Document ID: FDA-2011-N-0103-0008
Agency: fda
Document Type: Proposed Rule
Title: Microbiology Devices; Classification of In Vitro Diagnostic Devices for Bacillus Species Detection
Posted Date: 2015-11-17T05:00Z

[Federal Register Volume 80, Number 221 (Tuesday, November 17, 2015)]
[Proposed Rules]
[Pages 71756-71762]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-29275]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2011-N-0103]

Microbiology Devices; Classification of In Vitro Diagnostic 
Devices for Bacillus Species Detection

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule; reproposal of proposed rule.

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

SUMMARY: The Food and Drug Administration (FDA) is re-proposing to 
classify in vitro diagnostic devices for Bacillus species (spp.) 
detection into class II (special controls) after considering, among 
other information, the recommendations of the Microbiology Devices 
Advisory Panel (the Panel). FDA is re-proposing to establish special 
controls in a draft special controls guideline that the Agency believes 
are necessary to provide a reasonable assurance of the safety and 
effectiveness of the devices. In addition, FDA is re-proposing to 
restrict use and distribution of the devices. FDA is publishing in this 
proposed rule the recommendations of the Panel regarding the 
classification of the devices.

DATES: Submit either electronic or written comments on the proposed 
rule by February 16, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you

[[Page 71757]]

do not wish to be made available to the public, submit the comment as a 
written/paper submission and in the manner detailed (see ``Written/
Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2011-N-0103 for ``Microbiology Devices; Classification of In Vitro 
Diagnostic Devices for Bacillus Species Detection.'' Received comments 
will be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management 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  http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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 
``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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper 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: Beena Puri, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 5553, Silver Spring, MD 20993-0002, 301-796-6202.

SUPPLEMENTARY INFORMATION: 

I. Background

A. Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 
301 et seq.), as amended, 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) 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 section 513(d) of the FD&C Act, FDA refers to devices that 
were in commercial distribution before May 28, 1976 (the date of 
enactment of the Medical Device Amendments of 1976 (Pub. L. 94-295)), 
as ``preamendments devices.'' FDA classifies these devices after it: 
(1) Receives a recommendation from a device classification panel (an 
FDA advisory committee); (2) publishes the panel's recommendation for 
comment, along with a proposed regulation classifying the device; and 
(3) publishes a final regulation classifying the device. FDA has 
classified most preamendments devices under these procedures.
    A person may market a preamendments device that has been classified 
into class III through premarket notification procedures, without 
submission of a premarket approval application (PMA), until FDA issues 
a final order under section 515(b) of the FD&C Act (21 U.S.C. 360e(b)) 
requiring premarket approval.
    FDA refers to devices that were not in commercial distribution 
before May 28, 1976, as ``postamendments devices.'' These devices are 
classified automatically by statute (section 513(f)(1) of the FD&C Act) 
into class III without any FDA rulemaking process. These devices remain 
in class III and require premarket approval, unless and until FDA 
classifies or reclassifies the device into class I or class II or FDA 
issues an order finding the device to be substantially equivalent in 
accordance with section 513(i) of the FD&C Act, to a predicate device 
that does not require premarket approval. The Agency determines whether 
new devices are substantially equivalent to predicate devices by means 
of premarket notification procedures in section 510(k) of the FD&C Act 
(21 U.S.C. 360(k)) and 21 CFR part 807.
    Section 510(m) of the FD&C Act (21 U.S.C. 360(m)) 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.
    Section 520(e) of the FD&C Act (21 U.S.C. 360j(e)) authorizes FDA 
to issue regulations imposing restrictions on the sale, distribution, 
or use of a device, if, because of its potentiality for harmful effect 
or the collateral measures necessary to its use, FDA determines that 
absent such restrictions, there cannot be a reasonable assurance of its 
safety and effectiveness. Certain provisions of the FD&C Act relate 
specifically to FDA's authority over restricted devices. For example, 
section 502(q) and (r) of the FD&C Act (21 U.S.C. 352(q) and (r)) 
provide that a restricted device distributed or offered for sale in any 
state shall be deemed to be misbranded if its advertising is false or 
misleading or fails to include certain information regarding the 
device, or it is sold, distributed, or used in violation of regulations 
prescribed under section 520(e) of the FD&C Act, and section 704(a) of 
the FD&C Act (21 U.S.C. 374(a)) authorizes FDA to inspect certain 
records relating to restricted devices.

