The Fight for Access to Compounded Bioidentical Hormone Therapy (cBHT)
FDA-Commissioned NASEM Report Jeopardizes Access to cBHT
A report published in 2020 by the National Academies of Science, Engineering, and Medicine (NASEM) discussing compounded bioidentical hormone replacement therapies (cBHT) could jeopardize patient access to these drugs if FDA were to follow their proposal. The report, which was commissioned per FDA request, recommended several bioidentical hormones be placed on a difficult to compound (DTC) list. If this were to happen, compounding pharmacies and outsourcing facilities would be banned from preparing these drugs.
Compounders Reject Nasem and Garner Political Support
Since the NASEM report was released, however, a grassroots movement lead by the Alliance for Pharmacy Compounding has been mounting aimed to preserve patient access to cBHT. One such effort included a Freedom of Information Act (FOIA) request of FDA and NASEM, which lead to a 3rd party analysis of the data provided. The independent reviewers of NASEM data questioned the validity of the conclusions made based on the bias they uncovered. The doubts cast on the NASEM report along with backing from several prescribers of cBHT have gained the attention and support of certain members of congress. As of October 2, 2023, five senators have formally urged FDA to permit continued access to cBHT.
Difficult to Compound List is in Development
As per the Federal Food, Drug, and Cosmetic Act (FD&C Act), drug products or categories of drug products identified on a list by FDA that present demonstrable difficulties for compounding cannot be compounded by 503A compounding pharmacies or 503B outsourcing facilities.
FDA considers six criteria when evaluating whether a drug product or category of drug products is demonstrably difficult to compound:
The complexity of the formulation;
The complexity of the drug delivery mechanism;
The complexity of the dosage form;
The complexity of characterizing or controlling bioavailability;
The complexity of the compounding process; and
The complexity of physicochemical or analytical testing.
Compounded Bioidentical Hormones are on the Chopping Block
No regulations have been published yet but the FDA is currently contemplating including Compounded Bioidentical Hormone Therapy (cBHT) on the difficult to compound (DTC) list. Hormones that would be prohibited from compounding if FDA were to place them on the DTC list include:
Estradiol
Estrone
Estradiol cypionate
Estriol
Progesterone
Pregnenolone
Testosterone
Testosterone cypionate
Testosterone propionate
NASEM Report Recommends Prohibition of Bioidentical Hormone Compounding
In 2020, these hormones were recommended in a report from the National Academies of Science, Engineering, and Medicine (NASEM) to be placed on the demonstrably difficult to compound list. From their analysis, the authors concluded that evidence does not support the clinical utility of compounded bioidentical hormone therapies and therefore their use should be limited to patients who cannot use products approved by the US Food and Drug Administration (FDA).
An Independent Analysis Uncovers Bias and Flaws in the NASEM Report
Critics of the NASEM recommendation point out FDA’s historically negative stance on cBHT and potential influence on report findings. In 2008, FDA issued enforcement actions against seven pharmacies that compounded estriol preparations, citing they made false and misleading claims and then banned the use of the API. In response, the House of Representatives introduced a resolution calling on FDA to reverse its policy related to estriol. In 2018, FDA again tried to discourage bioidentical compounding.
Given FDA’s $1.3 million contribution to the NASEM compounded bioidentical hormone research, coupled with their preference for FDA-approved drug products, critics questioned the validity of the outcome.
To assess whether or not the NASEM report was scientifically valid, an independent analysis of the report was conducted and it was found that the study methods were flawed. Notably, the independent analysis of the NASEM report uncovered that the committee lacked representation from prescribers or pharmacists with substantial, patient-facing experience in dealing with compounded hormones. In addition, they concluded the studies the committee relied on failed to present an accurate or comprehensive depiction of compounded hormones. Moreover, the standards used for assessing the safety and efficacy of FDA-approved drugs were not easily applicable to highly personalized compounded medications. Finally, it was found the NASEM report committee ignored the body of evidence demonstrating the safety and efficacy of compounded hormones. As such, the independent researchers advised,
“Given the strong potential bias influencing the committee’s recommendations and the omission from the final report of key data supporting the safety and efficacy of cBHT, we recommend that FDA not rely on or consider the NASEM report.”
Meta-Analysis Says cBHT Does Not Pose Increased Risk
While not the only research available on bioidentical compounds, in 2022, an article published in the peer-reviewed journal, Menopause, analyzed 29 randomized controlled trials and 40 journal articles and found no evidence that compounded hormones pose an increased clinical risk compared to FDA approved products.
Who Would Be Affected if cBHT Were Placed on the DTC List?
It is estimated between 1 million to 2.5 million US women aged 40 years or older use compounded bioidentical hormone replacement therapies to manage perimenopausal and menopausal symptoms. It is also estimated 26 to 33 million compounded hormone prescriptions are filled annually. If FDA were to pull the plug on compounding bioidentical hormones, these patients would potentially be affected.
Compounding Industry Leads Grassroots Efforts to Maintain Access to cBHT
The Alliance for Pharmacy Compounding (APC) has expressed concerns of the NASEM report since its publication. As a result, attorneys for APC filed a Freedom of Information Act (FOIA) request of FDA and NASEM, which lead to the independent analysis of the data that cast doubt on the report findings.
They have also put forth great efforts to educate prescribers and legislators of the threats to hormone compounding eventually being considered difficult by FDA. This has resulted in the backing from several prescribers of cBHT. Additionally, as of October 2, 2023, five senators have formally urged FDA to permit continued access to cBHT.
Does Your Facility Produce Quality Preparations?
If you’re ready to bring quality to the center of your compounding operations, consultants at Restore Health Consulting LLC can help you design a robust quality management system to promote patient safety and regulatory compliance.