[Federal Register Volume 69, Number 91 (Tuesday, May 11, 2004)]
[Rules and Regulations]
[Pages 26036-26038]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-10592]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2004P-0126]


Medical Devices; Immunology and Microbiology Devices; 
Classification of the Immunomagnetic Circulating Cancer Cell Selection 
and Enumeration System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying the 
Immunomagnetic Circulating Cancer Cell Selection and Enumeration System 
device 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: Immunomagnetic Circulating Cancer 
Cell Selection and Enumeration System.'' The agency is taking this 
action in response to a petition submitted under the Federal Food, 
Drug, and Cosmetic Act (the act) as amended by the Medical Device 
Amendments of 1976 (the amendments), the Safe Medical Devices Act of 
1990 (the SMDA), the Food and Drug Administration Modernization Act of 
1997 (FDAMA), and the Medical Device User Fee and Modernization Act of 
2002 (MDUFMA). The agency is classifying the device into class II 
(special controls) in order to provide a reasonable assurance of safety 
and effectiveness of the device. Elsewhere in this issue of

[[Page 26037]]

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 is effective June 10, 2004. The classification was 
effective January 21, 2004.

FOR FURTHER INFORMATION CONTACT: Nina Chace, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 301-594-1293, ext. 138.

SUPPLEMENTARY INFORMATION:

I. Background

    In accordance with section 513(f)(1) of 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 amendments, 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 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 (513(f)(2) of the act).
    In accordance with section 513(f)(1) of the act, FDA issued a 
notice on December 24, 2003, classifying the CellSearch Epithelial Cell 
Kit/Cell Spotter Analyzer 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 December 24, 2003, Veridex, LLC, submitted 
a petition requesting classification of the CellSearch Epithelial Cell 
Kit/Cell Spotter Analyzer under section 513(f)(2) of the act. The 
manufacturer recommended that the device be classified into class II 
(Ref. 1).
    In accordance with 513(f)(2) of the act, FDA reviewed the petition 
in order to classify the device under the criteria for classification 
set forth in 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 CellSearch Epithelial Cell Kit/Cell 
Spotter Analyzer 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 immunomagnetic circulating 
cancer cell selection and enumeration system and is identified as a 
device consisting of biological probes, fluorochromes, and other 
reagents; preservation and preparation devices; and a semiautomated 
analytical instrument to select and count circulating cancer cells in a 
prepared sample of whole blood. This device is intended for adjunctive 
use in monitoring or predicting cancer disease progression, response to 
therapy, and for the detection of recurrent disease.
    FDA has identified no direct risks to health when tests are used as 
an aid to monitoring and predicting cancer disease progression and 
response to therapy. However, failure of the test to perform as 
indicated, or an error in interpretation of results, could lead to 
misdiagnosis and improper treatment, improper patient management, 
improper treatment selection and dosing, and failure to identify 
circulating cancer cells. Consequently, FDA has identified the 
following risks to health associated with this type of device: (1) 
False negative, false low cancer cell count; and (2) false positive, 
false high cancer cell count. Therefore, in addition to the general 
controls of the act, the device is subject to special controls, 
identified as the guidance document entitled ``Class II Special 
Controls Guidance Document: Immunomagnetic Circulating Cancer Cell 
Selection and Enumeration System.''
    The class II special controls guidance document provides 
information on how to meet premarket (510(k)) submission requirements 
for the device including recommendations on validation of performance 
characteristics, including software validation; control methods; 
reproducibility; and clinical studies. FDA believes that following the 
class II special controls guidance document addresses the risks to 
health identified in the previous paragraph. Therefore, on January 21, 
2004, FDA issued an order to the petitioner classifying the device into 
class II. FDA is codifying this classification by adding 21 CFR 
866.6020.
    Following the effective date of this final classification rule, any 
firm submitting a 510(k) premarket notification for an immunomagnetic 
circulating cancer cell selection and 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, FDA has 
determined that premarket notification is necessary to provide 
reasonable assurance of safety and effectiveness; therefore, the device 
is not exempt from premarket notification requirements. The device is 
used as an adjunct in monitoring or predicting cancer disease 
progression and response to therapy and for detection of recurrent 
disease. FDA's review of the test's sensitivity, specificity, and 
reproducibility with regard to key performance characteristics, test 
methodology and other relevant performance data, will ensure 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 
immunomagnetic circulating cancer cell selection and enumeration system 
they intend to market.

[[Page 26038]]

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.

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 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 it 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. 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, therefore, certifies 
that the final rule will not have a significant impact on a substantial 
number of small entities. In addition, this final rule will not impose 
costs of $100 million or more on either the private sector or State, 
local, and tribal governments in the aggregate and, therefore, a 
summary statement of analysis under section 202(a) of the Unfunded 
Mandates Reform Act is not required.

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 Veridex, LLC, dated December 24, 2003.

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 866.6020 is added to subpart G to read as follows:


Sec.  866.6020  Immunomagnetic circulating cancer cell selection and 
enumeration system.

    (a) Identification. An immunomagnetic circulating cancer cell 
selection and enumeration system is a device that consists of 
biological probes, fluorochromes, and other reagents; preservation and 
preparation devices; and a semiautomated analytical instrument to 
select and count circulating cancer cells in a prepared sample of whole 
blood. This device is intended for adjunctive use in monitoring or 
predicting cancer disease progression, response to therapy, and for the 
detection of recurrent disease.
    (b) Classification. Class II (special controls). The special 
control for this device is FDA's guidance document entitled ``Class II 
Special Controls Guidance Document: Immunomagnetic Circulating Cancer 
Cell Selection and Enumeration System.'' See Sec.  866.1(e) for 
availability of this guidance document.

    Dated: April 26, 2004.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 04-10592 Filed 5-10-04; 8:45 am]
BILLING CODE 4160-01-S