B. Regulatory History--Background of the Device

    After the enactment of the Medical Device Amendments of 1976, FDA 
undertook to identify and classify all preamendments devices in 
accordance with section 513(b) of the FD&C Act. However, in vitro 
diagnostic devices for Bacillus spp. detection were not identified and 
classified in FDA's initial efforts. FDA subsequently identified 
several preamendments devices for Bacillus spp. detection, including 
Bacillus spp. antisera conjugated with a

[[Page 71758]]

fluorescent dye (immunofluorescent reagents) used to presumptively 
identify bacillus-like organisms in clinical specimens, antigens used 
to identify antibodies to Bacillus anthracis (B. anthracis) (anti-toxin 
and anti-capsular) in serum, and bacteriophage used for differentiating 
B. anthracis from other Bacillus spp. based on susceptibility to lysis 
by the phage.
    Consistent with the FD&C Act, FDA held a panel meeting on March 7, 
2002, regarding the classification of the preamendments in vitro 
diagnostic devices for Bacillus spp. detection (Ref. 1). After the 
Panel meeting, FDA found three additional in vitro diagnostic devices 
for Bacillus spp. detection to be substantially equivalent to another 
device within that type. These three devices have the same intended use 
as their predicate devices, but make use of newer nucleic acid 
amplification technology. While they exhibit technological differences 
from the preamendments Bacillus spp. detection devices, FDA has 
determined that they are as safe and effective as, and do not raise 
different questions of safety and effectiveness than, their predicates. 
(See section 513(i) of the FD&C Act).
    In the Federal Register of May 18, 2011 (76 FR 28688; 76 FR 28689), 
FDA proposed to classify these devices into class II, establish special 
controls in a draft special controls guidance entitled ``Class II 
Special Controls Guidance Document: In Vitro Diagnostic Devices for 
Bacillus spp. Detection,'' and limit the distribution of these devices 
to laboratories with experienced personnel who have training in 
principles and use of microbiological culture identification methods 
and infectious disease diagnostics and with appropriate biosafety 
equipment and containment. In the Federal Register of May 6, 2015 (80 
FR 26059), FDA withdrew the previously issued draft special controls 
guidance entitled ``Class II Special Controls Guidance Document: In 
Vitro Diagnostic Devices for Bacillus spp. Detection.'' This withdrawal 
was part of FDA's Transparency Initiative and was part of a withdrawal 
of a number of guidances that had not been finalized for several years.

II. Panel Recommendation

    During a public meeting held on March 7, 2002, the Panel made the 
following recommendations regarding the classification of in vitro 
diagnostic devices for Bacillus spp. detection (Ref. 1).

A. Classification Recommendation

    The Panel recommended that in vitro diagnostic devices for Bacillus 
spp. detection be classified into class II. The Panel believed that 
general and special controls would provide reasonable assurance of the 
safety and effectiveness of the devices.
    The Panel recommended that the use of these devices be limited to 
prescription use, and also that distribution of the devices be limited 
to: (1) Persons with specific training or experience in the applicable 
testing methods and (2) facilities under the oversight of public health 
laboratories so that the laboratories could coordinate and communicate 
with state and local public health directors and so that performance of 
the devices in the laboratory might be systematically collated for 
interagency review (including FDA).
    The Panel suggested: (1) That FDA partner with the Centers for 
Disease Control and Prevention, United States Army Medical Research 
Institute for Infectious Diseases (USAMRIID), and other appropriate 
Agencies involved in laboratory performance issues to develop practical 
ways to evaluate the performance of these devices; (2) that appropriate 
biosafety handling of the diagnostic specimens be followed by 
laboratories; and (3) that FDA develop testing guidelines to include 
recommendations on specimen selection, procedures, interpretation of 
results, and possibly public health notification.

