[Federal Register Volume 85, Number 35 (Friday, February 21, 2020)]
[Proposed Rules]
[Pages 10110-10118]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-03515]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2019-N-5192]


Microbiology Devices; Reclassification of Human Immunodeficiency 
Virus Serological Diagnostic and Supplemental Tests and Human 
Immunodeficiency Virus Nucleic Acid Diagnostic and Supplemental Tests

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed amendment; proposed order.

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

SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
proposing to reclassify certain human immunodeficiency virus (HIV) 
serological diagnostic and supplemental tests and HIV nucleic acid 
(NAT) diagnostic and supplemental tests, postamendments class III 
devices with the product code MZF, into class II (special controls), 
subject to premarket notification. FDA is also proposing new device 
classification regulations along with special controls that the Agency 
believes are necessary to provide a reasonable assurance of safety and 
effectiveness for these devices. FDA is proposing this reclassification 
on its own initiative. If finalized, this order will reclassify these 
types of devices from class III (premarket approval) to class II 
(special controls) and reduce the regulatory burdens associated with 
these devices, as these types of devices will no longer be required to 
submit a premarket approval application (PMA) but can instead submit a 
premarket notification (510(k)) and receive clearance before marketing 
their device.

DATES: Submit either electronic or written comments by April 21, 2020. 
Please see section XI of this document for the proposed effective date 
when the new requirements apply and for the proposed effective date of 
a final order based on this proposed order.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before April 21, 2020. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of April 21, 2020. Comments received 
by mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are postmarked or the delivery service 
acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed below (see ``Written/Paper Submissions'' and 
``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2019-N-5192 for ``Microbiology Devices; Reclassification of human 
immunodeficiency virus serological diagnostic and supplemental tests 
and human immunodeficiency virus nucleic acid diagnostic and 
supplemental tests''. Received comments, those filed in a timely manner 
(see ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as

[[Page 10111]]

``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Jenifer Roe, Center for Biologics 
Evaluation and Review, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.

SUPPLEMENTARY INFORMATION: 

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended by 
the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L. 
94-295), the Safe Medical Devices Act of 1990 (Pub. L. 101-629), Food 
and Drug Administration Modernization Act of 1997 (Pub. L. 105-115), 
the Medical Device User Fee and Modernization Act of 2002 (Pub. L. 107-
250), the Medical Devices Technical Corrections Act (Pub. L. 108-214), 
the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110-
85), and the Food and Drug Administration Safety and Innovation Act 
(Pub. L. 112-144), among other amendments, establishes a comprehensive 
system for the regulation of medical devices intended for human use. 
Section 513 of the FD&C Act (21 U.S.C. 360c) established three 
categories (classes) of devices, reflecting the regulatory controls 
needed to provide reasonable assurance of their safety and 
effectiveness. The three categories of devices are class I (general 
controls), class II (general controls and special controls), and class 
III (general controls and premarket approval).
    Section 513(a)(1) of the FD&C Act defines the three classes of 
devices. Class I devices are those devices for which the general 
controls of the FD&C Act (controls authorized by or under sections 501, 
502, 510, 516, 518, 519, or 520 (21 U.S.C. 351, 352, 360, 360f, 360h, 
360i, or 360j) or any combination of such sections) are sufficient to 
provide reasonable assurance of safety and effectiveness; or those 
devices for which insufficient information exists to determine that 
general controls are sufficient to provide reasonable assurance of 
safety and effectiveness or to establish special controls to provide 
such assurance, but because the devices are not purported or 
represented to be for a use in supporting or sustaining human life or 
for a use which is of substantial importance in preventing impairment 
of human health, and do not present a potential unreasonable risk of 
illness or injury, are to be regulated by general controls (section 
513(a)(1)(A) of the FD&C Act). Class II devices are those devices for 
which general controls by themselves are insufficient to provide 
reasonable assurance of safety and effectiveness, and for which there 
is sufficient information to establish special controls to provide such 
assurance, including the promulgation of performance standards, 
postmarket surveillance, patient registries, development and 
dissemination of guidelines, recommendations, and other appropriate 
actions the Agency deems necessary to provide such assurance (section 
513(a)(1)(B) of the FD&C Act). Class III devices are those devices for 
which insufficient information exists to determine that general 
controls and special controls would provide a reasonable assurance of 
safety and effectiveness, and are purported or represented to be for a 
use in supporting or sustaining human life or for a use which is of 
substantial importance in preventing impairment of human health, or 
present a potential unreasonable risk of illness or injury (section 
513(a)(1)(C) of the FD&C Act).
    Devices that were not in commercial distribution prior to May 28, 
1976 (generally referred to as postamendments devices) are 
automatically classified by section 513(f)(1) of the FD&C Act into 
class III without any FDA rulemaking process. Those devices remain in 
class III and require premarket approval, unless, and until, (1) FDA 
reclassifies the device into class I or class II, or (2) 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. FDA 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 and part 807 
(21 CFR part 807), subpart E, of the regulations.
    A postamendments device that has been initially classified in class 
III under section 513(f)(1) of the FD&C Act may be reclassified into 
class I or II under section 513(f)(3) of the FD&C Act. Section 
513(f)(3) of the FD&C Act provides that FDA, acting by administrative 
order, can reclassify the device into class I or class II on its own 
initiative, or in response to a petition from the manufacturer or 
importer of the device. To change the classification of the device, the 
proposed new class must have sufficient regulatory controls to provide 
a reasonable assurance of the safety and effectiveness of the device 
for its intended use.
    FDA relies upon ``valid scientific evidence,'' as defined in 
section 513(a)(3) and 21 CFR 860.7(c)(2), in the classification process 
to determine the level of regulation for devices. To be considered in 
the reclassification process, the ``valid scientific evidence'' upon 
which the Agency relies must be publicly available (see section 520(c) 
of the FD&C Act). Publicly available information excludes trade secret 
and/or confidential commercial information, e.g., the contents of a 
pending PMA (see section 520(c) of the FD&C Act).
    In accordance with section 513(f)(3) of the FD&C Act, the Agency is 
issuing this proposed order to reclassify HIV serological diagnostic 
and supplemental tests and HIV NAT diagnostic and supplemental tests, 
postamendments class III devices, into class II (special controls), 
subject to premarket notification because the Agency believes the 
standard in section 513(a)(1)(B) of the FD&C Act is met because there 
is sufficient information to establish special controls, in addition to 
general controls, to provide reasonable assurance of the safety and 
effectiveness of the device.\1\
---------------------------------------------------------------------------

