68254 Federal Register / Vol. 69, No. 226 / Wednesday, November 24, 2004 / Rules and Regulations 

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.

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.

Federal Register / Vol. 69, No. 226 / Wednesday, November 24, 2004 / Rules and Regulations 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 § 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.

■ 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

■ 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.

■ 2. Section 862.1055 is added to subpart 

B to read as follows:

§ 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 § 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