[Federal Register: March 10, 2005 (Volume 70, Number 46)]
[Rules and Regulations]
[Page 11865-11867]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10mr05-17]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 862
[Docket No. 2005N-0067]
Medical Devices; Clinical Chemistry and Clinical Toxicology
Devices; Drug Metabolizing Enzyme Genotyping System
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is classifying drug
metabolizing enzyme (DME) genotyping test 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: Drug Metabolizing Enzyme Genotyping System.'' 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 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 April 11, 2005. The classification was
effective December 23, 2004.
FOR FURTHER INFORMATION CONTACT: Courtney Harper, Center for Devices
and Radiological Health (HFZ-440), Food and Drug Administration, 2098
Gaither Rd., Rockville, MD 20850, 240-276-0443, ext. 159.
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 (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 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), request FDA to classify the device under the criteria set
forth in section 513(a)(1). 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 a
notice on December 17, 2004, classifying the Roche Amplichip CYP450
Test (2D6) 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
to a device that was subsequently reclassified into class I or class
II. On December 20, 2004, Roche Molecular Systems, Inc., submitted a
petition requesting classification of the Roche Amplichip CYP450 Test
(2D6) 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). 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 Roche
Amplichip CYP450 Test (2D6) 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 ``drug metabolizing enzyme
genotyping system.'' It is identified as a device intended for use in
testing deoxyribonucleic acid (DNA) extracted from clinical samples to
identify the
[[Page 11866]]
presence or absence of human genotypic markers encoding a DME. This
device is used as an aid in determining treatment choice and
individualizing treatment dose for therapeutics that are metabolized
primarily by the specific enzyme about which the system provides
genotypic information.
FDA has identified the risks to health associated with this type of
device as failure to correctly identify the DME genotype, which could
result in incorrect patient management decisions. In these situations a
patient might be prescribed an incorrect drug or drug dose with
concomitant increased risk of adverse reactions due to increased or
decreased drug metabolism. Likewise, failure to properly interpret
genotyping results could lead to incorrect prediction of phenotype and
result in incorrect patient management decisions. The information
provided by this type of genetic test should only be used to supplement
other tools for therapeutic decisionmaking in conjunction with routine
monitoring by a physician.
The effect that a specific DME allele has on drug metabolism may
vary depending on the specific drug, even for drugs within a specific
class. Effects of specific alleles on drug metabolism are well-
documented for some drugs; for other drugs, they are less well-
documented. Therefore, clinicians should use professional judgment when
interpreting results from this type of test. In addition, results from
this type of assay should not be used to predict a patient's response
to drugs in cases where either (1) the DME activity of the allele has
not been determined or (2) the drug's metabolic pathway has not been
clearly established.
The class II special controls guidance document also provides
information on how to meet premarket (510(k)) submission requirements
for the device, including recommendations on validation of performance
characteristics and labeling. FDA believes that following the class II
special controls guidance document generally addresses the risks to
health identified above. Therefore, on December 23, 2004, FDA issued an
order to the petitioner classifying the device into class II. FDA is
codifying this classification by adding 21 CFR 862.3360.
Following the effective date of this final classification rule, any
firm submitting a 510(k) premarket notification for a DME genotyping
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), 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 to provide reasonable assurance of
safety and effectiveness. FDA review of 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 containing
information on the DME genotyping system before marketing the device.
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 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 $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 Roche Molecular Systems, Inc., dated December
20, 2004.
List of Subjects in 21 CFR Part 862
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
862 is amended as follows:
[[Page 11867]]
PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES
0
1. The authority citation for 21 CFR part 862 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
0
2. Section 862.3360 is added to subpart D to read as follows:
Sec. 862.3360 Drug metabolizing enzyme genotyping system.
(a) Identification. A drug metabolizing enzyme genotyping system is
a device intended for use in testing deoxyribonucleic acid (DNA)
extracted from clinical samples to identify the presence or absence of
human genotypic markers encoding a drug metabolizing enzyme. This
device is used as an aid in determining treatment choice and
individualizing treatment dose for therapeutics that are metabolized
primarily by the specific enzyme about which the system provides
genotypic information.
(b) Classification. Class II (special controls). The special
control is FDA's guidance document entitled ``Class II Special Controls
Guidance Document: Drug Metabolizing Enzyme Genotyping Test System.''
See Sec. 862.1(d) for the availability of this guidance document.
Dated: March 2, 2005.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 05-4762 Filed 3-9-05; 8:45 am]
BILLING CODE 4160-01-S