9946 Federal Register / Vol. 77, No. 34 / Tuesday, February 21, 2012 / Notices 

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. 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This draft guidance refers to 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 that 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). The 

collections of information in 21 CFR 

part 314 and 21 CFR part 312 have been 

approved under OMB control numbers 

0910–0001 and 0910–0014, respectively. 

The collections of information in 21 

CFR part 807, subpart E have been 

approved under 0910–0120; the 

collections of information in 21 CFR 

part 812 have been approved under 

0910–0078; and the collections of 

information in 21 CFR part 814 have 

been approved under 0910–0231. 

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/

GuidanceComplianceRegulatory

Information/default.htm, or http:// 

www.regulations.gov. 

Dated: February 14, 2012. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2012–3956 Filed 2–17–12; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2006–D–0036] (Formerly 

Docket No. 2006D–0344) 

Draft Guidance for Industry on Drug 

Interaction Studies—Study Design, 

Data Analysis, Implications for Dosing, 

and Labeling Recommendations; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a revised draft guidance 

for industry entitled ‘‘Drug Interaction 

Studies—Study Design, Data Analysis, 

Implications for Dosing, and Labeling 

Recommendations.’’ The revised draft 

guidance is intended to provide 

recommendations for sponsors of new 

drug applications (NDAs) and biologics 

license applications (BLAs) for 

therapeutic biologics regarding in vitro 

and in vivo studies of drug metabolism, 

drug transport, and drug-drug, or drugtherapeutic protein interactions. 

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 revised 

draft guidance before it begins work on 

the final version of the guidance, submit 

either electronic or written comments 

on the draft guidance by May 21, 2012. 

ADDRESSES: Submit written requests for 

single copies of the revised 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 selfaddressed 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 

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. 

FOR FURTHER INFORMATION CONTACT: 

Shiew-Mei Huang, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, rm. 3188, 

Silver Spring, MD 20993–0002, 301– 

796–1541; or 

Lei Zhang, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New 

Hampshire Ave., Bldg. 51, rm. 3106, 

Silver Spring, MD 20993–0002, 301– 

796–1635. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a revised draft guidance for industry 

entitled ‘‘Drug Interaction Studies— 

Study Design, Data Analysis, 

Implications for Dosing, and Labeling 

Recommendations.’’ Drug interactions 

can result when one drug alters the 

pharmacokinetics of another drug or its 

metabolites. Drug interactions also can 

reflect the additive nature of the 

pharmacodynamic effect of either drug 

when taken with the other drug. The 

main focus of this draft guidance is 

pharmacokinetic drug interactions. The 

revised draft guidance reflects the 

Agency’s view that the pharmacokinetic 

interactions between an investigational 

new drug and other drugs should be 

defined during drug development, as 

part of an adequate assessment of safety 

and effectiveness. It is important to 

understand the nature and magnitude of 

drug-drug interactions for several 

reasons. Concomitant medications, 

dietary supplements, and some foods, 

such as grapefruit juice, may alter 

metabolism and/or drug transport 

abruptly in individuals who previously 

had been receiving and tolerating a 

particular dose of a drug. Such an 

abrupt alteration in metabolism or 

transport can change the known safety 

and efficacy of a drug. 

The revised draft guidance provides 

recommendations for sponsors of NDAs 

and BLAs regarding in vitro and in vivo 

studies of drug metabolism, drug 

transport, and drug-drug, or drugtherapeutic protein interactions. 

Namely, the guidance describes in vitro 

study methodologies, criteria for in vivo 

studies, in vivo study design, and data 

analysis in the context of identifying 

potential drug interactions. The 

guidance also addresses the 

implications of drug interactions for 

dosing and labeling. 

In the Federal Register of September 

12, 2006 (71 FR 53696), FDA announced 

the availability of a draft guidance 

entitled ‘‘Drug Interaction Studies— 

Study Design, Data Analysis, and 

Implications for Dosing and Labeling.’’ 

Comments were received and have been 

considered during revision of the draft 

guidance. In addition, new 

developments in the field have been 

incorporated to reflect the Agency’s 

current thinking. The Agency is 

publishing the draft guidance as a 

revised draft guidance to collect 

additional public comments. The 

revised draft guidance includes detailed 

discussion of several major changes, 

including the following: (1) When 

transporter-mediated drug interaction 

information is needed (including 

decision-trees); (2) drug-therapeutic 

protein interactions, (3) the utility of 

pharmacogenetic data; and (4) the use of 

physiologically based pharmacokinetic 

modeling. 

