[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