B. Summary of Reasons and Data To Support the Recommendations

    At the March 7, 2002, meeting, the Panel considered information 
from the literature presented by FDA (Refs. 2 to7), information 
presented at the meeting by representatives from USAMRIID who shared 
the historical perspective on their institution's use of devices for 
the detection of B. anthracis and their personal experience using these 
devices, and the Panel's personal knowledge and experience.
    Evidence presented to the Panel addressed how the preamendments 
devices of this type work and some of their limitations (Ref. 1). 
Bacteriophage tests are used for differentiating B. anthracis from 
other Bacillus spp. based on susceptibility to lysis by the phage. They 
have been shown to specifically lyse vegetative B. anthracis and not 
Bacillus cereus (B. cereus) strains, although the phage can fail to 
lyse rare strains of B. anthracis or lyse Bacillus strains other than 
B. anthracis. Bacillus spp. antisera tests conjugated with a 
fluorescent dye (immunofluorescent reagents) are used to 
microscopically visualize specific binding with cultured bacteria. Gram 
positive rods with capsules that fluoresce are presumptive evidence for 
identification of B. anthracis and must be confirmed with further 
testing. Antigen tests are used to identify antibodies to B. anthracis 
(anti-toxin and anti-capsular) in serum. They can be used for 
confirmation of anthrax if the patient survives the disease, because 
early antibiotic treatment does not abrogate antibody expression. 
However, such serological testing is most useful for monitoring 
responses to anthrax vaccines and for epidemiological investigations.

III. Proposed Classification

    FDA is proposing the following identification based on the Panel's 
discussion and recommendation, FDA's experience with these devices, and 
other available information. An in vitro diagnostic device for Bacillus 
spp. detection is a prescription device used to detect and 
differentiate among Bacillus spp. and presumptively identify B. 
anthracis and other Bacillus spp. from cultured isolates or clinical 
specimens as an aid in the diagnosis of anthrax and other diseases 
caused by Bacillus spp. This device may consist of Bacillus spp. 
antisera conjugated with a fluorescent dye (immunofluorescent reagents) 
used to presumptively identify bacillus-like organisms in clinical 
specimens; bacteriophage used for differentiating B. anthracis from 
other Bacillus spp. based on susceptibility to lysis by the phage; or 
antigens used to identify antibodies to B. anthracis (anti-toxin and 
anti-capsular) in serum. Bacillus infections include anthrax 
(cutaneous, inhalational, or gastrointestinal) caused by B. anthracis, 
and gastrointestinal disease and non-gastrointestinal infections caused 
by B. cereus.
    FDA is proposing to classify these devices into class II because 
general controls are insufficient to provide reasonable assurance of 
the safety and effectiveness of the devices, and there is sufficient 
information to establish special controls to provide such assurance 
(see section V). For these devices, FDA believes that premarket 
notification is necessary to provide reasonable assurance of safety and 
effectiveness and, therefore, FDA does not intend to exempt the devices 
from premarket notification requirements.

IV. Risks to Health

    Based on the Panel's discussion and recommendations, FDA's 
experience with these devices, and other available information, we 
believe the risks to health associated with the use of the device type 
are those discussed below. No new risks or significant changes in

[[Page 71759]]

risks relating to this device type have been identified since the Panel 
meeting.
    Although there have been no reports to date, FDA believes that this 
type of device presents risks associated with false negative and false 
positive test results, which could result from device performance 
failures or errors in interpretation. A false positive result may lead 
to a patient undergoing unnecessary or ineffective treatment, and also 
could result in inaccurate epidemiological information on the presence 
of anthrax disease being publicized in a community, potentially leading 
to unnecessary prophylaxis and management of others. A false negative 
result may lead to delayed recognition by the physician of the presence 
or progression of disease and also could result in a failure to 
promptly recognize, control, and prevent additional infections. A false 
negative result could potentially delay diagnosis and treatment of 
infection caused by B. anthracis or other Bacillus spp.
    In addition, while there have been few reports to date, there may 
be risks to laboratory workers from handling cultures and control 
materials. Improper handling of cultures and control materials may 
expose laboratory workers to serious health problems associated with 
infection caused by B. anthracis or other Bacillus spp. Because 
handling the quality control organisms and those potentially present in 
the specimen may pose a risk to laboratory workers, FDA is proposing to 
restrict distribution of these products to laboratories that follow 
public health guidelines that address appropriate biosafety conditions, 
interpretation of test results, and coordination of findings with 
public health authorities.

