[Federal Register Volume 75, Number 187 (Tuesday, September 28, 2010)]
[Proposed Rules]
[Pages 59670-59672]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-23639]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. FDA-2010-N-0429]


Immunology and Microbiology Devices; Reclassification of the 
Herpes Simplex Virus Serological Assay Device

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
the special controls for the herpes simplex virus (HSV) serological 
assay device type, which is classified as class II (special controls). 
These device types are devices that consist of antigens and antisera 
used in various serological tests to identify antibodies to herpes 
simplex virus in serum, and the devices that consist of herpes simplex 
virus antisera conjugated with a fluorescent dye (immunofluorescent 
assays) used to identify herpes simplex virus directly from clinical 
specimens or tissue culture isolates derived from clinical specimens. 
Elsewhere in this issue of the Federal Register, FDA is announcing the 
availability of the revised draft guidance document entitled ``Class II 
Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 
Serological Assays'' that would serve as the special control for the 
device, if FDA amends the special controls. Because FDA is proposing to 
amend the special control for this device type, the agency is 
publishing the proposed rule that designates the revised guidance 
document as the special control for HSV serological devices.

DATES: Submit written or electronic comments on the proposed rule by 
November 29, 2010.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2010-
N-0429, by any of the following methods, except that comments on 
information collection issues under the Paperwork Reduction Act of 1995 
must be submitted to the Office of Regulatory Affairs, Office of 
Management and Budget (OMB) (see the ``Paperwork Reduction Act of 
1995'' section of this document).
Electronic Submissions
    Submit electronic comments in the following way:
    <bullet> Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
Written Submissions
    Submit written submissions in the following ways:
    <bullet> FAX: 301-827-6870.
    <bullet> Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of comments, FDA is no longer 
accepting comments submitted to the agency by email. FDA encourages you 
to continue to submit electronic comments by using the Federal 
eRulemaking Portal, as described previously, in the ADDRESSES portion 
of this document under Electronic Submissions.
    Instructions: All submissions received must include the agency name 
and Docket No(s). and Regulatory Information Number (RIN) (if a RIN 
number has been assigned) for this rulemaking. All comments received 
may be posted without change to http://www.regulations.gov, including 
any personal information provided. For additional information on 
submitting comments, see the ``Comments'' heading of the SUPPLEMENTARY 
INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.regulations.gov and insert the 
docket number(s), found in brackets in the heading of this document, 
into the ``Search'' box and follow the prompts and/or go to the 
Division of Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, 
MD 20852.

FOR FURTHER INFORMATION CONTACT: Haja Sittana El Mubarak, Center for 
Devices and Radiological Health, Bldg. 66, rm. 5519, Food and Drug 
Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 
301-796-6193.

SUPPLEMENTARY INFORMATION:

I. Regulatory Authorities

    The act (21 U.S.C. 301 et seq.), as amended by the Medical Device 
Amendments of 1976 (the 1976 amendments) (Public Law 94-295), Safe 
Medical Devices Act (SMDA) (Public Law 101-629), Food and Drug 
Administration Modernization Act (FDAMA) (Public Law 105-115), and the 
Medical Device User Fee and Modernization Act (MDUFMA) (Public Law 107-
250), established a comprehensive system for the regulation of medical 
devices intended for human use. Section 513 of the Federal Food, Drug, 
and Cosmetic Act (the FD&C Act) (21 U.S.C. 360c) established three 
categories (classes) of devices, defined

[[Page 59671]]

