20686 Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Notices 

(mitoxantrone hydrochloride) Injection, 

EQ 25 mg base/12.5 mL and EQ 30 mg 

base/15 mL, was withdrawn for reasons 

of safety or effectiveness. We have 

carefully reviewed our files for records 

concerning the withdrawal of 

NOVANTRONE (mitoxantrone 

hydrochloride) Injection, EQ 25 mg 

base/12.5 mL and EQ 30 mg base/15 mL, 

from sale. We have also independently 

evaluated relevant literature and data 

for possible postmarketing adverse 

events. We have found no information 

that would indicate that this product 

was withdrawn from sale for reasons of 

safety or effectiveness. 

Accordingly, the Agency will 

continue to list NOVANTRONE 

(mitoxantrone hydrochloride) Injection, 

EQ 25 mg base/12.5 mL and EQ 30 mg 

base/15 mL, in the ‘‘Discontinued Drug 

Product List’’ section of the Orange 

Book. The ‘‘Discontinued Drug Product 

List’’ delineates, among other items, 

drug products that have been 

discontinued from marketing for reasons 

other than safety or effectiveness. FDA 

will not begin procedures to withdraw 

approval of approved ANDAs that refer 

to NOVANTRONE Injection. Additional 

ANDAs for mitoxantrone hydrochloride 

injection, EQ 25 mg base/12.5 mL and 

EQ 30 mg base/15 mL, may also be 

approved by the Agency as long as they 

meet all other legal and regulatory 

requirements for the approval of 

ANDAs. If FDA determines that labeling 

for this drug product should be revised 

to meet current standards, the Agency 

will advise ANDA applicants to submit 

such labeling. 

Dated: April 6, 2011. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2011–8819 Filed 4–12–11; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–D–0164] 

Draft Guidance for Industry on Safety 

Labeling Changes; Implementation of 

the Federal Food, Drug, and Cosmetic 

Act; 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availability of a draft guidance for 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 ‘‘Safety Labeling 

Changes—Implementation of Section 

505(o)(4) of the Federal Food, Drug, and 

Cosmetic Act.’’ The Food and Drug 

Administration Amendments Act of 

2007 (FDAAA) added new provisions to 

the Federal Food, Drug, and Cosmetic 

Act (the FD&C Act) authorizing FDA to 

require certain drug and biological 

product application holders to make 

safety related labeling changes based 

upon new safety information that 

becomes available after the drug or 

biological product is approved under 

the FD&C Act or the Public Health 

Service Act (the PHS Act). This draft 

guidance provides information on the 

implementation of the new provisions, 

including a description of the types of 

safety labeling changes that ordinarily 

might be required under the new 

legislation, how FDA plans to determine 

what constitutes new safety 

information, the procedures involved in 

requiring safety labeling changes, and 

enforcement of the requirements for 

safety labeling changes. 

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 comment 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 July 12, 2011. 

ADDRESSES: Submit written requests for 

single copies of this 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 

Office of Communication, Outreach and 

Development (HFM–40), Center for 

Biologics Evaluation and Research 

(CBER), Food and Drug Administration, 

1401 Rockville Pike, Rockville, MD 

20852–1448. The guidance may also be 

obtained by mail by calling CBER at 1– 

800–835–4709 or 301–827–1800. Send 

one self-addressed adhesive label to 

assist the office in processing your 

requests. 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.regulations.gov. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the draft guidance 

document. 

FOR FURTHER INFORMATION CONTACT: 

Kristen Everett, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 6228, 

Silver Spring, MD 20993–0002, 301– 

796–5400, or Stephen Ripley, Center for 

Biologics Evaluation and Research 

(HFM–17), Food and Drug 

Administration, 1401 Rockville Pike, 

Rockville, MD 20852–1448, 301–827– 

6210. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Safety Labeling Changes— 

Implementation of Section 505(o)(4) of 

the Federal Food, Drug, and Cosmetic 

Act.’’ In the past, FDA has requested that 

holders of applications for approved 

products make labeling changes related 

to safety after approval to address 

serious risks. FDA learned of the 

potential for such serious risks from a 

variety of sources. In most cases, 

application holders responded to these 

requests by negotiating appropriate 

language with FDA staff to address the 

concerns, and then submitting a 

supplement or amended supplement to 

obtain approval of the change. 

Negotiations were often protracted, and 

FDA had few tools available at its 

disposal to end negotiations and require 

the changes. Congress recognized the 

limitations of FDA’s authority in this 

area and, in FDAAA, gave FDA new 

authority to require safety labeling 

changes in certain circumstances. 

Title IX, section 901 of FDAAA (Pub. 

L. 110–85) amended the FD&C Act by 

adding new section 505(o)(4) (21 U.S.C. 

355(o)(4)). Section 505(o)(4) authorizes 

FDA to require, and if necessary, order 

labeling changes if FDA becomes aware 

of new safety information that FDA 

believes should be included in the 

labeling of certain prescription drug and 

biological products approved under 

section 505 of the FD&C Act or section 

351 of the PHS Act (42 U.S.C. 262). 

