FDA Provides Clarity on Use of Estriol by Section 503A Compounding Pharmacies

The FDA has recently provided limited additional information in an informal email on whether a pharmacy may use certain bulk drug substances in compounding. Specifically, the FDA has indicated that drug products containing Estriol may be compounded in accordance with Section 503A by a licensed pharmacist pursuant to a patient-specific prescription, based on the fact that Estriol is the subject of an applicable USP monograph. The FDA provided this statement in an email response to this office following several questions submitted by us following the passage of the Drug Quality and Security Act of 2013.

Specifically, we had submitted a question in writing, asking whether, in light of the FDA’s past positions, the FDA would allow pharmacies to use and compound Estriol under Section 503A (since it had a valid USP monograph). In late October 2014 (nearly one year since we posed the question), a Drug Information Specialist from the Division of Drug Information, Small Business and Industry Assistance in the FDA’s Center for Drug Evaluation and Research responded in the affirmative, stating that “drug products containing estriol may be compounded in accordance with section 503A by a licensed pharmacist or licensed physician pursuant to a patient-specific prescription, because Estriol is the subject of an applicable USP monograph.” 

We view this as a very positive development, particularly given the fact that many payors had continued to view Estriol as an “investigational” drug and requested an approved IND application in order to compound with it. This recent response highlights the requirements for compounding under Section 503A. 

Section 503A of the Federal Food, Drug, and Cosmetic Act describes conditions that must be satisfied for drug products compounded by a pharmacy to be exempt from the FDA new drug approval requirements (Section 505), current good manufacturing practice (CGMP) requirements (Section 501(a)(2)(B)), and the requirements to label products with adequate directions for use (Section 502(f)(1)). A compounded drug product may qualify for these exemptions if, in addition to meeting other criteria:

• The drug product is compounded in compliance with the United States Pharmacopoeia (USP) chapters on pharmacy compounding using bulk drug substances, as defined in 21 CFR 207.3(a)(4), that comply with the standards of an applicable USP or National Formulary (NF) monograph, if one exists or
• If such a monograph does not exist, the drug substance(s) must be a component of an FDA-approved human drug product or
• If a monograph does not exist and the drug substance is not a component of an FDA-approved human drug product, it must appear on a list of bulk drug substances for use in compounding developed by FDA through regulation (Section 503A(b)(1)(A)(i))

Because Estriol has a valid USP monograph, the FDA noted in its email response that Estriol satisfies the first criteria noted above. However, the FDA did note that it had concerns with compounded hormone drugs being promoted as “bio-identical hormone replacement therapy (BHRT),” since some pharmacy compounders have claimed that their compounded BHRT drugs are a “natural” alternative to FDA-approved drugs. Given this statement, pharmacies must be careful to make sure they are not marketing Estriol as a safe and effective “natural” alternative to FDA approved drugs, and that they are not making unsupported claims regarding these products. We believe that the FDA will likely be monitoring pharmacies using Estriol to determine whether they are making such inappropriate representations.