
[Federal Register Volume 81, Number 192 (Tuesday, October 4, 2016)]
[Rules and Regulations]
[Pages 68293-68295]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-23899]



 ========================================================================
 Rules and Regulations
                                                 Federal Register
 ________________________________________________________________________
 
 This section of the FEDERAL REGISTER contains regulatory documents 
 having general applicability and legal effect, most of which are keyed 
 to and codified in the Code of Federal Regulations, which is published 
 under 50 titles pursuant to 44 U.S.C. 1510.
 
 The Code of Federal Regulations is sold by the Superintendent of Documents. 
 Prices of new books are listed in the first FEDERAL REGISTER issue of each 
 week.
 
 ========================================================================
 

  Federal Register / Vol. 81, No. 192 / Tuesday, October 4, 2016 / 
Rules and Regulations  

[[Page 68293]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 862

[Docket No. FDA-2016-P-1026]


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 (PMA).
    On November 21, 1997, the President signed into law FDAMA (Pub. L. 
105-115). Section 206 of FDAMA, in part, added a new section, 510(m), 
to the FD&C. 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) 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 a reasonable assurance of the safety and effectiveness of the 
device. This section requires FDA to publish in the Federal Register a 
notice of intent to exempt a device, or of the petition, and to provide 
a 30-day comment period. Within 120 days of publication of this 
document, FDA must publish in the Federal Register its final 
determination regarding the exemption of the device that was the 
subject of the notice. If FDA fails to respond to a petition under this 
section within 180 days of receiving it, the petition shall be deemed 
granted.
    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

[[Page 68294]]

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 March 18, 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 Martin O'Connor, 
Germaine Laboratories, Inc. (See Docket No. FDA-2016-P-1026).
    On May 4, 2016 (81 FR 26802), FDA published a notice in the Federal 
Register announcing that this petition had been received in accordance 
with section 510(m)(2) of the FD&C Act. On June 20, 2016 (81 FR 39929), 
FDA republished a notice of the petition due to an inadvertent error in 
the docket number and provided an opportunity for interested persons to 
submit comments on the petition by July 20, 2016. FDA received no 
comments regarding this petition.
    FDA has completed review of the 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 this 
document, 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 September 6, 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-1026).

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 a reasonable assurance of the 
safety and effectiveness of the device. Accordingly, FDA is denying the 
referenced petition for exemption from the premarket notification 
requirements.
    With regard to the first factor (see 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 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 does not address 
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 
healthcare and laboratory professionals understand the appropriate use 
of a copper reduction tablet test and that a definitive diagnostic or 
therapeutic decision should not be based on the result of this method. 
However, 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 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 risks. The 
petition claimed that users could employ positive or negative controls 
to validate the reagents performance. However, while available quality 
control materials may contain glucose, they 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 argued that well-established protocols and methods could 
ensure there is no material increase in risk. The petition provided 
insufficient information to support this argument 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 relevant 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

[[Page 68295]]

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 petition argued that the 
copper reduction tablet test is not intended for use in screening or 
diagnosis of familial and acquired genetic disorders, including inborn 
errors of metabolism, or for use in diabetes management. However, as 
explained previously, FDA disagrees and believes that the copper 
reduction tablet test described in the petition is intended for such 
uses and would likely exceed the limitations previously mentioned.
    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. 2016-23899 Filed 10-3-16; 8:45 am]
 BILLING CODE 4164-01-P


