[Federal Register Volume 76, Number 215 (Monday, November 7, 2011)]
[Proposed Rules]
[Pages 69034-69039]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-28724]



[[Page 69033]]

Vol. 76

Monday,

No. 215

November 7, 2011

Part V





Department of Health and Human Services





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Food and Drug Administration





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21 CFR Part 866





Microbiology Devices; Classification of In Vitro Diagnostic Device for 
Yersinia Species Detection and Draft Guidance for Industry and Food and 
Drug Administration Staff; Class II Special Controls Guidance Document: 
In Vitro Diagnostic Devices for Yersinia Species Detection; 
Availability; Proposed Rule and Notice

  Federal Register / Vol. 76, No. 215 / Monday, November 7, 2011 / 
Proposed Rules  

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2011-N-0729]


Microbiology Devices; Classification of In Vitro Diagnostic 
Device for Yersinia Species Detection

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to 
classify in vitro diagnostic devices for Yersinia species (spp.) 
detection into class II (special controls), in accordance with the 
recommendation of the Microbiology Devices Advisory Panel (the panel). 
FDA is publishing in this document the recommendation(s) of the panel 
regarding the classification of this device. After considering public 
comments on the proposed classification, FDA will publish a final 
regulation classifying this device.

DATES: Submit either electronic or written comments by February 6, 
2012. See section IV of this document for the proposed effective date 
of a final rule based on this proposed rule.

ADDRESSES: You may submit comments, identified with the FDA docket 
number found in brackets in the heading of this document, 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:
     FAX: (301) 827-6870.
     Mail/Hand delivery/Courier (For paper, disk, or CD-ROM 
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-2011-N-0729 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 ``Request for 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: 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. Legal Authority

    The Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 
301 et seq.), as amended by the Medical Device Amendments of 1976 (Pub. 
L. 94-295), the Safe Medical Devices Act of 1990 (Pub. L. 101-629), the 
Food and Drug Administration Modernization Act of 1997 (FDAMA) (Public 
Law 105-115), the Medical Device User Fee and Modernization Act (Pub. 
L. 107-250), and the Food and Drug Administration Amendments Act of 
2007 (Pub. L. 110-85), among other amendments, established 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, depending on 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). Elsewhere in this issue of the Federal Register, FDA is 
announcing the availability for comment of the draft guidance document 
that FDA proposes to designate as a special control for this device. In 
addition, the proposed rule would establish as a special control 
limitations on the distribution of this device.
    Under section 513 of the FD&C Act, FDA refers to devices that were 
in commercial distribution before May 28, 1976 (the date of enactment 
of the 1976 amendments), as ``preamendments devices.'' FDA classifies a 
device 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 type (see section 513(d) of the FD&C Act). FDA 
has classified most preamendments devices under these procedures.
    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) 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 II; (2) FDA issues an order 
classifying the device into class I or II in accordance with section 
513(f)(2) of the FD&C Act, as amended by the FDAMA; or (3) FDA issues 
an order finding the device to be substantially equivalent, under 
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 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 21 CFR part 807 of the regulations.
    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 until FDA promulgates a 
final regulation under section 515(b) of the FD&C Act (21 U.S.C. 
360e(b)) requiring premarket approval.
    Consistent with the FD&C Act and the regulations, FDA consulted 
with the panel, regarding the classification of this device.

B. Regulatory History of In Vitro Diagnostic Devices for Yersinia spp. 
Detection

    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 Yersinia spp. detection were not identified and 
classified in this initial effort. FDA subsequently identified several 
preamendments devices for Yersinia spp. detection, including Yersinia 
spp. antisera conjugated with a fluorescent dye (immunofluorescent 
reagents) used to presumptively identify Yersinia-like organisms in 
clinical specimens, antigens used to identify antibodies to Y. pestis 
(Fraction 1) in serum, and bacteriophage used for differentiating Y. 
pestis from other

[[Page 69035]]

Yersinia spp. based on susceptibility to lysis by the phage.
    Consistent with the FD&C Act and the regulations, FDA held a panel 
meeting on March 7, 2002, regarding the classification of the 
preamendments in vitro diagnostic devices for Yersinia spp. detection. 
After the panel meeting FDA found one additional in vitro diagnostic 
device for Yersinia spp. detection to be substantially equivalent to a 
preamendment device within that type. The additional device has the 
same intended use as its predicate device but makes use of newer 
nucleic acid amplification technology (NAAT). While it exhibits 
technological differences from the preamendments Yersinia spp. 
detection devices, FDA has determined that it is as safe and effective 
as, and does not raise different questions of safety and effectiveness 
from its predicate (see section 513(i) of the FD&C Act).

