Medical Devices: Immunology and Microbiology Devices: Classification of In Vitro Human Immunodeficiency Virus Drug Resistance Genotype Assay, 44380-44382 [E7-15475]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 72, Number 152 (Wednesday, August 8, 2007)]
[Rules and Regulations]
[Pages 44380-44382]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-15475]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2007N-0294]


Medical Devices: Immunology and Microbiology Devices: 
Classification of In Vitro Human Immunodeficiency Virus Drug Resistance 
Genotype Assay

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying an in 
vitro human immunodeficiency virus (HIV) drug resistance genotype assay 
into class II (special controls). The special control that will apply 
to this device is the guidance document entitled ``Class II Special 
Controls Guidance Document: In Vitro HIV Drug Resistance Genotype 
Assay.'' FDA is classifying the device into class II (special controls) 
in order to provide a reasonable assurance of safety and effectiveness 
of this device. Elsewhere in this issue of the Federal Register, FDA is 
announcing the availability of the guidance document that will serve as 
the special control for this device.

DATES: This rule becomes effective September 7, 2007. The 
classification of this device into class II became effective on 
September 26, 2001.

FOR FURTHER INFORMATION CONTACT: Nathaniel L. Geary, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 1401 
Rockville Pike, suite 200N, Rockville, MD 20852, 301-827-6210.

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. FDA determines whether new devices are 
substantially equivalent to predicate 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.
    In accordance with section 513(f)(1) of the act, FDA issued an 
order on June 27, 2001, classifying into class III the

[[Page 44381]]

Visible Genetics, Inc., TRUEGENE HIV Genotyping Kit and OpenGene DNA 
Sequencing System, because this device 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 
to a device which was subsequently reclassified into class I or class 
II. On July 11, 2001, Visible Genetics, Inc. submitted to FDA a 
petition requesting classification of the TRUEGENE HIV Genotyping Kit 
and OpenGene DNA Sequencing System under section 513(f)(2) of the act. 
The manufacturer recommended that the device be classified into class 
II (Ref. 1).
    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 Visible 
Genetics, Inc., TRUEGENE HIV Genotyping Kit and OpenGene DNA Sequencing 
System can be classified in class II with the establishment of special 
controls. FDA believes that special controls, in addition to general 
controls, are adequate to provide reasonable assurance of the safety 
and effectiveness of this device and that there is sufficient 
information to establish special controls to provide such assurance.
    This device is assigned the generic name, ``In vitro HIV drug 
resistance genotype assay.'' It is identified as an in vitro diagnostic 
device to be used to detect HIV genomic mutations that confer 
resistance to specific types of antiretroviral drugs, as an aid in 
monitoring and treating HIV infection.
    FDA has identified the risks to health associated with the use of 
the in vitro HIV drug resistance genotype assay. These risks include 
inaccurate detection of resistance mutations present in a patient's 
viral swarm that can result in continuance of therapies that are no 
longer appropriate, or changes to new, inadequate therapies. In both 
cases, the patient's viral load may increase, worsening the clinical 
prognosis and accelerating the development of drug resistant viruses. 
Patients may be needlessly subjected to serious, deleterious side 
effects of inappropriate antiviral drugs. Furthermore, failure of the 
assay to give any results at all (sequence failure) can deny or delay 
beneficial, appropriate therapies, which may also result in high viral 
loads and their attendant morbidity.
    FDA believes that the class II special controls guidance document 
will aid in mitigating the potential risks to health by providing 
recommendations on performance characteristics; other considerations 
such as design controls, statistical methods, and instruments and 
software; product modification; and labeling. The guidance document 
also provides recommendations for fulfilling the premarket (510(k)) 
submission requirements for this device. FDA believes that the class II 
special controls guidance document, in addition to general controls, 
addresses the risks to health identified in the previous paragraph and 
provides reasonable assurance of the safety and effectiveness of the in 
vitro HIV drug resistance assay. Therefore, on September 26, 2001, FDA 
issued an order to the petitioner classifying the device into class II. 
FDA is codifying this device classification at 21 CFR 866.3950.
    Following the effective date of this final classification rule, 
manufacturers submitting a 510(k) premarket notification for an in 
vitro HIV drug resistance genotype assay will need to address the 
issues covered in the special controls guidance. However, the 
manufacturer 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. FDA has determined that premarket 
notification is necessary to provide reasonable assurance of the safety 
and effectiveness of this type of device and, therefore, this type of 
device is not exempt from premarket notification requirements. Persons 
who intend to market this type of device must submit to FDA a premarket 
notification, before marketing the device, which contains information 
about the in vitro HIV drug resistance genotype assay they intend to 
market.

II. 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 this device 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 $122 million, using the most current (2005) 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

III. 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.

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

[[Page 44382]]

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 (OMB) under the 
Paperwork Reduction Act (PRA) of 1995 is not required. Elsewhere in 
this issue of the Federal Register, FDA is publishing a notice 
announcing the availability of the guidance document entitled ``Class 
II Special Controls Guidance Document: In Vitro HIV Drug Resistance 
Genotype Assay.'' FDA concludes that the special controls guidance 
document contains information collection provisions that are subject to 
review by the OMB under the PRA and that have been approved by OMB in 
accordance with the PRA under the regulations governing premarket 
notification submissions (part 807, subpart E, OMB control number 0910-
0120).

VI. References

    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 Visible Genetics, Inc., dated July 11, 2001.

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.

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2. Add Sec.  866.3950 to subpart D to read as follows:


Sec.  866.3950  In vitro human immunodeficiency virus (HIV) drug 
resistance genotype assay.

    (a) Identification. The in vitro HIV drug resistance genotype assay 
is a device that consists of nucleic acid reagent primers and probes 
together with software for predicting drug resistance/susceptibility 
based on results obtained with these primers and probes. It is intended 
for use in detecting HIV genomic mutations that confer resistance to 
specific antiretroviral drugs, as an aid in monitoring and treating HIV 
infection.
    (b) Classification. Class II (special controls). The special 
control for this device is FDA's guidance document entitled ``Class II 
Special Controls Guidance Document: In Vitro HIV Drug Resistance 
Genotype Assay.'' See Sec.  866.1(e) for the availability of this 
guidance document.

    Dated: August 2, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-15475 Filed 8-7-07; 8:45 am]
BILLING CODE 4160-01-S