    \1\ In December 2019, FDA began adding the term ``Proposed 
amendment'' to the ``ACTION'' caption for these documents, typically 
styled ``Proposed order'', to indicate that they ``propose to 
amend'' the Code of Federal Regulations. This editorial change was 
made in accordance with the Office of Federal Register's (OFR) 
interpretations of the Federal Register Act (44 U.S.C. chapter 15), 
its implementing regulations (1 CFR 5.9 and parts 21 and 22), and 
the Document Drafting Handbook.
---------------------------------------------------------------------------

    Section 510(m) of the FD&C Act provides that a class II device may 
be exempted from the premarket notification requirements under section 
510(k) of the FD&C Act if the Agency determines that premarket 
notification is not necessary to provide reasonable assurance of the 
safety and effectiveness of the device. FDA has determined that 
premarket notification is necessary to reasonably assure the safety and 
effectiveness of HIV serological diagnostic and supplemental tests and 
HIV NAT diagnostic and supplemental tests. Therefore, the Agency does 
not

[[Page 10112]]

intend to exempt this proposed class II device from premarket 
notification (510(k)) submission under section 510(m) of the FD&C Act.

II. Regulatory History of the Devices

    This proposed order covers HIV serological diagnostic and 
supplemental tests and HIV NAT diagnostic and supplemental tests. These 
are prescription tests that are assigned product code MZF. These 
postamendments devices are currently regulated as class III devices 
under section 513(f)(1) of the FD&C Act. Based on our review experience 
and consistent with the FD&C Act and FDA's regulations in 21 CFR 
860.134, FDA believes that these devices should be reclassified from 
class III into class II with special controls because there is 
sufficient information for these devices to establish special controls 
that can provide a reasonable assurance of the device's safety and 
effectiveness.
    FDA has regulated the devices subject to this proposed order for 
many years. The first serological test intended for use as an aid in 
the diagnosis of infection with HIV was approved in 1987. The first 
supplemental test intended for use as an aid in confirming diagnosis of 
infection with HIV was approved in 1992. Currently there are 11 
diagnostic serological tests and 6 supplemental serological tests on 
the market in the United States. In 2006, FDA approved one NAT test 
that is intended for use as an aid in the diagnosis of infection with 
HIV. This device is also approved as a supplemental NAT test.
    A review of the medical device reporting databases indicates that 
there is a low number of reported events for HIV serological diagnostic 
and supplemental tests and HIV NAT diagnostic tests. Over 100 million 
HIV tests subject to this proposed reclassification have been sold 
since 2000, with less than 1,000 reported events as of September 2019. 
Of these, fewer than 40 are reported to involve injuries due to false 
results; the remainder are malfunctions, user errors, or incorrect 
results that had no reported effect on the individual being tested. 
There have been less than 10 recalls specific to these tests, and no 
class I recalls, indicating a good safety record for this device class.

III. Device Description

    This proposed order applies to certain HIV serological diagnostic 
and supplemental tests that are prescription devices for the 
qualitative detection of HIV antigens and/or antibodies against HIV in 
human body fluids or tissues. As such, the prescription device must 
satisfy prescription labeling requirements for in vitro diagnostic 
products (see 21 CFR 809.10(a)(4) and (b)(5)(ii)). The tests are 
intended for use as an aid in the diagnosis of infection with HIV. 
These devices are not intended for monitoring patient status or for 
screening donors of blood, plasma, or human cells, tissues, or cellular 
or tissue-based products (HCT/Ps). HIV serological tests detect the 
presence of HIV by using anti-HIV antibodies and/or HIV antigens to 
detect the presence of HIV antigens and/or anti-HIV antibodies in human 
fluids. The analytes are detected by chemical, fluorescent, 
luminescent, or other methods to produce a qualitative output that 
determines the presence or absence of HIV in the sample. Supplemental 
serological tests are intended to be used as an additional test to 
confirm the presence of HIV antibodies or antigens in specimens found 
to be repeatedly reactive by a diagnostic screening device. These tests 
are intended for professional use only.
    This proposed order also applies to certain HIV NAT diagnostic and 
supplemental tests that are prescription devices for the detection of 
HIV nucleic acid in human body fluids or tissues. The tests are 
intended for use as an aid in the diagnosis of infection with HIV. 
These devices are not intended for monitoring patient status, or for 
screening donors of blood, plasma, or HCT/Ps. HIV NAT tests detect the 
presence of HIV by detecting HIV nucleic acid in human body fluids or 
from solutions after isolation of nucleic acid from cells or tissues. 
The nucleic acids are amplified and detected by labeled probes that 
produce a qualitative signal that indicates the presence or absence of 
HIV nucleic acid in the sample. Supplemental NAT tests are intended to 
be used as an additional test to confirm the presence of HIV nucleic 
acid in specimens found to be repeatedly reactive by a diagnostic 
screening device. These tests are intended for professional use only.

