Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Notices 20685 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1—Continued 

21 CFR Section/FDA Form No. Number of 

respondents 4

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

(in Hours) 

Total hours 

558.5(i) ............................................................................. 154 .01 1 .54 5 8 

514.1(b)(8) and 514.8(c)(1) 3 ........................................... 154 .21 32 .34 90 2,911 

FDA Form 356V ............................................................... 154 5 .1 785 .4 5 3,927 

Total .......................................................................... ........................ .......................... .......................... ........................ 33,319 

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

2Substantial Evidence—Because 21 CFR 514.4 only defines substantial evidence, it should not be viewed as creating additional collection burden. 3 NADAs and supplements regarding antimicrobial animal drugs that use a recommended approach to assessing antimicrobial concerns as 

part of the overall preapproval safety evaluation. 4Based on the number of sponsors subject to animal drug user fees, FDA estimates that there was an average of 154 annual respondents 

during the 5 fiscal years, from October 1, 2005, through September 30, 2010, on which these estimates were made. We use this estimate consistently throughout the table and calculate the ‘‘annual frequency per respondent’’ by dividing the total annual responses by the number of 

respondents. 

Dated: April 7, 2011. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2011–8906 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–2008–P–0485] 

Determination That NOVANTRONE 

(Mitoxantrone Hydrochloride) Injection, 

Equivalent to 25 Milligrams Base/12.5 

Milliliter and Equivalent to 30 

Milligrams Base/15 Milliliter, Was Not 

Withdrawn From Sale for Reasons of 

Safety or Effectiveness 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) has determined 

that NOVANTRONE (mitoxantrone 

hydrochloride) Injection, equivalent to 

(EQ) 25 milligrams (mg) base/12.5 

milliliters (mL) and EQ 30 mg base/15 

mL, was not withdrawn from sale for 

reasons of safety or effectiveness. This 

determination means that FDA will not 

begin procedures to withdraw approval 

of abbreviated new drug applications 

(ANDAs) that refer to this drug product, 

and it will allow FDA to continue to 

approve ANDAs that refer to the 

product as long as they meet relevant 

legal and regulatory requirements. 

FOR FURTHER INFORMATION CONTACT: 

Rachel Bressler, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, rm. 6302, 

Silver Spring, MD 20993–0002, 301– 

796–4288. 

SUPPLEMENTARY INFORMATION: In 1984, 

Congress enacted the Drug Price 

Competition and Patent Term 

Restoration Act of 1984 (Pub. L. 98–417) 

(the 1984 amendments), which 

authorized the approval of duplicate 

versions of drug products under an 

ANDA procedure. ANDA applicants 

must, with certain exceptions, show that 

the drug for which they are seeking 

approval contains the same active 

ingredient in the same strength and 

dosage form as the ‘‘listed drug,’’ which 

is a version of the drug that was 

previously approved. ANDA applicants 

do not have to repeat the extensive 

clinical testing otherwise necessary to 

gain approval of a new drug application 

(NDA). The only clinical data required 

in an ANDA are data to show that the 

drug that is the subject of the ANDA is 

bioequivalent to the listed drug. 

The 1984 amendments include what 

is now section 505(j)(7) of the Federal 

Food, Drug, and Cosmetic Act (21 U.S.C. 

355(j)(7)), which requires FDA to 

publish a list of all approved drugs. 

FDA publishes this list as part of the 

‘‘Approved Drug Products With 

Therapeutic Equivalence Evaluations,’’ 

which is known generally as the 

‘‘Orange Book.’’ Under FDA regulations, 

drugs are removed from the list if the 

Agency withdraws or suspends 

approval of the drug’s NDA or ANDA 

for reasons of safety or effectiveness or 

if FDA determines that the listed drug 

was withdrawn from sale for reasons of 

safety or effectiveness (21 CFR 314.162). 

A person may petition the Agency to 

determine, or the Agency may 

determine on its own initiative, whether 

a listed drug was withdrawn from sale 

for reasons of safety or effectiveness. 

This determination may be made at any 

time after the drug has been withdrawn 

from sale, but must be made prior to 

approving an ANDA that refers to the 

listed drug (§ 314.161 (21 CFR 314.161)). 

FDA may not approve an ANDA that 

does not refer to a listed drug. 

NOVANTRONE (mitoxantrone 

hydrochloride) Injection, EQ 25 mg 

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

is the subject of NDA 19–297, held by 

EMD Serono, and initially approved on 

December 23, 1987. NOVANTRONE is 

indicated for reducing neurologic 

disability and/or the frequency of 

clinical relapses in patients with 

secondary (chronic) progressive, 

progressive relapsing, or worsening 

relapsing-remitting multiple sclerosis 

(i.e., patients whose neurologic status is 

significantly abnormal between 

relapses). NOVANTRONE 

(mitoxantrone hydrochloride) Injection, 

EQ 25 mg base/12.5 mL and EQ 30 mg 

base/15 mL, is currently listed in the 

‘‘Discontinued Drug Product List’’ 

section of the Orange Book. There are 

approved ANDAs for NOVANTRONE 

(mitoxantrone hydrochloride) Injection, 

EQ 25 mg base/12.5 mL and EQ 30 mg 

base/15 mL; these ANDAs are listed in 

the Orange Book. 

Apotex, Inc., submitted a citizen 

petition dated September 3, 2008 

(Docket No. FDA–2008–P–0485), under 

21 CFR 10.30, requesting that the 

Agency determine whether 

NOVANTRONE (mitoxantrone 

hydrochloride) Injection, 25 mg/12.5 mL 

and 30 mg/15 mL, was withdrawn from 

sale for reasons of safety or 

effectiveness. 

After considering the citizen petition 

and reviewing Agency records, FDA has 

determined under § 314.161 that 

NOVANTRONE (mitoxantrone 

hydrochloride) Injection, EQ 25 mg 

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

was not withdrawn for reasons of safety 

or effectiveness. The petitioner has 

identified no data or other information 

suggesting that NOVANTRONE 

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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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