[Federal Register Volume 71, Number 173 (Thursday, September 7, 2006)]
[Notices]
[Pages 52800-52801]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-7499]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2006D-0347]


Draft Guidance for Industry, Clinical Laboratories, and FDA Staff 
on In Vitro Diagnostic Multivariate Index Assays; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of the draft guidance entitled ``Draft Guidance for 
Industry, Clinical Laboratories, and FDA Staff on In Vitro Diagnostic 
Multivariate Index Assays.'' This draft guidance addresses the 
definition and regulatory status of a class of in vitro diagnostic 
devices referred to as In Vitro Diagnostic Multivariate Index Assays 
(IVDMIAs). The guidance also addresses premarket and postmarket 
requirements with respect to IVDMIAs. An IVDMIA employs data, derived 
in part from one or more in vitro assays, and an algorithm that 
usually, but not necessarily, runs on software, to generate a result 
that diagnoses a disease or condition or is used in the cure, 
mitigation, treatment, or prevention of disease.

DATES: Submit written or electronic comments on this draft guidance by 
December 6, 2006.

ADDRESSES: Submit written requests for single copies of the draft 
guidance document entitled ``Draft Guidance for Industry, Clinical 
Laboratories, and FDA Staff on In Vitro Diagnostic Multivariate Index 
Assays'' to the Division of Small Manufacturers, International, and 
Consumer Assistance (HFZ-220), Center for Devices and Radiological 
Health, Food and Drug Administration, 1350 Piccard Dr., Rockville, MD 
20850. Send one self-addressed adhesive label to assist that office in 
processing your request, or fax your request to 240-276-3151. See the 
SUPPLEMENTARY INFORMATION section for information on electronic access 
to the guidance.
    Submit written comments concerning this draft guidance to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic 
comments to http://www.fda.gov/dockets/ecomments. Identify comments 
with the docket number found in brackets in the heading of this 
document.

FOR FURTHER INFORMATION CONTACT: Courtney Harper, Center for Devices 
and Radiological Health (HFZ- 440), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 240-276-0490, ext. 162.

SUPPLEMENTARY INFORMATION:

I. Background

    The definition of a device is set forth at section 201(h) of the 
Federal Food, Drug and Cosmetic Act (the act) (21 U.S.C. 321(h)). It 
provides in relevant part: ``The term `device' * * * means an 
instrument, apparatus, implement, machine, contrivance, implant, in 
vitro reagent, or other similar or related article, including any 
component, part, or accessory, which is * * * (2) intended for use in 
the diagnosis of disease or other conditions, or in the cure, 
mitigation, treatment, or prevention of disease, in man or other 
animals * * *'' (21 U.S.C. 321(h)). An IVDMIA is a test system that 
employs data, derived in part from one or more in vitro assays, and an 
algorithm that usually, but not necessarily, runs on software, to 
generate a result that diagnoses a disease or condition or is used in 
the cure, mitigation, treatment, or prevention of disease. An IVDMIA is

[[Page 52801]]