V. Special Controls

    Based on the Panel's discussion and recommendations, FDA's 
experience with these devices, and other available information, FDA is 
proposing to establish the special controls set forth in the draft 
guideline document entitled ``Class II Special Controls Guideline: In 
Vitro Diagnostic Devices for Bacillus spp. Detection'' (Ref. 8). FDA 
believes that these special controls, in combination with general 
controls, are necessary to provide a reasonable assurance of safety and 
effectiveness of the devices. As discussed further in section XI, for 
currently marketed devices, FDA does not intend to enforce compliance 
with the submission requirement for the special controls set forth in 
sections VI, VII, and IX of the special controls guideline. 
Manufacturers of such devices must comply with the underlying 
requirements for those special controls as well as the labeling special 
controls set forth in section VIII of the guideline.
    The class II special controls guideline, which sets forth criteria 
that are supplemental to other applicable requirements, addresses: (1) 
Specific information relating to the devices' intended use, components, 
testing procedures, specimen storage/shipping conditions, and 
interpretation/reporting that must be submitted to FDA; (2) detailed 
descriptive information submitted to FDA regarding the studies required 
to demonstrate appropriate performance and control against assays that 
may otherwise fail to perform to acceptable standards; (3) specific 
labeling requirements; and (4) certain information that must be 
submitted for in vitro diagnostic devices for Bacillus spp. detection 
that use nucleic acid amplification.
    First, the submission of specific information to FDA related to the 
devices' intended use, components, testing procedures, specimen 
storage/shipping conditions, and interpretation/reporting would help 
mitigate the risks of false positive and false negatives as well as the 
biosafety risks of such devices because such information would help FDA 
to assess the safety and effectiveness of the devices. Second, detailed 
descriptive information regarding the studies required to demonstrate 
performance and control would mitigate the risk of false negatives and 
false positives by helping to ensure that the devices performs to 
acceptable standards. Third, specific labeling requirements would 
mitigate the risk of false positives, false negatives, and biosafety 
risks associated with the devices by helping to ensure that users 
understand the appropriate uses and limitations of the devices as well 
as the biosafety risks associated with the devices. Lastly, certain 
information that must be submitted to FDA for in vitro diagnostic 
devices for Bacillus spp. detection that use nucleic acid amplification 
would mitigate the risk of false positives and false negatives, as such 
information would allow FDA to assess the safety and effectiveness of 
the devices and the regulatory controls necessary to address those 
issues as well as to ensure the devices performs to acceptable 
standards.
    Manufacturers of diagnostic devices for Bacillus spp. detection 
would 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 mitigation measures identified by the 
firm would provide at least an equivalent assurance of safety and 
effectiveness.

            Table 1--Identified Risks and Mitigation Measures
------------------------------------------------------------------------
            Identified risks                   Mitigation measures
------------------------------------------------------------------------
A false negative test result may lead    The FDA document entitled
 to delay of therapy and progression of   ``Class II Special Controls
 disease and failure to promptly          Guideline: In Vitro Diagnostic
 recognize, control, and prevent          Devices for Bacillus spp.
 disease in the community.                Detection,'' which addresses
                                          this risk through: Specific
                                          device description
                                          requirements, performance
                                          studies, labeling, and
                                          specific requirements for
                                          devices that use nucleic acid
                                          amplification.
A false positive test result may lead    The FDA document entitled
 to unnecessary or ineffective            ``Class II Special Controls
 treatment and incorrect                  Guideline: In Vitro Diagnostic
 epidemiological information being        Devices for Bacillus spp.
 publicized, potentially leading to       Detection,'' which addresses
 unnecessary prophylaxis and management   this risk through: Specific
 of others.                               device description
                                          requirements, performance
                                          studies, labeling, and
                                          specific requirements for
                                          devices that use nucleic acid
                                          amplification.
Biosafety risks to laboratory workers    The FDA document entitled
 handling test specimens and control      ``Class II Special Controls
 materials.                               Guideline: In Vitro Diagnostic
                                          Devices for Bacillus spp.
                                          Detection,'' which addresses
                                          this risk through: Specific
                                          device description
                                          requirements and labeling.
------------------------------------------------------------------------