Specifically, section 505(o)(4) of the 

FD&C Act applies to prescription drug 

products with an approved new drug 

application (NDA) under section 505(b) 

of the FD&C Act, biological products 

with an approved biologics license 

application (BLA) under section 351 of 

the PHS Act, or prescription drug 

products with an approved abbreviated 

new drug application (ANDA) under 

section 505(j) of the FD&C Act if the 

reference listed drug (RLD) with an 

approved NDA is not currently 

marketed. FDAAA imposes timeframes 

for application holders to submit and 

FDA staff to review such changes, and 

gives FDA new enforcement tools to 

bring about timely and appropriate 

labeling changes. This draft guidance 

provides information on the 

implementation of the new provisions, 

including a description of the types of 

safety labeling changes that ordinarily 

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Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Notices 20687 

might be required under the new 

legislation, how FDA plans to determine 

what constitutes new safety 

information, the procedures involved in 

requiring safety labeling changes, and 

enforcement of the requirements for 

safety labeling changes. 

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 the implementation of section 901 of 

FDAAA on safety labeling changes. 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) either electronic or written 

comments regarding this document. It is 

only necessary to send one set of 

comments. It is no longer necessary to 

send two copies of mailed comments. 

Identify comments 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. 

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 collections of 

information associated with this draft 

guidance that were not previously 

approved by OMB, described below, 

FDA invites comments on the following 

topics: (1) Whether the proposed 

information collected 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 information 

collected, including the validity of the 

methodology and assumptions used; (3) 

ways to enhance the quality, utility, and 

clarity of the information collected; and 

(4) ways to minimize the burden of 

information collected on the 

respondents, including through the use 

of automated collection techniques, 

when appropriate, and other forms of 

information technology. 

This draft guidance provides 

information on the implementation of 

section 901 of FDAAA, which 

authorizes FDA to require certain drug 

and biological product application 

holders to make safety related labeling 

changes based upon new safety 

information that becomes available after 

the drug or biological product is 

approved under the FD&C Act or the 

PHS Act. FDA plans to request safety 

labeling changes by sending a 

notification letter to the application 

holder. Under section 505(o)(4)(B), the 

application holder must respond to 

FDA’s notification by submitting a 

labeling supplement or notifying FDA 

that the applicant does not believe the 

labeling change is warranted and 

submitting a statement detailing the 

reasons why the application holder does 

not believe a change is warranted (a 

rebuttal statement). 

The submission of rebuttal statements 

may result in the collection of 

information that is not already approved 

by OMB. Based on FDA’s experience 

thus far with safety labeling changes 

requirements under section 505(o)(4), 

FDA estimates that approximately six 

application holders will elect to submit 

approximately one rebuttal statement 

each year and that each rebuttal 

statement will take approximately 6 

hours to prepare. 

In addition, in the draft guidance, the 

agency states that new labeling prepared 

in response to a safety labeling change 

notification should be available on the 

application holder’s Web site within 10 

calendar days of approval, which may 

result in the collection of information 

that is not already approved by OMB. 

FDA estimates that approximately 197 

application holders will post new 

labeling one time each year in response 

to a safety labeling change notification 

and that the posting of the labeling will 

take approximately 4 hours to prepare. 

FDA estimates the burden of the 

collections of information that have not 

already been approved by OMB, is as 

follows: 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1

Number of 

respondents 

Number of 

responses per 

respondent 

Total 

responses 

Hours per 

response Total hours 

Rebuttal statement ............................................................... 6 1 6 6 36 

Total .............................................................................. ........................ ........................ ........................ ........................ 36 

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

TABLE 2—ESTIMATED ANNUAL THIRD PARTY DISCLOSURE BURDEN 1

Type of submission Number of 

respondents 

Annual 

frequency per 

disclosure 

Total annual 

disclosures 

Hours per 

disclosure Total hours 

Post approved labeling on application holder’s Web site ... 197 1 197 4 788 

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

This draft guidance also refers to 

previously approved collections of 

information. Specifically, the draft 

guidance describes: Labeling 

supplements for NDAs, ANDAs, and 

BLAs submitted under 21 CFR 314.70, 

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20688 Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Notices 

314.71, 314.97 and 601.12; and the 

content and format of prescription drug 

labeling submitted under 21 CFR 201.56 

and 201.57. These collections of 

information are subject to review by 

OMB under the PRA act and are 

approved under OMB control numbers 

0910–0001, 0910–0338, and 0910–0572. 

Section V of the draft guidance refers to 

the guidance entitled ‘‘Formal Dispute 

Resolution: Appeals Above the Division 

Level,’’ which describes collections of 

information approved under OMB 

control number 0910–0430. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the document at http:// 

www.fda.gov/Drugs/Guidance

ComplianceRegulatoryInformation/ 

Guidances/default.htm, http:// 

www.fda.gov/BiologicsBloodVaccines/

GuidanceCompliance

RegulatoryInformation/Guidances/

default.htm, or http:// 

www.regulations.gov. 

