Immunology and Microbiology Devices; Reclassification of Herpes Simplex Virus (Types 1 and/or 2) Serological Assays, 1399-1403 [06-173]

Agencies

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

[Federal Register Volume 71, Number 5 (Monday, January 9, 2006)]
[Proposed Rules]
[Pages 1399-1403]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 06-173]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2005N-0471]


Immunology and Microbiology Devices; Reclassification of Herpes 
Simplex Virus (Types 1 and/or 2) Serological Assays

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to 
reclassify herpes simplex virus (HSV) (types 1 and/or 2) serological 
assays from class III (premarket approval) to class II (special 
controls). HSV serological assays (types 1 and/or 2) are intended for 
testing specimens from individuals who have signs and symptoms of 
infection consistent with HSV 1 and/or 2 or for determining if an 
individual has been previously infected with HSV 1 and/or 2, as well as 
for providing epidemiological information about these infections. The 
detection of HSV antibodies, in conjunction with other clinical 
laboratory findings, aids in the clinical laboratory diagnosis of an 
infection by HSV 1 and/or 2. FDA is proposing this reclassification on 
its own initiative based on new information. Elsewhere in this issue of 
the Federal Register, FDA is announcing the availability of a draft 
guidance document that would serve as the special control, if FDA 
reclassifies this device.

DATES: Submit written or electronic comments by April 10, 2006.

ADDRESSES: You may submit comments, identified by Docket No. 2005N-
0471, by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following ways:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments.
     Agency Web site: https://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
    Submit written submissions in the following ways:
     FAX: 301-827-6870.
     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 e-mail. FDA encourages 
you to continue to submit electronic comments by using the Federal 
eRulemaking Portal or the agency Web site, as described in the 
Electronic Submissions portion of this paragraph.
    Instructions: All submissions received must include the agency name 
and docket number and regulatory information number (RIN) (if a RIN 
number has been assigned) for this rulemaking. All comments received 
may be posted without change to https://www.fda.gov/ohrms/dockets/
default.htm, including any personal information provided. For detailed 
instructions on submitting comments and additional information on the 
rulemaking process, 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 https://www.fda.gov/ohrms/dockets/default.htm 
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: Sally Hojvat, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither

[[Page 1400]]

Rd., Rockville, MD 20850, 240-276-0496 x114.

SUPPLEMENTARY INFORMATION:

I. Background

A. Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (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), the Safe Medical Devices Act of 1990 
(SMDA) (Public Law 101-629), the Food and Drug Administration 
Modernization Act of 1997 (FDAMA) (Public Law 105-115), and the Medical 
Device User Fee and Modernization Act (Public Law 107-250), established 
a comprehensive system for the regulation of medical devices intended 
for human use. Section 513 of the act (21 U.S.C. 360c) established 
three categories (classes) of devices, defined 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 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 act).
    Under section 513 of the 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 act) into class III 
without any FDA rulemaking process. Those devices remain in class III 
and require premarket approval 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 act, as amended by FDAMA; or (3) issues an order 
finding the device to be substantially equivalent, under section 513(i) 
of the 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 act (21 
U.S.C. 360(k)) and 21 CFR part 807.
    A person may market a preamendments device that has been classified 
into class III through premarket notification procedures, without 
submission of a premarket approval application (PMA), until FDA issues 
a final regulation under section 515(b) of the act (21 U.S.C. 360e(b)) 
requiring premarket approval.
    Section 513(e) of the act governs reclassification of classified 
devices. This section provides that FDA may, by rulemaking, reclassify 
a device based upon ``new information.'' FDA can initiate a 
reclassification under section 513(e) of the act or an interested 
person may petition FDA to reclassify a preamendments device. The term 
``new information,'' as used in section 513(e) of the act, includes 
information developed as a result of a reevaluation of the data before 
the agency when the device was originally classified, as well as 
information not presented, not available, or not developed at that time 
(see, e.g., Holland Rantos v. United States Department of Health, 
Education, and Welfare, 587 F.2d 1173, 1174 n.1 (D.C. Cir. 1978); 
Upjohn v. Finch, 422 F.2d 944 (6th Cir. 1970); Bell v. Goddard, 366 
F.2d 177 (7th Cir. 1966)).
    Reevaluation of the data previously before the agency is an 
appropriate basis for subsequent regulatory action where the 
reevaluation is made in light of newly available regulatory authority 
(see Bell v. Goddard, supra, 366 F.2d at 181; Ethicon, Inc. v. FDA, 762 
F.Supp. 382, 389-91 (D.D.C. 1991)), or in light of changes in ``medical 
science'' (see Upjohn v. Finch, supra, 422 F.2d at 951). Whether data 
before the agency are past or new, the ``new information'' to support 
reclassification under section 513(e) of the act must be ``valid 
scientific evidence,'' as defined in section 513(a)(3) of the act and 
21 CFR 860.7(c)(2) (see, e.g., General Medical Co. v. FDA, 770 F.2d 214 
(D.C. Cir. 1985); Contact Lens Assoc. v. FDA, 766 F.2d 592 (D.C. Cir.), 
cert. denied, 474 U.S. 1062 (1985)).
    FDA relies upon valid scientific evidence in the classification 
process to determine the level of regulation for devices. To be 
considered in the reclassification process, the valid scientific 
evidence upon which the agency relies must be publicly available. 
Publicly available information excludes trade secret and/or 
confidential commercial information, e.g., the contents of a pending 
PMA (see section 520(c) of the act (21 U.S.C. 360j(c)).
    FDAMA added section 510(m) to the act that provides that a class II 
device may be exempted from the premarket notification requirements 
under section 510(k) of the act if the agency determines that premarket 
notification is not necessary to assure the safety and effectiveness of 
the device.

