[Federal Register Volume 70, Number 191 (Tuesday, October 4, 2005)]
[Rules and Regulations]
[Pages 57748-57750]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-19863]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 866

[Docket No. 2005N-0341]


Medical Devices; Immunology and Microbiology Devices; 
Classification of AFP-L3% Immunological Test Systems

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying AFP-L3% 
(alpha-fetoprotein L3 subfraction) immunological test systems into 
class II (special controls). The special control that will apply to the 
device is the guidance document entitled ``Class II Special Controls 
Guidance Document: AFP-L3% Immunological Test Systems.'' The agency is 
classifying the device into class II (special controls) in order to 
provide a reasonable assurance of safety and effectiveness of the 
device. Elsewhere in this issue of the Federal Register, FDA is 
announcing the availability of a guidance document that will serve as 
the special control for the device.

DATES: This rule is effective November 3, 2005. The classification was 
effective May 19, 2005.

FOR FURTHER INFORMATION CONTACT: Maria Chan, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 240-276-0496.

SUPPLEMENTARY INFORMATION:

I. What is the Background of this Rulemaking?

    In accordance with section 513(f)(1) of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 360c(f)(1)), devices that were not in 
commercial distribution before May 28, 1976, the date of enactment of 
the Medical Device Amendments of 1976 (the amendments), generally 
referred to as postamendments devices, are classified automatically by 
statute into class III without any FDA rulemaking process. These 
devices remain in class III and require premarket approval, unless and 
until the device is classified or reclassified into class I or II, or 
FDA issues an order finding the device to be substantially equivalent, 
in accordance with section 513(i) of the act, to a predicate device 
that does not require premarket approval. The agency determines whether 
new devices are substantially equivalent to 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 of FDA's regulations.
    Section 513(f)(2) of the act provides that any person who submits a 
premarket notification under section 510(k) of the act for a device 
that has not previously been classified may, within 30 days after 
receiving an order classifying the device in class III under section 
513(f)(1) of the act, request FDA to classify the device under the 
criteria set forth in section 513(a)(1) of the act. FDA shall, within 
60 days of receiving such a request, classify the device by written 
order. This classification shall be the initial classification of the 
device. Within 30 days after the issuance of an order classifying the 
device, FDA must publish a notice in the Federal Register announcing 
such classification (section 513(f)(2) of the act).
    In accordance with section 513(f)(1) of the act, FDA issued an 
order on April 1, 2005, classifying the Wako LBA (liquid-phase binding 
assay) AFP-L3 in class III, because it was not substantially equivalent 
to a device that was introduced or delivered for introduction into 
interstate commerce for commercial distribution before May 28, 1976, or 
a device that was subsequently reclassified into class I or class II. 
On April 6, 2005, Wako Chemical USA, Inc., submitted a petition 
requesting classification of the Wako AFP-L3 Test System under section 
513(f)(2) of the act. The manufacturer recommended that the device be 
classified into class II.
    In accordance with 513(f)(2) of the act, FDA reviewed the petition 
in order to classify the device under the criteria for classification 
set forth in 513(a)(1) of the act. Devices are to be classified into 
class II if general controls, by themselves, are insufficient to 
provide reasonable assurance of safety and effectiveness, but there is 
sufficient information to establish special controls to provide 
reasonable assurance of the safety and effectiveness of the device for 
its intended use. After review of the information submitted in the 
petition, FDA determined that the Wako LBA AFP-L3 Test System can be 
classified into class II with the establishment of special controls. 
FDA believes these special controls will provide reasonable assurance 
of the safety and effectiveness of the device.
    The device is assigned the generic name AFP-L3% immunological test 
system and it is identified as an in vitro device that consists of 
reagents and an automated instrument used to quantitatively measure, by 
immunochemical techniques, AFP and AFP-L3 subfraction in human serum. 
The device is intended for in vitro diagnostic use as an aid in the 
risk assessment of patients with chronic liver disease for development 
of hepatocellular carcinoma, in conjunction with other laboratory 
findings, imaging studies, and clinical assessment.
    FDA has identified the risks to health associated with this type of 
device as inappropriate risk assessment and improper patient 
management. Failure of the system to perform as indicated, or error in 
interpretation of results, could lead to inappropriate risk assessment 
and improper management of patients with chronic liver diseases. 
Specifically, a falsely low AFP-L3% could result in a determination 
that the patient is at a lower risk of developing hepatocellular 
carcinoma, which could delay appropriate monitoring and treatment. A 
falsely high AFP-L3% could result in a determination that the patient 
is at a