II. Panel Recommendation

    At a public meeting held on March 7, 2002, the panel recommended 
that in vitro diagnostic devices for Yersinia spp. detection (Ref. 1) 
be classified into class II.

A. Identification

    FDA is proposing the following identification based on the panel's 
recommendation and the available information. An in vitro diagnostic 
device for Yersinia spp. detection is used to detect and differentiate 
among Yersinia spp. and presumptively identify Y. pestis and other 
Yersinia spp. from cultured isolates or clinical specimens as an aid in 
the diagnosis of plague and other diseases caused by Yersinia spp. This 
device may consist of Yersinia spp. antisera conjugated with a 
fluorescent dye (immunofluorescent reagents) used to presumptively 
identify Yersinia-like organisms in clinical specimens or bacteriophage 
used for differentiating Y. pestis from other Yersinia spp. based on 
susceptibility to lysis by the phage or antigens used to identify 
antibodies to Y. pestis (Fraction 1) in serum. Diseases caused by 
Yersinia infections include three different forms of plague (bubonic, 
pneumonic, and septicemic), caused by Y. pestis, and gastrointestinal 
infection, caused by Y. pseudotuberculosis and Y. enterocolitica.

B. Classification Recommendation

    The panel recommended that in vitro diagnostic devices for Yersinia 
spp. detection be classified into class II. The panel believed that 
class II with special controls (guidance document and limitations on 
the distribution) would provide reasonable assurance of the safety and 
effectiveness of the device.

C. Summary of Reasons and Data To Support the Recommendation

    The panel considered information from the literature presented by 
FDA (Refs. 2 to 7), information presented at the meeting by 
representatives from the United States Army Medical Research Institute 
for Infectious Diseases who shared the historical perspective on their 
institution's use of devices for the detection of Y. pestis 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. Bacteriophage 
tests are used for differentiating Y. pestis from Y. 
pseudotuberculosis. The test is performed at 20-25 [deg]C because the 
bacteriophage can lyse Y. pseudotuberculosis at 37 [deg]C but not at 
lower temperatures. Lysis at 22-25 [deg]C provides presumptive evidence 
that a culture isolate is Y. pestis. The fluorescent antibody reagent 
is a fluorescein-labeled antibody against Fraction 1 (F1) antigen that 
is used to microscopically visualize specific binding with cultured 
bacteria. A protein from the capsular envelope of Y. pestis is used to 
microscopically visualize specific binding with cultured bacteria. The 
test can be performed with culture growth or can be done on clinical 
specimens that have gram-negative bacteria resembling Y. pestis. The 
presence of F1 antigen is presumptive evidence of Y. pestis, which must 
be confirmed with other testing. F1 antigen can be used to sensitize 
sheep erythrocytes for hemagglutination testing to detect antibody 
responses to F1 in human sera. Significant levels of human antibody to 
this antigen can be retrospective confirmation of Y. pestis infection 
or can be presumptive of Y. pestis infection when a single serum sample 
is tested.
    The panel discussed considerations about use of these devices, 
including the training, experience, and facilities necessary for safe 
handling of test materials and specimens, and for appropriate test 
execution and interpretation of test results. They also discussed the 
desirability of coordination by public health Agencies, including the 
Centers for Disease Control and Prevention, to ensure that appropriate 
performance standards and use guidelines are developed for these tests 
and to encourage that test results be reported to public health 
authorities.
    The panel recommended that in vitro diagnostic devices for Yersinia 
spp. detection should be classified into class II because they 
concluded that special controls, in addition to general controls, would 
provide reasonable assurance of the safety and effectiveness of the 
device, and there is sufficient information to establish special 
controls to provide such assurance.

