[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]


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

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.

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

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, Sheila.Connors@fda.hhs.gov.

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.
---------------------------------------------------------------------------

    \1\ For more information, see Medical Device Reporting (MDR) 
database at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/search.CFM.
---------------------------------------------------------------------------

    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