IV. Proposed Reclassification

    FDA is proposing to reclassify HIV serological diagnostic and 
supplemental tests and HIV NAT diagnostic and supplemental tests. FDA 
held a public meeting on July 19, 2018, of the Blood Products Advisory 
Committee, convened as a medical device Panel (``the Panel''), which 
unanimously agreed that special controls, in addition to general 
controls, are sufficient to mitigate the risks to health from HIV 
serological diagnostic and supplemental tests and HIV NAT diagnostic 
and supplemental tests. The Panel believed that class II with special 
controls would provide reasonable assurance of the safety and 
effectiveness of the device. The Panel discussed the proposed special 
controls (see section VII), especially the performance criteria and 
number of samples that would be required for testing. The Panel also 
recommended that FDA consider reclassification from class III to class 
II of HIV viral load tests indicated for use for monitoring patient 
status.
    The Agency believes that, at this time, sufficient data and 
information exist such that the risks to health identified in section V 
can be mitigated by establishing special controls that, together with 
general controls, can provide a reasonable assurance of the safety and 
effectiveness of these devices. Therefore, FDA proposes these devices 
be reclassified from class III to class II.
    In accordance with section 513(f)(3) of the FD&C Act and 21 CFR 
part 860, subpart C, FDA is proposing to reclassify postamendments HIV 
serological diagnostic and supplemental tests and NAT diagnostic and 
supplemental tests from class III into class II. FDA believes that 
there are sufficient data and information available through FDA's 
accumulated experience with these devices from review submissions, 
recommendations provided by the Panel, and from published literature to 
demonstrate that the proposed special controls, along with general 
controls, would effectively mitigate the risks to health identified in 
section V and provide a reasonable assurance of safety and 
effectiveness of these devices. Absent the special controls identified 
in this proposed order, general controls applicable to the device are 
insufficient to provide reasonable assurance of the safety and 
effectiveness of the device. FDA expects that the reclassification of 
these devices would enable more manufacturers to develop HIV 
serological diagnostic and supplemental and NAT diagnostic and 
supplemental tests such that patients would benefit from increased 
access to safe and effective tests.
    FDA is proposing to create separate classification regulations for 
HIV serological diagnostic and supplemental tests and HIV NAT 
diagnostic and supplemental tests that will be reclassified from class 
III to class II. Under this proposed order, if finalized, HIV 
serological diagnostic and supplemental tests and HIV NAT diagnostic 
and supplemental tests will be identified as prescription devices. In 
this proposed order the Agency has proposed the special controls under 
section 513(a)(1)(B) of the FD&C Act

[[Page 10113]]

that, together with general controls, would provide a reasonable 
assurance of the safety and effectiveness of HIV serological and NAT 
diagnostic and supplemental tests.
    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) of the FD&C Act if FDA determines that premarket notification is 
not necessary to provide reasonable assurance of the safety and 
effectiveness of the device. For these HIV serological diagnostic and 
supplemental tests and HIV NAT diagnostic and supplemental tests, FDA 
has determined that premarket notification is necessary to provide a 
reasonable assurance of the safety and effectiveness of the devices. 
Therefore, FDA does not intend to exempt these proposed class II 
devices from the 510(k) requirements. If this proposed order is 
finalized, persons who intend to market this type of device must submit 
to FDA a 510(k) and receive clearance prior to marketing the device.
    This proposal, if finalized, will decrease regulatory burden on 
industry, as manufacturers will no longer have to submit a PMA for 
these types of devices but can instead submit a 510(k) to the Agency 
for review prior to marketing their device. A 510(k) is a less 
burdensome pathway to market a device, which typically results in a 
shorter premarket review timeline compared to a PMA. This ultimately 
provides more timely access of these types of devices to patients.

V. Risks to Health

    HIV can be transmitted to others by blood transfusion, sex, sharing 
of contaminated needles by intravenous drug users, and from mother to 
child during pregnancy, childbirth, and breast feeding (Ref. 1). Left 
untreated, a significant proportion of those infected with HIV will 
develop acquired immunodeficiency syndrome (AIDS), which causes 
significant morbidity and mortality. However, with consistent anti-
retroviral treatment, HIV infection is a treatable, chronic condition 
with significantly improved survival and quality of life for people 
living with HIV and significantly decreased risk of transmission to 
others (Ref. 2). The Centers for Disease Control and Prevention (CDC) 
recommends that all persons ages 13 through 64 and pregnant women be 
tested at least once, with more frequent testing for individuals at 
high risk of infection. Nevertheless, at the present time, only about 
85 percent of people infected with HIV in the United States know that 
they are infected, and those who do not know their status are many 
times more likely to transmit the virus to others (Ref. 3). Therefore, 
improving access to HIV diagnostic devices is an urgent public health 
priority. After considering the recommendations of the panel, FDA's 
accumulated experience with these devices from review submissions, and 
the published literature, FDA has identified the following probable 
risks to health associated with HIV serological diagnostic and 
supplemental tests:
    (1) A false negative/false non-reactive test result may influence 
patient management decisions, such as the withholding or 
discontinuation of antiretroviral therapy, which can lead to serious 
injury including death. A false negative/false non-reactive test result 
also may contribute to public health risk by leading to inadvertent 
transmission of virus by an infected person. Factors that may cause 
decreased test sensitivity and/or increased rate of false negative/
false non-reactive test reporting include, but are not limited to, 
strain variability, acquisition of de novo mutations in genomic regions 
of HIV targeted by the device, the presence of interfering substances 
in the sample, acute infection at a stage that is too early for a 
device to detect the infection, and analyte concentrations that are too 
low to be detected by the device due to suppression of analyte 
expression by drugs used to treat or prevent HIV infection. False 
negative/false non-reactive results also can be caused by improper 
sample collection or sample handling, loss of sensitivity of the 
device, failure of detection reagents, and failure of instruments. They 
also can be caused by misinterpretation of invalid results as negative.
    (2) A false positive/false reactive test result may contribute to 
unnecessary initiation of treatment. It can also lead to unnecessary 
interventions such as an unnecessary Caesarian section for women during 
childbirth, unnecessary treatment of infants with anti-retroviral 
medications, withholding of breastfeeding, and significant emotional 
stress. Factors that may lead to false positive/false reactive results 
include cross-reactivity with other substances in the sample, 
contamination of the sample, patient participation in vaccine trials, 
and improper sample handling and instrument use.

