Federal Register / Vol. 72, No. 143 / Thursday, July 26, 2007 / Notices 41081 

800–835–4709 or 301–827–1800. See 

the SUPPLEMENTARY INFORMATION section 

for electronic access to the draft 

guidance document. 

Submit written comments on the 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. 

FOR FURTHER INFORMATION CONTACT: 

Valerie A. Butler, Center for Biologics 

Evaluation and Research (HFM–17), 

Food and Drug Administration, 1401 

Rockville Pike, Suite 200N, Rockville, 

MD 20852–1448, 301–827–6210. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft document entitled ‘‘Guidance for 

Industry: Cell Selection Devices for 

Point of Care Production of Minimally 

Manipulated Autologous Peripheral 

Blood Stem Cells (PBSCs)’’ dated July 

2007. The draft guidance document 

discusses certain cell selection devices 

that minimally manipulate autologous 

PBSCs at the point of care for specific 

clinical indications, and the 

applicability of the requirements of 21 

CFR part 1271 to such PBSCs. The 

guidance also discusses the submission 

of data intended to support approval of 

cell selection devices. 

The draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent FDA’s current thinking on this 

topic. 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 requirement 

of the applicable statutes and 

regulations. 

II. 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This draft guidance refers to 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 part 812 have 

been approved under 0910–0078; the 

collections of information in 21 CFR 

part 814 have been approved under 

0910–0231; the collections of 

information in 21 CFR part 820 have 

been approved under 0910–0073; and 

the collections of information in 21 CFR 

part 822 have been approved under 

0910–0449. 

III. Comments 

The draft guidance is being 

distributed for comment purposes only 

and is not intended for implementation 

at this time. Interested persons may 

submit to the Division of Dockets 

Management (see ADDRESSES) written or 

electronic comments regarding the draft 

guidance. 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 the 

brackets in the heading of this 

document. A copy of the draft guidance 

and received comments are available for 

public examination in the Division of 

Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the draft guidance at either 

http://www.fda.gov/cber/guidelines.htm 

or http://www.fda.gov/ohrms/dockets/ 

default.htm. 

Dated: July 20, 2007. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 07–3659 Filed 7–23–07; 12:02 pm] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2006D–0347] 

Draft Guidance for Industry and Food 

and Drug Administration Staff; 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 a revised draft guidance 

entitled ‘‘In Vitro Diagnostic 

Multivariate Index Assays.’’ FDA is 

issuing this revised draft guidance to 

address the definition and regulatory 

status of a class of In Vitro Diagnostic 

Devices referred to as In Vitro 

Diagnostic Multivariate Index Assays 

(IVDMIAs). The revised draft guidance 

also addresses premarket and 

postmarket requirements with respect to 

IVDMIAs. The initial draft of this 

guidance was issued September 7, 2006. 

DATES: Submit written or electronic 

comments on this draft guidance by 

August 27, 2007. 

ADDRESSES: Submit written requests for 

single copies of the draft guidance 

document entitled ‘‘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 or to the Office of 

Communication, Training, and 

Manufacturers Assistance (HFM–40), 

Center for Biologics Evaluation and 

Research (CBER), Food and Drug 

Administration, 1401 Rockville Pike, 

suite 200N, Rockville, MD 20852–1448. 

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 draft 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–

0694. 

For further information concerning 

the guidance as it related to devices 

regulated by CBER: Martin Ruta, Center 

for Biologics Evaluation and Research, 

Food and Drug Administration, 1401 

Rockville Pike, Rockville, MD 20852, 

301–827–3518. 

SUPPLEMENTARY INFORMATION: 

I. Background 

In the Federal Register of September 

7, 2006 (71 FR 52800). FDA published 

a notice of availability of the initial draft 

guidance to address the definition and 

regulatory status of a class of in vitro 

diagnostic devices referred to as ‘‘In 

Vitro Diagnostic Multivariate Index 

Assays (IVDMIAs).’’ The initial draft 

guidance also addressed premarket and 

postmarket requirements with respect to 

IVDMIAs. 

An IVDMIA, as defined in the draft 

guidance document, is a device within 

the meaning of the Federal Food, Drug, 

and Cosmetic Act (the act). Some 

IVDMIAs are laboratory-developed tests 

(LDTs); laboratory-developed IVDMIAs 

are a specific subset of LDTs. While 

FDA has stated that ‘‘clinical 

laboratories that develop (in-house) tests 


rwilkins on PROD1PC63 with NOTICES
41082 Federal Register / Vol. 72, No. 143 / Thursday, July 26, 2007 / Notices 

are acting as manufacturers of medical 

devices and are subject to FDA 

jurisdiction under the Act,’’ 62 FR 

62243 to 62249 (November 21, 1997), 

the agency has generally exercised 

enforcement discretion over most 

standard LDTs. However, in the draft 

guidance, FDA recognizes that IVDMIAs 

include elements that are not among the 

primary ingredients of standard LDTs 

(e.g., complex, unique, interpretation 

functions). IVDMIAs thus do not fall 

within the scope of LDTs over which 

FDA has generally exercised 

enforcement discretion. 

