52800 Federal Register / Vol. 71, No. 173 / Thursday, September 7, 2006 / Notices 

the Internet. To receive ‘‘Commercially 

Distributed Analyte Specific Reagents 

(ASRs): Frequently Asked Questions, ‘‘

you may either send an e-mail request 

to dsmica@fda.hhs.gov 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 1590 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This draft guidance refers to 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 21 CFR 809.10 and 

809.30 (§ 809.30) have been approved 

under OMB control number 0910–0485; 

and the collections of information in 21 

CFR 814.20 have been approved under 

OMB control number 0910–0231. 

The draft guidance includes 

discussion of the restrictions on the 

sale, distribution, and use of ASRs 

(§ 809.30). Under this regulation, a 

laboratory that develops an in-house test 

using an ASR must add a disclaimer 

when reporting the test result to the 

practitioner (§ 809.30(e)). Advertising 

and promotional materials for ASRs 

must not make any statement regarding 

analytical or clinical performance 

(§ 809.30(d)(4)). In addition, the labeling 

for Class I, exempt ASRs must bear the 

statement, ‘‘Analyte Specific Reagent. 

Analytical and performance 

characteristics are not established.’’

Class II or III ASRs must bear the 

statement, ‘‘Analyte Specific Reagent. 

Except as a component of the approved/ 

cleared test (name of approved/cleared 

test), analytical and performance 

characteristics are not established’’

(§ 809.30(d)(2) and (d)(3)). The 

disclaimer and these statements do not 

constitute ‘‘collections of information’’

under the PRA. Rather, they are ‘‘public 

disclosure of information originally 

supplied by the Federal government to 

the recipient for the purpose of 

disclosure to the public’’ (5 CFR 

1320.3(c)(2)). 

V. Comments 

Interested persons may submit to the 

Division of Dockets Managment (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. Recieved 

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. 06–7500 Filed 9–5–06; 4:00 pm] 

BILLING CODE 4160–01–S 

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. 

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 


rwilkins on PROD1PC63 with NOTICES
Federal Register / Vol. 71, No. 173 / Thursday, September 7, 2006 / Notices 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) (§§ 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 inhouse 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 (§ 864.4020), 

general purpose reagents (§ 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 inhouse tests and that, therefore, raise 

safety and effectiveness concerns. 

Also, as stated previously, FDA 

decided to exclude laboratorydeveloped 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 postmarket 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 

dsmica@fda.hhs.gov 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 §§ 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 


rwilkins on PROD1PC63 with NOTICES