D. Risks to Health

    Based on the panel's discussion and recommendations, and FDA's 
experience with these devices, we believe the following are risks to 
health associated with the use of the device type.
    Failure of in vitro diagnostic devices for Yersinia spp. detection 
to perform as indicated or an error in interpretation of results may 
lead to misdiagnosis and improper patient management or inaccurate 
epidemiological information that may contribute to inappropriate public 
health responses. FDA believes that this type of device presents risks 
associated with a false-negative test result and a false-positive test 
result, as explained in this document. In addition, there may be risks 
to laboratory workers resulting from handling positive cultures and 
control materials.
    A false-positive result may lead to a medical decision causing a 
patient to undergo unnecessary or ineffective treatment, as well as 
inaccurate epidemiological information on the presence of plague 
disease in a community. A false-negative result may lead to delayed 
recognition by the physician of the presence or progression of disease 
and inaccurate epidemiological information to control and prevent 
additional infections. A false-negative result could potentially delay 
diagnosis and treatment of infection caused by Y. pestis or other 
Yersinia spp.
    Additionally, exposure to organisms potentially present in test 
specimens and those used as control materials poses a risk of infection 
of Yersinia to laboratory workers.

E. Special Controls

    Based on the panel's discussion and recommendations, FDA believes 
that, in addition to general controls, the proposed special controls 
discussed in this document are adequate to address the risks to health.
    FDA believes that the draft guidance document entitled ``Class II 
Special Controls Guidance Document: In Vitro Diagnostic Devices for 
Yersinia spp. Detection'' and limitations on distribution of these 
devices, set forth in the proposed classification regulation,

[[Page 69036]]

will address the risks identified previously in this document and 
provide a reasonable assurance of safety and effectiveness of the 
device. The class II special controls guidance document provides 
information on how to meet premarket (510(k)) submission requirements 
for the assays in sections that discuss performance studies and 
labeling. The guidance document provides specific recommendations for 
NAAT tests and tests using the technologies employed by the 
preamendments devices. The performance studies section of the guidance 
describes studies to demonstrate appropriate performance and control 
against assays that may otherwise fail to perform to acceptable 
standards. The labeling section of the guidance addresses factors such 
as directions for use, quality control, and precautions for use and 
interpretation. The special controls guidance recommendations will 
allow the manufacturer to identify the causes of false-positive and 
false-negative test results and appropriately label their device to 
limit the occurrence of false positives and false negatives.
    In addition, FDA proposes as a special control that distribution of 
these devices be limited 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. As noted, the panel 
was concerned about improper use of these devices and recommended that 
these devices be used only by personnel sufficiently skilled to 
maximize their performance and to appropriately interpret and make use 
of test results. FDA believes that this proposed distribution 
limitation will appropriately help assure the safe and effective use of 
these devices and that it is consistent with the intent of the panel in 
its discussion of limitations on the use of the devices and on 
monitoring of test results.

            Table 1--Risks to Health and Mitigation Measures
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            Identified risks                    Mitigation measures
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A false-negative test result may lead to  Device description--
 delay of therapy and progression of       recommended.
 disease and epidemiological failure to   Performance studies--
 promptly recognize disease in the         recommended.
 community.                               Labeling--recommended.
                                          Limited distribution--
                                           required.
A false-positive test result may lead to  Device description--
 unnecessary treatment and incorrect       recommended.
 epidemiological information that leads   Performance studies--
 to unnecessary prophylaxis and            recommended.
 management of others.                    Labeling--recommended.
                                          Limited distribution--
                                           required.
Biosafety and a risk of transmission of   Labeling--recommended.
 Yersinia infection to laboratory         Limited distribution--
 workers handling test specimens and       required.
 control materials.
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III. Proposed Classification

    FDA agrees with the panel's recommendation that in vitro diagnostic 
devices for Yersinia spp. detection should be classified into class II 
because special controls, in addition to general controls, will provide 
reasonable assurance of the safety and effectiveness of the device, and 
there is sufficient information to establish special controls to 
provide such assurance.

IV. Proposed Effective Date

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

V. Environmental Impact

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

VI. Analysis of Impacts

A. Introduction

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and 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 as defined by 
the 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 this proposed rule would create no new 
burdens, the Agency proposes to certify that the final 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 $136 million, using the most current (2010) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
proposed rule to result in any 1-year expenditure that would meet or 
exceed this amount.