VI. Summary of the Reasons for Reclassification

    FDA believes that HIV serological diagnostic and supplemental tests 
and HIV NAT diagnostic and supplemental tests should be reclassified 
from class III (PMA) into class II (special controls) because special 
controls, in addition to general controls, can be established to 
mitigate the risks to health identified in section V and provide 
reasonable assurance of the safety and effectiveness of these device 
types. The proposed special controls are identified by FDA in section 
VII. FDA's reasons for reclassification are as follows:
    (1) There is substantial scientific and medical information 
available regarding the nature, complexity, and risks associated with 
HIV serological diagnostic and supplemental tests and NAT diagnostic 
and supplemental tests. The safety and effectiveness of this device 
type has been well-established by the performance of the more than 20 
devices currently available (Ref. 4).
    (2) Risks associated with the failure of the device to perform as 
indicated (e.g., false negative/false non-reactive or false positive/
false reactive test results) can be mitigated through a combination of 
special controls, including performance criteria and requirements for 
submission of certain aspects of labeling, submission of certain 
manufacturing information, and submission of a complaint log. 
Performance criteria will consist primarily of analytical and clinical 
study design specifications and performance criteria that are based on 
public information regarding the performance and validation of 
previously approved devices. Examples of labeling mitigations include 
appropriate limitations, including that results should be confirmed 
according to current guidelines as promulgated by the CDC and other 
public health authorities, which are necessary to ensure that the 
devices are used and the results are interpreted appropriately, given 
the diversity of environments in which they are intended to be used. 
Manufacturing information submitted will include summaries of 
strategies to detect new types, subtypes, genotypes and mutations to 
ensure the tests continue to detect clinically relevant forms of HIV, a 
summary of the design matrix that determines the severity of events to 
ensure appropriate adverse event reporting, protocols for assessing 
stability, evaluation of test performance at the extremes of 
specifications to ensure the tests have been validated to function 
correctly under diverse conditions. The complaint log that will be 
submitted annually for 5 years following clearance of a traditional 
510(k) is the log required to be maintained by device manufacturers 
under 21 CFR 820.198(a). We are proposing as a special control to 
require submission of all complaints, whether or not the complaint was 
reported under part 803 (21 CFR part 803). We are not

[[Page 10114]]

requiring submission of an annual report as described in 21 CFR 814.84. 
Review of the complaint log will allow FDA to closely monitor issues 
with manufacturing and implementation of new devices that may not rise 
to the level of adverse event reporting required under 21 CFR 
820.198(a) but that may have an effect on the performance of the 
devices.
    Taking into account the probable health benefits of the use of the 
device and the nature and known incidence of the risk of the device, 
FDA, on its own initiative, is proposing to reclassify these 
postamendments devices from class III into class II. FDA believes that, 
when used as indicated, HIV serological and NAT diagnostic and 
supplemental tests can provide significant benefits to clinicians and 
patients.

VII. Proposed Special Controls

    FDA believes that these devices can be classified into class II 
with the establishment of special controls. FDA believes that these 
special controls, in addition to general controls, will provide a 
reasonable assurance of the safety and efficacy of these devices. 
Tables 1 and 2 demonstrate how these proposed special controls will 
mitigate each of the identified risks to health in section V.

  Table 1--Risks to Health and Mitigation Measures for HIV Serological
                    Diagnostic and Supplemental Tests
------------------------------------------------------------------------
    Identified risks to health               Mitigation measures
------------------------------------------------------------------------
A false negative/false non-         Labeling limitations, warnings, and
 reactive test result may            interpretation requirements.
 influence patient management       Analytical and clinical sensitivity
 decisions, such as the              performance criteria.
 withholding of antiviral therapy,  Clinical testing on appropriate
 which can lead to serious injury    populations.
 including death.                   Acceptable strategies for monitoring
                                     emergence of and ability of the
                                     test to detect new or altered
                                     circulating forms of HIV.
A false negative/false non-         Acceptable processes for failure
 reactive test result may            mode analysis, testing performance
 contribute to public health risk    at extremes of specifications,
 by leading to inadvertent           determining severity of adverse
 transmission of virus by an         events and malfunctions.
 infected person.                   Submission of a complaint log to
                                     monitor decreases in test
                                     performance or manufacturing
                                     failures.
A false positive/false reactive     Labeling instructions for
 test result may contribute to       appropriate confirmation of
 unnecessary initiation of           results.
 treatment or other medical         Analytical and clinical specificity
 interventions, which increases      performance criteria.
 patient risk to the potential      Clinical testing on appropriate
 adverse effects of such             populations.
 treatments or medical              Acceptable validation of
 interventions.                      susceptibility to interference and
                                     cross-reactivity.
                                    Acceptable processes for failure
                                     mode analysis, testing performance
                                     at extremes of specifications,
                                     determining severity of adverse
                                     events and malfunctions.
                                    Submission of a complaint log to
                                     monitor trends in false positive
                                     results.
------------------------------------------------------------------------


