
[Federal Register Volume 79, Number 104 (Friday, May 30, 2014)]
[Rules and Regulations]
[Pages 31023-31028]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-12544]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2013-N-0544]


Microbiology Devices; Reclassification of Nucleic Acid-Based 
Systems for Mycobacterium tuberculosis Complex in Respiratory Specimens

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is reclassifying 
nucleic acid-based in vitro diagnostic devices for the detection of 
Mycobacterium tuberculosis complex in respiratory specimens from class 
III (premarket approval) into class II (special controls). FDA is also 
issuing the special controls guideline entitled ``Class II Special 
Controls Guideline: Nucleic Acid-Based In Vitro Diagnostic Devices for 
the Detection of Mycobacterium tuberculosis Complex in Respiratory 
Specimens.'' These devices are intended to be used as an aid in the 
diagnosis of pulmonary tuberculosis.

DATES: This rule is effective June 30, 2014.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2013-
N-0544, by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following ways:
     Mail/Hand delivery/Courier (for paper submissions): 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name 
and Docket No. FDA-2013-N-0544 for this rulemaking. All comments 
received may be posted without change to http://www.regulations.gov, 
including any personal information provided. For additional information 
on submitting comments, see the ``Comments'' heading of the 
SUPPLEMENTARY INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://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 Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Janice A. Washington, Center for 
Devices and Radiological Health, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 66, Rm. 5554, Silver Spring, MD 20993-0002, 
301-796-6207.

SUPPLEMENTARY INFORMATION:

I. Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the 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), the 
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) establish 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) establishes 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 (special 
controls), and class III (premarket approval).
    Under the FD&C Act, FDA clears or approves the three classes of 
medical devices for commercial distribution in the United States 
through three

[[Page 31024]]

regulatory processes: Premarket approval (PMA), product development 
protocol, and premarket notification (a premarket notification is 
generally referred to as a ``510(k)'' after the section of the FD&C Act 
where the requirement is found). The purpose of a premarket 
notification is to demonstrate that the new device is substantially 
equivalent to a legally marketed predicate device. Under section 513(i) 
of the FD&C Act, a device is substantially equivalent if it has the 
same intended use and technological characteristics as a predicate 
device, or has different technological characteristics but data 
demonstrate that the new device is as safe and effective as the 
predicate device and does not raise different issues of safety or 
effectiveness.
    FDA determines whether new devices are substantially equivalent to 
previously offered 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 of the regulations (21 CFR part 807). Section 510(k) of the 
FD&C Act and the implementing regulations in part 807, subpart E, 
require a person who intends to market a medical device to submit a 
premarket notification submission to FDA before proposing to begin the 
introduction, or delivery for introduction into interstate commerce, 
for commercial distribution of a device intended for human use.
    In accordance with section 513(f)(1) of the FD&C Act, devices that 
were not in commercial distribution before May 28, 1976, the date of 
enactment of the 1976 amendments, generally referred to as 
postamendment 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 FDA classifies the 
device into class I or class II by issuing 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 or the device is reclassified into class I or class II. 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 and part 807 of FDA's regulations.
    Section 513(f)(2) of the FD&C Act establishes procedures for ``de 
novo'' risk-based review and classification of postamendment devices 
automatically classified into class III by section 513(f)(1). Under 
these procedures, any person whose device is automatically classified 
into class III by section 513(f)(1) of the FD&C Act may seek 
reclassification into class I or II, either after receipt of an order 
finding the device to be not substantially equivalent, in accordance 
with section 513(i), to a predicate device that does not require 
premarket approval, or at any time after determining there is no 
legally marketed device upon which to base a determination of 
substantial equivalence. In addition, under section 513(f)(3) of the 
FD&C Act, FDA may initiate, or the manufacturer or importer of a device 
may petition for, the reclassification of a device classified into 
class III under section 513(f)(1).

II. Regulatory Background of the Device

    A nucleic acid-based in vitro diagnostic device for the detection 
of M. tuberculosis complex in respiratory specimens is a postamendment 
device classified into class III under section 513(f)(1) of the FD&C 
Act in 1995. Consistent with the FD&C Act and FDA's regulations in 21 
CFR 860.130(a), FDA is reclassifying these devices from class III into 
class II because there is sufficient information from FDA's accumulated 
experience with these devices to establish special controls that can 
provide a reasonable assurance of the device's safety and 
effectiveness.

