[Federal Register Volume 71, Number 27 (Thursday, February 9, 2006)]
[Rules and Regulations]
[Pages 6677-6679]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-1206]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2003P-0564]


Microbiology Devices; Reclassification of Hepatitis A Virus 
Serological Assays

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule 
to reclassify hepatitis A virus (HAV) serological assays from class III 
(premarket approval) into class II (special controls). FDA is taking 
this action after reviewing a reclassification petition submitted by 
Beckman Coulter, Inc. Elsewhere in this issue of the Federal Register, 
FDA is announcing the availability of the guidance document entitled 
``Guidance for Industry and FDA Staff: Class II Special Controls 
Guidance Document: Hepatitis A Virus Serological Assays'' that will 
serve as the class II special control for these devices.

DATES:  This rule is effective March 13, 2006.

FOR FURTHER INFORMATION CONTACT: Sally Hojvat, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 240-276-0496.

SUPPLEMENTARY INFORMATION:

I. Background

    The Federal Food, Drug, and Cosmetic Act (the act), as amended by 
the Medical Device Amendments of 1976 (the 1976 amendments) (Public Law 
94-295), the Safe Medical Devices Act (SMDA) (Public Law 101-629), and 
the Food and Drug Administration Modernization Act (FDAMA) (Public Law 
105-115), 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, 
depending on the regulatory controls needed to provide reasonable 
assurance of their safety and

[[Page 6678]]

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 act, devices that were in commercial 
distribution before May 28, 1976 (the date of enactment of the 1976 
amendments), generally referred to as preamendments devices, are 
classified after FDA has: (1) Received a recommendation from a device 
classification panel (an FDA advisory committee); (2) published the 
panel's recommendation for comment, along with a proposed regulation 
classifying the device; and (3) published a final regulation 
classifying the device. FDA has classified most preamendments devices 
under these procedures.
    Devices that were not in commercial distribution prior to 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 generally remain in 
class III until the device is reclassified into class I or II, or FDA 
issues an order finding the device to be substantially equivalent, 
under section 513(i) of the act, to a legally marketed device. The 
agency determines whether new devices are substantially equivalent to 
predicate 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 preamendments device that has been classified into class III may 
be marketed, by means of 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(f)(3) allows FDA to initiate reclassification of a 
postamendments device classified into class III under section 513(f)(1) 
of the act, or the manufacturer or importer of a device to petition the 
Secretary of the Department of Health and Human Services for the 
issuance of an order classifying the device into class I or class II. 
FDA's regulations in section 21 CFR 860.134 set forth the procedures 
for the filing and review of a petition for reclassification of such 
class III devices. To change the classification of the device, it is 
necessary that the proposed new classification have sufficient 
regulatory controls to provide reasonable assurance of the safety and 
effectiveness of the device for its intended use.

II. Regulatory History of the Device

    In the Federal Register of September 30, 2004 (69 FR 58371), FDA 
published a proposed rule to reclassify HAV serological assays into 
class II, after reviewing information contained in a reclassification 
petition submitted by Beckman Coulter, Inc. HAV serological assays are 
in vitro diagnostic devices used to support the clinical laboratory 
diagnosis of HAV. Specimens from individuals who have symptoms 
consistent with acute HAV or who may have previously been infected with 
HAV are tested for HAV-specific antibodies. The presence of these HAV-
specific antibodies in human serum or plasma is laboratory evidence of 
HAV infection. Interested persons were invited to comment on the 
proposed rule by December 29, 2004. FDA also identified the draft 
guidance document entitled ``Class II Special Controls Guidance 
Document: Hepatitis A Serological Assays for the Clinical Laboratory 
Diagnosis of Hepatitis A Virus'' as the proposed special control 
capable of providing reasonable assurance of safety and effectiveness 
for these devices.