B. Need for Regulation

    In vitro diagnostic devices used to identify and differentiate 
among Yersinia spp. are currently unclassified preamendment devices. 
Heightened interest in biological warfare and bioterrorism has 
generated interest in devices that would identify Y. pestis, the 
pathogen responsible for plague and other diseases. FDA has identified 
information for the safe and effective use of such devices and has 
applied this information in its clearance of a device that identifies 
Y. pestis. However, the lack of a formal device classification and 
published guidance may deter additional firms from entering the market 
for such devices. Devices are typically classified, and these 
designations are published in the Federal Register.
    Market failure can occur when market participants lack important 
information or when they possess incorrect information. Because this 
device lacks a

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formal classification and published data recommendations, potential 
manufacturers may be unable to assess whether to enter this market. 
Even manufacturers in possession of these standards that would 
otherwise enter this market might interpret the absence of a formal 
classification as FDA uncertainty about its premarket review 
requirements or that FDA may be about to change these requirements, 
making market entry seem riskier than it is. The market failure we 
intend to address is one of imperfect information. Classifying this 
device would provide valuable information to manufacturers about what 
is needed to obtain FDA clearance. Manufacturers lacking this 
information might choose not to enter the market for this device when a 
well-informed manufacturer would. Moreover, the submission process may 
be unclear to both manufacturers and FDA because the data requirements 
are not clearly articulated.

C. Background

    Y. pestis, the causative agent of plague, is associated with over 
100 million deaths worldwide during three historical pandemics. Rodents 
and other mammals have historically served as reservoirs of plague, 
while fleas feeding on these animals are vectors that can transmit the 
disease to humans. Improved urban sanitary conditions, including 
improved rodent control, has dramatically reduced the incidence of 
plague, while availability of antibiotics has dramatically lowered the 
mortality rate.
    Plague has been endemic in the continental United States since at 
least 1900. The United States averaged 18 cases of plague per year in 
the 1980s and 9 cases per year since 1990. In 2006, a total of 13 human 
plague cases were reported among residents of four states. This is the 
largest number of cases reported in a single year in the United States 
since 1994. Two of the 13 cases were fatal.
    Those infected with plague are likely to survive if they are 
treated with antibiotics soon after the symptoms appear. Treatment 
generally consists of taking antibiotics for at least 7 days. Without 
treatment, mortality is 60 percent for bubonic plague and 100 percent 
for pneumonic and septicemic plague. The primary public health issue 
associated with plague, however, would be its potential use in warfare 
or in an act of terrorism, where hundreds or thousands of individuals 
could be infected. Effective treatment would require rapid diagnosis, 
the timely administration of antibiotics, and public health measures to 
minimize the risk of further infection.
    In the event of a potential massive plague outbreak, one would want 
to be able to test for Y. pestis quickly and accurately. Rapid 
identification of Y. pestis and diagnosis of plague would improve the 
ability to treat infected individuals and minimize the chances of 
infecting others. Reducing the likelihood of false-negative testing 
results would minimize the possibility that infected individuals would 
be left untreated and that the disease would go undetected by public 
health officials. Reducing the likelihood of false-positive testing 
results would minimize potential costs associated with unnecessary 
therapy and unnecessary infection control measures.
    The Microbiology Devices Panel met March 7, 2002, to recommend a 
classification for in vitro diagnostic products for the identification 
of Yersinia spp. The panel recommended that the devices be classified 
as class II, without exemption from premarket notification 
requirements, and that special controls include testing guidelines, 
performance characteristics, and restrictions on distribution. FDA 
generally concurs with these recommendations.
    In vitro diagnostic devices for Yersinia spp. detection are 
preamendment, unclassified devices. As such, manufacturers of new 
devices for Yersinia spp. detection may market these devices through 
premarket notification procedures and are not required to submit 
premarket approval applications. In 2007, a manufacturer obtained FDA 
clearance for a device to detect Y. pestis through the 510(k) premarket 
notification procedures. Throughout the process, FDA advised the 
applicant on the studies that would establish the performance 
characteristics of the device, device labeling, and distribution 
restrictions to demonstrate substantial equivalence to a preamendment 
device. This data submission was consistent with the recommendations of 
the 2002 panel. Absent this rulemaking effort, FDA would continue to 
regulate this device in this fashion.

