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Compounded Bioidentical Hormone Replacement Therapy (cBHRT) in Jeopardy of Being Added to the FDA’s “Difficult to Compound List”

Currently, cBHRT is not on FDA’s list of difficult to compound products, falling under certain exemptions of the FD&C Act, particularly, Sections 503A and 503B. Under Section 503A, a human drug compounded for an identified individual patient based on a prescription qualifies for exemption from three sections of the FD&C Act: 1) current good manufacturing practice for drugs; 2) labeling of drugs with adequate directions for use; and 3) approval of human drug products under new drug applications or abbreviated new drug applications. One of the criteria for these exemptions is that the Secretary has not identified the drug, by regulation, as a drug product that presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product. However, before the Secretary may promulgate regulations to add a drug to the difficult to compound list, it must convene and consult an advisory committee on compounding of such drug(s), unless the Secretary finds that issuance of such regulations before consultation is necessary to protect the public.

Similarly, under Section 503B, which addresses drugs compounded under direct supervision of a pharmacist, a human drug may be exempt from inclusion on the difficult to compound list for the following reasons: 1) labeling of drugs with adequate directions for use; 2) approval of human drug products under new drug applications or abbreviated new drug applications; and 3) drug supply chain security requirements. In order to qualify for the exemptions under Section 503B the drug i) is not identified, directly or as part of a category of drugs, on a list published by the Sectary of drugs or categories of drugs that present demonstrable difficulties for compounding, or ii) is compounded in accordance with all applicable conditions identified on the list as conditions that are necessary to prevent the drug or category of drugs from presenting such demonstrable difficulties. Before issuing regulations to add drugs or categories of drugs to the difficult to compound list, the Secretary must convene and consult an advisory committee.

To satisfy the requirements that FDA convene and consult an advisory committee as discussed above, in July 2000, the Pharmacy Compounding Advisory Committee (“PCAC”) provided FDA with advice with respect to developing a list of difficult to compound drugs. Further, in 2013, the FDA invited all interested persons (practitioners, pharmacists, consumers, and others) to nominate drug products to be included on the list. More discussions between the PCAC and FDA occurred over the next few years. During this time, cBHRT drugs were not added to the list. Then along comes the National Academies of Sciences, Engineering, and Medicine (“NASEM”).

The FDA entered into an agreement with NASEM to convene an ad hoc committee to conduct a study on the clinical utility of cBHRT. See NASEM’s report dated July 1, 2020, “The Clinical Utility of Compounded Bioidentical Hormone Therapy (Clinical Utility of Treating Patients with Compounded “Bioidentical Hormone Replacement Therapy” | National Academies). This report discusses problems with the benefits and risks of cBHRT, encouraging practitioners to limit prescribing cBHRT to a small number of patients who cannot benefit from FDA-approved hormone therapy products. NASEM states that prescribing cBHRT should be limited to patients allergic to FDA-approved products or when a patient requires a specific dose or form not available as an FDA-approved product. NASEM found that there is insufficient evidence to support clinical utility in widespread use of cBHRT. However, other journals cast doubt on the accuracy of the NASEM report for focusing only on a limited number of studies of cBHRT in determining that cBHRT are dangerous.

Notwithstanding any flaws the NASEM report may contain, FDA may be moving forward to adding cBHRT, including testosterone, estradiol, progesterone, and others, to its difficult to compound list. If this happens, practitioners will need to be ready to prove that their patients require a specific dose or form of cBHRT not available as an FDA approved product. Practitioners will need to consider having more frequent encounters with patients using cBHRT, performing more frequent diagnostic testing to determine a patient’s hormone levels, writing detailed notes to patient records (including use of patient questionnaires and specific references to benefits and side effects).

Should the FDA add cBHRT to its list of difficult to compound products, it may make it very difficult for practitioners to prescribe and pharmacies to prepare, cBHRT specifically formulated for a particular patient. This could spell trouble for the millions of men and women who are prescribed cBHT to combat age-related decreases in hormones due to menopause or hypogonadism, or for other medical reasons, such as testosterone deficiency (not due to age). It also means practitioners may need to be ready to move towards other therapies to meet patients’ needs. Practitioners and patients need to be aware that cBHRT that has proved beneficial may in the future become virtually unavailable if the FDA marches forward with embracing the NASEM report. If this happens, practitioners will need to be prepared to push back on the FDA and challenge its position.