 Table 2--Risks to Health and Mitigation Measures for HIV NAT Diagnostic
                         and Supplemental Tests
------------------------------------------------------------------------
    Identified risks to health               Mitigation measures
------------------------------------------------------------------------
A false negative/false non-         Labeling limitations, warnings, and
 reactive test result may            interpretation requirements.
 influence patient management       Analytical and clinical sensitivity
 decisions, such as the              performance criteria.
 withholding of antiviral therapy,  Clinical testing on appropriate
 which can lead to serious injury    populations.
 including death.
A false negative/false non-         Acceptable strategies for monitoring
 reactive test result may            emergence of and ability of the
 contribute to public health risk    test to detect new or altered
 by leading to inadvertent           circulating forms of HIV.
 transmission of virus by an        Acceptable processes for failure
 infected person.                    mode analysis, testing performance
                                     at extremes of specifications,
                                     determining severity of adverse
                                     events and malfunctions.
                                    Submission of a complaint log to
                                     monitor decreases in test
                                     performance or manufacturing
                                     failures.
A false positive/false reactive     Labeling instructions for
 result may contribute to            appropriate confirmation of
 unnecessary initiation of           results.
 treatment or other medical         Analytical and clinical specificity
 intervention, which increases       performance criteria.
 patient risk to the potential      Clinical testing on appropriate
 adverse effects of such             populations.
 treatments or medical              Acceptable validation of
 interventions.                      susceptibility to interference and
                                     cross-reactivity.
                                    Acceptable processes for failure
                                     mode analysis, testing performance
                                     at extremes of specifications,
                                     determining severity of adverse
                                     events and malfunctions.
                                    Submission of a complaint log to
                                     monitor trends in false positive
                                     results.
------------------------------------------------------------------------

    If this proposed order is finalized, HIV serological diagnostic and 
supplemental tests and HIV NAT diagnostic and supplemental tests will 
be reclassified into class II (special controls). As discussed below, 
the reclassification will be codified in 21 CFR 866.3956 (serological) 
and 21 CFR 866.3957 (NAT) tests. Firms submitting a 510(k) for an HIV 
serological diagnostic and/or supplemental or HIV NAT diagnostic and/or 
supplemental test will be required to comply with the particular 
mitigation measures set forth in the special controls. Adherence to the 
special controls, in addition to the general controls, is necessary to 
provide a reasonable assurance of the safety and effectiveness of the 
devices.

VIII. Analysis of 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 nor an environmental impact statement is required.

IX. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no new 
collection of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(PRA) (44 U.S.C. 3501-3521) is not required. This proposed order refers 
to previously approved FDA collections of information. These 
collections of

[[Page 10115]]

information are subject to review by the OMB under the PRA. 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 have been approved under OMB 
control number 0910-0485.

X. Codification of Orders

    Under section 513(f)(3) of the FD&C Act, FDA may issue final orders 
to reclassify devices. FDA will continue to codify classifications and 
reclassifications in the Code of Federal Regulations (CFR). Changes 
resulting from final orders will appear in the CFR as newly codified 
orders. Therefore, under section 513(f)(3), in the proposed order, we 
are proposing to codify HIV serological diagnostic and/or supplemental 
tests in the new 21 CFR 866.3956, under which HIV serological 
diagnostic and/or supplemental tests would be reclassified from class 
III to class II, and HIV NAT diagnostic and/or supplemental tests in 
the new 21 CFR 866.3957, under which HIV NAT diagnostic and/or 
supplemental tests would be reclassified from class III to class II.

XI. Proposed Effective Date

    FDA proposes that any final order based on this proposed order 
become effective 30 days after its date of publication in the Federal 
Register.

XII. References

    The following references have been placed on display in the Dockets 
Management Staff (see ADDRESSES) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday; they are also 
available electronically at https://www.regulations.gov. FDA has 
verified the website addresses, as of the date this document publishes 
in the Federal Register, but websites are subject to change over time.

    1. Branson, B.M., H.H. Handsfield, M.A. Lampe, et al., ``Revised 
Recommendations for HIV Testing of Adults, Adolescents, and Pregnant 
Women in Health-Care Settings,'' MMWR. Recommendations and Reports: 
Morbidity and Mortality Weekly Report, 55(RR14): 1-17, 2007.
    2. Collaboration, T.A.T.C., ``Survival of HIV-Positive Patients 
Starting Antiretroviral Therapy Between 1996 and 2013: A 
Collaborative Analysis of Cohort Studies,'' Lancet HIV, 2017.
    3. Dailey, A.F., B.E. Hoots, H.I. Hall, et al., ``Vital Signs: 
Human Immunodeficiency Virus Testing and Diagnosis Delays--United 
States,'' MMWR. Recommendations and Reports: Morbidity and Mortality 
Weekly Report, 66: 1300-1306, 2017.
    4. ``Reclassification of HIV Point of Care and Laboratory-Based 
Serological and NAT Diagnostic Devices from Class III (PMA) to Class 
II 510(k); Issue Summary; Prepared for the July 19, 2018, Meeting of 
the Blood Products Advisory Committee (BPAC)).'' Available at: 
https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/BloodProductsAdvisoryCommittee/ucm597841.htm.

List of Subjects in 21 CFR Part 866

    Biologics, Laboratories, Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 866 be amended as follows:

PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES

0
1. The authority citation for part 866 continues to read as follows:

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

0
2. Add Sec.  866.3956 to subpart D to read as follows:


Sec.  866.3956  Human immunodeficiency virus (HIV) serological 
diagnostic and/or supplemental test.

