[Federal Register Volume 68, Number 24 (Wednesday, February 5, 2003)]
[Rules and Regulations]
[Pages 5825-5827]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-2656]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 97P-0313]


Medical Devices; Reclassification and Codification of Fully 
Automated Short-Term Incubation Cycle Antimicrobial Susceptibility 
Devices From Class III to Class II

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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

SUMMARY: The Food and Drug Administration (FDA) is reclassifying the 
fully automated short-term incubation cycle antimicrobial 
susceptibility device for use in determining in vitro susceptibility of 
bacterial pathogens isolated from clinical specimens from class III to 
class II (special controls). The special control that will apply to 
this device is a guidance document entitled ``Class II Special Controls 
Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; 
Guidance for Industry and FDA.'' The agency is also announcing that it 
has issued an order in the form of a letter to BioMerieux Vitek, Inc., 
reclassifying the device. The agency is classifying this device into 
class II because special controls, in addition to the general controls, 
will provide reasonable assurance of the safety and effectiveness of 
the device and there is sufficient information to establish special 
controls.

DATES: This rule is effective May 6, 2003.

FOR FURTHER INFORMATION CONTACT: Freddie M. Poole, Center for Devices 
and Radiological Health (HFZ-440), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 301-594-2096.

SUPPLEMENTARY INFORMATION:

I. Background (Regulatory Authorities)

    The Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301 
et seq.), as amended by the Medical Device Amendments of 1976 (the 1976 
amendments) (Public Law 94-295), the Safe Medical Devices Act of 1990 
(the SMDA) (Public Law 101-629), and the Food and Drug Administration 
Modernization Act of 1997 (the FDAMA) (Public Law 105-115), established 
a comprehensive system for the regulation of medical devices intended 
for human use. Section 513 of the 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).
    Under the 1976 amendments, class II devices were defined as devices 
for which there is insufficient information to show that general 
controls themselves will assure safety and effectiveness, but for which 
there is sufficient information to establish performance standards to 
provide such assurance. The SMDA broadened the definition of class II 
devices to mean devices for which there is insufficient information to 
show that general controls themselves will assure safety and 
effectiveness, but for which there is sufficient information to 
establish special controls to provide such assurance, including 
performance standards, postmarket surveillance, patient registries, 
development and dissemination of guidance, recommendations, and any 
other appropriate actions the agency deems necessary (section 
513(a)(1)(B) of the act).
    Under section 513 of the act, devices that were in commercial 
distribution before May 28, 1976 (the date of enactment of the 1976 
amendments), generally referred to as preamendments devices, are 
classified after FDA has: (1) Received a recommendation from a device 
classification panel (an FDA advisory committee); (2) published the 
panel's recommendation for comment, along with a proposed regulation 
classifying the device; and (3) published a final regulation 
classifying the device. FDA has classified most preamendments devices 
under these procedures.
    Devices that were not in commercial distribution prior to May 28, 
1976, generally referred to as postamendments devices, are classified 
automatically by statute (section 513(f) of the act) into class III 
without any FDA rulemaking process. Those devices remain in class III 
and require premarket approval, unless and until: (1) The device is 
reclassified into class I or II; (2) FDA issues an order classifying 
the device into class I or II in accordance with new section 513(f)(2) 
of the 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 
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 act (21 U.S.C. 360(k)) and part 807 
of the regulations (21 CFR part 807).
    A preamendments device that has been classified into class III may 
be marketed, by means of premarket notification procedures, without 
submission of a premarket approval application (PMA) until FDA issues a 
final regulation under section 515(b) of the act (21 U.S.C. 360e(b)) 
requiring premarket approval.
    Reclassification of postamendments devices is governed by section 
513(f)(3) of the act, formerly section 513(f)(2) of the act. This 
section provides that FDA may initiate the reclassification of a device 
classified into class III under section 513(f)(1) of the act, or the 
manufacturer or importer of a device may petition the Secretary of 
Health and Human Services (the Secretary) for the issuance of an order 
classifying the device in class I or class II. FDA's regulations in 
Sec.  860.134 (21 CFR 860.134) set forth the procedures for the filing 
and review of a petition for reclassification of such class III 
devices. In order to change the classification of the device, it is 
necessary that the proposed new class have sufficient regulatory 
controls to provide reasonable assurance of the safety and 
effectiveness of the device for its intended use.
    The FDAMA added a new section 513(f)(2) to the act which addresses 
classification of postamendments devices. New section 513(f)(2) of the 
act