Dated: April 7, 2011. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2011–8895 Filed 4–12–11; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–1998–D–0281] 

Guidance for Industry and Food and 

Drug Administration Staff; 30-Day 

Notices, 135-Day Premarket Approval 

Supplements and 75-Day Humanitarian 

Device Exemption Supplements for 

Manufacturing Method or Process 

Changes; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of the guidance entitled ‘‘30- 

Day Notices, 135-Day Premarket 

Approval (PMA) Supplements and 75- 

Day Humanitarian Device Exemption 

(HDE) Supplements for Manufacturing 

Method or Process Changes.’’ This 

document provides guidance on the 

type of changes to an approved 

application that FDA believes may 

qualify for submission as 30-day 

notices, the type of information to 

submit in a 30-day notice, and the user 

fees associated with these submissions. 

The guidance document is immediately 

in effect, but it remains subject to 

comment in accordance with the 

Agency’s good guidance practices 

(GGP). 

DATES: Submit either electronic or 

written comments on this guidance at 

any time. General comments on Agency 

guidance documents are welcome at any 

time. 

ADDRESSES: Submit written requests for 

single copies of this guidance to the 

Division of Small Manufacturers, 

International, and Consumer Assistance, 

Center for Devices and Radiological 

Health (CDRH), Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 4613, Silver Spring, 

MD 20993–0002; or to the Office of 

Communication, Outreach and 

Development (HFM–40), Center for 

Biologics Evaluation and Research 

(CBER), Food and Drug Administration, 

1401 Rockville Pike, Rockville, MD 

20852–1448. Send one self-addressed 

adhesive label to assist that office in 

processing your request. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the guidance. 

Submit electronic comments on the 

guidance to http://www.regulations.gov. 

Submit written comments to the 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, Rm. 1061, Rockville, 

MD 20852. 

FOR FURTHER INFORMATION CONTACT: 

For devices regulated by CDRH: 

Anastacia Bilek, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 3656, Silver Spring, 

MD 20993–0002, 301–796–5588. 

For devices regulated by CBER: 

Stephen Ripley, Center for Biologics 

Evaluation and Research (HFM–17), 

Food and Drug Administration, 1401 

Rockville Pike, Suite 200N, Rockville, 

MD 20852, 301–827–6210. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a guidance for industry entitled ‘‘30-Day 

Notices, 135-Day Premarket Approval 

(PMA) Supplements and 75-Day 

Humanitarian Device Exemption (HDE) 

Supplements for Manufacturing Method 

or Process Changes.’’ This guidance is 

being issued consistent with FDA’s GGP 

regulation (§ 10.115 (21 CFR 10.115). 

This guidance is being implemented 

without prior public comment because 

the Agency has determined that prior 

public participation is not feasible or 

appropriate (§ 10.115(g)(2)). The Agency 

made this determination because 

statutory provisions regarding medical 

device user fees under the Food and 

Drug Administration Amendments Act 

of 2007 (FDAAA) (Pub. L. 110–85) are 

in effect and being implemented, and 

guidance is needed to help effect such 

implementation. Although this guidance 

is immediately in effect, it remains 

subject to comment in accordance with 

the Agency’s GGP regulation. 

The Medical Device User Fee and 

Modernization Act of 2002 (MDUFMA) 

(Pub. L. 107–250) amended the Federal 

Food, Drug, and Cosmetic Act (the 

FD&C Act) (21 U.S.C. et seq.) to 

authorize FDA to collect user fees for 

the review of certain premarket 

submissions (See section 708 of the 

FD&C Act (21 U.S.C. 379j).) FDAAA 

further amended the FD&C Act to 

extend FDA’s authority to collect 

medical device user fees through 

September 30, 2012, and added 30-day 

notices to the types of premarket 

submissions subject to user fees (21 

U.S.C. 379j(a)(2)(A)(vi)). For additional 

information on the MDUFMA, please 

see http://www.fda.gov/MedicalDevices/ 

DeviceRegulationandGuidance/

Overview/MedicalDeviceUser

FeeandModernizationActMDUFMA/

default.htm. 

This guidance supersedes the 

previous guidance document entitled 

‘‘30-Day Notices and 135-Day PMA 

Supplements for Manufacturing Method 

or Process Changes, Guidance for 

Industry and CDRH,’’ that published in 

the Federal Register of February 25, 

1998 (63 FR 9570). This guidance 

describes the user fees authorized, 

updates the previous guidance to clarify 

the process for submitting a 30-day 

notice, and provides additional 

information on the types of changes that 

may be submitted. The previous 

guidance did not include information 

on HDEs even though certain 

modifications to a manufacturing 

procedure or method of manufacture for 

HDEs are subject to the 30-day notice 

provisions. The current guidance 

includes this information. 

The guidance represents the Agency’s 

current thinking on 30-day notices, 135- 

day PMA supplements and 75-Day HDE 

supplements for manufacturing method 

or process changes. 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. 

II. Paperwork Reduction Act of 1995 

This 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– 

mstockstill on DSKH9S0YB1PROD with NOTICES