III. Analysis of Comments and FDA's Response

    FDA received several comments on the proposed rule and guidance 
document. One comment supported the reclassification of HAV serological 
assays stating that these devices afford a long history of safe and 
effective use and that class II status would be appropriate. Another 
comment supported the proposed reclassification of HAV serological 
assays, but suggested modified wording to clarify the definition of 
``human tissue'' as used in the codification language and in the 
guidance document. FDA believes the use of ``solid or soft tissue 
donors'' adequately describes the individuals who are currently 
required to be tested.
    Other comments suggested specific modifications to the documents. 
One suggestion was to broaden the scope to include the intended use of 
determining whether individuals are susceptible to HAV infection. FDA 
agreed with the suggestion and revised language in the guidance 
document and classification regulation. These comments also suggested 
revising the general study recommendations in the following ways:
    (Comment 1) One comment recommended that the study include a 
representative sample of vaccines currently licensed in the United 
States, rather than every vaccine that is currently licensed in the 
United States. FDA disagrees with this comment. FDA believes it is 
essential to have data to show that the submitted assay will detect 
antibodies produced from any U.S.-licensed vaccine.
    (Comment 2) A comment recommended removing or revising the 
recommendation that manufacturers collect samples beginning at 2 to 4 
weeks. FDA has clarified this section to recommend collecting specimens 
no earlier than 4 weeks post-vaccination.
    (Comment 3) Another comment recommended FDA remove or revise the 
recommendation that a manufacturer establish reproducibility for 
devices indicated for use in matrices other than serum. FDA concurs and 
has revised this recommendation and added information within the 
guidance document to address this issue.
    (Comment 4) Another comment asked FDA to remove the notation of 
anti-nuclear antibodies, rheumatoid factor, and heterophilic antibodies 
under the ``interference'' section because it is duplicative of the 
analysis recommended under the ``cross-reactivity'' section. FDA 
concurs and has revised the guidance document accordingly.
    (Comment 5) Another comment asked FDA to clarify the recommended 
study population. FDA has revised the appropriate section of the 
guidance document to clarify the recommended study population, taking 
into account the sporadic incidence of HAV infection within the United 
States.

IV. Conclusion

    Based on the information discussed in the preamble to the proposed 
rule (69 FR 58371), FDA concludes that special controls, in conjunction 
with general controls, will provide reasonable assurance of the safety 
and effectiveness for HAV serological assays. The agency is, therefore, 
reclassifying HAV serological assays from class III (premarket 
approval) into class II (special controls). Elsewhere in this issue of 
the Federal Register, FDA is announcing the availability of the 
guidance document entitled ``Guidance for Industry and FDA Staff: Class 
II Special Controls Guidance Document: Hepatitis A Virus Serological 
Assays'' as the special control capable of providing reasonable 
assurance of safety and effectiveness for these devices. Following the 
effective date of this final classification rule, any firm submitting a 
510(k) premarket notification for a HAV serological assay 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

[[Page 6679]]

some other way provides equivalent assurances of safety and 
effectiveness.
    FDA is now codifying the classification for HAV serological assays 
by adding new Sec.  866.3310. For the convenience of the reader, 21 CFR 
866.1 informs the reader where to find guidance documents referenced in 
21 CFR part 866.
    Section 510(m) of the act provides that FDA may exempt a class II 
device from the premarket notification requirements under section 
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, this 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 HAV serological assay 
they intend to market.

V. Environmental Impact

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

VI. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866, 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. Reclassification of HAV serological assays from 
class III into class II will relieve manufacturers of the cost of 
complying with the premarket approval requirements in section 515 of 
the act. Because reclassification will reduce regulatory costs with 
respect to these devices, it will impose no significant economic impact 
on any small entities, and it may permit small potential competitors to 
enter the marketplace by lowering their costs.
    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.

VII. 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

VIII. Paperwork Reduction Act of 1995

    FDA concludes that this rule contains no new collections of 
information. Therefore, clearance by the Office of Management and 
Budget under the Paperwork Reduction Act of 1995 is not required.

List of Subjects in 21 CFR Part 866

    Biologics, Laboratories, 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 866.3310 is added to subpart D to read as follows:


Sec.  866.3310   Hepatitis A virus (HAV) serological assays.

    (a) Identification. HAV serological assays are devices that consist 
of antigens and antisera for the detection of hepatitis A virus-
specific IgM, IgG, or total antibodies (IgM and IgG), in human serum or 
plasma. These devices are used for testing specimens from individuals 
who have signs and symptoms consistent with acute hepatitis to 
determine if an individual has been previously infected with HAV, or as 
an aid to identify HAV-susceptible individuals. The detection of these 
antibodies aids in the clinical laboratory diagnosis of an acute or 
past infection by HAV in conjunction with other clinical laboratory 
findings. These devices are not intended for screening blood or solid 
or soft tissue donors.
    (b) Classification. Class II (special controls). The special 
control is ``Guidance for Industry and FDA Staff: Class II Special 
Controls Guidance Document: Hepatitis A Virus Serological Assays.'' See 
Sec.  866.1(e) for the availability of this guidance document.

    Dated: February 1, 2006.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 06-1206 Filed 2-8-06; 8:45 am]
BILLING CODE 4160-01-S