[[Page 71760]]

VI. Restrictions on Distribution and Use

    FDA also believes that restrictions on the distribution and use of 
the devices are necessary to provide a reasonable assurance of safety 
and effectiveness. FDA proposes to restrict distribution of the devices 
to laboratories that follow public health guidelines that address the 
appropriate biosafety conditions, interpretation of test results, and 
coordination of findings with public health authorities. As noted, the 
Panel was concerned that these devices be used by personnel 
sufficiently skilled to maximize device performance and to 
appropriately interpret and make use of test results. FDA believes that 
this proposed distribution restriction is necessary to provide a 
reasonable assurance of safety and effectiveness of these devices, and 
that it would be consistent with the intent of the Panel in its 
discussion of limitations on the distribution of the devices and on 
monitoring of test results.
    Further, FDA proposes to restrict use of these devices to be a 
prescription device in accordance with the terms set forth in proposed 
21 CFR 866.3045(d).

VII. Electronic Access

    Persons interested in obtaining a copy of the draft 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 draft 
guideline is also available at  http://www.regulations.gov. Persons 
unable to download an electronic copy of ``Class II Special Controls 
Guideline: In Vitro Diagnostic Devices for Bacillus spp. Detection,'' 
may send an email request to CDRH-Guidance@fda.hhs.gov to receive an 
electronic copy of the document. Please use the document number 1400038 
to identify the guideline you are requesting.

VIII. Environmental Impact

    The Agency has determined that under 21 CFR 25.34(b) and (f), this 
proposed 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

    This proposed 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 (the PRA) (44 U.S.C. 3501-
3520). The collections of information in 21 CFR part 807, subpart E, 
have been approved under OMB control number 0910-0120 and the 
collections of information in 21 CFR parts 801 and 809 have been 
approved under OMB control number 0910-0485.
    The labeling referenced in sections VI(A), VIII(A), and VIII(C) of 
the draft special controls guideline do not constitute a ``collection 
of information'' under the PRA because the labeling is a ``public 
disclosure of information originally supplied by the Federal government 
to the recipient for the purpose of disclosure to the public'' (5 CFR 
1320.3(c)(2)).

X. Clarifications to Special Controls Guidelines

    The draft special controls guideline reflects changes the Agency 
has made since the initial proposed rule 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 (21 U.S.C. 360c(a)), which the Agency 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 draft guideline clarifies that firms 
submitting 510(k)s would 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 draft 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.

XI. Implementation Strategy

    FDA proposes the implementation strategy set forth below for these 
devices if a final rule becomes effective.
     Devices that have not been legally marketed prior to the 
date of publication of any final rule, or devices that have been 
legally marketed, but are required to submit a new 510(k) under 21 CFR 
807.81(a)(3) because the device is about to be significantly changed or 
modified: Manufacturers must obtain 510(k) clearance and comply with 
special controls before marketing the new or changed device.
     Devices that have been legally marketed prior to the date 
of publication of any final rule, and devices for which 510(k) 
submissions have been submitted before the date of publication of any 
final rule: FDA does not intend to enforce compliance with the 
submission requirement for the special controls set forth in sections 
VI, VII, and IX of the special controls guideline. Manufacturers of 
such devices must comply with the underlying requirements for those 
special controls as well as the labeling special controls set forth in 
section VIII of the guideline.

XII. Analysis of Impacts

A. Economic Analysis of Impacts

    FDA has examined the impacts of this proposed 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 proposed rule is not a 
significant regulatory action under 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 of the minor impact expected from this 
proposed action, the Agency proposes to certify that the proposed rule, 
when finalized, 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 $144 million, using the most current (2014) Implicit 
Price Deflator for the Gross National Product. FDA does not expect this 
proposed rule, when finalized, to

[[Page 71761]]

result in any 1-year expenditure that would meet or exceed this amount.

