[Federal Register Volume 81, Number 192 (Tuesday, October 4, 2016)]
[Rules and Regulations]
[Pages 68295-68297]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-23901]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 862
[Docket No. FDA-2016-P-0159]
Medical Devices; Exemption From Premarket Notification; Method,
Metallic Reduction, Glucose (Urinary, Nonquantitative) Test System in a
Reagent Tablet Format
AGENCY: Food and Drug Administration, HHS.
ACTION: Final order.
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SUMMARY: The Food and Drug Administration (FDA) is publishing an order
denying a petition requesting exemption from the premarket notification
requirements for method, metallic reduction, glucose (urinary,
nonquantitative) devices that are in a reagent tablet format and are
classified as class II devices as urinary glucose (nonquantitative)
test system (hereinafter referred to as ''copper reduction tablet
test''). Urinary glucose (nonquantitative) measurements are used in the
diagnosis and treatment of carbohydrate metabolism disorders including
diabetes mellitus, hypoglycemia, and hyperglycemia. FDA is publishing
this order in accordance with procedures established by the Food and
Drug Administration Modernization Act of 1997 (FDAMA).
DATES: This order is effective October 4, 2016.
FOR FURTHER INFORMATION CONTACT: Sheila Connors, Center for Devices and
Radiological Health (CDRH), Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 66, Rm. 4620, Silver Spring, MD 20993-0002, 301-
796-6181, [email protected].
SUPPLEMENTARY INFORMATION:
I. Statutory Background
Under section 513 of the Federal Food, Drug, and Cosmetic Act (the
FD&C Act) (21 U.S.C. 360c), FDA must classify devices into one of three
regulatory classes: Class I, class II, or class III. FDA classification
of a device is determined by the amount of regulation necessary to
provide a reasonable assurance of the safety and effectiveness of the
device. Under the Medical Device Amendments of 1976 (1976 amendments)
(Pub. L. 94-295), as amended by the Safe Medical Devices Act of 1990
(Pub. L. 101-629), devices are to be classified into class I (general
controls) if there is information showing that the general controls of
the FD&C Act are sufficient to assure safety and effectiveness; into
class II (special controls) if general controls, by themselves, are
insufficient to provide reasonable assurance of safety and
effectiveness, but there is sufficient information to establish special
controls to provide such assurance; and into class III (premarket
approval) if there is insufficient information to support classifying a
device into class I or class II and the device is a life-sustaining or
life-supporting device, or is for a use which is of substantial
importance in preventing impairment of human health, or presents a
potential unreasonable risk of illness or injury.
Section 510(k) of the FD&C Act (21 U.S.C. 360(k)) and the
implementing regulations (21 CFR part 807) require persons who intend
to market a device intended for human use to submit a premarket
notification (510(k)) to FDA containing information that allows FDA to
determine whether the device is ``substantially equivalent'' within the
meaning of section 513(i) of the FD&C Act to a legally marketed device
that does not require premarket approval.
On November 21, 1997, the President signed into law FDAMA (Pub. L.
105-115). Section 206 of FDAMA, in part, added section 510(m) to the
FD&C Act. Section 510(m)(1) of the FD&C Act requires FDA, within 60
days after enactment of FDAMA, to publish in the Federal Register a
list of each type of class II device that does not require a report
under section 510(k) of the FD&C Act to provide reasonable assurance of
safety and effectiveness. Section 510(m) of the FD&C Act further
provides that a 510(k) will no longer be required for these devices
upon the date of publication of the list in the Federal Register. FDA
published that list in the Federal Register of January 21, 1998 (63 FR
3142).
Section 510(m)(2) of the FD&C Act provides that 1 day after the
date of publication of the list under section 510(m)(1), FDA may exempt
a class II device on its own initiative or upon petition of an
interested person, if FDA determines that a 510(k) is not necessary to
provide reasonable assurance of the safety and effectiveness of the
device.
