33438 Federal Register / Vol. 73, No. 114 / Thursday, June 12, 2008 / Notices 

III. Paperwork Reduction Act of 1995 

This electronic ICSR draft guidance 

refers to proposed collections of 

information required by Public Law 

109–462 and subject to review by the 

Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995 (the PRA) (44 U.S.C. 3501–

3520). As required by the PRA, FDA is 

now requesting public comment (see 

DATES) on these proposed collections of 

information. The agency’s analysis and 

estimates of the proposed collections of 

information in the electronic ICSR draft 

guidance that are required by Public 

Law 109–462 have been described 

previously in FDA’s notice of 

availability for a draft guidance entitled 

‘‘Postmarketing Adverse Event 

Reporting for Nonprescription Human 

Drug Products Marketed Without an 

Approved Application’’ (72 FR 58316, 

October 15, 2007) (the October 2007 

PRA analysis). For burden estimates for 

the proposed collections of information 

in the electronic ICSR draft guidance, 

see the October 2007 PRA analysis. 

This electronic ICSR draft guidance 

also refers to previously approved 

collections of information found in FDA 

regulations. The collections of 

information in 21 CFR 310.305, 314.80, 

600.80, and 1271.350 have been 

approved under OMB control numbers 

0910–0291, 0910–0230, 0910–0308, and 

0910–0543 respectively. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the document athttp:// 

www.fda.gov/cder/guidance/index.htm, 

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

guidelines.htm, or http:// 

www.regulations.gov. 

Dated: June 2, 2008. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E8–13269 Filed 6–11–08; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2008–D–0339] 

Draft Guidance for Industry on 

Updating Labeling for Susceptibility 

Test Information in Systemic 

Antibacterial Drug Products and 

Antimicrobial Susceptibility Testing 

Devices; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft guidance for 

industry entitled ‘‘Updating Labeling for 

Susceptibility Test Information in 

Systemic Antibacterial Drug Products 

and Antimicrobial Susceptibility 

Testing Devices.’’ The Food and Drug 

Administration Amendments Act of 

2007 (FDAAA) includes a requirement 

that FDA identify and periodically 

update susceptibility test interpretive 

criteria for antibacterial drug products 

and make those findings publicly 

available. This draft guidance informs 

industry of how FDA intends to comply 

with the FDAAA requirement. 

Specifically, the draft guidance 

describes procedures and 

responsibilities for updating 

information on susceptibility test 

interpretive criteria, susceptibility test 

methods, and quality control parameters 

in the labeling for systemic antibacterial 

drug products for human use. This draft 

guidance also describes procedures for 

making corresponding changes to 

susceptibility test interpretive criteria 

for antimicrobial susceptibility testing 

(AST) devices. 

DATES: Although you can comment on 

any guidance at any time (see 21 CFR 

10.115(g)(5)), to ensure that the agency 

considers your comments on this draft 

guidance before it begins work on the 

final version of the guidance, submit 

written or electronic comments on the 

draft guidance by August 11, 2008. 

Submit written comments on the 

proposed collection of information by 

August 11, 2008. 

ADDRESSES: Submit written requests for 

single copies of the draft guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, rm. 2201, 

Silver Spring, MD 20993–0002 or the 

Division of Small Manufacturers 

Assistance (HFZ–220), Center for 

Devices and Radiological Health, Food 

and Drug Administration, 1350 Piccard 

Dr., Rockville, MD 20850–4307. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. Submit written comments on 

the draft guidance, including comments 

regarding proposed collection of 

information, 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.regulations.gov. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the draft guidance 

document. 