    (a) Identification. Human immunodeficiency virus (HIV) serological 
diagnostic and supplemental tests are prescription devices for the 
qualitative detection of HIV antigen(s) and/or detection of antibodies 
against HIV in human body fluids or tissues. The tests are intended for 
use as an aid in the diagnosis of infection with HIV. The test results 
are intended to be interpreted in conjunction with other relevant 
clinical and laboratory findings. For professional use only. These 
tests are not intended to be used for monitoring patient status, or for 
screening donors of blood, plasma, or human cells, tissues, and 
cellular and tissue-based products (HCT/Ps).
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) For all HIV serological diagnostic and supplemental tests
    (i) The labeling must include:
    (A) An intended use that states that the device is not intended for 
use for screening donors of blood, plasma, or HCT/Ps.
    (B) A detailed explanation of the principles of operation and 
procedures used for performing the assay.
    (C) A detailed explanation of the interpretation of results and 
recommended actions to take based on results.
    (D) Limitations, which must be updated to reflect current clinical 
practice and disease presentation and management. The limitations must 
include, but are not limited to, statements that indicate:
    (1) The matrices with which the device has been cleared, and that 
use of this test kit with specimen types other than those specifically 
cleared for this device may result in inaccurate test results.
    (2) The test is not intended to be used to monitor individuals who 
are undergoing treatment for HIV infection.
    (3) A specimen with a reactive result should be investigated 
further following current guidelines.
    (4) All test results should be interpreted in conjunction with the 
individual's clinical presentation, history, and other laboratory 
results.
    (5) A test result that is nonreactive does not exclude the 
possibility of exposure to or infection with HIV. Nonreactive results 
in this assay may be due to analyte levels that are below the limit of 
detection of this assay.
    (ii) Device verification and validation must include:
    (A) Detailed device description, including the device components, 
ancillary reagents required but not provided, and an explanation of the 
methodology. Additional information appropriate to the technology must 
be included such as the amino acid sequence of antigen(s) and design of 
capture antibodies.
    (B) For devices with assay calibrators, the design of all primary, 
secondary, and subsequent quantitation standards used for calibration 
as well as their traceability to a reference material. In addition, 
analytical testing must be performed following the release of a new lot 
of the standard material that was used for device clearance, or when 
there is a transition to a new calibration standard.
    (C) Detailed documentation of analytical performance studies 
conducted as appropriate to the technology, specimen types tested, and 
intended use of the device, including, but not limited to, limit of 
blank, limit of detection, cutoff determination, precision, endogenous 
and exogenous interferences, cross reactivity, carry-over, quality 
control, matrix equivalency, and sample and reagent stability. Samples 
selected for use in analytical studies or used to prepare samples for 
use in analytical studies must be from subjects with clinically 
relevant circulating genotypes in the United States.

[[Page 10116]]

    (D) Multisite reproducibility study that includes the testing of 
three independent production lots.
    (E) Analytical sensitivity of the test must be the same as or 
better than that of other cleared or approved tests. Samples tested 
must include appropriate numbers and types of samples, including real 
clinical samples near the lower limit of detection. Analytical 
specificity of the test must be the same as or better than that of 
other cleared or approved tests. Samples must include appropriate 
numbers and types of samples from patients with different underlying 
illnesses or infections and from patients with potential endogenous 
interfering substances.
    (F) Detailed documentation of performance from a multisite clinical 
study. Performance must be analyzed relative to an FDA-cleared or 
approved comparator. This study must be conducted using patient 
samples, with an appropriate number of HIV positive and HIV negative 
samples in applicable risk categories. Additional subgroups or types 
must be validated using appropriate numbers and types of samples. The 
samples may be a combination of fresh and repository samples, sourced 
from within and outside the United States, as appropriate. The study 
designs, including number of samples tested, must be sufficient to meet 
the following criteria:
    (1) Clinical sensitivity of the test must have a lower bound of the 
95 percent confidence interval of greater than or equal to 99 percent.
    (2) Clinical specificity of the test must have a lower bound of the 
95 percent confidence interval of greater than or equal to 99 percent.
    (G) Strategies for detection of new strains, types, subtypes, 
genotypes, and genetic mutations as they emerge.
    (H) Risk analysis and management strategies, such as Failure Modes 
Effects Analysis and/or Hazard Analysis and Critical Control Points 
summaries and their impact on test performance.
    (I) Final release criteria to be used for manufactured test lots 
with appropriate evidence that lots released at the extremes of the 
specifications will meet the claimed analytical and clinical 
performance characteristics as well as the stability claims.
    (J) All stability protocols, including acceptance criteria.
    (K) Proposed procedure(s) for evaluating customer complaints and 
other device information that determines when to submit a medical 
device report.
    (L) Premarket notification submissions must include the information 
contained in paragraph (b)(1)(ii)(A) through (K) of this section.
    (iii) Manufacturers must submit a log of all complaints. The log 
must include the following information regarding each complaint: The 
type of event (false negative/false non-reactive or false positive/
false reactive), lot, date, population, and whether or not the 
complaint was reported under part 803 of this chapter (Medical Device 
Reporting). The log must be submitted annually on the anniversary of 
clearance, for 5 years following initial clearance of a new traditional 
510(k).
    (2) If the test is intended for Point of Care (PoC) use, the 
following special controls, in addition to those listed in paragraph 
(b)(1) of this section apply:
    (i) The intended use must include a statement that the test is for 
PoC use.
    (ii) The PoC intended use must include the following information:
    (A) That distribution of the test is limited to clinical 
laboratories that have an adequate quality assurance program, including 
planned systematic activities that provide adequate confidence that 
requirements for quality will be met and where there is assurance that 
operators will receive and use the instructional materials.
    (B) That the test is for use only by an agent of a clinical 
laboratory.
    (C) That individuals must receive the ``Subject Information 
Notice'' prior to specimen collection and appropriate information when 
test results are provided.
    (iii) PoC labeling must include instructions to follow current 
guidelines for informing the individual of the test result and its 
interpretation.
    (iv) The instructions must state that reactive results are 
considered preliminary and should be confirmed following current 
guidelines.
    (v) Device verification and validation for the PoC claim must 
include:
    (A) Detailed documentation of performance from a multisite clinical 
study. Performance must be analyzed relative to an FDA cleared or 
approved comparator. This study must be conducted using patient 
samples, with appropriate numbers of HIV positive and HIV negative 
samples in applicable risk categories. Additional subgroup or type 
claims must be validated using appropriate numbers and types of 
samples. The samples may be a combination of fresh and repository 
samples, sourced from within and outside the United States, as 
appropriate. If the test is intended solely for PoC use, the test must 
meet only the performance criteria in paragraph (b)(2)(v)(A)(1) and (2) 
of this section and not the criteria in paragraph (b)(1)(ii)(F) of this 
section:
    (1) Clinical sensitivity of the test must have a lower bound of the 
95 percent confidence interval of greater than or equal to 98 percent.
    (2) Clinical specificity of the test must have a lower bound of the 
95 percent confidence interval of greater than or equal to 98 percent.
    (B) Premarket notification submissions must include the information 
contained in paragraph (b)(2)(v)(A) of this section.
    (3) If the test is intended for supplemental use in addition to use 
as an aid in initial diagnosis, the following special controls, in 
addition to those listed in paragraphs (b)(1) and (2) of this section, 
as appropriate, apply:
    (i) For the additional supplemental claim, a clinical study must be 
performed that includes samples that were initially reactive and 
repeatedly reactive on a diagnostic test but were negative or 
indeterminate on a different confirmatory test.
    (ii) The intended use must include a statement that the test is 
intended for use as an additional test to confirm the presence of HIV 
antibodies or antigens in specimens found to be repeatedly reactive by 
a diagnostic screening test.
    (4) If the test is intended solely as a supplemental test, the 
following special controls, in addition to those listed in paragraphs 
(b)(1) and (2) of this section, except those in paragraphs 
(b)(1)(ii)(F) and (b)(2)(v)(A) of this section, as appropriate, apply:
    (i) The labeling must include a statement that the test is intended 
for use as an additional test to confirm the presence of HIV antibodies 
or antigens in specimens found to be repeatedly reactive by a 
diagnostic screening test.
    (ii) The labeling must clearly state that the test is not for use 
for initial diagnosis or is not intended as a first-line test.
    (iii) A clinical study must be performed that includes samples that 
were initially reactive and repeatedly reactive on a diagnostic test 
but were negative or indeterminate on a confirmatory test.
    (5) If the test is intended to differentiate different HIV types, 
the following special controls, in addition to those listed in 
paragraphs(b)(1) through (4) of this section, as appropriate, apply:
    (i) The labeling must include the statement that the test is 
intended for the confirmation of initial results from a diagnostic test 
and differentiation of different HIV types.
    (ii) Analytical and clinical sensitivity and specificity for each 
of the HIV