B. Regulatory History of the Device

    In the Federal Register of April 22, 1980 (45 FR 27258), FDA 
published a proposed rule to classify the preamendment HSV serological 
reagents into class II. FDA received three comments on the proposal. 
All three comments expressed concern about the health of newborn 
infants, specifically regarding risks associated with infection with 
HSV. Two comments requested that FDA apply class III controls to this 
device because of these risks to health and because medical 
practitioners would rely on the accuracy of the test results to make 
important clinical decisions, such as whether or not to perform a 
cesarean section delivery of an infant. The third comment urged that, 
before performance standards are established, clinical data be obtained 
that compare the sensitivity and specificity of HSV serological 
reagents with the accuracy of diagnosis of the infection by viral 
culture.
    A final rule classifying HSV devices into class III published in 
the Federal Register of November 9, 1982 (47 FR 50814). The agency 
determined that class III was appropriate because the device presented 
a potential unreasonable risk of illness or injury because failure to 
accurately identify the virus or its antibodies may result in a serious 
risk to the health of the newborn infant. In addition, inaccurate 
results may cause a practitioner to perform an unnecessary cesarean 
section delivery of

[[Page 1401]]

an infant that may result in a serious risk to the health of the 
mother. The agency decided that until standards were established, 
clinical data should be obtained that compare the sensitivity and 
specificity of HSV serological reagents with the accuracy of diagnosis 
of the infection by viral culture. At that time, FDA believed there 
were insufficient data to establish a standard to provide reasonable 
assurance of the safety and effectiveness of the device. FDA also 
changed the scope of the classification to reflect a revised panel 
recommendation and comments received in response to the proposed rule. 
The final rule classified direct fluorescent antibody reagents, as well 
as all reagents employed in more recently developed laboratory methods 
(e.g., enzyme immunoassays) of testing for HSV antibodies in patients' 
serum, into class III.
    In the Federal Register of August 14, 1995 (60 FR 41984 and 60 FR 
41986), FDA published two orders for certain class III devices 
requiring the submission of safety and effectiveness information in 
accordance with the Preamendments Class III Strategy for implementing 
section 515(i) of the act. Each of the orders described in detail the 
format for submitting the type of information required by section 
515(i) of the act so that the information submitted would clearly 
support reclassification or indicate that a device should remain in 
class III. The orders also scheduled the required submissions in groups 
of nine devices at 6-month intervals beginning August 14, 1996. The 
August 14, 1995, orders included the device proposed for 
reclassification in this proposed rule. In response, 11 manufacturers, 
in 16 submissions, submitted information supporting FDA 
reclassification of the device from class III to class II.
    In accordance with sections 513(e) of the act and 21 CFR 
860.130(b)(1), based on new information with respect to the device, 
FDA, on its own initiative, is now proposing to reclassify this device 
from class III to class II when HSV 1 and/or 2 assays are used for the 
following purposes: (1) Testing specimens from individuals who have 
signs and symptoms of infection consistent with HSV 1 and/or 2, (2) 
determining if an individual has been previously infected with HSV 1 
and/or 2, or (3) providing epidemiological information about these 
infections. Additionally, FDA is proposing to modify the description of 
the device to clarify terminology.

