Document ID: FDA-2014-N-1112-0001
Agency: fda
Document Type: Rule
Title: Medical Devices; Clinical Chemistry and Clinical Toxicology Devices;
Classification of Hemoglobin A1c Test System
Posted Date: 2014-08-25T04:00Z

[Federal Register Volume 79, Number 164 (Monday, August 25, 2014)]
[Rules and Regulations]
[Pages 50549-50551]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-20022]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 862

[Docket No. FDA-2014-N-1112]

Medical Devices; Clinical Chemistry and Clinical Toxicology 
Devices; Classification of Hemoglobin A1c Test System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA) is classifying 
hemoglobin A1c test system into class II (special controls). The 
special controls that will apply to this device are identified in this 
order and will be part of the codified language for the hemoglobin A1c 
test system classification. The Agency is classifying 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 September 24, 2014. The classification 
was applicable May 23, 2013.

FOR FURTHER INFORMATION CONTACT: Meshaun Payne, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 5650, Silver Spring, MD 20993-0002, 301-796-6668.

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 (Public Law 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, within 30 days of 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

[[Page 50550]]

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.
    In accordance with section 513(f)(1) of the FD&C Act, FDA issued an 
order on March 14, 2013, classifying the COBAS INTEGRA 800 Tina-quant 
HbA1cDx Gen.2 assay into class III, because it was not substantially 
equivalent to a device that was introduced or delivered for 
introduction into interstate commerce for commercial distribution 
before May 28, 1976, or a device which was subsequently reclassified 
into class I or class II. On March 29, 2013, Roche Diagnostics 
Corporation submitted a request for classification of the COBAS INTEGRA 
800 Tina-quant HbA1cDx Gen.2 assay under section 513(f)(2) of the FD&C 
Act. The manufacturer recommended that the device be classified into 
class II.
    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). FDA classifies devices 
into class II 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 
reasonable assurance of the safety and effectiveness of the device for 
its intended use. After review of the information submitted in the de 
novo request, FDA determined that the device can be classified into 
class II with the establishment of special controls. FDA believes these 
special controls, in addition to general controls, will provide 
reasonable assurance of the safety and effectiveness of the device.
    Therefore, on May 23, 2013, FDA issued an order to the requestor 
classifying the device into class II. FDA is codifying the 
classification of the device by adding Sec.  862.1373.
    Following the effective date of this final classification 
administrative order, any firm submitting a premarket notification 
(510(k)) for a hemoglobin A1c test system will need to comply with the 
special controls named in the final administrative order.
    The device is assigned the generic name hemoglobin A1c test system, 
and it is identified as a device used to measure the percentage 
concentration of hemoglobin A1c in blood. Measurement of hemoglobin A1c 
is used as an aid in the diagnosis of diabetes mellitus and as an aid 
in the identification of patients at risk for developing diabetes 
mellitus.
    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
----------------------------------------------------------------------------------------------------------------
                    Identified risks                                       Required mitigations
----------------------------------------------------------------------------------------------------------------
False negative result due to inadequate device           Special controls (1) and (2).
 performance.
False positive result due to inadequate device           Special controls (1) and (2).
 performance.
Use of the test for patients with hemoglobin variants    Special control (3).
 that may interfere with the test system, and lead to
 incorrect results.
----------------------------------------------------------------------------------------------------------------

    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. The device must have initial and annual standardization 
verification by a certifying glycohemoglobin standardization 
organization deemed acceptable by FDA.
    2. The premarket notification submission must include performance 
testing to evaluate precision, accuracy, linearity and interference, 
including the following:
     Performance testing of device precision must, at a 
minimum, use blood samples with concentrations near 5.0 percent, 6.5 
percent, 8.0 percent and 12 percent hemoglobin A1c. This testing must 
evaluate precision over a minimum of 20 days using at least three lots 
of the device and three instruments, as applicable.
     Performance testing of device accuracy must include a 
minimum of 120 blood samples that span the measuring interval of the 
device and compare results of the new device to results of a 
standardized test method. Results must demonstrate little or no bias 
versus the standardized method.
     Total error of the new device must be evaluated using 
single measurements by the new device compared to results of the 
standardized test method, and this evaluation must demonstrate a total 
error less than or equal to 6 percent.
     Performance testing must demonstrate that there is little 
to no interference from common hemoglobin variants, including 
Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin 
S.
    3. When assay interference from Hemoglobin F or interference with 
other hemoglobin variants with low frequency in the population is 
observed, a warning statement must be placed in a black box and must 
appear in all labeling material for these devices describing the 
interference and any affected populations.
    Hemoglobin A1c test system devices are prescription devices 
restricted to patient use only upon the authorization of a practitioner 
licensed by law to administer or use the device. (See section 520(e) of 
the FD&C Act (21 U.S.C. 360j(e)) and 21 CFR 801.109 (Prescription 
devices).). Prescription-use restrictions are a type of general control 
as defined in section 513(a)(1)(A)(i) of the FD&C Act.
    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) 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 has determined that premarket 
notification is necessary to provide reasonable assurance of the safety 
and effectiveness of the device. Therefore, this device type is not 
exempt from premarket notification requirements. Persons who intend to 
market this type of device must submit to FDA a premarket notification, 
prior to marketing the device, which contains information about the 
hemoglobin A1c test system they intend to market.

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

[[Page 50551]]

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; the 
collections of information in 21 CFR part 820 have been approved under 
OMB control number 0910-0073; 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 862

    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 
862 is amended as follows:

PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES

0
1. The authority citation for 21 CFR part 862 continues to read as 
follows:

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

0
2. Add Sec.  862.1373 to subpart B to read as follows:

Sec.  862.1373  Hemoglobin A1c test system.

    (a) Identification. A hemoglobin A1c test system is a device used 
to measure the percentage concentration of hemoglobin A1c in blood. 
Measurement of hemoglobin A1c is used as an aid in the diagnosis of 
diabetes mellitus and as an aid in the identification of patients at 
risk for developing diabetes mellitus.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) The device must have initial and annual standardization 
verification by a certifying glycohemoglobin standardization 
organization deemed acceptable by FDA.
    (2) The premarket notification submission must include performance 
testing to evaluate precision, accuracy, linearity, and interference, 
including the following:
    (i) Performance testing of device precision must, at a minimum, use 
blood samples with concentrations near 5.0 percent, 6.5 percent, 8.0 
percent, and 12 percent hemoglobin A1c. This testing must evaluate 
precision over a minimum of 20 days using at least three lots of the 
device and three instruments, as applicable.
    (ii) Performance testing of device accuracy must include a minimum 
of 120 blood samples that span the measuring interval of the device and 
compare results of the new device to results of a standardized test 
method. Results must demonstrate little or no bias versus the 
standardized method.
    (iii) Total error of the new device must be evaluated using single 
measurements by the new device compared to results of the standardized 
test method, and this evaluation must demonstrate a total error less 
than or equal to 6 percent.
    (iv) Performance testing must demonstrate that there is little to 
no interference from common hemoglobin variants, including Hemoglobin 
C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S.
    (3) When assay interference from Hemoglobin F or interference with 
other hemoglobin variants with low frequency in the population is 
observed, a warning statement must be placed in a black box and must 
appear in all labeling material for these devices describing the 
interference and any affected populations.

    Dated: August 19, 2014.
Peter Lurie,
Associate Commissioner for Policy and Planning.
[FR Doc. 2014-20022 Filed 8-22-14; 8:45 am]
BILLING CODE 4164-01-P