Compounded Hormone Replacement Products: FDA’s Latest “Statement” (?) Addressing Adverse Event Reporting

September 16, 2019By Karla L. Palmer

FDA published a statement on September 9, 2019, linking to an article by Janet Woodcock and others concerning reporting of adverse events involving compounded bioidentical hormone replacement therapy (BHRT) products, including ingredients such as progesterone and testosterone.  FDA states there were over 4,200 adverse events from the use of these products (specifically, hormone pellets) from a single entity that were discovered during a routine 2018 FDA inspection (unrelated to compounded drugs), which had never been reported to the Agency.  The adverse events allegedly included possible association with endometrial cancer, prostate cancer, strokes, heart attacks, deep vein thrombosis, cellulitis and pellet extrusion.  Due to an alleged lack of certain “critical information” (and likely the lack of any requirement to report) FDA was only able to attribute about 61 reports (such as pellet extrusion and cellulitis) at the facility between 2013-2018 to pellets containing testosterone.  FDA notes that patients are using these BHRT products in lieu of FDA-approved products.  Evidently, FDA claims that some compounders state these products are not only “natural” but also safer than their FDA-approved counterparts.  FDA adds that there is no assurance of safety and efficacy with compounded BHRT formulations.

FDA also states that outsourcing facilities, unlike compounding pharmacies, are required to report adverse events.  FDA notes that two outsourcing facilities produced certain BHRT pellets at issue, but the pellets were marketed by BioTe Medical, which was not registered with FDA as an outsourcing facility, yet it collected adverse event data for products it marketed.   While BioTe Medical (who was inspected by FDA) evidently had an online portal to collect adverse drug event information, and collected over 4000 averse events concerning BHRT, these events were not reported to FDA.  FDA states it is using this episode to take steps to improve adverse event reporting, and to do the “most we can to protect patients.”  To that end, FDA states it will work with outsourcing facilities on reporting adverse events, and will work with states to finalize the Memorandum of Understanding between FDA and states, which likely will contain requirements for adverse event reporting for products shipped interstate for those states that ultimately sign the final MOU.  FDA reminds readers that it has contacted with the National Academy of Sciences, Engineering and Medicine (NASEM) to conduct a study on the risks of compounding BHTR (back in 2018, mentioned here).

FDA states it is still investigating the BHRT matter involving the two outsourcing facilities and BioTe Medical, and thus cannot discuss the case.  FDA continues on, stating that outsourcing facilities are subject to enforcement action if they do not appropriately “labeled their drugs with adverse event reporting information.”  Is FDA telegraphing that it will take some form of enforcement action against outsourcing facilities that allegedly provided the compounded formulations to the patients for failure to appropriately label a compounded formulation?  Were the formulations at issue actually improperly “labeled”?  Whose name(s) were on the label, and did the label warn about adverse events, including required reporting instructions?  What about Congress’ prohibition in section 503B against wholesaling and transfer of a drug product (503B(a)(8))?  What happened here?  Does that section come into play?  Were the compounded formulations transferred or resold, or were they simply marketed and advertised by BioTe Medical?  So many questions…. We will stay tuned as FDA’s investigation – which FDA has generally chosen to cast into a cautionary public tale, with little specifics revealed – moves forward.