III. Identification

    Nucleic acid-based in vitro diagnostic devices for the detection of 
M. tuberculosis complex in respiratory specimens are qualitative 
nucleic acid-based in vitro diagnostic devices intended to detect M. 
tuberculosis complex nucleic acids extracted from human respiratory 
specimens. These devices are non-multiplexed and intended to be used as 
an aid in the diagnosis of pulmonary tuberculosis when used in 
conjunction with clinical and other laboratory findings. These devices 
do not include devices intended to detect the presence of organism 
mutations associated with drug resistance. Respiratory specimens may 
include sputum (induced or expectorated), bronchial specimens (e.g., 
bronchoalveolar lavage or bronchial aspirate), or tracheal aspirates.

IV. Background for Reclassification Decision

    At an FDA/Centers for Disease Control (CDC)/National Institute of 
Allergy and Infectious Diseases public workshop entitled ``Advancing 
the Development of Diagnostic Tests and Biomarkers for Tuberculosis,'' 
held in Silver Spring, MD, on June 7 and 8, 2010, the class III 
designation for nucleic acid-based in vitro diagnostic devices for the 
detection of M. tuberculosis complex in respiratory specimens was 
raised as a barrier to advancing M. tuberculosis diagnostics (Ref. 1). 
Based on discussion at the public workshop, FDA agreed to consider this 
issue further and subsequently convened a meeting of the Microbiology 
Devices Panel of the Medical Devices Advisory Committee on June 29, 
2011. Panel members were asked to discuss if sufficient risk mitigation 
was possible for FDA to initiate the reclassification process from 
class III to class II devices for this intended use through the 
drafting of a special controls guidance. All panel members expressed 
the opinion that sufficient data and information exist such that the 
risks of false positive and false negative results can be mitigated to 
allow a special controls guidance to be created that would support 
reclassification from class III to class II for nucleic acid-based in 
vitro diagnostic devices for the detection of M. tuberculosis complex 
in respiratory specimens (Ref. 2). All outside speakers at the open 
public hearing session during the meeting also spoke in favor of 
reclassification.
    No comments were received on the proposed rule issued on June 19, 
2013.

V. Classification

    FDA is reclassifying nucleic acid-based in vitro diagnostic devices 
for the detection of M. tuberculosis complex in respiratory specimens 
from class III to class II. FDA believes that reclassifying this device 
into class II with special controls (guideline document) provides 
reasonable assurance of the safety and effectiveness of the device. 
Section 510(m) of the FD&C Act provides that a class II device may be 
exempt from the premarket notification requirements under section 
510(k), if the Agency determines that premarket notification is not 
necessary to provide reasonable assurance of the safety and 
effectiveness of the device. For this device, FDA believes that 
premarket notification is necessary to provide reasonable assurance of 
safety and effectiveness and, therefore, is not exempting the device 
from the premarket notification requirements.

VI. Risks to Health

    After considering the information discussed by the Microbiology 
Devices Panel during the June 29, 2011, meeting, the published 
literature, and the medical device reporting system reports, FDA 
believes the following risks are associated with nucleic acid-based in 
vitro diagnostic devices for the detection of M. tuberculosis complex 
in respiratory specimens: (1) False positive test results may lead to 
incorrect

[[Page 31025]]

treatment of the individual with possible adverse effects. The patient 
may be subjected to unnecessary isolation and/or other human contact 
limitations. Unnecessary contact investigations may also occur; (2) 
false negative test results could result in disease progression and the 
risk of transmitting disease to others; and (3) biosafety risks to 
health care workers handling specimens and control materials with the 
possibility of transmission of tuberculosis infection to health care 
workers.

