[Federal Register Volume 79, Number 52 (Tuesday, March 18, 2014)]
[Notices]
[Pages 15131-15132]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-05849]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-0204]


Draft Guidance for Industry on Bioavailability and Bioequivalence 
Studies Submitted in New Drug Applications or Investigational New Drug 
Applications--General Considerations; 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availability of a draft guidance for industry entitled 
``Bioavailability and Bioequivalence Studies Submitted in NDAs or 
INDs--General Considerations'' (draft BA and BE guidance for NDAs). The 
draft guidance provides recommendations to sponsors and/or applicants 
planning to include bioavailability (BA) and bioequivalence (BE) 
information for drug products in investigational new drug applications 
(INDs), new drug applications (NDAs), and NDA supplements. This draft 
guidance revises those parts of the March 2003 guidance entitled 
``Bioavailability and Bioequivalence Studies for Orally Administered 
Drug Products--General Considerations'' relating to BA and BE studies 
for INDs, NDAs, and NDA supplements.

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draft guidance before it begins work on the final version of the 
guidance, submit written or electronic comments on the draft guidance 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 May 19, 2014.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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access to the draft guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov.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: Dakshina Chilukuri, Office of Clinical 
Pharmacology, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave. Bldg. 51, Rm. 3177, Silver 
Spring, MD 20993-0002, 301-796-5008, or [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance entitled 
``Bioavailability and Bioequivalence Studies Submitted in NDAs or 
INDs--General Considerations.'' The draft guidance provides 
recommendations to sponsors and/or applicants planning to include BA 
and BE information for drug products in INDs, NDAs, and NDA 
supplements. The draft guidance is applicable to orally administered 
drug products and may also be applicable to non-orally administered 
drug products when reliance on systemic exposure measures is suitable 
to document BA and BE (e.g., transdermal delivery systems and certain 
rectal and nasal drug products). The guidance should be helpful for 
applicants conducting BA and BE studies during the IND period for an 
NDA and also for applicants conducting BE studies during the 
postapproval period for certain changes to drug products that are the 
subject of

[[Page 15132]]

an NDA. This guidance document is not intended to provide 
recommendations on studies conducted in support of demonstrating 
comparability or biosimilarity for biological products licensed under 
section 351 of the Public Health Service Act (42 U.S.C. 262).
    Studies to measure BA and/or establish BE of a product are 
important elements in support of INDs, NDAs, and NDA supplements. BA 
means the rate and extent to which the active ingredient or active 
moiety is absorbed from a drug product and becomes available at the 
site of action (21 CFR 320.1(a)). BA data provide an estimate of the 
fraction of the drug absorbed, as well as provide information related 
to the pharmacokinetics of the drug. BA for orally administered drug 
products can be documented by a systemic exposure profile obtained by 
measuring concentrations of active ingredients and/or active moieties 
over time and, when appropriate, active metabolites over time in 
samples collected from the systemic circulation as compared to that of 
a suitable reference.
    BE means the absence of a significant difference in the rate and 
extent to which the active ingredient or active moiety in 
pharmaceutical equivalents or pharmaceutical alternatives becomes 
available at the site of drug action when administered at the same 
molar dose under similar conditions in an appropriately designed study 
(21 CFR 320.1(e)). Studies to establish BE between two products are 
important for certain formulation or manufacturing changes occurring 
during the drug development and postapproval stages. In BE studies, the 
systemic exposure profile of a test drug product is compared to that of 
a reference drug product.
    In the Federal Register of March 19, 2003 (68 FR 13316), FDA 
announced the availability of a final guidance entitled 
``Bioavailability and Bioequivalence Studies for Orally Administered 
Drug Products--General Considerations'' (March 2003 BA and BE 
guidance). Since the March 2003 guidance was issued, FDA has determined 
that separating guidances according to application type will be 
beneficial to sponsors. Thus, FDA is issuing this draft BA and BE 
guidance for NDAs, and has also issued a draft guidance entitled 
``Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs 
Submitted Under an ANDA'' (draft BE guidance for ANDAs) (December 5, 
2013; 78 FR 73199). This draft BA and BE guidance for NDAs revises 
those parts of the March 2003 BA and BE guidance relating to BA and BE 
studies for INDs, NDAs, and NDA supplements. This draft guidance also 
provides additional information in the section on modified-release 
products, and adds new sections including the following topics: (1) 
Concomitant administration of drug products and combination drug 
products, (2) alcoholic beverage effects on modified-release dosage 
forms, (3) endogenous substances, and (4) drug products with high 
intrasubject variability. This draft guidance should be useful for 
applicants planning to conduct BA and/or BE studies during the IND 
period for submissions to an NDA, and BA and BE studies conducted in 
the postapproval period for certain changes in NDAs.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance 
represents the Agency's current thinking on conducting BA and BE 
studies for INDs and NDAs. 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. 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. 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 collection of information submitted under 21 CFR part 312 
(investigational new drug applications) has been approved under OMB 
control number 0910-0014. The collection of information submitted under 
21 CFR part 314 (new drug applications) has been approved under OMB 
control number 0910-0001.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: March 12, 2014.
Peter Lurie,
Acting Associate Commissioner for Policy and Planning.
[FR Doc. 2014-05849 Filed 3-17-14; 8:45 am]
BILLING CODE 4160-01-P