This revised draft guidance is being 

issued consistent with FDA’s good 

guidance practices regulation (21 CFR 

10.115). The draft guidance, when 

mstockstill on DSK4VPTVN1PROD with NOTICES

Federal Register / Vol. 77, No. 34 / Tuesday, February 21, 2012 / Notices 9947 

finalized, will represent the Agency’s 

current thinking on conducting drug 

interaction studies during drug 

development to support marketing 

approval. 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 requirement 

of the applicable statutes and 

regulations. 

II. Paperwork Reduction Act of 1995 

This revised draft guidance refers to 

previously approved collections of 

information that 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). The 

collections of information in 21 CFR 

201.57 have been approved under OMB 

control number 0910–0572. 

III. 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. 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. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the document at either 

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

ComplianceRegulatoryInformation/

Guidances or http:// 

www.regulations.gov. 

Dated: February 15, 2012. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2012–3958 Filed 2–17–12; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2010–D–0500] 

Guidance for Industry: Early Clinical 

Trials With Live Biotherapeutic 

Products: Chemistry, Manufacturing, 

and Control Information; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a document entitled 

‘‘Guidance for Industry: Early Clinical 

Trials With Live Biotherapeutic 

Products: Chemistry, Manufacturing, 

and Control Information ’’ dated 

February 2012. The guidance provides 

certain Investigational New Drug 

Application (IND) sponsors with 

recommendations in connection with 

the submission of INDs for early clinical 

trials with live biotherapeutic products 

(LBPs). The guidance announced in this 

notice finalizes the draft guidance of the 

same title dated September 2010. 

DATES: Submit either electronic or 

written comments on Agency guidances 

at any time. 

ADDRESSES: Submit written requests for 

single copies of this guidance to the 

Office of Communication, Outreach and 

Development (HFM–40), Center for 

Biologics Evaluation and Research 

(CBER), Food and Drug Administration, 

1401 Rockville Pike, suite 200N, 

Rockville, MD 20852–1448. Send one 

self-addressed adhesive label to assist 

the office in processing your requests. 

The guidance may also be obtained by 

mail by calling CBER at 1–800–835– 

4709 or 301–827–1800. 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: 

Benjamin A. Chacko, Center for 

Biologics Evaluation and Research 

(HFM–17), Food and Drug 

Administration, 1401 Rockville Pike, 

suite 200N, Rockville, MD 20852–1448, 

301–827–6210. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a document entitled ‘‘Guidance for 

Industry: Early Clinical Trials With Live 

Biotherapeutic Products: Chemistry, 

Manufacturing, and Control 

Information’’ dated February 2012. The 

guidance provides certain IND sponsors 

with recommendations in connection 

with IND submissions for early clinical 

trials for LBPs in the United States. The 

guidance focuses on the chemistry, 

manufacturing, and control information 

that should be provided in an IND for 

early clinical trials evaluating LBPs. The 

guidance is applicable to INDs of LBPs, 

whether clinical trials are conducted 

commercially, in an academic setting, or 

otherwise. 

In the Federal Register of October 14, 

2010 (75 FR 63188), FDA announced the 

availability of the draft guidance of the 

same title dated September 2010. FDA 

received a few comments on the draft 

guidance and those comments were 

considered as the guidance was 

finalized. In response to comments, 

changes incorporated in the final 

guidance include the addition of text 

related to the scope, definitions and 

background section of the guidance. In 

addition, editorial changes were made 

to improve clarity. The guidance 

announced in this notice finalizes the 

draft guidance dated September 2010. 

The guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents FDA’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. Paperwork Reduction Act of 1995 

The 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). The collections of information in 

21 CFR part 312 have been approved 

under 0910–0014. 

III. 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. 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. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the guidance at either 

http://www.fda.gov/BiologicsBlood

Vaccines/GuidanceCompliance

RegulatoryInformation/Guidances/

default.htm or http:// 

www.regulations.gov. 

Dated: February 14, 2012. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2012–3957 Filed 2–17–12; 8:45 am] 

BILLING CODE 4160–01–P 

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