[[Page 5826]]

provides that, upon receipt of a ``not substantially equivalent'' 
determination, a 510(k) applicant may request FDA to classify a 
postamendments device into class I or class II. Within 60 days from the 
date of such a written request, FDA must classify the device by written 
order. If FDA classifies the device into class I or II, the applicant 
has then received clearance to market the device and it can be used as 
a predicate device for other 510(k)s. It is expected that this process 
will be used for low risk devices. This process does not apply to 
devices that have been classified by regulation into class III, i.e., 
preamendments class III devices, or class III devices for which a PMA 
is appropriate.
    Under section 513(f)(3)(B)(i) of the act, formerly section 
513(f)(2)(B)(i) of the act, the Secretary may, for good cause shown, 
refer a petition to a device classification panel. If a petition is 
referred to a panel, the panel shall make a recommendation to the 
Secretary respecting approval or denial of the petition. Any such 
recommendation shall contain: (1) A summary of the reasons for the 
recommendation, (2) a summary of the data upon which the recommendation 
is based, and (3) an identification of the risks to health (if any) 
presented by the device with respect to which the petition was filed.

II. Recommendation of the Panel

    On July 2, 1997, FDA filed the reclassification petition submitted 
by BioMerieux Vitek, Inc., requesting reclassification of the fully 
automated short-term incubation cycle antimicrobial susceptibility 
devices from class III to class II. FDA consulted with the Microbiology 
Devices Panel (the panel). During an open public meeting on February 
13, 1998, the panel unanimously recommended that FDA reclassify the 
fully automated short-term incubation cycle antimicrobial 
susceptibility device for use in determining in vitro susceptibility of 
bacterial pathogens isolated from clinical specimens from class III to 
class II. The panel identified the risks to health regarding use of 
this device as the reporting of erroneous results, citing that 
insufficient testing of each unique antimicrobial agent with an 
inappropriate clinical and challenge organism, the use of an 
uncalibrated inoculum, or a nonstandardized acceptable error endpoint 
can result in such erroneous reports.
    FDA considered the panel's recommendations and tentatively agreed 
that the generic type of device, the fully automated short-term 
incubation cycle antimicrobial susceptibility device for use in 
determining in vitro susceptibility of bacterial pathogens isolated 
from clinical specimens, be reclassified from class III to class II. 
Subsequently, in the Federal Register of March 8, 2000 (65 FR 12268), 
FDA issued a notice of the panel's recommendation for public comment.
    After reviewing the information in the petition and presenting it 
before the panel, and after considering the panel's recommendation and 
the comments received in response to the notice of panel 
recommendation, FDA issued an order to the petitioner on December 28, 
2001, reclassifying the fully automated short-term incubation cycle 
antimicrobial susceptibility device and substantially equivalent 
devices of this generic type, from class III to class II with the 
implementation of special controls. The special control applicable to 
this generic type of device is a guidance document entitled ``Class II 
Special Controls Guidance Document: Antimicrobial Susceptibility Test 
(AST) Systems; Guidance for Industry and FDA.'' FDA has identified the 
administration of an inappropriate antimicrobial agent to the patient 
as the risk to health associated with use of this device. The guidance 
document contains sections that discuss the use of appropriate 
challenge strains; standardized preparation of inoculum; the 
application of ``acceptable error'' as a range with confidence 
intervals; and appropriate clinical performance testing. In this way, 
the guidance will minimize the sources of erroneous reporting 
associated with the fully automated short-term incubation cycle 
antimicrobial susceptibility device. Testing and labeling 
recommendations are also discussed in the guidance document and also 
help manufacturers address the risk to health. Following the effective 
date of this final classification rule, any firm submitting a 510(k) 
premarket notification for a fully automated short-term incubation 
cycle antimicrobial susceptibility device will need to address the 
issues covered in the special control guidance. However, the firm need 
only show that its device meets the recommendations of the guidance or 
in some other way provides equivalent assurances of safety and 
effectiveness.
    Accordingly, as required by Sec.  860.134(b)(6) and (b)(7) of the 
regulations, FDA is announcing the reclassification of the fully 
automated short-term incubation cycle antimicrobial susceptibility 
device from class III into class II. FDA is codifying the 
reclassification and the special control guidance by adding new Sec.  
866.1645. For the convenience of the reader, FDA is also adding a new 
Sec.  866.1(e) to inform the reader where to find guidance documents 
referenced in 21 CFR part 866.

