Federal Register / Vol. 79, No. 234 / Friday, December 5, 2014 / Notices 72185 

1Section 505–1 of the FD&C Act applies to any 

application for approval of a prescription drug 

submitted under section 505(b) or (j) of the FD&C 

Act (including both NDAs submitted under section 

505(b)(2) and ANDAs submitted under section 

505(j)), as well as applications submitted under 

section 351 of the Public Health Service Act (42 

U.S.C. 262). 

will have a significant impact on small 

entities. 

In addition, section 1102(b) of the Act 

requires us to prepare a regulatory 

impact analysis if a rule may have a 

significant impact on the operations of 

a substantial number of small rural 

hospitals. This analysis must conform to 

the provisions of section 604 of the 

RFA. For purposes of section 1102(b) of 

the Act, we define a small rural hospital 

as a hospital that is located outside of 

a Metropolitan Statistical Area for 

Medicare payment regulations and has 

fewer than 100 beds. We are not 

preparing an analysis for section 1102(b) 

of the Act because we have determined, 

and the Secretary certifies, that this 

notice would not have a significant 

impact on the operations of a substantial 

number of small rural hospitals. 

Section 202 of the Unfunded 

Mandates Reform Act of 1995 (UMRA) 

also requires that agencies assess 

anticipated costs and benefits before 

issuing any rule whose mandates 

require spending in any 1 year of $100 

million in 1995 dollars, updated 

annually for inflation. In 2014, that 

threshold is approximately $141 

million. The Agency has determined 

that there will be minimal impact from 

the costs of this notice, as the threshold 

is not met under the UMRA. 

Executive Order 13132 establishes 

certain requirements that an agency 

must meet when it promulgates a 

proposed rule (and subsequent final 

rule) that imposes substantial direct 

requirement costs on state and local 

governments, preempts state law, or 

otherwise has federalism implications. 

Since this notice does not impose 

substantial direct costs on state or local 

governments, the requirements of 

Executive Order 13132 are not 

applicable. 

In accordance with the provisions of 

Executive Order 12866, this notice was 

reviewed by the Office of Management 

and Budget. 

Dated: October 22, 2014. 

Marilyn Tavenner, 

Administrator, Centers for Medicare & 

Medicaid Services. 

[FR Doc. 2014–28503 Filed 12–2–14; 4:15 pm] 

BILLING CODE 4120–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2014–D–1891] 

How To Obtain a Letter From the Food 

and Drug Administration Stating That 

Bioequivalence Study Protocols 

Contain Safety Protections 

Comparable to Applicable Risk 

Evaluation and Mitigation Strategies 

for Reference Listed Drugs; Draft 

Guidance for Industry; 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 ‘‘How to Obtain a 

Letter from FDA Stating that 

Bioequivalence Study Protocols Contain 

Safety Protections Comparable to 

Applicable REMS for RLD.’’ This draft 

guidance describes how a prospective 

abbreviated new drug application 

(ANDA) applicant may request a letter 

stating that FDA has determined the 

following: The potential applicant’s 

bioequivalence (BE) study protocol 

contains safety protections comparable 

to those in the risk evaluation and 

mitigation strategy (REMS) with 

elements to assure safe use (ETASU) 

applicable to the reference listed drug 

(RLD) and FDA will not consider it a 

violation of the REMS for the RLD 

sponsor to provide a sufficient quantity 

of the RLD to the interested generic firm 

or its agent to allow the firm to perform 

the testing necessary to support its 

ANDA. 

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 

either electronic or written comments 

on the draft guidance by February 3, 

2015. 

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. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the guidance document. 

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: 

Elizabeth Giaquinto, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 75, Rm. 1670, 

Silver Spring, MD 20993, 240–402– 

7930, Elizabeth.Giaquinto@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘How to Obtain a Letter from FDA 

Stating that Bioequivalence Study 

Protocols Contain Safety Protections 

Comparable to Applicable REMS for 

RLD.’’ Section 505–1(a)(1) of the FD&C 

Act authorizes FDA to require 

applicants to submit a proposed REMS 

as a part of the relevant application 1 if 

FDA determines that a REMS is 

necessary to ensure that the benefits of 

a drug outweigh its risks (21 U.S.C. 355– 

1(a)(1)). A REMS is a required risk 

management plan that uses tools beyond 

routine professional labeling (such as a 

medication guide, a patient package 

insert, and/or a communication plan) to 

ensure that the benefits of a drug 

outweigh its risks (section 505–1(f) of 

the FD&C Act). In addition, FDA may 

require ETASU in some circumstances 

when such elements are necessary to 

mitigate the risks associated with the 

drug. ETASU may include, for example, 

requirements that health care providers 

who prescribe or administer the drug 

have particular training or certification; 

that patients using the drug be 

monitored and/or enrolled in a registry; 

or that pharmacies, practitioners, or 

health care settings that dispense the 

drug be specially certified. 

FDA is aware of instances in which an 

RLD sponsor has refused to sell drug 

products to a prospective ANDA 

applicant seeking to conduct the testing 

needed to obtain approval, and the RLD 

sponsor has cited the REMS ETASU as 

justification. In the interest of 

facilitating prospective generic 

applicants’ access to RLD products to 

conduct the testing necessary to support 

ANDA approval, FDA has, on request, 

reviewed the BE study protocols 

proposed by a prospective ANDA 


wreier-aviles on DSK5TPTVN1PROD with NOTICES
72186 Federal Register / Vol. 79, No. 234 / Friday, December 5, 2014 / Notices 

applicant to assess whether they 

provide safety protections comparable 

to those in the applicable REMS 

ETASU. When the Agency has 

determined that comparable protections 

existed, FDA has issued letters to the 

RLD sponsor stating so, and indicating 

that FDA would not consider it to be a 

violation of the REMS for the RLD 

sponsor to provide drug product to the 

prospective ANDA applicant or its 

agent. 