[[Page 68296]]
This section requires FDA to publish in the Federal Register a notice
of intent to exempt a device, or of the petition, and to provide a 30-
day comment period. Within 120 days of publication of this document,
FDA must publish in the Federal Register its final determination
regarding the exemption of the device that was the subject of the
notice. If FDA fails to respond to a petition under this section within
180 days of receiving it, the petition shall be deemed granted.
FDA classified the urinary glucose (nonquantitative) test system
into class II effective July 30, 1987 (52 FR 16102 at 16122, May 1,
1987). The classification for urinary glucose (nonquantitative) test
system is at Sec. 862.1340 (21 CFR 862.1340). The urinary glucose
(nonquantitative) test system is identified as a device that is
intended to measure glucosuria (glucose in urine). Urinary glucose
(nonquantitative) measurements are used in the diagnosis and treatment
of carbohydrate metabolism disorders including diabetes mellitus,
hypoglycemia, and hyperglycemia. Devices under this classification
regulation require premarket notification under section 510(k) of the
FD&C Act.
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
guidance the Agency issued on February 19, 1998, entitled ``Procedures
for Class II Device Exemptions from Premarket Notification, Guidance
for Industry and CDRH Staff'' (Ref. 1). Accordingly, FDA generally
considers the following factors to determine whether premarket
notification is necessary: (1) The device does not have a significant
history of false or misleading claims or 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. Petition
On January 7, 2016, FDA received a petition requesting an exemption
from premarket notification requirements for copper reduction tablet
tests that are classified as class II devices under Sec. 862.1340,
urinary glucose (nonquantitative) test system, from Evelyn Mirza,
Biorex Labs, LLC. (See Docket No. FDA-2016-P-0159).
On March 24, 2016 (81 FR 15728), FDA published a notice in the
Federal Register announcing that this petition had been received and
provided an opportunity for interested persons to submit comments on
the petition by April 25, 2016, in accordance with section 510(m)(2) of
the FD&C Act. FDA received no comments regarding this petition.
FDA has completed review of the previously referenced petition and
assessed the need for 510(k) clearance for copper reduction tablet test
against the criteria laid out in section II. For the reasons described
in section IV, FDA has determined that premarket notification is
necessary to provide a reasonable assurance of the safety and
effectiveness of the copper reduction tablet tests classified under
Sec. 862.1340 and assigned the classification product code JIM.
Accordingly, FDA responded to the petition by letter dated July 1,
2016, denying the petition within the 180-day timeframe under section
510(m)(2) of the FD&C Act. (See Docket No. FDA-2016-P-0159.)
IV. Order
After reviewing the petition, FDA has determined that the petition
failed to provide information to demonstrate that premarket
notification is not necessary to provide reasonable assurance of the
safety and effectiveness of the device. Accordingly, FDA is denying the
previously referenced petition for exemption from the premarket
notification requirements.
With regard to the first factor (section II, Criteria for
Exemption), although there have been no medical device reports reported
to the Agency in recent years, there have been numerous reports to the
Agency \1\ and in medical literature of risks associated with the
inherent characteristics of this device, including possible device-
associated deaths, serious injuries, and malfunctions such as burns,
explosions of the product bottle due to heat, and consumption of the
device. For instance, there have been reports in the medical literature
of patients consuming the tablets because of their similarity to pills,
which has led to poisoning and one report of a death. Therefore, FDA
does not agree with the petitioner that the use of the device is well
established without any reports of patient or user injury, or that the
device does not have a significant history of risks associated with
inherent characteristics of the device.
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\1\ For more information, see Medical Device Reporting (MDR)
database at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/search.CFM.
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Additionally, failure to observe the reaction at all times after
the tablet has been added to the sample is another risk associated with
the inherent characteristics of the device. This can lead to a false-
negative result and result in improper patient management, which can
lead to serious injury or possibly death. The petition failed to
demonstrate how the device's inherent risks can be mitigated or
controlled without premarket notification to provide a reasonable
assurance of the safety and effectiveness of the device.