IVDMIAs raise significant issues of 

safety and effectiveness. These types of 

tests are developed based on observed 

correlations between multivariate data 

and clinical outcome, such that the 

clinical validity of the claims is not 

transparent to patients, laboratorians, 

and clinicians who order these tests. 

Additionally, IVDMIAs frequently have 

a high risk intended use. FDA is 

concerned that patients and healthcare 

practitioners are relying upon IVDMIAs 

with high risk intended uses to make 

critical healthcare decisions without 

any independent assurance that the 

IVDMIA has been properly clinically 

validated, and without any ability to 

assess whether the test yields clinically 

valid results. 

With this revised draft guidance 

document, FDA seeks to identify 

IVDMIAs as a discrete category of 

device, and to clarify that, even when 

offered as LDTs, IVDMIAs must meet 

pre- and post-market device 

requirements under the act and FDA 

regulations, including premarket review 

requirements in the case of most class 

II and III devices. 

FDA received and considered 

approximately 60 sets of comments on 

the initial draft guidance document, 

including comments provided at a 

public meeting that was held on 

February 8, 2007. After taking the 

comments into consideration, the FDA 

has updated the draft guidance 

document to provide clarifications as 

needed. 

Certain comments on the initial draft 

guidance document requested that FDA 

undertake notice and comment 

rulemaking rather than issue a guidance 

document in order to allow sufficient 

opportunity for public input. In 

response to this concern, FDA extended 

the comment period on the draft 

guidance document from 90 days to 180 

days, March 5, 2007 (71 FR 68822), and 

held a public meeting to provide a 

forum for presentations and comments 

on the draft guidance document. The 

meeting was attended by 266 people 

representing a cross-section of 

interested stakeholders including 

industry, consumer groups, and the 

medical community. FDA has carefully 

considered the comments it has 

received. Many comments reflect that 

stakeholders construed the definition of 

IVDMIAs in the initial draft guidance 

document to encompass a wider range 

of tests than FDA had intended. The 

initial draft guidance document has 

been revised to clarify the definition of 

an IVDMIA and to provide examples of 

tests that the agency does and does not 

consider to be IVDMIAs. This section of 

the draft guidance was modified so that 

stakeholders can more easily 

understand the nature of tests 

designated as IVDMIAs, and 

manufacturers can more easily 

determine whether their tests are 

IVDMIAs. However, the clarifications do 

not alter the scope or intent of the 

definition of an IVDMIA found in the 

initial draft guidance document. 

In response to additional comments 

received, the revised draft guidance 

document now clarifies FDA regulatory 

mechanisms in general, such as how 

devices are classified and reviewed 

based on the risk of the intended use, 

how laboratory-developed IVDMIAs 

should be labeled, and how 

manufacturers can update and improve 

cleared or approved devices using 

existing mechanisms within the 

regulatory framework. These existing 

mechanisms enable manufacturers to 

bring innovative new tests to the market 

and ensure that they can be updated and 

improved as new scientific information 

becomes available. While this 

information is generally available in 

existing regulations, guidance 

documents, and on the FDA Web site, 

the revised draft guidance provides a 

summary of this information with a 

focus on IVDMIAs in order to assist 

those stakeholders who are not familiar 

with existing FDA requirements. 

In other comments, some stakeholders 

expressed concern that requiring FDA 

regulatory compliance for IVDMIAs has 

the potential to discourage the 

development of new tests for rare 

diseases. A manufacturer of an IVDMIA 

for a disease or condition that affects 

small patient populations may find that 

research and development costs exceed 

market returns. The draft guidance has 

been revised to indicate FDA’s intent to 

exercise enforcement discretion for 

laboratory-developed IVDMIAs that are 

intended to diagnose rare diseases (i.e., 

IVDMIAs that meet the definition of 

Humanitarian Use Devices under 21 

CFR part 814 Subpart H). 

Finally, the draft guidance document 

clarifies that laboratories that 

manufacture IVDMIAs should follow 

the Medical Device Reporting 

requirements for manufacturers, 21 CFR 

part 803 for their IVDMIA device(s). As 

in the initial draft guidance, the revised 

draft guidance indicates that FDA 

intends to issue guidance to assist 

laboratories that manufacture IVDMIAs 

in complying with the Quality System 

regulation (QS), 21 CFR part 820. In 

response to comments that expressed 

concern about coming into compliance 

with the QS regulation, the revised draft 

guidance indicates that until such a 

final guidance is published, FDA 

intends to exercise enforcement 

discretion with regard to post-market 

QS requirement enforcement for 

laboratories that manufacture IVDMIAs, 

recognizing that some Clinical 

Laboratory Improvement Amendments 

of 1988 (CLIA’ 88) requirements may 

partially fulfill corresponding QS 

regulation requirements. 

FDA is issuing this revised draft in 

order to gather significant new 

comments before issuing a final version 

of the guidance. Because the agency 

believes it has addressed the most 

important concerns raised by the 

comments it received on the initial 

draft, and because it is important to 

issue a final guidance to provide clarity 

for stakeholders, FDA is providing a 

comment period of 30 days following 

publication of this document. 