FOR FURTHER INFORMATION CONTACT: 

Regarding antibacterial drug 

products: Edward Cox, Center for 

Drug Evaluation and Research, 

Food and Drug Administration, 

10903 New Hampshire Ave., Bldg. 

22, rm. 6414, Silver Spring, MD 

20993–0002, 301–796–1300, or 

Regarding AST devices: Freddie 

Poole, Center for Devices and 

Radiological Health (HFZ–440), 

Food and Drug Administration, 

2098 Gaither Rd., Rockville, MD 

20850, 240–276–0712. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Antibacterial susceptibility testing is 

used to determine if bacteria that are 

isolated from a patient with an infection 

are likely to be killed or inhibited by a 

particular antibacterial drug product at 

the concentrations of the drug that are 

attainable at the site of infection using 

the dosing regimen(s) indicated in the 

drug product’s labeling. The results 

from antibacterial susceptibility testing 

generally categorize bacteria as 

‘‘susceptible,’’ ‘‘intermediate,’’ or 

‘‘resistant’’ to each of the antibacterial 

drugs that are tested. When available, 

culture and susceptibility testing results 

are one of the factors that physicians 

consider when selecting an 

antimicrobial drug product for treating a 

patient. 

The numerical values generated by 

susceptibility testing to determine 

whether a particular microorganism is 

susceptible to a particular antimicrobial 

drug—the antimicrobial susceptibility 

test interpretive criteria—are commonly 

referred to as breakpoints. These 

breakpoints are specified in the 

antimicrobial drug product’s label. The 

antimicrobial susceptibility test 

interpretive criteria can be used to 

interpret results from either manual or 

automated AST devices. 

On September 27, 2007, the President 

signed FDAAA (Public Law 110–85) 

into law. Section 1111 of FDAAA 

requires FDA to identify and 

periodically update susceptibility test 

interpretive criteria for antibacterial 

drug products and to make those 

findings publicly available. By enacting 

section 1111 of FDAAA, Congress 

recognized the importance of 

maintaining updated susceptibility test 

interpretive criteria. 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Updating Labeling for Susceptibility 

Test Information in Systemic 

Antibacterial Drug Products and 

Antimicrobial Susceptibility Testing 

Devices’’ to inform industry of how FDA 

intends to comply with section 1111 of 

FDAAA. The draft guidance explains 

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Federal Register / Vol. 73, No. 114 / Thursday, June 12, 2008 / Notices 33439 

the importance of making available to 

health care providers the most current 

information regarding susceptibility test 

interpretive criteria for antibacterial 

drug products. The draft guidance 

describes procedures for FDA, drug 

application holders, and AST device 

manufacturers to ensure that updated 

susceptibility test information is 

available to health care providers for the 

following reasons: (1) To address 

concerns about antibacterial drug 

product labeling with out-of-date 

information on susceptibility test 

interpretive criteria, quality control 

parameters, and susceptibility test 

methods and (2) to comply with the new 

requirements of section 1111 of FDAAA. 

Where appropriate, FDA intends to 

identify susceptibility test interpretive 

criteria, quality control parameters, and 

susceptibility test methods by 

recognizing annually, in a Federal 

Register notice, standards developed by 

one or more nationally or 

internationally recognized standard 

development organizations. Drug 

application holders of approved 

antibacterial drug products will then 

have the option of relying on FDA 

recognized standards to update their 

product labeling. 

The draft guidance describes possible 

approaches that holders of new drug 

applications (NDAs) and those 

abbreviated new drug applications 

(ANDAs) that are designated as a 

reference listed drug can use to meet 

their responsibilities to update their 

product labeling for systemic 

antibacterial drug products. Application 

holders can use the following 

approaches: 

• Submit a labeling supplement that 

relies upon a standard recognized by the 

agency. 

• Submit a labeling supplement that 

includes data supporting a proposed 

change to the microbiology information 

in the labeling that differs from the 

agency’s recognized standard. 

Alternatively, in the event that 

application holders do not believe that 

any labeling changes are necessary, they 

should provide written justification in 

support of the current information in 

the Microbiology subsection of the 

product labeling. 

The agency will make the updated 

information available by publicly 

posting changes to the product labeling 

within 30 days of approval of a 

supplement that includes a change to 

the Microbiology subsection of the 

product labeling. 