III. Environmental Impact

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

IV. Analysis of Impacts

    FDA has examined the impacts of the notice under Executive Order 
12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and the 
Unfunded Mandates Reform Act of 1995 (Public Law 104-4)). Executive 
Order 12866 directs 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 final rule is consistent with the regulatory philosophy and 
principles identified in the Executive order. In addition, the final 
rule is not a significant regulatory action as defined by the Executive 
order and so is not subject to review under the Executive order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Reclassification of the device from class III to 
class II will relieve all manufacturers of the device of the cost of 
complying with the premarket approval requirements in section 515 of 
the act. Because reclassification will reduce regulatory costs with 
respect to this device, it will impose no significant economic impact 
on any small entities, and it may permit small potential competitors to 
enter the marketplace by lowering their costs. The agency therefore 
certifies that this rule will not have a significant economic impact on 
a substantial number of small entities. In addition, this rule will not 
impose costs of $110 million or more on either the private sector or 
State, local, and tribal governments in the aggregate, and therefore a 
summary statement or analysis pursuant to section 202(a) of the 
Unfunded Mandates Reform Act of 1995 is not required.

V. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth

[[Page 5827]]

in Executive Order 13132. FDA has determined that the rule does not 
contain policies that have substantial direct effects on the States, on 
the relationship between the National Government and the States, or on 
the distribution of power and responsibilities among the various levels 
of government. Accordingly, the agency has concluded that the rule does 
not contain policies that have federalism implications as defined in 
the order and, consequently, a federalism summary impact statement is 
not required.

VI. Paperwork Reduction Act of 1995

    This final rule contains no collections of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

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 866.1 is amended by adding paragraph (e) to read as 
follows:


Sec.  866.1  Scope.

* * * * *
    (e) Guidance documents referenced in this part are available on the 
Internet at http:www.fda.gov/cdrh.guidance.html.
    3. Section 866.1645 is added to subpart B to read as follows:


Sec.  866.1645  Fully automated short-term incubation cycle 
antimicrobial susceptibility system.

    (a) Identification. A fully automated short-term incubation cycle 
antimicrobial susceptibility system is a device that incorporates 
concentrations of antimicrobial agents into a system for the purpose of 
determining in vitro susceptibility of bacterial pathogens isolated 
from clinical specimens. Test results obtained from short-term (less 
than 16 hours) incubation are used to determine the antimicrobial agent 
of choice to treat bacterial diseases.
    (b) Classification. Class II (special controls). The special 
control for this device is FDA's guidance document entitled ``Class II 
Special Controls Guidance Document: Antimicrobial Susceptibility Test 
(AST) Systems; Guidance for Industry and FDA.''

    Dated: January 9, 2003.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 03-2656 Filed 2-4-03; 8:45 am]
BILLING CODE 4160-01-S