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 represents 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 ‘‘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 


rwilkins on PROD1PC63 with NOTICES
Federal Register / Vol. 72, No. 143 / Thursday, July 26, 2007 / Notices 41083 

Register reprints, information on 

premarket submissions (including lists 

of approved applications and 

manufacturers’ addresses), small 

manufacturers’ 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 CBER Internet site at http:// 

www.fda.gov/cber/guidelines.htm or on 

the Division of Dockets Management 

Internet site at http://www.fda.gov/ 

ohrms/dockets. 

IV. Paperwork Reduction Act of 1995 

This draft guidance contains 

information collection provisions that 

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 the draft guidance 

document have been approved by OMB 

in accordance with the PRA under the 

regulations governing premarket 

notifications (21 CFR part 807, subpart 

E, OMB control number 0910–0120) 

premarket approval applications (21 

CFR part 814, OMB control number 

0910–0231), investigational device 

exemptions (21 CFR part 812, OMB 

control number 0910–0078), quality 

system regulation (21 CFR part 820, 

OMB control number 0910–0073), and 

medical device reporting (21 CFR part 

803, OMB control number 0910–0437). 

The labeling provisions addressed in 

this guidance have been approved by 

OMB under OMB control number 0910–

0485. 

V. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES), written or electronic 

comments regarding this document on 

or before August 27, 2007. Submit 

electronic comments to http:// 

www.fda.gov/dockets/ecomments. 

Submit two paper copies of any mailed 

comments, except that individuals may 

submit one copy. Comments are to be 

identified with the docket number 

found in brackets in the heading of this 

document. Comments received may be 

seen in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday. 

Dated: July 20, 2007. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 07–3660 Filed 7–23–07; 12:02 pm] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2004D–0333] 

Guidance; Emergency Use 

Authorization of Medical Products; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a guidance entitled 

‘‘Emergency Use Authorization of 

Medical Products.’’ The guidance 

explains FDA’s policies for authorizing 

the use of an unapproved medical 

product or an unapproved use of an 

approved medical product during a 

declared emergency. This guidance 

finalizes the draft guidance published in 

the Federal Register of July 5, 2005 (70 

FR 38689). 

DATES: Submit written or electronic 

comments on agency guidances at any 

time. 

ADDRESSES: Submit written requests for 

single copies of this guidance to the 

Office of Counterterrorism Policy and 

Planning (HF–29), Food and Drug 

Administration, 5600 Fishers Lane, rm. 

14C–26, Rockville, MD 20857. Send one 

self-addressed adhesive label to assist 

that office in processing your request, or 

fax your request to 301–827–5671. 

Submit written comments on the 

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. See 

the SUPPLEMENTARY INFORMATION section 

for information on electronic access to 

the guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Charlotte Christin, Office of 

Counterterrorism Policy and Planning 

(HF–29), Food and Drug 

Administration, 5600 Fishers Lane, 

Rockville, MD 20857, 301–827–4067. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a guidance for industry, government 

agencies, and FDA staff entitled 

‘‘Emergency Use Authorization of 

Medical Products.’’ This guidance 

describes the agency’s general 

recommendations and procedures for 

issuance of emergency use 

authorizations (EUA) under section 564 

of the Federal Food, Drug, and Cosmetic 

Act (the act) (21 U.S.C. 360bbb–3), 

which was amended by the Project 

BioShield Act of 2004 (Public Law 108–

276). 

Section 564 of the act provides for 

authorization of ‘‘emergency use’’ of a 

medical product, after a declaration of 

emergency justifying an authorization is 

issued by the Secretary of Health and 

Human Services (the Secretary) based 

on one of the following grounds: A 

determination by the Secretary of 

Homeland Security that there is an 

actual or potential ‘‘domestic 

emergency;’’ a determination by the 

Secretary of Defense that there is an 

actual or potential ‘‘military 

emergency;’’ or a determination by the 

Secretary that there is a public health 

emergency under section 319 of the 

Public Health Service Act that affects or 

has the significant potential to affect 

national security. The Commissioner of 

Food and Drugs may issue an EUA for 

an unapproved drug, device, or biologic, 

or an unapproved use of an approved 

drug, device, or biologic, during a 

declared emergency if the statutory 

criteria set forth in section 564 of the act 

are met. 

On July 5, 2005, FDA published for 

comment in the Federal Register a draft 

of this guidance. Comments received 

from industry, associations, health care 

professionals, consumers, and staff of 

other Federal agencies have been taken 

into consideration in finalizing this 

guidance. Changes are based on a 

thorough review of all comments 

received. As revised, the guidance 

includes a more detailed discussion of 

the scope of preemption (where 

applicable) and also provides points of 

contact for further information on 

several Federal liability protection and 

compensation programs. 

This guidance document is being 

issued consistent with FDA’s good 

guidance practices regulation (21 CFR 

10.115). It represents the agency’s 

current thinking on emergency use 

authorizations of medical products. 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 statutes 

and regulations. 


rwilkins on PROD1PC63 with NOTICES