Federal Register / Vol. 77, No. 29 / Monday, February 13, 2012 / Notices 7585 

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The draft guidance, when finalized, will 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) 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 

This draft guidance refers to 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). In the draft 

guidance, FDA advises drug and 

medical device manufacturers who 

receive and use crude heparin to 

manufacture drugs and medical devices 

to notify the Agency of crude heparin 

found to contain any amount of OSCS 

(for human drugs 21 CFR 

314.81(b)(1)(ii); for animal drugs 21 CFR 

514.80(b); for medical devices 21 CFR 

803.50). The collections of information 

in 21 CFR 314.81(b)(1)(ii) have been 

approved under OMB control number 

0910–0001; in 21 CFR 514.80(b) under 

OMB control number 0910–0284; and in 

21 CFR 803.50 under OMB control 

number 0910–0437. 

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, http://

www.fda.gov/AnimalVeterinary/

GuidanceComplianceEnforcement/ 

GuidanceforIndustry/default.htm, 

http://www.fda.gov/MedicalDvices/

DeviceRegulationandGuidance/ 

GuidanceDocuments/default.htm, or 

http://www.regulations.gov. 

Dated: February 8, 2012. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2012–3229 Filed 2–10–12; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2007–D–0369] 

Draft Guidance for Industry on 

Bioequivalence Recommendations for 

Rifaximin Tablets; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of two draft guidances for 

industry entitled ‘‘Bioequivalence 

Recommendations for Rifaximin,’’ one 

for the 200-milligram (mg) strength 

(rifaximin-200) and one for the 550-mg 

strength (rifaximin-550). The 

recommendations provide specific 

guidance on the design of 

bioequivalence (BE) studies to support 

abbreviated new drug applications 

(ANDAs) for rifaximin tablets. 

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 the draft 

guidances before it begins work on the 

final versions of the guidances, submit 

either electronic or written comments 

on the draft guidances by April 13, 

2012. 

ADDRESSES: Submit written requests for 

single copies of the draft guidances 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 draft guidance documents. 

Submit electronic comments on the 

draft guidances 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: 

Doan T. Nguyen, Center for Drug 

Evaluation and Research (HFD–600), 

Food and Drug Administration, 7519 

Standish Pl., Rockville, MD 20855, 240– 

276–8608. 

SUPPLEMENTARY INFORMATION: 

I. Background 

In the Federal Register of June 11, 

2010 (75 FR 33311), FDA announced the 

availability of a guidance for industry 

entitled ‘‘Bioequivalence 

Recommendations for Specific 

Products,’’ which explained the process 

that would be used to make productspecific BE recommendations available 

to the public on FDA’s Web site at 

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

GuidanceComplianceRegulatory

Information/Guidances/default.htm. As 

described in that guidance, FDA 

adopted this process as a means to 

develop and disseminate productspecific BE recommendations and 

provide a meaningful opportunity for 

the public to consider and comment on 

those recommendations. This notice 

announces the availability of two draft 

BE recommendations, one for rifaximin200 and one for rifaximin-550. 

Xifaxan (rifaximin) 200-mg tablets, 

approved by FDA in May 2004, are 

indicated for the treatment of patients 

(≥ 12 years of age) with travelers’ 

diarrhea caused by noninvasive strains 

of Escherichia coli. Xifaxan (rifaximin) 

550-mg tablets, approved by FDA in 

March 2010, are indicated for reduction 

in risk of hepatic encephalopathy 

recurrence in patients ≥ 18 years of age. 

Xifaxan, 200 mg, and Xifaxan, 550 mg, 

are designated the reference listed drugs 

(RLDs) and therefore any ANDAs for 

generic rifaximin-200 or rifaximin-550 

must demonstrate BE to the relevant 

RLD prior to approval. There are no 

approved ANDAs for these products. 

In November 2011, FDA posted on its 

Web site a draft guidance for industry 

on the Agency’s recommendations for 

BE studies to support ANDAs for 

rifaximin-200 (Draft Rifaximin-200 BE 

Recommendations). FDA is now issuing 

a draft guidance for industry on BE 

recommendations for generic rifaximin550 (Draft Rifaximin-550 BE 

Recommendations). 

In May 2008, Salix Pharmaceuticals, 

Inc. (Salix), manufacturer of the RLD, 

Xifaxan (200 mg), filed a citizen petition 

requesting that FDA refuse to receive for 

substantive review, or approve, ANDAs 

for generic rifaximin-200 unless the 

ANDAs contain certain data to 

demonstrate BE (Docket No. FDA–2008– 

P–0300). FDA is reviewing the issues 

raised in the petition and will consider 

any comments on the Draft Rifaximin200 BE Recommendations before 

responding to Salix’s citizen petition 

and finalizing its BE recommendations 

for rifaximin-200. 