C. Device Description

    HSV serological assays are devices that consist of antigens and 
antisera used in various serological tests to identify antibodies to 
HSV in serum. Additionally, some of the assays consist of HSV antisera 
conjugated with a fluorescent dye (immunofluorescent assays) used to 
identify HSV directly from clinical specimens or tissue culture 
isolates derived from clinical specimens. The identification aids in 
the diagnosis of diseases caused by HSV and provides epidemiological 
information on these diseases. HSV 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 mild infection to severe generalized disease with 
a fatal outcome.
    Currently marketed HSV 1 and/or 2 serological assays are usually 
based on manual enzyme-linked immunosorbent assay, enzyme immunoassay, 
immunofluorescence assay, or enzyme-linked virus induction assay. FDA 
has also approved a test based on a chemiluminescent enzyme 
immunoassay. Serological assays typically rely on specific binding of 
specimen antibodies to a fixed HSV antigen, which is then detected by a 
labeled secondary (anti-IgM or anti-IgG) antibody. Serum and plasma are 
the common matrices for currently marketed tests for detecting HSV 1 
and/or 2 antibodies. Antigen detection assays rely on specific binding 
of labeled antibodies to an HSV antigen, which is then detected by a 
reader or immunofluorescent microscope.

II. Proposed Rule

    FDA is proposing to reclassify HSV (types 1 and/or 2) serological 
assays from class III to class II (special controls). These devices are 
used for testing specimens from individuals who have signs and symptoms 
of infection caused by HSV 1 and/or 2, determining if an individual has 
been previously infected with HSV 1 and/or 2, or providing 
epidemiological information about these infections. FDA believes that 
class II with a special controls guidance document will provide 
reasonable assurance of safety and effectiveness. FDA has considered 
HSV (types 1 and/or 2) serological assays in accordance with section 
510(m) of the act and determined that the device does need premarket 
notification to assure the safety and effectiveness of HSV (types 1 
and/or 2) serological assays.
    HSV serological assays of types other than type 1 and/or 2 will 
remain in class III. HSV nucleic acid amplification assays are not 
within the device types classified in 21 CFR 866.3305.
    FDA is also proposing to modify the description of the device by 
replacing the word ``reagents'' with the word ``assays'' to 
differentiate serological assays from replacement reagents and analyte-
specific reagents.

III. Risks to Health

    After considering the information received from the 11 
manufacturers, the published literature, FDA's experience with HSV 1 
and/or 2 serological assays, and the medical device reports filed on 
HSV 1 and/or 2 serological assays, FDA has determined that failure of 
HSV 1 and/or 2 serological assays to perform as indicated, or an error 
in interpretation of results, may lead to improper patient management. 
False positive results may subject pregnant women or a newborn to 
unnecessary treatment with antiviral drugs, which could place both the 
mother and the fetus/infant at risk, or it may lead to an unnecessary 
cesarean delivery of the fetus. False positive results may also lead to 
potentially toxic therapy in immunocompromised patients who may be at 
risk for reactivation of latent herpes virus infection and/or 
disseminated HSV infection. False negative results in pregnant women 
may lead to neonatal transmission of a primary herpes infection during 
vaginal delivery, which may result in life-threatening conditions such 
as encephalitis. False negative results in pretransplant and/or 
immunocompromised populations could falsely identify transplant donors, 
which could lead to the transplant of herpes positive organs to 
nonimmune patients.

IV. Summary of Reasons for Reclassification

    FDA believes that HSV 1 and/or 2 serological assays should be 
reclassified into class II because special controls, in addition to 
general controls, can provide reasonable assurance of the safety and 
effectiveness of the device, and there is now sufficient information to 
establish special controls. FDA review of performance characteristics 
will provide reasonable assurance that acceptable levels of performance 
for both safety and effectiveness are addressed before marketing 
clearance.