[[Page 10117]]

types, strains, and subtypes of HIV intended to be differentiated must 
be evaluated.
    (iii) The results interpretation must include instructions for the 
user on how to interpret the results, including un-typeable and co-
infection results.
0
3. Add Sec.  866.3957 to subpart D to read as follows:


Sec.  866.3957  Human immunodeficiency virus (HIV) nucleic acid (NAT) 
diagnostic and/or supplemental test.

    (a) Identification. Human immunodeficiency virus (HIV) nucleic acid 
(NAT) diagnostic and supplemental tests are prescription devices for 
the qualitative detection of HIV nucleic acid in human body fluids or 
tissues. The tests are intended for use as an aid in the diagnosis of 
infection with HIV. The test results are intended to be interpreted in 
conjunction with other relevant clinical and laboratory findings. For 
prescription use only. These tests are not intended to be used for 
monitoring patient status, or for screening donors of blood, plasma, or 
human cells, tissues, or cellular or tissue-based products (HCT/Ps).
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) For all HIV NAT diagnostic and/or supplemental tests
    (i) The labeling must include:
    (A) An intended use that states that the device is not intended for 
use for screening donors of blood, plasma, or HCT/Ps.
    (B) A detailed explanation of the principles of operation and 
procedures used for performing the assay.
    (C) A detailed explanation of the interpretation of results and 
recommended actions to take based on results.
    (D) Limitations, which must be updated to reflect current clinical 
practice and disease presentation and management. The limitations must 
include, but are not limited to, statements that indicate:
    (1) The matrices with which the device has been cleared, and that 
use of this test kit with specimen types other than those specifically 
cleared for this device may result in inaccurate test results.
    (2) The test is not intended to be used to monitor individuals who 
are undergoing treatment for HIV infection.
    (3) A specimen with a reactive result should be investigated 
further following current guidelines.
    (4) All test results should be interpreted in conjunction with the 
individual's clinical presentation, history, and other laboratory 
results.
    (5) A test result that is nonreactive does not exclude the 
possibility of exposure to or infection with HIV. Nonreactive results 
in this assay may be due to analyte levels that are below the limit of 
detection of this assay.
    (ii) Device verification and validation must include:
    (A) Detailed device description, including the device components, 
ancillary reagents required but not provided, and an explanation of the 
methodology. Additional information appropriate to the technology must 
be included such as design of primers and probes.
    (B) For devices with assay calibrators, the design and nature of 
all primary, secondary, and subsequent quantitation standards used for 
calibration as well as their traceability to a reference material. In 
addition, analytical testing must be performed following the release of 
a new lot of the standard material that was used for device clearance, 
or when there is a transition to a new calibration standard.
    (C) Detailed documentation of analytical performance studies 
conducted as appropriate to the technology, specimen types tested, and 
intended use of the device, including, but not limited to, limit of 
blank, limit of detection, cutoff determination, precision, endogenous 
and exogenous interferences, cross reactivity, carry-over, quality 
control, matrix equivalency, and sample and reagent stability. Samples 
selected for use in analytical studies or used to prepare samples for 
use in analytical studies must be from subjects with clinically 
relevant circulating genotypes in the United States. The effect of each 
claimed nucleic-acid isolation and purification procedure on detection 
must be evaluated.
    (D) Multisite reproducibility study that includes the testing of 
three independent production lots.
    (E) Analytical sensitivity of the test must be the same as or 
better than that of other cleared or approved tests. Samples tested 
must include appropriate numbers and types of samples, including real 
clinical samples near the lower limit of detection. Analytical 
specificity of the test must be as the same as or better than that of 
other cleared or approved tests. Samples must include appropriate 
numbers and types of samples from patients with different underlying 
illnesses or infections and from patients with potential endogenous 
interfering substances.
    (F) Detailed documentation of performance from a multisite clinical 
study. Performance must be analyzed relative to an FDA cleared or 
approved comparator. This study must be conducted using appropriate 
patient samples, with appropriate numbers of HIV positive and negative 
samples in applicable risk categories. Additional subtype, strain, or 
types must be validated using appropriate numbers and types of samples. 
The samples may be a combination of fresh and repository samples, 
sourced from within and outside the United States, as appropriate. The 
study designs, including number of samples tested, must be sufficient 
to meet the following criteria:
    (1) Clinical sensitivity of the test must have a lower bound of the 
95 percent confidence interval of greater than or equal to 99 percent.
    (2) Clinical specificity of the test must have a lower bound of the 
95 percent confidence interval of greater than or equal to 99 percent.
    (G) Strategies for detection of new strains, types, subtypes, 
genotypes, and genetic mutations as they emerge.
    (H) Risk analysis and management strategies, such as Failure Modes 
Effects Analysis and/or Hazard Analysis and Critical Control Points 
summaries and their impact on test performance.
    (I) Final release criteria to be used for manufactured test lots 
with appropriate evidence that lots released at the extremes of the 
specifications will meet the claimed analytical and clinical 
performance characteristics as well as the stability claims.
    (J) All stability protocols, including acceptance criteria.
    (K) Proposed procedure(s) for evaluating customer complaints and 
other device information that determine when to submit a medical device 
report.
    (L) Premarket notification submissions must include the information 
contained in paragraph (b)(1)(ii)(A) through (K) of this section.
    (iii) Manufacturers must submit a log of all complaints. The log 
must include the following information regarding each complaint: The 
type of event (false negative/false non-reactive or false positive/
false reactive), lot, date, population, and whether or not the 
complaint was reported under part 803 of this chapter (Medical Device 
Reporting). The log must be submitted annually on the anniversary of 
clearance, for 5 years following initial clearance of a new traditional 
510(k).
    (2) If the test is intended for Point of Care (PoC) use, the 
following special controls, in addition to those listed in paragraph 
(b)(1) of this section, apply:
    (i) The intended use must include a statement that the test is for 
PoC use.