by the regulatory controls needed to provide reasonable assurance of 
their safety and effectiveness. The three categories of devices are 
class I (general controls), class II (special controls), and class III 
(premarket approval).
    Under section 513 of the FD&C Act, FDA refers to devices that were 
in commercial distribution before May 28, 1976 (the date of enactment 
of the 1976 amendments), as preamendments devices. FDA classifies these 
devices after it takes the following steps: (1) Receives a 
recommendation from a device classification panel (an FDA advisory 
committee); (2) publishes the panel's recommendation for comment, along 
with a proposed regulation classifying the device; and (3) publishes a 
final regulation classifying the device. FDA has classified most 
preamendments devices under these procedures.
    Devices that were not in commercial distribution before May 28, 
1976, generally referred to as postamendments devices are classified 
automatically by statute (section 513(f) of the FD&C Act) into class 
III without any FDA rulemaking process. Those devices remain in class 
III until FDA does the following: (1) Reclassifies the device into 
class I or II; (2) issues an order classifying the device into class I 
or II in accordance with section 513(f)(2) of the FD&C Act; or (3) 
issues an order finding the device to be substantially equivalent, in 
accordance with section 513(i) of the FD&C Act, to a legally marketed 
device that has been classified into class I or class II. 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 FD&C Act (21 U.S.C. 360(k)) and 21 
CFR part 807 of the regulations.
    Under the 1976 amendments, class II devices were defined as devices 
for which there was insufficient information to show that general 
controls themselves would provide reasonable assurance of safety and 
effectiveness, but for which there was sufficient information to 
establish performance standards to provide such assurance. SMDA 
broadened the definition of class II devices to mean those devices for 
which the general controls by themselves are insufficient to provide 
reasonable assurance of safety and effectiveness, but for which there 
is sufficient information to establish special controls to provide such 
assurance, including performance standards, postmarket surveillance, 
patient registries, development and dissemination of guidelines, 
recommendations, and any other appropriate actions the Agency deems 
necessary (section 513(a)(1)(B) of the FD&C Act).

II. Regulatory Background of the Device

    In the Federal Register of April 3, 2007 (72 FR 15830), FDA 
published a final rule to reclassify HSV 1 and 2 serological assays 
into class II. These assays are used as an aid in the clinical 
laboratory diagnosis of diseases caused by HSV 1 and 2. FDA identified 
the guidance document entitled ``Class II Special Controls Guidance 
Document: Herpes Simplex Virus Types 1 and 2 Serological Assays'' as 
the special control.

III. Summary of the Reasons for Revising Special Controls

    FDA believes that the special controls for HSV 1 and 2 serological 
assays should be revised because the new special controls, in addition 
to general controls, would provide reasonable assurance of the safety 
and effectiveness of the device. FDA believes there is sufficient 
additional safety and efficacy profile information to justify revising 
the special controls to better provide such assurance. We have revised 
the existing guidance by rewriting the method comparison section and 
the sample selection inclusion and exclusion criteria section. The 
revisions defined and differentiated the required studies and the study 
populations for the assessment of the safety and effectiveness of the 
different types of HSV 1 and HSV 2 serological assays. Additionally, we 
made several corrections and clarifications throughout the document to 
ensure accuracy, consistency, and ease of reading.

IV. Special Controls

    In addition to general controls, FDA believes that the revised 
draft guidance document entitled ``Class II Special Controls Guidance 
Document: Herpes Simplex Virus Types 1 and 2 Serological Assays'' (the 
class II special controls guidance document) is a special control that 
is adequate to address the risks to health associated with the use of 
the device. FDA believes that the revised class II special controls 
guidance document, which incorporates voluntary consensus standards and 
describes labeling recommendations, in addition to general controls, 
provides reasonable assurance of the safety and effectiveness of the 
device. Elsewhere in this issue of the Federal Register, FDA is 
publishing a notice of availability of the revised draft class II 
special controls guidance document that the Agency would use as the 
special control for this device.
    The revised draft class II special controls guidance document sets 
forth the information FDA believes should be included in premarket 
notification submissions (510(k)s) for HSV 1 and 2 serological assays. 
FDA believes that addressing these risks to health in a 510(k) in the 
manner identified in the revised class II special controls guidance 
document, or in an acceptable alternative manner, is necessary to 
provide reasonable assurance of the safety and effectiveness of the 
device.

V. FDA's Findings

    As discussed previously in this document, FDA believes HSV 1 and 2 
serological assays should be classified into class II because special 
controls, in addition to general controls, provide reasonable assurance 
of the safety and effectiveness of the device and because there is 
sufficient information to establish special controls to provide such 
assurance. FDA, therefore, is proposing to establish the revised draft 
class II special controls guidance document as a special control for 
the device.
    Section 510(m) of the FD&C Act provides that a class II device may 
be exempt from the premarket notification requirements under section 
510(k) of the FD&C Act, if the Agency determines that premarket 
notification is not necessary to provide reasonable assurance of the 
safety and effectiveness of the device. For this device, FDA believes 
that premarket notification is necessary to provide reasonable 
assurance of safety and effectiveness and, therefore, does not intend 
to exempt the device from the premarket notification requirements.