therefore a device within the meaning of the act.
    FDA is aware of some confusion about the regulation of IVDMIAs that 
are developed by and used in a laboratory. We believe this confusion 
derives in part from FDA's approach to regulation of laboratory-
developed tests that use commercially available ASRs and other 
commercially available, FDA-regulated components. FDA seeks to dispel 
the existing confusion and clarify its approach to regulation of 
IVDMIAs with this guidance document.
    Some of the apparent confusion is associated with the rules that 
classify and regulate analyte specific reagents (ASRs) that move in 
commerce (hereinafter ASR rule) (Sec. Sec.  864.4020, 809.10(e), and 
809.30 (21 CFR parts 864 and 809)). The ASR rule does not extend to 
tests developed in-house by clinical laboratories using commercially 
available ASRs and used exclusively by that laboratory, or ASRs created 
in-house and used exclusively by that laboratory for in-house testing. 
(November 21, 1997 Federal Register, 62 FR 62243, 62249.) While FDA 
stated in the preamble to the final ASR rule that ``clinical 
laboratories that develop [in-house] tests are acting as manufacturers 
of medical devices and are subject to FDA jurisdiction under the act,'' 
62 FR 62249, FDA chose not to extend the rule to such tests and it has 
generally exercised enforcement discretion over laboratory-developed 
ASRs and laboratory-developed tests that use commercially available and 
laboratory-developed ASRs.
    FDA took this approach because it believed it was regulating ``the 
primary ingredients of most in-house developed tests,'' and because it 
believed that laboratories certified as high complexity under the 
Clinical Laboratory Improvement Amendments, 42 U.S.C. 263a, ``have 
demonstrated expertise and ability to use ASRs in test procedures and 
analyses.'' (62 FR 62249 (emphasis added)).
    FDA believed it was regulating the primary ingredients of most in-
house tests because it was regulating the common elements of in-house 
tests, including most ASRs (Sec.  864.4020), general purpose reagents 
(Sec.  864.4010), general purpose laboratory equipment (21 CFR 
862.2050), other laboratory instrumentation (21 CFR part 864, subpart 
D), and controls (21 CFR 862.1660). IVDMIAs include elements, as 
described in the section on ``Definition and Regulatory Status of 
IVDMIAs'' of this guidance, that are not among these primary 
ingredients of in-house tests and that, therefore, raise safety and 
effectiveness concerns.
    Also, as stated previously, FDA decided to exclude laboratory-
developed tests from the ASR rule due to its confidence in high-
complexity laboratories' ability to use ASRs. The manufacture of an 
IVDMIA involves steps that are not synonymous with the use of ASRs and 
that are not within the ordinary ``expertise and ability'' of 
laboratories that FDA referred to when it issued the ASR rule. 
Therefore, IVDMIAs do not fall within the scope of laboratory-developed 
tests over which FDA has generally exercised enforcement discretion. 
FDA intends to issue guidance regarding those laboratory-developed 
tests over which it has in the past generally exercised, and over which 
it intends to continue to exercise, enforcement discretion. IVDMIAs 
must meet pre- and post-market device requirements under the act and 
FDA regulations, including premarket review requirements in the case of 
class II and III devices.

II. Significance of Guidance

    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized will represent the agency's current thinking on IVDMIAs. It 
does not create or confer any rights for or on any person and does not 
operate to bind FDA or the public. An alternative approach may be used 
if such approach satisfies the requirements of the applicable statute 
and regulations.

III. Electronic Access

    Persons interested in obtaining a copy of the draft guidance may do 
so by using the Internet. To receive ``Draft Guidance for Industry, 
Clinical Laboratories, and FDA Staff on In Vitro Diagnostic 
Multivariate Index Assays,'' you may either send an e-mail request to 
[email protected] to receive an electronic copy of the document or 
send a fax request to 240-276-3151 to receive a hard copy. Please use 
the document number 1610 to identify the guidance you are requesting.
    CDRH maintains an entry on the Internet for easy access to 
information including text, graphics, and files that may be downloaded 
to a personal computer with Internet access. Updated on a regular 
basis, the CDRH home page includes device safety alerts, Federal 
Register reprints, information on premarket submissions (including 
lists of approved applications and manufacturers' addresses), small 
manufacturer's assistance, information on video conferencing and 
electronic submissions, Mammography Matters, and other device-oriented 
information. The CDRH Web site may be accessed at http://www.fda.gov/cdrh. A search capability for all CDRH guidance documents is available 
at http://www.fda.gov/cdrh/guidance.html. Guidance documents are also 
available on the Division of Dockets Management Internet site at http://www.fda.gov/ohrms/dockets.

IV. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collections of information in 21 CFR 807.87 have been approved under 
OMB control number 0910-0120; the collections of information in 
Sec. Sec.  809.10 and 809.30 have been approved under OMB control 
number 0910-0485; the collections of information in 21 CFR 814.20 have 
been approved under OMB control number 0910-0231; the collections of 
information in 21 CFR part 812 have been approved under OMB control 
number 0910-0078; the collections of information in 21 CFR part 820 
have been approved under OMB control number 0910-0073; and the 
collections of information in 21 CFR part 803 have been approved under 
OMB control number 0910-0437.

V. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES), written or electronic comments regarding this 
document. Submit a single copy of electronic comments or two paper 
copies of any mailed comments, 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.

    Dated: September 1, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 06-7499 Filed 9-5-06; 4:00 pm]
BILLING CODE 4160-01-S