[Federal Register Volume 69, Number 226 (Wednesday, November 24, 2004)]
[Rules and Regulations]
[Pages 68254-68255]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-25975]



[[Page 68254]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 862

[Docket No. 2004N-0482]


Medical Devices; Clinical Chemistry and Clinical Toxicology 
Devices; Classification of Newborn Screening Test Systems for Amino 
Acids, Free Carnitine, and Acylcarnitines Using Tandem Mass 
Spectrometry

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is classifying newborn 
screening test systems for amino acids, free carnitine, and 
acylcarnitines using tandem mass spectrometry 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: Newborn Screening Test Systems for Amino Acids, Free 
Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry.'' The 
agency is taking this action in response to a petition submitted under 
the Federal Food, Drug, and Cosmetic Act (the act) as amended by the 
Medical Device Amendments of 1976, the Safe Medical Devices Act of 
1990, the Food and Drug Administration Modernization Act of 1997, and 
the Medical Device User Fee and Modernization Act of 2002. 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 
publishing a notice of availability of a guidance document that is the 
special control for this device.

DATES: This rule becomes effective December 27, 2004. The 
classification was effective August 24, 2004.

FOR FURTHER INFORMATION CONTACT: Carol Benson, Center for Devices and 
Radiological Health (HFZ-440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 301-594-1243, ext. 144.

SUPPLEMENTARY INFORMATION:

I. Background

    In accordance with section 513(f)(1) of 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 previously marketed devices by means of 
premarket notification procedures in section 510(k) of the act (21 
U.S.C. 360(k)) and part 807 (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 a 
notice on June 9, 2004, classifying the Perkin Elmer Life and 
Analytical Sciences' NeoGram Amino Acids and Acylcarnitines Tandem Mass 
Spectrometry Kit 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 which was subsequently reclassified 
into class I or class II. On July 2, 2004, Perkin Elmer Life and 
Analytical Sciences submitted a petition requesting classification of 
the NeoGram Amino Acids and Acylcarnitines Tandem Mass Spectrometry Kit 
under section 513(f)(2) of the act. The manufacturer recommended that 
the device be classified into class II.
    In accordance with section 513(f)(2) of the act, FDA reviewed the 
petition in order to classify the device under the criteria for 
classification set forth in section 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 Perkin 
Elmer Life and Analytical Sciences' NeoGram Amino Acids and 
Acylcarnitines Tandem Mass Spectrometry Kit can be classified in class 
II with the establishment of special controls. FDA believes these 
special controls, in addition to general controls, will provide 
reasonable assurance of safety and effectiveness of the device.
    The device is assigned the generic name ``newborn screening test 
system for amino acids, free carnitine, and acylcarnitines using tandem 
mass spectrometry.'' It is identified as a device intended for the 
measurement and evaluation of amino acids, free carnitine, and 
acylcarnitine concentrations from newborn whole blood filter paper 
samples. The quantitative analysis of amino acids, free carnitine, and 
acylcarnitines and their relationship with each other provides analyte 
concentration profiles that may aid in screening newborns for one or 
more inborn errors of amino acid, free carnitine, and acyl-carnitine 
metabolism.
    FDA has identified no direct risks to health related to use of 
newborn screening test systems for amino acids, free carnitine, and 
acylcarnitines using tandem mass spectrometry. However, failure of the 
test to perform as indicated or error in interpretation of results may 
lead to the indirect risk of improper medical management of patients 
with inborn errors of metabolism. For example, a false negative (false 
normal) measurement could contribute to failure to detect a possible 
inborn error of metabolism, which could lead to functional impairment 
or death. A false positive (false abnormal) measurement could 
contribute to unnecessary additional patient testing and added concern 
and apprehension of parents and physicians.
    The class II special controls guidance document provides 
information on how to meet premarket (510(k)) submission requirements 
for the device, including recommendations on validation of performance 
characteristics and labeling. FDA believes that following the class II 
special controls guidance document generally addresses the risk to 
health identified in the previous paragraph. Therefore, on August 24, 
2004, FDA issued an order to the petitioner classifying the device into 
class II. FDA is codifying this classification by adding 21 CFR 
862.3840.

[[Page 68255]]

    Following the effective date of this final classification rule, any 
firm submitting a 510(k) premarket notification for a newborn screening 
test system for amino acids, free carnitine, and acylcarnitines using 
tandem mass spectrometry 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 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, however, FDA has 
determined that premarket notification is necessary because FDA review 
of performance characteristics, test methodology, and labeling to 
satisfy requirements of Sec.  807.87(e), will provide reasonable 
assurance that acceptable levels of performance for both safety and 
effectiveness will be addressed before marketing clearance. Thus, 
persons who intend to market this type of device must submit to FDA a 
premarket notification containing information on the newborn test 
system before marketing the device.

II. 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.

III. 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. Because classification of these devices 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 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 $110 million. 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. Paperwork Reduction Act of 1995

    This final rule contains no collections of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

VI. Reference

    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 Perkin Elmer Life and Analytical Sciences, 
dated July 2, 2004.

List of Subjects in 21 CFR Part 862

    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 
862 is amended as follows:

PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES

0
1. The authority citation for 21 CFR part 862 continues to read as 
follows:

    Authority:  21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

0
2. Section 862.1055 is added to subpart B to read as follows:


Sec.  862.1055   Newborn screening test system for amino acids, free 
carnitine, and acylcarnitines using tandem mass spectrometry.

    (a) Identification. A newborn screening test system for amino 
acids, free carnitine, and acylcarnitines using tandem mass 
spectrometry is a device that consists of stable isotope internal 
standards, control materials, extraction solutions, flow solvents, 
instrumentation, software packages, and other reagents and materials. 
The device is intended for the measurement and evaluation of amino 
acids, free carnitine, and acylcarnitine concentrations from newborn 
whole blood filter paper samples. The quantitative analysis of amino 
acids, free carnitine, and acylcarnitines and their relationship with 
each other provides analyte concentration profiles that may aid in 
screening newborns for one or more inborn errors of amino acid, free 
carnitine, and acyl-carnitine metabolism.
    (b) Classification. Class II (special controls). The special 
control is FDA's guidance document entitled ``Class II Special Controls 
Guidance Document: Newborn Screening Test Systems for Amino Acids, Free 
Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry.'' See 
Sec.  862.1(d) for the availability of this guidance document.

    Dated: November 15, 2004.
Linda S. Kahan,
Deputy Director, Center for Devices and Radiological Health.
[FR Doc. 04-25975 Filed 11-23-04; 8:45 am]
BILLING CODE 4160-01-S