V. Summary of Data Upon Which the Reclassification Is Based

    The effectiveness of HSV 1 and/or 2 serological assays has been 
well-established over the past 25 years. The

[[Page 1402]]

sensitivities of these tests for detection of HSV antibodies vary from 
80 percent to 98 percent and the specificities of these assays are 
usually greater than or equal to 95 percent. Technological improvements 
have increased the reliability and performance of these devices for 
clinical sensitivity and specificity. Further information on the 
performance of these assays has been established by comparison with a 
masked, characterized serum panel obtained from the Centers for Disease 
Control and Prevention.
    Based on the available information, FDA believes that the special 
control discussed in section VI of this document is capable of 
providing reasonable assurance of the safety and effectiveness of HSV 
(types 1 and/or 2) serological assays with regard to the identified 
risks to health of this device.

VI. Special Controls

    FDA believes that, in addition to general controls, the class II 
special control guidance document entitled ``Class II Special Controls 
Guidance Document: Herpes Simplex Virus Type 1 and 2 Serological 
Assays'' is adequate to control the risks to health described in 
section III of this document. The class II special controls draft 
guidance provides information on how to meet premarket notification 
requirements for the assays in sections that discuss performance 
characteristics and labeling. The performance characteristics section 
describes studies integral to the demonstration of appropriate 
performance and, in this way, controls against assays that may fail to 
meet current standards. The labeling section addresses factors such as 
directions for use, quality control, and precautions for use and 
interpretation, which will help mitigate errors in the interpretation 
of results. FDA tentatively believes that complying with the act and 
following the recommendations in the draft special controls guidance 
document will provide reasonable assurance of safety and effectiveness 
of these devices and adequately address the risks to health identified 
in section III of this document.
    Elsewhere in this issue of the Federal Register, FDA is announcing 
the availability of a draft guidance document that would serve as the 
special control, if FDA reclassifies these devices. If implemented, 
following the effective date of a final rule classifying the devices, 
any firm submitting a premarket notification under section 510(k) of 
the act for these devices would need to address the issues covered in 
the class II special controls guidance document. However, the firm need 
only show that its device meets the recommendations of the guidance 
document or in some other way provides equivalent assurances of safety 
and effectiveness.

VII. 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.

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 (Pub. L. 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 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, and may 
permit small potential competitors to enter the marketplace by lowering 
their costs, the agency certifies that the proposed 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 
proposed rule to result in any 1-year expenditure that would meet or 
exceed this amount.

IX. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the proposed 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.

X. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no 
collections of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(the PRA) (44 U.S.C. 3501-3520) is not required.
    FDA also tentatively concludes that the special controls guidance 
document identified by this proposed rule 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 the 
draft guidance document entitled ``Class II Special Controls Guidance 
Document: Herpes Simplex Virus Type 1 and 2 Serological Assays''; the 
notice contains an analysis of the paperwork burden for the draft 
guidance.

XI. Comments

    Interested persons may submit to the Division of Dockets Management 
Branch (see ADDRESSES) written or electronic comments regarding this 
document. Submit a single copy of electronic comments or two paper 
copies of any mailed comment, except that individuals may submit one 
paper copy. Comments are to be identified 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.

XII. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 am. and 4 pm., Monday through Friday.
    1. Arvin, A.M. and C.G. Prober, ``Herpes Simplex Viruses,'' 
Manual of Clinical Microbiology, 6th edition, Eds: E.J. Baron,

[[Page 1403]]