VI. Effective Date

    FDA proposes that any final regulation based on this proposal 
become effective 30 days after its date of publication in the Federal 
Register.

VII. Environmental Impact

    The agency has determined under 21 CFR 25.34(b) that this proposed 
reclassification 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.

VIII. Analysis of Impacts

    FDA has examined the impacts of the proposed 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

[[Page 59672]]

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 proposed rule is not a significant 
regulatory action as defined by 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 the changes to the guidance are minimal, the 
Agency proposes to certify 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 $135 million, using the most current (2009) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
proposed rule to result in any 1-year expenditure that would meet or 
exceed this amount.
    The changes to the guidance include adding specific recommendations 
on appropriate comparators for tests for antibodies and antigens, as 
well as recommendations for sample selection inclusion and exclusion 
criteria to define the target populations for HSV 1 and HSV 2 
serological assays. These recommended changes would increase the 
usefulness of the guidance while imposing a minimal burden.

IX. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. Section 4(a) of the 
Executive order requires agencies to ``construe * * * a Federal statute 
to preempt State law only where the statute contains an express 
preemption provision or there is some other clear evidence that the 
Congress intended preemption of State law, or where the exercise of 
State authority conflicts with the exercise of Federal authority under 
the Federal statute.'' Federal law includes an express preemption 
provision that preempts certain state requirements ``different from or 
in addition to'' certain Federal requirements applicable to devices. 
(See section 521 of the FD&C Act (21 U.S.C. 360k); Medtronic v. Lohr 
518 U.S. 470 (1996); and Riegel v. Medtronic, 128 S. Ct. 999 (2008)). 
If this proposed rule is made final, the special controls established 
by the final rule would create ``requirements'' for specific medical 
devices under 21 U.S.C. 360k, even though product sponsors have some 
flexibility in how they meet those requirements (see Papike v. 
Tambrands, Inc., 107 F.3d 737, 740-742 (9th Cir. 1997)).

X. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no new 
collections of information. Therefore, clearance by OMB under the 
Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-3520) is not 
required.
    This proposed rule designates a revised guidance document as a 
special control. FDA also tentatively concludes that the revised draft 
special control guidance document does not contain new information 
collection provisions that are subject to review and clearance by OMB 
under the PRA. Elsewhere in this issue of the Federal Register, FDA is 
publishing a notice announcing the availability of that revised draft 
guidance document entitled ``Class II Special Controls Guidance 
Document: Herpes Simplex Virus Types 1 and 2 Serological Assays,'' 
which contains an analysis of the paperwork burden for the draft 
guidance.

XI. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed comments. Identify 
comments with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.

List of Subjects in 21 CFR Part 866

    Medical devices.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 866 be amended as follows:

PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES

    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.
    2. Revise Sec.  866.3305 to read as follows:


Sec.  866.3305  Herpes simplex virus serological assays.

    (a) Identification. Herpes simplex virus serological assays are 
devices that consist of antigens and antisera used in various 
serological tests to identify antibodies to herpes simplex virus in 
serum. Additionally, some of the assays consist of herpes simplex virus 
antisera conjugated with a fluorescent dye (immunofluorescent assays) 
used to identify herpes simplex virus directly from clinical specimens 
or tissue culture isolates derived from clinical specimens. The 
identification aids in the diagnosis of diseases caused by herpes 
simplex viruses and provides epidemiological information on these 
diseases. Herpes simplex viral infections range from common and mild 
lesions of the skin and mucous membranes to a severe form of 
encephalitis (inflammation of the brain). Neonatal herpes virus 
infections range from a mild infection to a severe generalized disease 
with a fatal outcome.
    (b) Classification. Class II (special controls). The device is 
classified as class II (special controls). The special control for the 
device is FDA's revised guidance document entitled ``Class II Special 
Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 
Serological Assays.'' For availability of the revised guidance 
document, see Sec.  866.1(e).

    Dated: September 16, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-23639 Filed 9-27-10; 8:45 am]
BILLING CODE 4160-01-S