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Immunology and Microbiology Devices; Reclassification of Herpes Simplex Virus (Types 1 and/or 2) Serological Assays
Note: EPA no longer updates this information, but it may be useful as a reference or resource.
[Federal Register: January 9, 2006 (Volume 71, Number 5)]
[Proposed Rules]
[Page 1399-1403]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09ja06-7]
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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the Federal Register, FDA is announcing the availability of a draft
guidance document that would serve as the special control, if FDA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: http://www.regulations.gov. 
Follow the instructions for submitting comments.
? Agency Web site: http://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 http://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 http://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