M.A. Pfaller, F.C Tenover, and R.H. Yolken, ASM Press, Washington, 
DC, pp. 876-883, 1995.
    2. Ashley, R., ``Herpes Simplex Viruses,'' Diagnostic Procedures 
for Viral, Rickettsial, and Chlamydial Infections, 7th edition, Eds: 
E.H. Lenette, D.A. Lenette, and E.T. Lenette, American Public Health 
Association, Inc., New York, NY, pp. 375-395, 1995.
    3. ``Screening for Genital Herpes Simplex, Recommendation,'' 
Guide to Clinical Preventive Services, 2nd edition, Report of the 
U.S. Preventive Services Task Force, Eds: C. DiGuiseppi, D. Atkins, 
and S.H. Woolf, International Medical Publishing, Alexandria, VA, 
pp. 335-345, 1996.
    4. Prober, C.G., et al., ``The Management of Pregnancies 
Complicated by Genital Infections with Herpes Simplex Virus,'' 
Clinical Infectious Diseases, 15:1031-1038, 1992.
    5. Ashley, R., et al., ``Inability of Enzyme Immunoassays to 
discriminate Between Infections with Herpes Simplex Virus Types 1 
and 2,'' Annals of Internal Medicine, 115:520-526, 1991.
    6. Stewart, J.A., ``Herpes Simplex Virus,'' Manual of Clinical 
Laboratory Immunology, 4th edition, American Society for 
Microbiology, Washington, DC, pp. 554-559, 1992.
    7. Whitley, R.J., ``Herpes Simplex Viruses,'' Fields Virology, 
3rd edition, Eds: B.N. Fields, et al., Lippincott-Raven, 
Philadelphia, PA, pp. 2297-2333, 1996.
    8. Prober, C.G., et al., ``Low Risk of Herpes Simplex Virus 
Infections in Neonates Exposed to the Virus at the Time of Vaginal 
Delivery to Mothers with Recurrent Genital Herpes Simplex Virus 
Infections,'' New England Journal of Medicine, 316(5):240-244, 1987.
    9. Nahmias, A.J., et al., ``Herpes Simplex Viruses 1 and 2,'' 
Viral Infections of Humans--Epidemiology and Control, 3rd edition, 
Eds: A.S. Evans, Plenum Medical Book Co., New York, NY, pp. 393-417, 
1991.
    10. National Committee for Clinical Laboratory Standards, 
``Specifications for Immunological Testing for Infectious Diseases; 
Approved Guideline,'' I/LA18-A, 1994
    11. National Committee for Clinical Laboratory Standards, 
``Statistical Control for Quantitative Measurements: Principles and 
Definitions; Approved Guideline--Second Edition,'' C24-A, 1999.
    12. National Committee for Clinical Laboratory Standards, 
``Assessment of the Clinical Accuracy of Laboratory Tests Using 
Receiver Operating Characteristics (ROC) Plots; Approved Guideline, 
GP10-A, 1995.
    13. National Committee for Clinical Laboratory Standards, 
Evaluation of ``Precision Performance of Clinical Chemistry Devices; 
Approved Guideline,'' EP5-A, 1999.
    14. National Committee for Clinical Laboratory Standards, 
``Molecular Diagnostic Methods for Infectious Diseases; Approved 
Guideline,'' MM3-A, 1995.
    15. FDA Microbiology Branch Guidance Document, ``Review Criteria 
for in vitro Diagnostic Devices for Detection of IgM Antibodies to 
Viral Agents.''
    16. Centers for Disease Control and Prevention, ``HSV IgG Panel 
of Well Characterized Sera (for Device Validation Available From 
CDC).''
    17. ``Case Definitions for Public Health Surveillance,'' 
Morbidity and Mortality Weekly Report, Recommendations and Reports, 
39:RR-13, 1990.
    18. Arkin, C.F. and M.S. Wachtel, ``How Many Patients are 
Necessary to Access Test Performance?'', Journal of the American 
Medical Association, 263:275-278, 1990.
    19. Centers for Disease Control and Prevention, ``Sexually 
Transmitted Diseases Guidelines, Genital Herpes Simplex Virus 
Infections,'' Morbidity and Mortality Weekly Report, 51:RR-6, 2002.
    20. Brown, Z.A., et al. ``Effect of Serologic Status and 
Cesarean Delivery on Transmission Rates of Herpes Simplex Virus From 
Mother to Infant,'' Journal of the American Medical Association, 
289:203-209, 2003.
    21. De Tiege, X., et al. ``Limits of Early Diagnosis of Herpes 
Simplex Encephalitis in Children: A Retrospective Study of 38 Cases, 
Brief Report,'' Clinical Infectious Diseases, 36:1335-1339, 2003.

List of Subjects in 21 CFR Part 866

    Biologics, laboratories, 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. Section 866.3305 is revised 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. (1) Class II (special controls). The device is 
classified as class II if the herpes simplex virus serological assay is 
type 1 and/or 2. The special control for the device is FDA's guidance 
document entitled ``Class II Special Controls Guidance Document: Herpes 
Simplex Virus Type 1 and 2 Serological Assays.'' For availability of 
the guidance document, see Sec.  866.1(e).
    (2) Class III (premarket approval). The device is classified as 
class III if the herpes simplex virus serological assay is a type other 
than type 1 and/or 2.
    (c) Date PMA or notice of completion of a PDP is required. No 
effective date has been established for the requirement for premarket 
approval for the devices described in paragraph (b)(2) of this section. 
See Sec.  866.3.

    Dated: December 21, 2005.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 06-173 Filed 1-6-06; 8:45 am]
BILLING CODE 4160-01-S