[[Page 10118]]

    (ii) The PoC intended use must include the following information:
    (A) That distribution of the test is limited to clinical 
laboratories that have an adequate quality assurance program, including 
planned systematic activities that provide adequate confidence that 
requirements for quality will be met and where there is assurance that 
operators will receive and use the instructional materials.
    (B) That the test is for use only by an agent of a clinical 
laboratory.
    (C) That individuals must receive the ``Subject Information 
Notice'' prior to specimen collection and appropriate information when 
test results are provided.
    (iii) PoC labeling must include instructions to follow current 
guidelines for informing the individual of the test result and its 
interpretation.
    (iv) The instructions must state that reactive results are 
considered preliminary and should be confirmed following current 
guidelines.
    (v) Device verification and validation for the PoC claim must 
include:
    (A) Detailed documentation from a well-conducted multisite clinical 
study. Performance must be analyzed relative to an FDA cleared or 
approved comparator. This study must be conducted using patient 
samples, with appropriate numbers of HIV positive and HIV negative 
samples in applicable risk categories. Additional subgroup or type 
claims must be validated using appropriate numbers and types of 
samples. The samples may be a combination of fresh and repository 
samples, sourced from within and outside the United States, as 
appropriate. If the test is intended solely for PoC use, the test must 
meet only the performance criteria in paragraphs (b)(2)(v)(A)(1) and 
(2) of this section and not the criteria in paragraph (b)(2)(ii)(F) of 
this section:
    (1) Clinical sensitivity of the test must have a lower bound of the 
95 percent confidence interval of greater than or equal to 98 percent.
    (2) Clinical specificity of the test must have a lower bound of the 
95 percent confidence interval of greater than or equal to 98 percent.
    (B) Premarket notification submissions must include the information 
contained in paragraph (b)(2)(v)(A) of this section.
    (3) If the test is intended for supplemental use in addition to use 
as an aid in initial diagnosis, the following special controls, in 
addition to those listed in paragraphs (b)(1) and (2) of this section, 
as appropriate, apply:
    (i) For the additional supplemental claim, a clinical study must be 
performed that includes samples that were initially reactive and 
repeatedly reactive on a diagnostic test but were negative or 
indeterminate on a confirmatory test.
    (ii) The intended use must include a statement that the test is 
intended for use as an additional test to confirm the presence of HIV 
viral nucleic acid in specimens found to be repeatedly reactive by a 
diagnostic screening test.
    (4) If the test is intended solely as a supplemental test, the 
following special controls, in addition to those listed in paragraphs 
(b)(1) and (2) of this section, except those in paragraphs(b)(1)(ii)(F) 
and (b)(2)(v)(A) of this section, as appropriate, apply:
    (i) The labeling must include a statement that the test is intended 
for use as an additional test to confirm the presence of HIV viral 
nucleic acid in specimens found to be repeatedly reactive by a 
diagnostic screening test.
    (ii) The labeling must clearly state that the test is not for use 
for initial diagnosis or is not intended as a first-line test.
    (iii) A clinical study must be performed that includes samples that 
were initially reactive and repeatedly reactive on a diagnostic test 
but were negative or indeterminate on a confirmatory test.
    (5) If the test is intended to differentiate different HIV types, 
the following special controls, in addition to those listed in 
paragraphs (b)(1) through (4) of this section, as appropriate, apply:
    (i) The labeling must include the statement that the test is 
intended for the confirmation of initial results and differentiation of 
different HIV types.
    (ii) Analytical and clinical sensitivity and specificity for each 
of the types, strains, and subtypes of HIV intended to be 
differentiated must be evaluated.
    (iii) The results interpretation must include instructions for the 
user on how to interpret the results, including un-typeable and co-
infection results.

    Dated: February 18, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-03515 Filed 2-20-20; 8:45 am]
 BILLING CODE 4164-01-P


