[Federal Register Volume 70, Number 55 (Wednesday, March 23, 2005)]
[Rules and Regulations]
[Pages 14532-14534]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-5643]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2005N-0081]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Automated Fluorescence in situ Hybridization 
Enumeration Systems

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying 
automated fluorescence in situ hybridization (FISH) enumeration systems 
into class II (special controls). The special control that will apply 
to the device is the guidance document entitled ``Class II Special 
Controls Guidance Document: Automated Fluorescence in situ 
Hybridization (FISH) Enumeration Systems.'' The agency is classifying 
the device into class II (special controls) in order to provide a 
reasonable assurance of safety

[[Page 14533]]

and effectiveness of the device. Elsewhere in this issue of the Federal 
Register, FDA is publishing a notice of availability of a guidance 
document that is the special control for this device.

DATES: This rule becomes effective April 22, 2005. The classification 
was effective December 13, 2004.

FOR FURTHER INFORMATION CONTACT: Maria Chan, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 240-276-0493, ext. 130.

SUPPLEMENTARY INFORMATION:

I. Background

    In accordance with section 513(f)(1) of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 360c(f)(1)), devices that were not in 
commercial distribution before May 28, 1976, the date of enactment of 
the Medical Device Amendments of 1976, generally referred to as 
postamendments devices, are classified automatically by statute into 
class III without any FDA rulemaking process. These devices remain in 
class III and require premarket approval, unless and until the device 
is classified or reclassified into class I or II, or FDA issues an 
order finding the device to be substantially equivalent, in accordance 
with 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 marketed devices by means of 
premarket notification procedures in section 510(k) of the act (21 
U.S.C. 360(k)) and part 807 (21 CFR part 807) of FDA's regulations.
    Section 513(f)(2) of the act provides that any person who submits a 
premarket notification under section 510(k) of the act for a device 
that has not previously been classified may, within 30 days after 
receiving an order classifying the device in class III under section 
513(f)(1) of the act, request FDA to classify the device under the 
criteria set forth in section 513(a)(1) of the act. FDA shall, within 
60 days of receiving such a request, classify the device by written 
order. This classification shall be the initial classification of the 
device. Within 30 days after the issuance of an order classifying the 
device, FDA must publish a notice in the Federal Register announcing 
such classification (section 513(f)(2) of the act).
    In accordance with section 513(f)(1) of the act, FDA issued an 
order on October 1, 2004, classifying the VYSIS AUTOVYSION SYSTEM in 
class III, because it was not substantially equivalent to a device that 
was introduced or delivered for introduction into interstate commerce 
for commercial distribution before May 28, 1976, or a device which was 
subsequently reclassified into class I or class II. On October 13, 
2004, Vysis, Inc. submitted a petition requesting classification of the 
VYSIS AUTOVYSION SYSTEM under section 513(f)(2) of the act. The 
manufacturer recommended that the device be classified into class II.
    In accordance with section 513(f)(2) of the act, FDA reviewed the 
petition in order to classify the device under the criteria for 
classification set forth in section 513(a)(1) of the act. Devices are 
to be classified into class II if general controls, by themselves, are 
insufficient to provide reasonable assurance of safety and 
effectiveness, but there is sufficient information to establish special 
controls to provide reasonable assurance of the safety and 
effectiveness of the device for its intended use. After review of the 
information submitted in the petition, FDA determined that the VYSIS 
AUTOVYSION SYSTEM can be classified in class II with the establishment 
of special controls. FDA believes these special controls, in addition 
to general controls, will provide reasonable assurance of safety and 
effectiveness of the device.
    The device is assigned the generic name automated FISH enumeration 
system. It is identified as a device that consists of an automated 
scanning microscope, image analysis system, and customized software 
applications for FISH assays. This device is intended for in vitro 
diagnostic use with FISH assays as an aid in the detection, counting, 
and classification of cells based on recognition of cellular color, 
size, and shape, and in the detection and enumeration of FISH signals 
in interphase nuclei of formalin-fixed, paraffin-embedded human tissue 
specimens.
    FDA has identified the risks to health associated with this type of 
device as inaccurate results that could lead to improper patient 
management. Improper patient management, which includes misdiagnosis 
and improper treatment, could result from failure of the test to 
perform as indicated or error in interpretation of results. A falsely 
low fluorescence signal count, or false negative, could contribute to a 
delay in detecting the disease, disease recurrence, disease prognosis, 
or a false indication of response to therapy. A falsely high 
fluorescence signal count, or false positive, could contribute to 
unnecessary monitoring, inappropriate treatment decisions, or failure 
to treat adequately. In addition, use of assay results to adjust a 
treatment regimen without consideration of other clinical factors could 
pose a risk.
    The class II special controls guidance document aids in mitigating 
potential risks by providing recommendations on validation of 
performance characteristics, including software validation; control 
methods; reproducibility; and clinical studies. The guidance document 
also provides information on how to meet premarket (510(k)) submission 
requirements for the device. FDA believes that following the class II 
special controls guidance document generally addresses the risks to 
health identified in the previous paragraph. Therefore, on December 13, 
2004, FDA issued an order to the petitioner classifying the device into 
class II. FDA is codifying this classification by adding Sec.  
866.4700.
    Following the effective date of this final classification rule, any 
firm submitting a 510(k) premarket notification for an automated FISH 
enumeration system will need to address the issues covered in the 
special controls guidance. However, the firm need only show that its 
device meets the recommendations of the guidance, or in some other way 
provides equivalent assurance of safety and effectiveness.
    Section 510(m) of the act provides that FDA may exempt a class II 
device from the premarket notification requirements under section 
510(k) of the act, if FDA determines that premarket notification is not 
necessary to provide reasonable assurance of the safety and 
effectiveness of the device. For this type of device, however, FDA has 
determined that premarket notification is necessary because FDA's 
review of the system's key performance characteristics, test 
methodology and labeling to satisfy requirements of Sec.  807.87(e), 
will provide reasonable assurance that acceptable levels of performance 
for both safety and effectiveness will be addressed before marketing 
clearance. Thus, persons who intend to market this type of device must 
submit to FDA a premarket notification, prior to marketing the device, 
which contains information about the automated FISH enumeration system 
they intend to market.