[[Page 57749]]

higher risk for hepatocellular carcinoma, which could lead to 
unnecessary evaluation and testing, or inappropriate treatment 
decisions. Use of assay results without consideration of other 
laboratory findings, imaging studies, and clinical assessment could 
also pose a risk.
    The class II special controls guidance document aids in mitigating 
potential risks by providing recommendations on validation of 
performance characteristics, including software validation, control 
methods, reproducibility, and clinical studies. The guidance document 
also provides information on how to meet premarket (510(k)) submission 
requirements for the device. FDA believes that following the 
recommendations in the class II special controls guidance document 
generally addresses the risks to health identified in the previous 
paragraph.
    Following the effective date of this final classification rule, any 
firm submitting a 510(k) premarket notification for an AFP-L3% 
immunological test system will need to address the issues covered in 
the special controls guidance. However, the firm need only show that 
its device meets the recommendations of the guidance, or in some other 
way provides equivalent assurance of safety and effectiveness.
    Section 510(m) of the act provides that FDA may exempt a class II 
device from the premarket notification requirements under 510(k) of the 
act if FDA determines that premarket notification is not necessary to 
provide reasonable assurance of the safety and effectiveness of the 
device. For this type of device, FDA has determined that premarket 
notification is necessary to provide reasonable assurance of the safety 
and effectiveness of the device and, therefore, the type of device is 
not exempt from premarket notification requirements. Persons who intend 
to market this type of device must submit to FDA a premarket 
notification, prior to marketing the device, which contains information 
about the AFP-L3% immunological test system they intend to market.

II. What is the Environmental Impact of This Rule?

    The agency has determined under 21 CFR 25.34(b) that this action is 
of type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

III. What is the Economic Impact of This Rule?

    FDA has examined the impacts of the final rule under Executive 
Order 12866, 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 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 (21 
U.S.C. 360e), and may permit small potential competitors to enter the 
marketplace by lowering their costs, the agency certifies that the 
final rule will not have a significant economic impact on a substantial 
number of small entities.
    Section 202 (a) of the Unfunded Mandates Reform Act of 1995 
requires that agencies prepare a written statement, which includes an 
assessment of anticipated costs and benefits, before proposing ``any 
rule that includes any Federal mandate that may result in the 
expenditure by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100,000,000 or more (adjusted annually 
for inflation) in any one year.'' The current threshold after 
adjustment for inflation is $115 million, using the most current (2003) 
Implicit Price Deflator for the Gross Domestic Product. FDA does not 
expect this final rule to result in any 1-year expenditure that would 
meet or exceed this amount.

IV. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, the agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

V. How Does This Rule Comply with the Paperwork Reduction Act of 1995?

    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. 3501-3502) is not required.
    FDA also tentatively concludes that the special controls guidance 
document identified by this rule contains 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: AFP-L3% 
Immunological Test Systems.''

VI. What References Are on Display?

    The following reference has been placed on display in the Division 
of Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. Petition from Wako Chemical USA, Inc., received April 7, 
2005.

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 866.6030 is added to subpart G to read as follows:


Sec.  866.6030  AFP-L3% immunological test system.

    (a) Identification. An AFP-L3% immunological test system is an in 
vitro device that consists of reagents and an automated instrument used 
to quantitatively measure, by immunochemical techniques, AFP and AFP-L3 
subfraction in human serum. The device is intended for in vitro

[[Page 57750]]

diagnostic use as an aid in the risk assessment of patients with 
chronic liver disease for development of hepatocellular carcinoma, in 
conjunction with other laboratory findings, imaging studies, and 
clinical assessment.
    (b) Classification. Class II (special controls). The special 
control is FDA's guidance document entitled ``Class II Special Controls 
Guidance Document: AFP-L3% Immunological Test Systems.'' See Sec.  
866.1(e) for the availability of this guidance document.

    Dated: September 9, 2005.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 05-19863 Filed 10-3-05; 8:45 am]
BILLING CODE 4160-01-S