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Bioequivalence Recommendations for Estradiol Vaginal Cream; Draft Guidance for Industry; Availability

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Information about this document as published in the Federal Register.

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This document has been published in the Federal Register. Use the PDF linked in the document sidebar for the official electronic format.

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Food and Drug Administration, HHS.




The Food and Drug Administration (FDA) is announcing the availability of a revised draft guidance for industry entitled “Draft Guidance on Estradiol.” The guidance provides specific recommendations on the design of bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs) for estradiol vaginal cream. This draft guidance is a revised version of a previously issued draft guidance of the same subject.


Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comments on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by November 21, 2014.


Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993. 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 See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

Submit electronic comments on the draft guidance to Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

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Kris André, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 75, Rm. 1615, Silver Spring, MD 20993, 240-402-7800.

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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 product-specific BE recommendations available to the public on FDA's Web site at​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm. As described in that guidance, FDA adopted this process as a means to develop and disseminate product-specific BE recommendations and to provide a meaningful opportunity for the public to consider and comment on those recommendations. This notice announces the availability of revised draft BE recommendations for estradiol vaginal cream.

ANDA 086069 for Estrace Cream (estradiol vaginal cream, USP, 0.01%) was initially approved by FDA in January 1984. In August 2009, FDA issued a draft guidance for industry on BE recommendations for generic estradiol vaginal cream. FDA is now issuing a revised version of the draft BE recommendations for estradiol vaginal cream. This revised draft guidance changes the recommendation for an in Start Printed Page 56589vivo pharmacokinetic BE study from a parallel study design to a crossover study design, but is the same in all other respects.

In January 2005, Warner Chilcott, Inc., submitted a citizen petition requesting that FDA stay final approval and/or the effective date of final approval of any ANDA that relies on Estrace Cream as the reference listed drug unless the ANDA meets certain requirements related to demonstrating bioequivalence. FDA reviewed the issues raised in the petition and is responding to the petition (see FDA letter to Warner Chilcott, Inc, Docket No. FDA-2005-P-0006, available at

This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the Agency's current thinking on the design of BE studies to support ANDAs for estradiol vaginal cream. 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 either electronic comments regarding this document to 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

III. Electronic Access

Persons with access to the Internet may obtain the document at either​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm or

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Dated: September 16, 2014.

Leslie Kux,

Assistant Commissioner for Policy.

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[FR Doc. 2014-22450 Filed 9-19-14; 8:45 am]