II. Environmental Impact

    The agency has determined under 21 CFR 25.34(b) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

[[Page 14534]]

III. Analysis of Impacts

    FDA has examined the impacts of the final rule 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 not a significant regulatory action 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. Because classification of these devices into class 
II will relieve manufacturers of the device of the cost of complying 
with the premarket approval requirements of section 515 of the act (21 
U.S.C. 360e), and may permit small potential competitors to enter the 
marketplace by lowering their costs, the agency certifies that the 
final rule will not have a significant 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 $115 million, using the most current (2003) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.

IV. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth 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 Executive order and, consequently, a 
federalism summary impact statement is not required.

V. 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.

VI. Reference

    The following reference has been placed on display in the Division 
of Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. Petition from Vysis, Inc., dated October 13, 2004.

List of Subjects in 21 CFR Part 866

    Biologics, Laboratories, Medical devices.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
866 is amended as follows:

PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES

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

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

0
2. Section 866.4700 is added to subpart E to read as follows:


Sec.  866.4700  Automated fluorescence in situ hybridization (FISH) 
enumeration systems.

    (a) Identification. An automated FISH enumeration system is a 
device that consists of an automated scanning microscope, image 
analysis system, and customized software applications for FISH assays. 
This device is intended for in vitro diagnostic use with FISH assays as 
an aid in the detection, counting and classification of cells based on 
recognition of cellular color, size, and shape, and in the detection 
and enumeration of FISH signals in interphase nuclei of formalin-fixed, 
paraffin-embedded human tissue specimens.
    (b) Classification. Class II (special controls). The special 
control is FDA's guidance document entitled ``Class II Special Controls 
Guidance Document: Automated Fluorescence in situ Hybridization (FISH) 
Enumeration Systems.'' See Sec.  866.1(e) for the availability of this 
guidance document.

    Dated: March 10, 2005.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 05-5643 Filed 3-22-05; 8:45 am]
BILLING CODE 4160-01-S