VII. Summary of the Reasons for Reclassification

    FDA, consistent with the opinions expressed by the Microbiology 
Devices Panel of the Medical Devices Advisory Committee, believes that 
the establishment of special controls, in addition to general controls, 
provides reasonable assurance of the safety and effectiveness of 
nucleic acid-based in vitro diagnostic devices for the detection of M. 
tuberculosis complex in respiratory specimens.
    1. The safety and effectiveness of nucleic acid-based systems for 
M. tuberculosis complex have become well-established since approval of 
the first device for this use in 1995.
    2. The risk of false positive test results can be mitigated by 
specifying minimum performance standards in the special controls 
guideline and including information regarding patient populations 
appropriate for testing in the device labeling. Additional risk 
mitigation strategies include the indication for use that the device be 
used as an aid to the diagnosis of pulmonary tuberculosis in 
conjunction with other clinical and laboratory findings. The device 
also should be accurately described and have labeling that addresses 
issues specific to these types of devices.
    3. The risk of false negative test results can be mitigated by 
specifying minimum performance standards for test sensitivity in the 
special controls guideline and ensuring that different patient 
populations are included in clinical trials. Additional risk mitigation 
strategies include the indication for use that the device be used as an 
aid to the diagnosis of pulmonary tuberculosis in conjunction with 
other clinical and laboratory findings. The device also should be 
accurately described and have appropriate labeling that addresses 
issues specific to these types of devices.
    4. Biosafety risks to health care workers handling specimens and 
control materials with the possibility of transmission of tuberculosis 
infection to health care workers could be addressed similarly to 
existing devices of this type that we have already approved. It is 
believed there are no additional biosafety risks introduced by 
reclassification from class III to class II. The need for appropriate 
biosafety measures can be addressed in labeling recommendations that 
are included in the special controls guideline and by adherence to 
recognized laboratory biosafety procedures.
    Based on FDA's review of published literature, the information 
presented by outside speakers invited to the Microbiology Devices 
meeting, and the opinions of panel members expressed at that meeting, 
FDA believes that there is a reasonable basis to determine that nucleic 
acid-based in vitro diagnostic devices for the detection of M. 
tuberculosis complex in respiratory specimens can provide the 
significant benefit of rapid detection of infection in patients with 
suspected tuberculosis as compared to traditional means of diagnosis. 
For patients with acid-fast smear negative tuberculosis, nucleic acid-
based in vitro diagnostic devices for the detection of M. tuberculosis 
complex in respiratory specimens are currently the only laboratory 
tests available for rapid detection of active pulmonary tuberculosis. 
Rapid identification of patients with active tuberculosis may have 
significant benefits to the infected patient by earlier diagnosis and 
management as well as potentially significant effects on the public 
health by limiting disease spread.
    Nucleic acid-based in vitro diagnostic devices for the detection of 
M. tuberculosis complex in respiratory specimens have been approved for 
marketing by FDA for over 15 years. There is substantial scientific and 
medical information available regarding the nature, complexity, and 
problems associated with these devices. Revised public health 
recommendations for use, published by CDC on January 16, 2009, 
recommended the use of nucleic acid amplification testing in 
conjunction with acid-fast microscopy and culture and specifically 
states that ``Nucleic acid amplification testing should be performed on 
at least one respiratory specimen from each patient with signs and 
symptoms of pulmonary [tuberculosis] for whom a diagnosis of 
[tuberculosis] is being considered but has not yet been established, 
and for whom the test result would alter case management or 
[tuberculosis] control activities'' (Ref. 3).

VIII. Special Controls

    FDA believes that the measures set forth in the special controls 
guideline entitled ``Nucleic Acid-Based In Vitro Diagnostic Devices for 
the Detection of Mycobacterium tuberculosis Complex in Respiratory 
Specimens'' are necessary, in addition to general controls, to mitigate 
the risks to health described in section VI. As seen in table 1, the 
special controls set forth in the guideline for this device address 
each of the identified risks.

            Table 1--Risks to Health and Mitigation Measures
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            Identified risks                   Mitigation measures
------------------------------------------------------------------------
False positive test results may lead to  Device description containing
 incorrect treatment of the individual    the information specified in
 with possible adverse effects. The       the special control guideline.
 patient may be subjected to             Performance studies.
 unnecessary isolation and/or other      Labeling.
 human contact limitations. Unnecessary
 contact investigations may also occur.
False negative test results could        Device description containing
 result in disease progression, and the   the information specified in
 risk of transmitting disease to others.  the special control guideline.
                                         Performance studies.
                                         Labeling.
Biosafety risks to health care workers   Labeling.
 handling specimens and control
 materials with the possibility of
 transmission of tuberculosis infection
 to health care workers.
------------------------------------------------------------------------

    As of the effective date of this rule, nucleic acid-based in vitro 
diagnostic devices for the detection of M. tuberculosis complex in 
respiratory specimens will be reclassified into class II. The 
reclassification will be codified

[[Page 31026]]

in 21 CFR 866.3372. Firms submitting a 510(k) for a nucleic acid-based 
in vitro diagnostic device for the detection of M. tuberculosis complex 
in respiratory specimens will need either to: (1) Comply with the 
particular mitigation measures set forth in the special controls 
guideline or (2) use alternative mitigation measures, but demonstrate 
to the Agency's satisfaction that alternative measures identified by 
the firm will provide at least an equivalent assurance of safety and 
effectiveness. Adherence to the criteria in the guideline, in addition 
to the general controls, is necessary to provide a reasonable assurance 
of the safety and effectiveness of the devices.