D. Description of the Proposed Rule

    Through this proposal, FDA intends to follow the recommendations of 
the 2002 Microbiology Devices Panel. This proposed rule would place 
devices used for the in vitro identification of Yersinia spp. into 
class II (special controls). General controls alone would be inadequate 
for safe and effective use, and the class III premarket application 
process would be unnecessary. The proposed special controls are 
consistent with the principle of applying the appropriate regulatory 
control necessary to provide reasonable assurance of safety and 
effectiveness. The application of this intermediate level of regulatory 
oversight and these specific special controls would be consistent with 
FDA's treatment of other devices with similar risk profiles. Reagents 
for detection of specific novel influenza A viruses, for example, are 
class II devices.
    In addition to the general controls, FDA would require special 
controls in the form of a guidance document that would include 
recommendations for the types of information that should be included in 
premarket submissions and restrictions on device distribution. The 
guidance document would include a section on performance 
characteristics, describing studies to demonstrate appropriate device 
performance, and a section on labeling that would include device 
intended use, instructions for use of the device, precautions, and the 
interpretation and reporting of test results. The special controls 
would also include the restricted distribution of these devices. Under 
these special controls, the device would be limited 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. 
These specific special controls are needed because of the public health 
issues associated with Y. pestis infection.
    Erroneous test results when testing for Y. pestis can result in 
serious public health consequences. Individuals infected with Y. pestis 
are unlikely to survive if they are not treated in a timely manner. In 
the case of a potential massive outbreak of Y. pestis, such as might 
occur with the use of the pathogen as an instrument of bioterrorism, 
the potential consequences could be substantial. False negatives or 
otherwise mishandled test results could not only delay the treatment of 
infected individuals, but also could prevent public health officials 
from taking steps to prevent the transmission of plague to others. 
False positives could lead to unnecessary use of antibiotics and 
patient isolation, and would have serious economic and public health 
consequences if the reporting of these results were to contribute to a 
public health panic.
    FDA intends to address risks to public health not adequately 
controlled by general controls through special controls. The device 
description section of the special controls guidance

[[Page 69038]]

document would explain to manufacturers the need to include in the 
premarket submission information on the nature of the device and its 
proper use. The section on performance studies would recommend the 
types of information and data manufacturers need to collect in order to 
establish the performance of their device, clarifying regulatory 
requirements. The special control on labeling would provide users with 
information on the device's intended use, directions for use, 
interpretation of results, and potential precautions. The control on 
distribution would ensure that those using this device would have the 
training and equipment needed to perform the test safely and 
effectively, and that test results would be appropriately reported to 
the public health authorities.

E. Costs and Benefits of the Proposed Regulation

    This proposed rule would not create any additional burdens or 
directly result in significant benefits. Both current practice and this 
proposed rule are applications of the recommendations of the 2002 
Microbiology Devices Advisory Panel. The requirements associated with 
class II and the chosen special controls do not change the requirements 
FDA imposes on manufactures. Indirectly, however, the classification of 
this device and publication of the special controls would benefit both 
manufacturers and FDA. Manufacturers would benefit from published 
regulatory requirements in that they would know the burdens associated 
with entering this market before starting the premarket notification 
process, and they would submit premarket notification submissions 
containing the appropriate information. Improved knowledge of the 
submission requirements would reduce the need for consultation with FDA 
during the clearance process to facilitate FDA review and accelerate 
product availability. Classification of this device and publication of 
the requirements would also reduce FDA resources consumed in these 
consultations and improve premarket review consistency.
    The Regulatory Flexibility Act requires Agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because this proposed rule would impose no new 
burdens, the Agency proposes to certify that this proposed rule would 
not have a significant economic impact on a substantial number of small 
entities.

VII. Federalism

    FDA has analyzed this proposed 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. 21 
U.S.C. 360k; See Medtronic v. Lohr, 518 U.S. 470 (1996); Riegel v. 
Medtronic, Inc. 552 U.S. 312 (2008). The special controls established 
by this proposed rule, if finalized, would create ``requirements'' to 
restrict the distribution of these devices and to address each 
identified risk to health presented by these specific medical devices 
under 21 U.S.C. 360(k), even though product sponsors may have 
flexibility in how they meet those requirements Cf. Papike v. 
Tambrands, Inc., 107 F.3d 737, 740-42 (9th Cir. 1997).