These draft guidances are being 

issued consistent with FDA’s good 


erowe on DSK2VPTVN1PROD with NOTICES
7586 Federal Register / Vol. 77, No. 29 / Monday, February 13, 2012 / Notices 

guidance practices regulation (21 CFR 

10.115). The draft guidances, when 

finalized, will represent the Agency’s 

current thinking on the design of BE 

studies to support ANDAs for rifaximin200 and rifaximin-550. They do not 

create or confer any rights for or on any 

person and do 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. Electronic Access 

Persons with access to the Internet 

may obtain the documents at either 

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

GuidanceCompliance

RegulatoryInformation/Guidances/

default.htm or http:// 

www.regulations.gov. 

Dated: February 7, 2012. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2012–3234 Filed 2–10–12; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2007–D–0369] 

Draft Guidance for Industry on 

Bioequivalence Recommendation for 

Nitroglycerin Metered Spray/ 

Sublingual Products and Metered 

Aerosol/Sublingual Products; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of two draft guidances for 

industry entitled ‘‘Bioequivalence 

Recommendations for Nitroglycerin,’’ 

one for nitroglycerin metered spray/ 

sublingual products and one for 

nitroglycerin metered aerosol/ 

sublingual products. The 

recommendations provide specific 

guidance on the design of 

bioequivalence (BE) studies to support 

abbreviated new drug applications 

(ANDAs) for these products. The draft 

guidances are revised versions of 

previously published draft guidances on 

the subject. 

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 the draft 

guidances before it begins work on the 

final versions of the guidances, submit 

either electronic or written comments 

on the draft guidances by April 13, 

2012. 

ADDRESSES: Submit written requests for 

single copies of the draft guidances 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 draft guidance documents. 

Submit electronic comments on the 

draft guidances 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: 

Doan T. Nguyen, Center for Drug 

Evaluation and Research (HFD–600), 

Food and Drug Administration, 7519 

Standish Pl., Rockville, MD 20855, 240– 

276–8608. 

SUPPLEMENTARY INFORMATION: 

I. Background 

In the Federal Register sof June 11, 

2010 (75 FR 33311), FDA announced the 

availability of a guidance for industry, 

‘‘Bioequivalence Recommendations for 

Specific Products,’’ which explained the 

process that would be used to make 

product-specific BE recommendations 

available to the public on FDA’s Web 

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

GuidanceComplianceRegulatory

Information/Guidances/default.htm. As 

described in that guidance, FDA 

adopted this process as a means to 

develop and disseminate productspecific BE recommendations and 

provide a meaningful opportunity for 

the public to consider and comment on 

those recommendations. This document 

announces the availability of two 

revised draft BE recommendations, one 

for nitroglycerin metered spray/ 

sublingual products and one for 

nitroglycerin metered aerosol/ 

sublingual products. 

Nitrolingual Pumpspray (nitroglycerin 

lingual spray), approved by FDA in 

October 1985, is a metered dose spray 

indicated for acute relief of an attack or 

prophylaxis of angina pectoris due to 

coronary artery disease. Nitromist 

(nitroglycerin lingual aerosol), approved 

by FDA in November 2006, is another 

metered dose spray indicated for acute 

relief of an attack or acute prophylaxis 

of angina pectoris due to coronary artery 

disease. Nitrolingual Pumpspray and 

Nitromist are designated as reference 

listed drugs (RLDs), and therefore any 

ANDAs for generic nitroglycerin lingual 

spray or generic nitroglycerin lingual 

aerosol must demonstrate BE to the 

relevant RLD prior to approval. There 

are no approved ANDAs for these 

products. 

In February 2010, FDA posted on its 

Web site a draft guidance for industry 

on the Agency’s recommendations for 

BE studies to support ANDAs for 

nitroglycerin metered spray/sublingual 

products (Draft Nitroglycerin Spray BE 

Recommendations of February 2010). In 

that draft guidance, FDA recommended 

three studies to demonstrate BE of 

generic nitroglycerin metered spray/ 

sublingual products: An in vivo fasting 

study, an in vitro study of unit dose and 

uniformity of unit dose, and an in vitro 

study of priming and tail off. 

In March 2010, FDA posted on its 

Web site a draft guidance for industry 

on the Agency’s recommendations for 

BE studies to support ANDAs for 

nitroglycerin metered aerosol/ 

sublingual products (Draft Nitroglycerin 

Aerosol BE Recommendations of March 

2010). In that draft guidance, FDA 

recommended three studies to 

demonstrate BE of generic nitroglycerin 

metered aerosol/sublingual products: 

An in vivo fasting study, an in vitro 

study of unit dose and uniformity of 

unit dose, and an in vitro study of 

priming and tail off. 

FDA has reconsidered the 

recommendations for both of these draft 

guidances and has decided to revise 

them. In November 2011, FDA 

withdrew the Draft Nitroglycerin Spray 

BE Recommendations of February 2010 

and the Draft Nitroglycerin Aerosol BE 

Recommendations of March 2010. FDA 

is now issuing revised draft guidances 

for industry on BE recommendations for 

nitroglycerin metered spray/sublingual 

products (Revised Draft Nitroglycerin 

Spray BE Recommendations) and 

nitroglycerin metered aerosol/ 

sublingual products (Revised Draft 

Nitroglycerin Aerosol BE 

Recommendations). In these revised 

draft guidances, FDA recommends one 


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