IX. Electronic Access to the Special Controls Guideline

    Persons interested in obtaining a copy of the guideline may do so 
by using the Internet. A search capability for all Center for Devices 
and Radiological Health guidelines and guidance documents is available 
at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. The guideline is also available at 
http://www.regulations.gov.
    To receive ``Class II Special Controls Guideline: Nucleic Acid-
Based In Vitro Diagnostic Devices for the Detection of Mycobacterium 
tuberculosis Complex in Respiratory Specimens,'' you may either send an 
email request to dsmica@fda.hhs.gov to receive an electronic copy of 
the document or send a fax request to 301-847-8149 to receive a hard 
copy. Please use the document number 1788 to identify the guideline you 
are requesting.

X. Environmental Impact

    The Agency has determined under 21 CFR 25.34(b) that this 
reclassification 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.

XI. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. Section 4(a) of the Executive order 
requires Agencies to ``construe * * * a Federal statute to preempt 
State law only where the statute contains an express preemption 
provision or there is some other clear evidence that the Congress 
intended preemption of State law, or where the exercise of State 
authority conflicts with the exercise of Federal authority under the 
Federal statute.'' Federal law includes an express preemption provision 
that preempts certain state requirements ``different from or in 
addition to'' certain Federal requirements applicable to devices. (See 
section 521 of the FD&C Act (21 U.S.C. 360k); Medtronic v. Lohr, 518 
U.S. 470 (1996); and Riegel v. Medtronic, 128 S. Ct. 999 (2008)). The 
special controls established by this final rule create ``requirements'' 
for specific medical devices under 21 U.S.C. 360k, even though product 
sponsors have some flexibility in how they meet those requirements. 
(See Papike v. Tambrands, Inc., 107 F.3d 737, 740-42 (9th Cir. 1997)).

XII. Paperwork Reduction Act of 1995

    This rule refers to previously approved collections of information 
found in 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 21 CFR 56.115 have been approved under OMB control 
number 0910-0130; the collections of information in 21 CFR part 807, 
subpart E have been approved under OMB control number 0910-0120; the 
collections of information in 21 CFR part 812 have been approved under 
OMB control number 0910-0078; 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 part 801 and 21 CFR 809.10 have 
been approved under OMB control number 0910-0485.

XIII. Clarifications to Special Controls Guideline

    This special controls guideline reflects changes the Agency is 
making to clarify its position on the binding nature of special 
controls. The changes include referring to the document as a 
``guideline,'' as that term is used in section 513(a) of the FD&C Act, 
which the Secretary has developed and disseminated to provide a 
reasonable assurance of safety and effectiveness for class II devices, 
and not a ``guidance,'' as that term is used in 21 CFR 10.115. The 
guideline clarifies that firms will need either to: (1) Comply with the 
particular mitigation measures set forth in the special controls 
guideline or (2) use alternative mitigation measures, but demonstrate 
to the Agency's satisfaction that those alternative measures identified 
by the firm will provide at least an equivalent assurance of safety and 
effectiveness. Finally, the guideline uses mandatory language to 
emphasize that firms must comply with special controls to legally 
market their class II devices. These revisions do not represent a 
change in FDA's position about the binding effect of special controls, 
but rather are intended to address any possible confusion or 
misunderstanding.

XIV. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct Agencies to assess all 
costs and benefits of available regulatory alternatives and, when 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety, and other advantages; distributive impacts; and 
equity). The Agency believes that this rule is not a significant 
regulatory action as defined by Executive Order 12866.
    The Regulatory Flexibility Act requires Agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because the reclassification relieves manufacturers 
of premarket approval requirements of section 515 of the FD&C Act (21 
U.S.C. 360e) it would not create new burdens. Thus, the Agency 
certifies that the rule will not have a significant economic impact on 
a substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that Agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $141 million, using the most current (2013) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
rule to result in any 1-year expenditure that would meet or exceed this 
amount.
    The proposed rule was issued on June 19, 2013 (78 FR 36698). The 
comment period closed August 19, 2013, and FDA did not receive any 
comments. We revise the analysis of impact presented in the proposed 
rule with more current data, and adjust for inflation. Our estimate of 
benefits annualized over 20 years is $12.34 million at a 3 percent 
discount rate and $8.02 million at a 7

[[Page 31027]]

percent discount rate. The change in pre- and post-marketing 
requirements between a 510(k) and a PMA lead to benefits in the form of 
reduced submission costs, review-related activities, and inspections. 
Another unquantifiable benefit from the rule is that a decrease in 
entry could lead to further product innovation. FDA is unable to 
quantify the costs that could arise if there is a change in risk which 
could lead to adverse events, recalls, warning letters, or unlisted 
letters. Table 2 summarizes the estimated costs and benefits.
    The full discussion of economic impacts is available in docket FDA-
2013-N-0544 at http://www.regulations.gov, and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm (Ref. 
4).