The draft guidance also describes how 

manufacturers of in vitro diagnostic 

AST devices should update the 

susceptibility test information in their 

labeling to incorporate an FDA 

recognized standard or a change in 

labeling for a relevant antibacterial drug 

product. 

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 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 

requirements of the applicable statutes 

and regulations. 

II. 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. 

Please note that on January 15, 2008, 

the FDA Division of Dockets 

Management Web site transitioned to 

the Federal Dockets Management 

System (FDMS). FDMS is a 

Government-wide, electronic docket 

management system. Electronic 

comments or submissions will be 

accepted by FDA only through FDMS at 

http://www.regulations.gov. 

III. Paperwork Reduction Act of 1995 

Under the Paperwork Reduction Act 

of 1995 (the PRA) (44 U.S.C. 3501–

3520), Federal agencies must obtain 

approval from the Office of Management 

and Budget (OMB) for each collection of 

information that they conduct or 

sponsor. ‘‘Collection of information’’ is 

defined in 44 U.S.C. 3502(3) and 5 CFR 

1320.3(c) and includes agency requests 

or requirements that members of the 

public submit reports, keep records, or 

provide information to a third party. 

Section 3506(c)(2)(A) of the PRA (44 

U.S.C. 3506(c)(2)(A)) requires Federal 

agencies to provide a 60-day notice in 

the Federal Register for each proposed 

collection of information before 

submitting the collection to OMB for 

approval. To comply with this 

requirement, FDA is publishing this 

notice of the proposed collection of 

information set forth in this document. 

With respect to the collection of 

information associated with this draft 

guidance, FDA invites comments on the 

following topics: (1) Whether the 

proposed collection of information is 

necessary for the proper performance of 

FDA’s functions, including whether the 

information will have practical utility; 

(2) the accuracy of FDA’s estimated 

burden of the proposed collection of 

information, including the validity of 

the methodology and assumptions used; 

(3) ways to enhance the quality, utility, 

and clarity of the information to be 

collected; and (4) ways to minimize the 

burden of the collection of information 

on respondents, including through the 

use of automated collection techniques, 

when appropriate, and other forms of 

information technology. 

Application holders can use one of 

the following approaches to meet their 

responsibilities to update their product 

labeling under the draft guidance and 

FDA regulations: Submit a labeling 

supplement that relies upon a standard 

recognized by FDA in a Federal Register 

notice, or submit a labeling supplement 

that includes data supporting a 

proposed change to the microbiology 

information in the labeling. In addition, 

application holders should include in 

their annual report an assessment of 

whether the information in the 

Microbiology subsection of their product 

labeling is current or changes are 

needed. This information collection is 

already approved by OMB under control 

number 0910–0572 (the requirement in 

21 CFR 201.56(a)(2) to update labeling 

when new information becomes 

available that causes the labeling to 

become inaccurate, false, or misleading) 

and control number 0910–0001 (the 

requirement in 21 CFR 314.70(b)(2)(v) to 

submit labeling supplements for certain 

changes in the product’s labeling, and 

the requirement in 21 CFR 

314.81(b)(2)(i) to include in the annual 

report a brief summary of significant 

new information from the previous year 

that might affect the labeling of the drug 

product). 

In addition, under the draft guidance, 

if the information in the applicant’s 

product labeling differs from the 

standards recognized by FDA in the 

Federal Register notice, and the 

applicant believes that changes to the 

labeling are not needed, the applicant 

should provide written justification to 

FDA. This justification should explain 

why the recognized standard does not 

apply to its drug product and why 

changes are not needed to the 

Microbiology subsection of the product’s 

labeling. This justification should also 

be submitted as general correspondence 

to the product’s application, and a 

statement indicating that no change is 

currently needed and the supporting 

justification should be included in the 

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33440 Federal Register / Vol. 73, No. 114 / Thursday, June 12, 2008 / Notices 

annual report. Based on our knowledge 

of the need to update information on 

susceptibility test interpretive criteria, 

susceptibility test methods, and quality 

control parameters in the labeling for 

systemic antibacterial drug products for 

human use, we estimate that, annually, 

only 2 applicants will submit the 

written justification described 

previously and in the draft guidance. 

