7584 Federal Register / Vol. 77, No. 29 / Monday, February 13, 2012 / Notices 

Agency records and based on the 

information we have at this time, FDA 

has determined under § 314.161 that 

WILPO (phentermine hydrochloride) 

Tablets, 8 mg, was not withdrawn for 

reasons of safety or effectiveness. The 

petitioner KVK–Tech has identified no 

data or other information suggesting that 

WILPO (phentermine hydrochloride) 

Tablets, 8 mg, was withdrawn for 

reasons of safety or effectiveness. We 

have carefully reviewed our files for 

records concerning the withdrawal of 

WILPO (phentermine hydrochloride) 

Tablets, 8 mg, 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withdrawn from sale for reasons of 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 WILPO (phentermine 

hydrochloride) Tablets, 8 mg, 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. ANDAs that refer 

to WILPO (phentermine hydrochloride) 

Tablets, 8 mg, may 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: February 7, 2012. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2012–3232 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–2012–D–0083] 

Draft Guidance for Industry on Heparin 

for Drug and Medical Device Use; 

Monitoring Crude Heparin for Quality; 

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availability of a draft guidance for 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 ‘‘Heparin for Drug and 

Medical Device Use: Monitoring Crude 

Heparin for Quality.’’ This draft 

guidance is intended to alert 

manufacturers of active pharmaceutical 

ingredients (APIs), pharmaceutical and 

medical device manufacturers of 

finished products, and others to the 

potential risk of crude heparin 

contamination. 

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 

electronic or written comments on the 

draft guidance by April 13, 2012. 

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. 

Submit electronic comments on the 

draft 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. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the draft guidance 

document. 

FOR FURTHER INFORMATION CONTACT: 

Frank W. Perrella, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, rm. 4337, 

Silver Spring, MD 20993–0002, 301– 

796–3265; or Dennis M. Bensley, Jr., 

Center for Veterinary Medicine (HFV– 

140), Food and Drug Administration, 

7519 Standish Pl., Rockville, MD 20855, 

240–276–8268; or Jason Brookbank, 

Center for Devices and Radiological 

Health, Food and Drug Administration, 

10903 New Hampshire Ave., Bldg. 66, 

rm. 3558, Silver Spring, MD 20993– 

0002, 301–796–5770. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Heparin for Drug and Medical Device 

Use: Monitoring Crude Heparin for 

Quality.’’ This draft guidance provides 

recommendations that will help API 

manufacturers, pharmaceutical and 

medical device manufacturers of 

finished products, and others, to better 

control their use of crude heparin that 

might contain oversulfated chondroitin 

sulfate (OSCS) or non-porcine material 

(especially ruminant material) 

contaminants. This draft guidance on 

crude heparin recommends strategies to 

test for contamination and should be 

used in addition to the United States 

Pharmacopeia (USP) monograph testing 

required for other forms of heparin to 

detect the presence of OSCS. 

Following reports of serious adverse 

events (including deaths) among 

patients injected with heparin sodium 

in 2008, FDA identified the contaminant 

OSCS in heparin API manufactured in 

China. FDA is also concerned about the 

potential for contamination of heparin 

with the bovine spongiform 

encephalopathy (BSE) agent derived 

from ruminant materials. The control of 

the quality of crude heparin is critical 

to ensure the safety of drugs and devices 

and to protect public health. FDA 

developed this draft guidance to alert 

manufacturers to the risks of crude 

heparin contaminants and to 

recommend strategies to ensure that the 

heparin supply chain is not 

contaminated with OSCS or any nonporcine origin material, especially 

ruminant material (unless specifically 

approved or cleared as part of drug or 

medical device application). 

The draft guidance recommends that 

manufacturers test and confirm the 

species origin of crude heparin in each 

shipment before use in the manufacture 

or preparation of a drug or medical 

device containing heparin. The test 

method should be qualified for use in 

testing crude heparin and for the 

identification of species origin. The 

method should be based on good 

scientific principles (e.g., sufficient 

accuracy and specificity) and possess a 

level of sensitivity commensurate with 

the current state of scientific knowledge 

and risk. Likewise, the draft guidance 

recommends that manufacturers test for 

OSCS in crude heparin in each 

shipment before use, using a qualified 

test method that is suitable for detecting 

low levels of OSCS concentrations and 

is based on good scientific principles. 

Manufacturers should reject for use and 

control or destroy crude heparin found 

to contain any amount of OSCS and 

notify FDA of any such finding. The 

draft guidance also recommends that 

manufacturers identify and audit crude 

heparin suppliers and heparin API 

suppliers to ensure conformance to 

current good manufacturing practice 

(CGMP), employ the controls described 

in the guidance for industry ‘‘Q7 Good 

Manufacturing Practice Guidance for 

Active Pharmaceutical Ingredients,’’ and 

comply with the quality system 

regulations (as applicable). 

This draft guidance is being issued 

consistent with FDA’s good guidance 


erowe on DSK2VPTVN1PROD with NOTICES
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 


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