With regard to the second factor, the petition stated that a copper
reduction tablet test can be used to evaluate pediatric patients for
possible hereditary metabolic disorders through detection of reducing
substances. For example, although all States require mandatory newborn
screening for genetic metabolic defects, clinical laboratories may
still use this device as a screening test on pediatric urine samples if
there are any suspicions of metabolic disease prior to receiving
newborn screening results or if the newborn screening results do not
match the clinical state of the newborn. Although further diagnostic
testing may be performed to confirm the result(s), physicians may
immediately treat the newborn relying solely on the result of this test
while awaiting the results for any followup diagnostic tests. False
negative results also present a safety and effectiveness concern
because followup diagnostic testing may not be performed, leading to
the failure to start needed treatment for the newborn. The petition
also stated that this device is used in the diagnosis, monitoring, and
treatment of metabolic disorders such as diabetes mellitus. However,
the petition failed to demonstrate that a premarket submission is not
necessary to provide a reasonable assurance of the safety and
effectiveness of the device for such uses, and FDA does not agree that
the characteristics of the device necessary for its safe and effective
use are well established.
With regard to the third factor, FDA also does not agree that
changes in the device that could affect safety and effectiveness will
either be readily detectable or not materially increase
[[Page 68297]]
risks. For example, available quality control materials may contain
glucose but do not contain other reducing sugars (e.g., galactose,
lactose). Therefore, such materials might not readily detect an issue
with the device's safety or effectiveness in detecting other reducing
sugars, before causing harm. The petition provided insufficient
information to support the position that changes in the device that
could affect safety and effectiveness will either be readily detectable
or not materially increase risks. Moreover, changes in the device that
could affect safety and effectiveness might materially increase the
risk of injury, incorrect diagnosis, or ineffective treatment given the
device type's intended uses. The petition also did not provide
information to the contrary. The petition did not provide any
information regarding the fourth factor.
In addition to these four factors, FDA considers the ``limitations
on exemption.'' Manufacturers of any commercially distributed device
for which FDA has granted an exemption from the requirement of
premarket notification must still submit a premarket notification to
FDA prior to marketing the device when any of the limitations of
exemption are exceeded. The general limitations of exemption from
premarket notification contained in Sec. 862.9 (21 CFR 862.9) are
broadly applicable to in vitro diagnostic (IVD) devices classified
under part 862 (21 CFR part 862). Under Sec. 862.9, the exemption from
the premarket notification requirements applies, in the case of IVD
devices, only to those devices under part 862 for which misdiagnosis,
as a result of using the device, would not be associated with high
morbidity or mortality. FDA has previously assessed that this
limitation is exceeded, and a premarket notification is necessary to
provide a reasonable assurance of the safety and effectiveness of an
IVD device, when such device is intended for use in screening or
diagnosis of familial or acquired genetic disorders, including inborn
errors of metabolism (Sec. 862.9(c)(2)) or intended for use in
diabetes management (Sec. 862.9(c)(5)). The copper reduction tablet
test described in the petition is intended for such uses and would
likely exceed the limitations just described.
Accordingly, for all of the foregoing reasons, the petition failed
to demonstrate that a premarket submission is not necessary to provide
a reasonable assurance of the safety and effectiveness of the device
intended for such uses. Therefore, FDA is issuing this order denying
the petition requesting exemption for a method, metallic reduction,
glucose (urinary, nonquantitative) test system in a reagent tablet
format that is intended to measure glucosuria (glucose in urine) from
the premarket notification requirements. Manufacturers of this device
type must continue to submit and receive FDA clearance of a 510(k)
before marketing their device, as well as comply with all other
applicable requirements under the FD&C Act.
V. Reference
The following reference is on display in the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, and is available for viewing by
interested persons between 9 a.m. and 4 p.m., Monday through Friday; it
is also available electronically at http://www.regulations.gov. FDA has
verified the Web site address, as of the date this document publishes
in the Federal Register, but Web sites are subject to change over time.
1. ``Procedures for Class II Device Exemptions from Premarket
Notification, Guidance for Industry and CDRH Staff,'' February 1998,
available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM080199.pdf.
Dated: September 28, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-23901 Filed 10-3-16; 8:45 am]
BILLING CODE 4164-01-P