VIII. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no 
collection of information. Therefore, clearance by the Office of 
Management and Budget under the Paperwork Reduction Act of 1995 is not 
required. FDA also concludes that the special controls guidance 
document identified by this rule refers to previously approved 
collections of information found in FDA regulations. Elsewhere in this 
issue of the Federal Register, FDA is publishing a notice announcing 
the availability of a guidance entitled ``Class II Special Controls 
Guidance Document: In Vitro Diagnostic Devices for Yersinia spp. 
Detection.'' The notice contains an analysis of the paperwork burden 
for the guidance.

IX. Request for Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed comments. Identify 
comments with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.

X. 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. 
(FDA has verified the Web site address, but FDA is not responsible for 
any subsequent changes to the Web site after this document publishes in 
the Federal Register.)

1. Transcript of the FDA Microbiology Devices Panel meeting, March 
7, 2002 (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfAdvisory/details.cfm?mtg=348).
2. Bibel, D.J. and T.H. Chen, ``Diagnosis of Plague: An Analysis of 
the Yersin-Kitasato Controversy,'' vol. 40, pp. 633-651, 
Bacteriological Reviews, 1976.
3. Cavanaugh, DC and S.F. Quan, ``Rapid Identification of 
Pasteurella pestis Using Specific Bacteriophage Lyophilized on 
Strips of Filter Paper; a Preliminary Report,'' vol. 23, pp. 619-
620, American Journal of Clinical Pathology, 1953.
4. Chen, T.H. and K.F. Meyer, ``An Evaluation of Pasteurella pestis 
Fraction-1-Specific Antibody for the Confirmation of Plague 
Infections,'' vol. 34, pp. 911-918, Bulletin of the World Health 
Organization, 1966.
5. Marshall, J.D., Jr., J.A. Mangiafico, and D.C. Cavanaugh, 
``Comparison of the Reliability and Sensitivity of Three Serological 
Procedures in Detecting Antibody to Yersinia pestis (Pasteurella 
pestis),'' vol. 24, pp. 202-204, Applied Microbiology, 1972.
6. Perry, R.D. and J.D. Fetherston, ``Yersinia pestis--Etiologic 
Agent of Plague,'' vol. 10, pp. 35-66, Clinical Microbiology 
Reviews, 1997.
7. Rust J.H., Jr., S. Berman, W.H. Habig, et al., ``Stable Reagent 
for the Detection of Antibody to the Specific Fraction 1 Antigen to 
Yersinia pestis,'' vol. 23, pp. 721-724, Applied Microbiology, 1972.

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

    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.

    2. Section 866.3945 is added to subpart D to read as follows:


Sec.  866.3945  In vitro diagnostic device for Yersinia spp. detection.

    (a) Identification. An in vitro diagnostic device for Yersinia spp.

[[Page 69039]]

detection is a device that is used to detect and differentiate among 
Yersinia spp. and presumptively identify Y. pestis and other Yersinia 
spp. from cultured isolates or clinical specimens as an aid in the 
diagnosis of plague and other diseases caused by Yersinia spp. Diseases 
caused by Yersinia infections include three different forms of plague 
(bubonic, pneumonic, and septicemic), caused by Y. pestis, and 
gastrointestinal infection, caused by Y. pseudotuberculosis and Y. 
enterocolitica. This device may consist of Yersinia spp. antisera 
conjugated with a fluorescent dye (immunofluorescent reagents) used to 
presumptively identify Yersinia-like organisms in clinical specimens or 
bacteriophage used for differentiating Y. pestis from other Yersinia 
spp. based on susceptibility to lysis by the phage; or antigens used to 
identify antibodies to Y. pestis (Fraction 1) in serum.
    (b) Classification. Class II (special controls). The special 
controls are:
    (1) ``Class II Special Controls Guidance Document: In Vitro 
Diagnostic Devices for Yersinia spp. Detection; Guidance for Industry 
and Food and Drug Administration Staff.'' See Sec.  878.1(e) for 
availability information of this guidance document; and
    (2) Distribution is limited 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.

    Dated: November 1, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-28724 Filed 11-4-11; 8:45 am]
BILLING CODE 4160-01-P