                                      Table 2--Summary of Benefits, Costs and Distributional Effects of Final Rule
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                 Units
                                                                                   ---------------------------------
                    Category                       Primary       Low        High                Discount    Period                  Notes
                                                   estimate    estimate   estimate     Year       rate     covered
                                                                                     dollars   (percent)   (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
    Annualized.................................        $8.02  .........  .........       2012          7         20
    Monetized $millions/year...................       $12.34  .........  .........       2012          3         20
    Annualized.................................  ...........  .........  .........       2012          7         20
    Quantified.................................  ...........  .........  .........       2012          3         20
    Qualitative................................
Costs:
    Annualized.................................  ...........  .........  .........       2012          7         20
    Monetized $millions/year...................  ...........  .........  .........       2012          3         20
    Annualized.................................  ...........  .........  .........       2012          7         20
    Quantified.................................  ...........  .........  .........       2012          3         20
--------------------------------------------------------------------------------------------------------------------------------------------------------
    Qualitative................................    FDA is unable to quantify the
                                                  costs that could arise if there
                                                  is a change in risk which could
                                                  lead to adverse events, recalls,
                                                    warning letters, or unlisted
                                                              letters.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers:
    Federal....................................  ...........  .........  .........       2012          7         20
    Annualized.................................  ...........  .........  .........       2012          3         20
                                                --------------------------------------------------------------------------------------------------------
    Monetized $millions/year...................  From:
                                                 To:
                                                --------------------------------------------------------------------------------------------------------
    Other......................................  ...........  .........  .........       2012          7         20
    Annualized.................................  ...........  .........  .........       2012          3         20
                                                --------------------------------------------------------------------------------------------------------
    Monetized $millions/year...................  From:
                                                 To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
    State, Local or Tribal Government: None estimated...................................................................................................
    Small Business: The proposed rule will not have a significant impact on a substantial number of small entities......................................
    Wages: None estimated...............................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------

XV. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday, 
and are available electronically at http://www.regulations.gov. (FDA 
has verified all the Web site addresses in this reference section, but 
we are not responsible for any subsequent changes to the Web sites 
after this document publishes in the Federal Register.)

    1. Transcript of the Tuberculosis Public Workshop, June 7. 2010. 
(Available at: http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/CriticalPathInitiative/UpcomingEventsonCPI/UCM289182.doc.)
    2. Transcript of FDA's Microbiology Devices Panel Meeting, June 
29, 2011. (Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/MicrobiologyDevicesPanel/UCM269469.pdf.)
    3. ``Updated Guidelines for the Use of Nucleic Acid 
Amplification Tests in the Diagnosis of Tuberculosis,'' Morbidity 
and Mortality Weekly Report (MMWR), vol. 58, pp. 7-10, January 16, 
2009. (Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5801a3.htm.)
    4. Full Disclosure Final Regulatory Impact Analysis of the final 
rule ``Microbiology Devices; Reclassification of Nucleic Acid-Based 
Systems for Mycobacterium tuberculosis Complex in Respiratory 
Specimens,'' Docket No. FDA-2013-N-0544. (Available at: http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.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, 21 CFR part 
866 is 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, 371.


0
2. Add Sec.  866.3372 to subpart D to read as follows:

[[Page 31028]]

Sec.  866.3372  Nucleic acid-based in vitro diagnostic devices for the 
detection of Mycobacterium tuberculosis complex in respiratory 
specimens.

    (a) Identification. Nucleic acid-based in vitro diagnostic devices 
for the detection of Mycobacterium tuberculosis complex in respiratory 
specimens are qualitative nucleic acid-based in vitro diagnostic 
devices intended to detect Mycobacterium tuberculosis complex nucleic 
acids extracted from human respiratory specimens. These devices are 
non-multiplexed and intended to be used as an aid in the diagnosis of 
pulmonary tuberculosis when used in conjunction with clinical and other 
laboratory findings. These devices do not include devices intended to 
detect the presence of organism mutations associated with drug 
resistance. Respiratory specimens may include sputum (induced or 
expectorated), bronchial specimens (e.g., bronchoalveolar lavage or 
bronchial aspirate), or tracheal aspirates.
    (b) Classification. Class II (special controls). The special 
control for this device is the FDA document entitled ``Class II Special 
Controls Guideline: Nucleic Acid-Based In Vitro Diagnostic Devices for 
the Detection of Mycobacterium tuberculosis Complex in Respiratory 
Specimens.'' For availability of the guideline document, see Sec.  
866.1(e).

    Dated: May 27, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-12544 Filed 5-29-14; 8:45 am]
BILLING CODE 4160-01-P