Requesting or obtaining such a letter 

from FDA is not a legal requirement. If 

a prospective ANDA applicant chooses 

to request such a letter, this guidance is 

intended to clarify the process for doing 

so. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents the Agency’s 

current thinking on how a prospective 

generic applicant can obtain a letter 

stating that its BE study protocols 

contain safety protections comparable to 

those in the applicable REMS for the 

RLD. It does not create or confer any 

rights for or on any person and does not 

operate to bind FDA or the public. 

II. Comments 

Interested persons may submit either 

electronic comments regarding this 

document to http://www.regulations.gov 

or written comments to the Division of 

Dockets Management (see ADDRESSES). It 

is only necessary to send one set of 

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, and 

will be posted to the docket at http://

www.regulations.gov. 

III. The Paperwork Reduction Act of 

1995 

This guidance refers to previously 

approved collections of information that 

are subject to review by the Office of 

Management and Budget under the 

Paperwork Reduction Act of 1995 (44 

U.S.C. 3501–3520). The collections of 

information in 21 CFR parts 312 and 

314 have been approved under OMB 

control numbers 0910–0014 and 0910– 

0001. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the document at either 

http://www.fda.gov/Drugs/Guidance

ComplianceRegulatoryInformation/

Guidances/default.htm or http://www.

regulations.gov. 

Dated: December 1, 2014. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2014–28540 Filed 12–4–14; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2014–N–1795] 

Mallinckrodt Inc. et al.; Withdrawal of 

Approval of 23 New Drug Applications 

and 68 Abbreviated New Drug 

Applications 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is withdrawing 

approval of 23 new drug applications 

(NDAs) and 68 abbreviated new drug 

applications (ANDAs) from multiple 

applicants. The holders of the 

applications notified the Agency in 

writing that the drug products were no 

longer marketed and requested that the 

approval of the applications be 

withdrawn. 

DATES: Effective Date: January 5, 2015. 

FOR FURTHER INFORMATION CONTACT: 

Florine P. Purdie, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 6248, 

Silver Spring, MD 20993–0002, 301– 

796–3601. 

SUPPLEMENTARY INFORMATION: The 

holders of the applications listed in 

table 1 in this document have informed 

FDA that these drug products are no 

longer marketed and have requested that 

FDA withdraw approval of the 

applications pursuant to the process in 

§ 314.150(c) (21 CFR 314.150(c)). The 

applicants have also, by their requests, 

waived their opportunity for a hearing. 

Withdrawal of approval of an 

application or abbreviated application 

under § 314.150(c) is without prejudice 

to refiling. 

TABLE 1 

Application No. Drug Applicant 

NDA 002852 ...... Plexofer (multivitamins) Syrup ................................................. Mallinckrodt Inc., 675 McDonnell Blvd., Hazelwood, MO 

63042. 

NDA 008719 ...... Levo-Dromoran (levorphanol tartrate) Injection, 2 milligrams 

(mg)/milliliter (mL).

Valeant Pharmaceuticals North America LLC, 400 Somerset 

Corporate Blvd., Bridgewater, NJ 08807. 

NDA 008720 ...... Levo-Dromoran (levorphanol tartrate) Tablets, 2 mg .............. Do. 

NDA 011777 ...... Sodium Phosphate P 32 Solution ............................................ Mallinckrodt Inc. 

NDA 012366 ...... Soma Compound with Codeine (carisoprodol, aspirin, and 

codeine phosphate).

Meda Pharmaceuticals Inc., 265 Davidson Ave., Suite 300, 

Somerset, NJ 08873–4120. 

NDA 012708 ...... Diutensen-R (methyclothiazide and reserpine) Tablets, 2.5 

mg/0.1 mg.

Do. 

NDA 016245 ...... Vercyte (pipobroman) Tablets .................................................. AbbVie, Inc., 1 North Waukegan Rd., Dept. PA 77/Bldg. 

AP30, North Chicago, IL 60064. 

NDA 017463 ...... Motrin (ibuprofen) Tablets, 300 mg, 400 mg, 600 mg, and 

800 mg.

McNeil Consumer Healthcare Division of McNeil-PPC, Inc., 

7050 Camp Hill Rd., Fort Washington, PA 19034–2299. 

NDA 018310 ...... Lymphazurin (isosulfan blue), 1% ............................................ Covidien, 60 Middletown Ave., North Haven, CT 06473. 

NDA 018340 ...... Aerobid (flunisolide) Inhalation Aerosol 1 ................................. Roche Palo Alto LLC, c/o Genentech Inc., 1 DNA Way, 

South San Francisco, CA 94080–4990. 

NDA 018731 ...... Buspar (buspirone hydrochloride (HCl)) Tablets, 5 mg, 10 

mg, 15 mg, and 30 mg.

Bristol-Myers Squibb Co., P.O. Box 4000, Princeton, NJ 

08543–4000. 

NDA 019453 ...... Drixoral (dexbrompheniramine maleate, pseudoephedrine 

sulfate, and acetaminophen) Extended-Release Tablets, 3 

mg, 60 mg, and 500 mg.

Merck Consumer Care, 556 Morris Ave., Summit, NJ 07901. 


wreier-aviles on DSK5TPTVN1PROD with NOTICES