[Federal Register: August 25, 2005 (Volume 70, Number 164)]
[Rules and Regulations]
[Page 49862-49864]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25au05-5]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 866
[Docket No. 2005N-0263]
Medical Devices; Immunology and Microbiology Devices;
Classification of Ribonucleic Acid Preanalytical Systems
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is classifying
ribonucleic acid (RNA) preanalytical 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: RNA Preanalytical Systems (RNA Collection, Stabilization, and
Purification Systems for RT-PCR Used in Molecular Diagnostic
Testing).'' 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 announcing the availability of a guidance document
that will serve as the special control for the device.
DATES: This rule is effective September 26, 2005. The classification
was effective April 18, 2005.
FOR FURTHER INFORMATION CONTACT: Uwe Scherf, Center for Devices and
Radiological Health (HFZ-440), Food and Drug Administration, 2098
Gaither Rd., Rockville, MD 20850, 240-276-0496.
SUPPLEMENTARY INFORMATION:
I. What is the Background of this Rulemaking?
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 previous 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 (section 513(f)(2) of the act).
In accordance with section 513(f)(1) of the act, FDA issued an
order on February 18, 2005, classifying the PAXgene\TM\ Blood RNA
System into 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 February 28, 2005, PreAnalytiX GmbH, c/o Becton, Dickinson and Co.,
submitted a petition requesting classification of the PAXgene\TM\ Blood
RNA System under section 513(f)(2) of the act. The manufacturer
recommended that the device be classified into class II.
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 PAXgene\TM\ Blood RNA System can be
classified into class II with the establishment of special controls.
FDA believes these special controls will provide reasonable assurance
of the safety and effectiveness of the device.
The device is assigned the generic name RNA Preanalytical Systems
and it is identified as a device intended to collect, store, and
transport patient specimens, and stabilize intracellular RNA from the
specimens, for subsequent isolation and purification of the
intracellular RNA for reverse transcriptase polymerase chain reaction
(RT-PCR) used in in vitro molecular diagnostic testing. The device may
consist of sample collection devices, nucleic acid isolation and
purification reagents, and processing reagents/equipment (tubes,
columns, etc.). It also may contain instruments for automation of the
nucleic acid isolation and purification steps.
FDA has identified the following risks to health associated
specifically with this type of device: (1) Inaccurate results and
improper patient management, (2) delay in diagnosis, and (3) a need for
patient specimen recollection.
Failure of the system during specimen collection, or during RNA
stabilization or purification could yield an RNA sample of low quality
and quantity. Low quality RNA, when tested, could result in falsely low
or falsely high RNA transcript signal levels leading to inaccurate
diagnosis and/or improper patient management. Low quantity of RNA could
render the samples unusable for downstream RT-PCR applications;
specimens would need to be recollected, causing possible delay in
diagnosis. In addition, depending on specimen type, recollection could
pose additional patient risk (e.g., tissue biopsy). The degree of risk
varies depending on the disease or condition/stage being diagnosed or
managed. Results of RNA testing should always be considered in
conjunction with other clinical factors.
[[Page 49863]]
FDA believes that the class II special controls guidance document
aids in mitigating the potential risks to health by providing
recommendations on validation of performance characteristics, including
RNA stability, purity, integrity, yield, repeatability,
reproducibility, and suitability for use in RT-PCR assays. The guidance
document also provides information on how to meet premarket (510(k))
submission requirements for the device. FDA believes that the special
controls guidance document, in addition to general controls, addresses
the risks to health identified previously and provides reasonable
assurance of the safety and effectiveness of the device. Therefore, on
April 18, 2005, FDA issued an order to the petitioner classifying the
device into class II. FDA is codifying this device by adding Sec.
866.4070.
Following the effective date of this final classification rule, any
firm submitting a 510(k) premarket notification for an RNA
preanalytical 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 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 the safety
and effectiveness of the device and, therefore, the 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, prior to marketing the device, which contains information
about the RNA Preanalytical Systems they intend to market.
II. What is the Environmental Impact of This Rule?
The agency has determined under 21 CFR 25.34(b) that this action is
of 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. What is the Economic Impact of This Rule?
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 economic 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. How Does This Rule Comply With the 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. What References Are on Display?
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 PreAnalytiX GmbH, c/o Becton, Dickinson and Co.,
dated February 28, 2005.
List of Subjects in 21 CFR Part 866
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 866.4070 is added to subpart E to read as follows:
Sec. 866.4070 RNA Preanalytical Systems.
(a) Identification. RNA Preanalytical Systems are devices intended
to collect, store, and transport patient specimens, and stabilize
intracellular RNA from the specimens, for subsequent isolation and
purification of the intracellular RNA for RT-PCR used in in vitro
molecular diagnostic testing.
(b) Classification. Class II (special controls). The special
control is FDA's guidance document entitled ``Class II Special Controls
Guidance Document: RNA Preanalytical Systems (RNA Collection,
Stabilization and Purification System for RT-PCR Used in Molecular
Diagnostic Testing).'' See Sec. 866.1(e) for the availability of this
guidance document.
[[Page 49864]]
Dated: August 9, 2005.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 05-16914 Filed 8-24-05; 8:45 am]
BILLING CODE 4160-01-S