OT:RR:NC:N3:138
Kamesh Venugopal
Encube Ethicals, Inc.
200 Meredith Drive
Durham, NC 27713
RE: The country of origin of Estradiol Vaginal Cream USP, 0.01% in dosage form
Dear Mr. Venugopal:
In your letter dated May 15, 2026, you requested a country of origin ruling on Estradiol Vaginal Cream USP,
0.01% in dosage form.
Estradiol Vaginal Cream is a medicinal preparation containing estradiol hemihydrate, an estrogen hormone,
as the active ingredient. It is indicated for the treatment of moderate to severe symptoms of vulvar and
vaginal atrophy due to menopause.
You stated that the active pharmaceutical ingredient (API), estradiol hemihydrate, is manufactured in the
Netherlands and that the finished cream in dosage form is made in India. In India, estradiol hemihydrate will
be mixed with various inactive ingredients to produce the final Estradiol Vaginal Cream in dosage form.
When determining the country of origin, the substantial transformation analysis is applicable. See, e.g.,
Headquarters Ruling Letter (“HQ”) H301619, dated November 6, 2018. The test for determining whether a
substantial transformation will occur is whether an article emerges from a process with a new name,
character, or use different from that possessed by the article prior to processing. See Texas Instruments Inc. v.
United States, 681 F.2d 778 (C.C.P.A. 1982). This determination is based on the totality of the evidence. See
National Hand Tool Corp. v. United States, 16 C.I.T. 308 (1992), aff’d, 989 F.2d 1201 (Fed. Cir. 1993).
In this case, we find the mixing of the active ingredient estradiol hemihydrate (made in the Netherlands) with
the inactive ingredients into the final Estradiol Vaginal Cream 0.01% in dosage form in India does not result
in a substantial transformation and the country of origin will be the Netherlands.
You also submitted pictures of labels for our review. Based upon the labels provided, the subject product
does not appear to be legally marked with the proper country of origin. The labels state the product is
manufactured in India. However, the country of origin is the Netherlands where the API is made and should
be marked “Made in”, “Product of,” or other words of similar meaning with “Netherlands” as the country of
origin.
This merchandise may be subject to the Federal Food, Drug, and Cosmetic Act and/or The Public Health
Security and Bioterrorism Preparedness and Response Act of 2002 (The Bioterrorism Act), which are
administered by the U.S. Food and Drug Administration (FDA). Information on the Federal Food, Drug, and
Cosmetic Act, as well as The Bioterrorism Act, can be obtained by calling the FDA at 1-888-463-6332, or by
visiting their website at www.fda.gov.
The holding set forth above applies only to the specific factual situation and merchandise description as
identified in the ruling request. This position is clearly set forth in Title 19, Code of Federal Regulations
(CFR), Section 177.9(b)(1). This section states that a ruling letter is issued on the assumption that all of the
information furnished in the ruling letter, whether directly, by reference, or by implication, is accurate and
complete in every material respect. In the event that the facts are modified in any way, or if the goods do not
conform to these facts at time of importation, you should bring this to the attention of U.S. Customs and
Border Protection (CBP) and submit a request for a new ruling in accordance with 19 CFR 177.2.
Additionally, we note that the material facts described in the foregoing ruling may be subject to periodic
verification by CBP.
This ruling is being issued under the provisions of Part 177 of the Customs and Border Protection
Regulations (19 C.F.R. 177).
A copy of the ruling or the control number indicated above should be provided with the entry documents
filed at the time this merchandise is imported. If you have any questions regarding the ruling, please contact
National Import Specialist Judy Lee at [email protected].
Sincerely,
(for)
James P. Forkan
Director
National Commodity Specialist Division