B. Summary of Costs and Benefits

    The proposed rule would require the adoption of practices most of 
which manufacturers of currently marketed in vitro diagnostic devices 
for Bacillus spp. detection already follow. The costs of the proposed 
rule, when finalized, will be due to manufacturers ensuring that 
product labeling is consistent with the special controls guideline 
document as well as conducting likely periodic quality control testing 
to assure that marketed devices continue to operate at appropriate 
levels of safety and effectiveness. The costs associated with ensuring 
labeling is consistent with the guideline are expected to be minor. The 
required labeling is similar to the cleared indications for use of 
currently cleared devices and so little change from current labeling is 
expected. However, because of this regulatory action, it is possible 
that these additional activities will result in minor cost increases. 
We have estimated that the proposed rule, if finalized, could result 
in, at most, annualized costs of approximately $2,300 (3 percent) or 
$2,500 (7 percent).
    There are unlikely to be any direct public health benefits from the 
proposed rule, if finalized, because the rule would require the 
adoption of practices most of which manufacturers of currently marketed 
devices already follow and would not change the expected use of the 
diagnostic product. However, we estimate the proposed regulation, when 
final, will result in quantifiable benefits of reducing the number of 
inquiries and incomplete 510(k) submissions from manufacturers to FDA 
(thereby reducing FDA resources needed to answer those inquiries and 
review those submissions) to be between approximately $1,400 and $3,400 
per year. We believe that the unquantified benefits of the draft 
special controls guideline, which would help to ensure the quality of 
these devices, maintain their predictive value, and avoid potential 
future laboratory errors, cannot be estimated, but represent real 
benefits to the public health.
    The full discussion of economic impacts is available in Docket No. 
FDA-2011-N-0103 and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm (Ref. 9).

XIII. References

    The following references are on display in the Division of Dockets 
Management (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also 
available electronically at http://www.regulations.gov. FDA has 
verified the Web site addresses, as of the date this document publishes 
in the Federal Register, but Web sites are subject to change over time.

1. Transcript of the FDA Microbiology Devices Panel meeting, March 
7, 2002, available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfAdvisory/details.cfm?mtg=348.
2. Abshire, T. G., J. E. Brown, and J. W. Ezzell, ``Validation of 
the Use of Gamma Phage for Identifying Bacillus anthracis,'' 102nd 
American Society for Microbiology Annual Meeting (poster #C122), 
2001.
3. Abshire, T. G., et al., ``Production and Validation of the Use of 
Gamma Phage for the Identification of Bacillus anthracis,'' Journal 
of Clinical Microbiology, vol. 43(9), pp. 4780-8, 2005, available at 
http://www.ncbi.nlm.nih.gov/pubmed/16145141.
4. Brown, E. R. and W. B. Cherry, ``Specific Identification of 
Bacillus anthracis by Means of a Variant Bacteriophage,'' Journal of 
Infectious Disease, vol. 96, p. 34, 1955, available at http://jid.oxfordjournals.org/content/96/1/34.long.
5. Brown, E. R. et al., ``Differential Diagnosis of Bacillus cereus, 
Bacillus anthracis, and Bacillus cereus var. mycoides,'' Journal of 
Bacteriology, vol. 75, p. 499, 1958, available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC290100/pdf/jbacter00512-0024.pdf.
6. Buck C. A., R .L. Anacker, F. S. Newman, et al., ``Phage Isolated 
from Lysogenic Bacillus anthracis,'' Journal of Bacteriology, vol. 
85, p. 423, 1963, available at http://jb.asm.org/content/85/6/1423.full.pdf+html?sid=c14df35d-1d7b-4cac-b55b-2097931a4623.
7. Parry, J. M., P. C. B. Turnbull, and J. R. Gibson, A Colour Atlas 
of Bacillus Species, Wolfe Medical Publications Ltd., London, 1983.
8. Draft Guideline for Industry and Food and Drug Administration 
Staff, ``Class II Special Controls Guideline: In Vitro Diagnostic 
Devices for Bacillus spp. Detection,'' issued November 16, 2015, 
available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM470760.pdf.
9. ``Preliminary Regulatory Impact Analysis, Initial Regulatory 
Flexibility Analysis, and Unfunded Mandates Reform Act Analysis for 
Microbiology Devices; Classification of In Vitro Diagnostic Device 
for Bacillus Species Detection,'' 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, it is 
proposed that 21 CFR part 866 is amended as follows:

PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES

0
1. The authority citation for 21 CFR part 866 continues to read as 
follows:

    Authority:  21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
0
2. Section 866.3045 is added to subpart D to read as follows:

Sec.  866.3045  In vitro diagnostic device for ``Bacillus'' spp. 
detection.

    (a) Identification. An in vitro diagnostic device for Bacillus 
species (spp.) detection is a prescription device used to detect and 
differentiate among Bacillus spp. and presumptively identify B. 
anthracis and other Bacillus spp. from cultured isolates or clinical 
specimens as an aid in the diagnosis of anthrax and other diseases 
caused by Bacillus spp. This device may consist of Bacillus spp. 
antisera conjugated with a fluorescent dye (immunofluorescent reagents) 
used to presumptively identify bacillus-like organisms in clinical 
specimens; bacteriophage used for differentiating B. anthracis from 
other Bacillus spp. based on susceptibility to lysis by the phage; or 
antigens used to identify antibodies to B. anthracis (anti-toxin and 
anti-capsular) in serum. Bacillus infections include anthrax 
(cutaneous, inhalational, or gastrointestinal) caused by B. anthracis, 
and gastrointestinal disease and non-gastrointestinal infections caused 
by B. cereus.
    (b) Classification. Class II (special controls). The special 
controls are set forth in FDA's guideline document entitled ``Class II 
Special Controls Guideline: In Vitro Diagnostic Devices for Bacillus 
spp. Detection; Guideline for Industry and Food and Drug Administration 
Staff.'' See Sec.  866.1(e) for information on obtaining this document.
    (c) The distribution of these devices is limited to laboratories 
that follow public health guidelines that address appropriate biosafety 
conditions, interpretation of test results, and coordination of 
findings with public health authorities.
    (d) The use of this device is restricted to prescription use and 
must comply with the following:
    (1) The device must be in the possession of:
    (i)(A) A person, or his agents or employees, regularly and lawfully 
engaged in the manufacture,

[[Page 71762]]

transportation, storage, or wholesale or retail distribution of such 
device; or
    (B) A practitioner, such as a physician, licensed by law to use or 
order the use of such device; and
    (ii) The device must be sold only to or on the prescription or 
other order of such practitioner for use in the course of his 
professional practice.
    (2) The label of the device shall bear the statement ``Caution: 
Federal law restricts this device to sale by or on the order of a 
____'', the blank to be filled with the word ``physician'' or with the 
descriptive designation of any other practitioner licensed by the law 
of the State in which he practices to use or order the use of the 
device.
    (3) Any labeling, as defined in section 201(m) of the FD&C Act, 
whether or not it is on or within a package from which the device is to 
be dispensed, distributed by, or on behalf of the manufacturer, packer, 
or distributor of the device, that furnishes or purports to furnish 
information for use of the device contains adequate information for 
such use, including indications, effects, routes, methods, and 
frequency and duration of administration and any relevant hazards, 
contraindications, side effects, and precautions, under which 
practitioners licensed by law to employ the device can use the device 
safely and for the purposes for which it is intended, including all 
purposes for which it is advertised or represented. This information 
will not be required on so-called reminder-piece labeling which calls 
attention to the name of the device but does not include indications or 
other use information.
    (4) All labeling, except labels and cartons, bearing information 
for use of the device also bears the date of the issuance or the date 
of the latest revision of such labeling.

    Dated: November 10, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-29275 Filed 11-16-15; 8:45 am]
 BILLING CODE 4164-01-P