We also estimate that each justification 

will take approximately 16 hours to 

prepare and submit to FDA as general 

correspondence and as part of the 

annual report. 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1

No. of 

Respondents 

No. of Responses per 

Respondent Total Responses Hours Per Response Total Hours 

Justification submitted as general 

correspondence and in the annual report 2 1 2 16 32 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the document at either 

http://www.fda.gov/cder/guidance/ 

index.htm or http:// 

www.regulations.gov. 

Dated: June 9, 2008. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. 08–1350 Filed 6–10–08; 11:31 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2008–0321] 

Hospira, Inc., et al.; Withdrawal of 

Approval of One New Drug Application 

and Two Abbreviated New Drug 

Applications 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is withdrawing 

approval of one new drug application 

(NDA) and two abbreviated new drug 

applications (ANDAs) for edetate 

disodium injection. The holders of these 

applications have agreed in writing to 

permit FDA to withdraw approval of the 

applications and have waived their 

opportunity for a hearing. 

DATES: Effective June 12, 2008. 

FOR FURTHER INFORMATION CONTACT: 

Florine P. Purdie, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, rm. 6366, 

Silver Spring, MD 20993–0002, 301–

796–3601. 

SUPPLEMENTARY INFORMATION: FDA 

informed the holders of the following 

applications that the agency believes a 

potential problem associated with 

edetate disodium is sufficiently serious 

that the following drug products should 

be removed from the market: 

Application No. Drug Applicant 

NDA 11–355 ENDRATE (edetate disodium) Injection Hospira, Inc., 275 North Field Dr., 

Lake Forest, IL 60045– 5046 

ANDA 40–376 Edetate Disodium Injection Apotex Inc., 150 Signet Dr., Toronto, 

Ontario, Canada M9L 1T9 

ANDA 40–437 Edetate Disodium Injection Bioniche Pharma, 272 E. Deerpath Rd., 

suite 304, Lake Forest, IL 60045 

Edetate disodium is indicated for the 

treatment of hypercalcemia and for the 

control of ventricular arrhythmias 

associated with digitalis toxicity. 

Hospira, Inc. (Hospira), Apotex Inc. 

(Apotex), and Bioniche Pharma 

(Bioniche) have agreed in writing to 

permit FDA to withdraw approval of 

their respective applications (listed in 

the table of this document), and to 

voluntarily remove their respective 

products from the market, under 

§ 314.150(d) (21 CFR 314.150(d)). 

On January 16, 2008, FDA issued a 

public health advisory to alert patients 

and healthcare professionals about 

important safety information concerning 

the drug edetate disodium (see ‘‘FDA 

Public Health Advisory: Edetate 

Disodium (Marketed as ENDRATE and 

Generic Products),’’ available on the 

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

drug/infopage/edetateldisodium/ 

default.htm). As noted in the January 

16, 2008, Public Health Advisory, there 

have been cases where children and 

adults have died when they were 

mistakenly given edetate disodium 

instead of edetate calcium disodium 

(calcium disodium versenate) or when 

edetate disodium was used for 

indications other than those approved 

by FDA. FDA asked Hospira, Apotex, 

and Bioniche to voluntarily remove 

their products (listed in the table of this 

document) from the market because of 

safety concerns. 

Hospira’s NDA 11–355 for ENDRATE 

was initially approved in 1959 solely on 

the basis of safety. The 1962 

amendments to the Federal Food, Drug, 

and Cosmetic Act (the act) required that 

drugs be shown to be effective as well. 

To accomplish this, FDA initiated the 

Drug Efficacy Study Implementation 

(DESI) review to evaluate the 

effectiveness of drugs that had been 

previously approved on safety grounds 

alone. In its DESI review of edetate 

disodium, FDA concluded that edetate 

disodium was effective for the treatment 

of hypercalcemia and for the control of 

ventricular arrhythmias associated with 

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