types identified in table 1. This exemption will
decrease regulatory burdens on the medical device industry and will
eliminate private costs and
[[Page 25914]]
expenditures required to comply with Federal regulations.
V. List of Class II Devices
FDA is identifying the following list of class II devices that will
no longer require premarket notification under section 510(k) of the
FD&C Act, subject to the general limitations to the exemptions found in
Sec. Sec. 862.9 to 892.9 and any partial exemption limitations
identified in table 1:
Table 1--Class II Devices
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Partial exemption
21 CFR section Device type Product code limitation (if applicable)
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862.1840............................ Total 25-hydroxyvitamin PSL ...........................
D Mass Spectrometry
Test System.
866.5950............................ Genetic Health Risk PTA Exemption is limited to a
Assessment System. genetic health risk
assessment system that has
received a first-time FDA
marketing authorization
(e.g., 510(k) clearance)
for the genetic health
risk assessment system (a
``one-time FDA reviewed
genetic health risk
assessment system'').
876.1500............................ Endoscope Disinfectant PUP ...........................
Basin.
880.6710............................ Purifier, Water, KMG ...........................
Ultraviolet, Medical.
884.5960............................ Vibrator for KXQ ...........................
Therapeutic Use,
Genital.
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FDA is revising the name of product code PUP to further clarify the
device type that this product code is intended to represent. The device
type was previously ``Endoscope Maintenance System.'' To more
accurately reflect the devices which fall within this device type
(product code PUP), the device type has been renamed ``Endoscope
Disinfectant Basin.'' Specifically, these devices are described as
``Wall-mounted tube(s) for holding disinfectant solution and endoscope
insertion tubes and accessories.'' This description has not changed
since publication of the November 2017 notice.
VI. Analysis of Environmental Impact
The Agency has determined under 21 CFR 25.30(h) 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.
VII. Paperwork Reduction Act of 1995
This final order refers to previously approved collections of
information found in other FDA regulations and guidance. 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
21 CFR Part 862
Medical devices.
21 CFR Part 866
Biologics, Laboratories, Medical devices.
21 CFR Parts 876, 880, and 884
Medical devices.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts
862, 866, 876, 880, and 884 are amended as follows:
PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES
0
1. The authority citation for part 862 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. In Sec. 862.1840, revise paragraph (b) introductory text to read as
follows:
Sec. 862.1840 Total 25-hydroxyvitamin D mass spectrometry test
system.
* * * * *
(b) Classification. Class II (special controls). The device is
exempt from the premarket notification procedures in part 807, subpart
E, of this chapter subject to the limitations in Sec. 862.9. The
device must comply with the following special controls:
* * * * *
PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES
0
3. The authority citation for part 866 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
4. In Sec. 866.5950, revise paragraph (b) introductory text to read as
follows:
Sec. 866.5950 Genetic health risk assessment system.
* * * * *
(b) Classification. Class II (special controls). The genetic health
risk assessment system device, when it has previously received a first-
time FDA marketing authorization (e.g., 510(k) clearance) for the
genetic health risk assessment system (a ``one-time FDA reviewed
genetic health risk assessment system''), is exempt from the premarket
notification procedures in part 807, subpart E, of this chapter subject
to the limitations in Sec. 866.9. The device must comply with the
following special controls:
* * * * *
PART 876--GASTROENTEROLOGY-UROLOGY DEVICES
0
5. The authority citation for part 876 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
6. In Sec. 876.1500, revise paragraph (b)(1) to read as follows:
Sec. 876.1500 Endoscope and accessories.
* * * * *
(b) * * *
(1) Class II (performance standards). The device, when intended as
an endoscope disinfectant basin, which consists solely of a container
that holds disinfectant and endoscopes and accessories, is exempt from
the premarket notification procedures in part 807, subpart E, of this
chapter subject to the limitations in Sec. 876.9.
* * * * *
[[Page 25915]]
PART 880--GENERAL HOSPITAL AND PERSONAL USE DEVICES
0
7. The authority citation for part 880 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
8. In Sec. 880.6710, revise paragraph (b) to read as follows:
Sec. 880.6710 Medical ultraviolet water purifier.
* * * * *
(b) Classification. Class II (performance standards). The device is
exempt from the premarket notification procedures in part 807, subpart
E, of this chapter subject to the limitations in Sec. 880.9.
PART 884--OBSTETRICAL AND GYNECOLOGICAL DEVICES
0
9. The authority citation for part 884 continues to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
10 In Sec. 884.5960, revise paragraph (b) to read as follows:
Sec. 884.5960 Genital vibrator for therapeutic use.
* * * * *
(b) Classification. Class II (performance standards). The device is
exempt from the premarket notification procedures in part 807, subpart
E, of this chapter subject to the limitations in Sec. 884.9.
Dated: May 29, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-11879 Filed 6-1-18; 8:45 am]
BILLING CODE 4164-01-P