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Statement from Janet Woodcock, M.D., director of the Center for Drug Evaluation and Research on improving adverse event reporting of compounded drugs to protect patients

SILVER SPRING, Md., Sept. 9, 2019 /PRNewswire/ -- Compounded drugs can serve an important medical need for certain patients, however, they also present risks to patients since they are not evaluated by the FDA for safety, effectiveness and quality. The FDA's compounding program aims to help protect patients from poor-quality compounded drugs, while preserving access to lawfully-marketed compounded drugs for patients who have a medical need for them.  Along with the development of policy and enforcement of the law, and collaboration with states and industry, our inspections of compounding facilities are vital aspects of this effort. Understanding the nature of the activity these compounders—especially outsourcing facilities— are engaged in helps minimize the risks to patients. While the FDA inspects outsourcing facilities regularly according to our risk-based schedule, we also rely on them to do their part in alerting us to issues that may endanger the health of patients.

As part of this work, several colleagues and I recently called attention to a particular issue associated with compounded hormones (specifically, in the form of pellets). During an inspection in 2018 of BioTE Medical, our investigators uncovered information about 4,202 adverse events that had never been reported to the agency. The adverse event information our investigators found suggested compounded hormone pellets were possibly associated with endometrial cancer, prostate cancer, strokes, heart attacks, deep vein thrombosis, cellulitis and pellet extrusion. However, because the reports lacked certain critical information, the FDA was able to attribute only a small percentage of the adverse events (61 reports), such as pellet extrusion and cellulitis, to the use of compounded hormone pellets containing testosterone. The company that collected the adverse events did not send them to us during the five years they occurred between 2013 and 2018. However, in light of this discovery, the FDA is continuing to take multiple steps to help protect patients, which we wanted to highlight today in the interest of public health.

Compounded bioidentical hormone replacement therapy (BHRT) products such as progesterone and testosterone, are used at times instead of FDA-approved drugs for hormone replacement therapy. Some compounders market BHRT products as superior to FDA-approved drugs by making assertions that they are more natural, safer or better for patients than FDA-approved drug products. FDA-approved hormone therapy treatments have been reviewed for safety and effectiveness for specific uses, and the FDA has measures in place to ensure quality during manufacturing. However, because, compounded BHRT products are not approved by the agency, there is no assurance of safety and efficacy. Outsourcing facilities, such as those that produced these products, are required to report certain adverse events to the FDA.

The agency uses adverse event reports to monitor safety issues to help protect the public. Adverse event reports can assist the FDA in identifying potential safety problems with a particular product. However, this is more difficult when information is outdated or missing. We maintain a public database to ensure patients and health care professionals can access adverse event data about drugs. Outsourcing facilities are required to report adverse events to the agency and include adverse event reporting information on compounded drug labeling, and we encourage all companies, health care professionals and patients to report adverse events as soon as they know about them. Every year, the FDA receives adverse event reports of patient illnesses and deaths associated with compounded drugs. Information on the safety history of compounded drugs, through the reporting of adverse events is vital to protecting the public health.

Because compounding can serve an important role for patients whose medical needs cannot be met by an FDA-approved drug, we must work to protect patients from the risk of contaminated or otherwise harmful products. As we develop our policy and oversight program, the FDA continually strives to strike a balance between preserving access to compounded drugs for patients who have a medical need for them while protecting patients from the risks associated with compounded drugs that are not made in accordance with applicable quality standards or other requirements.

In this case, outsourcing facilities, Carie Boyd's Prescription Shop and AnazaoHealth Corporation, produced the pellets, but they were marketed by BioTe Medical, which was not registered with the agency as an outsourcing facility. While BioTe had an online portal to collect adverse event data from its customers, it never reported that information to the FDA nor did it provide this information to the outsourcing facilities.

The FDA is still investigating this matter, with respect to Carie Boyd's Prescription Shop, AnazaoHealth Corporation or BioTe and we cannot discuss the status. Outsourcing facilities are subject to regulatory and enforcement action if they do not appropriately label their drugs with adverse event reporting information and to report events to the FDA. The agency intends to take appropriate action if outsourcing facilities do not comply with the adverse event reporting requirements. We remind outsourcing facilities to develop thorough procedures to compile and investigate adverse event reports and share them with the FDA.

We're also using the information we learned from this episode to take steps to improve adverse event reporting and analyses to ensure we're doing the most we can to protect patients. We will continue to work with outsourcing facilities to improve mechanisms for obtaining reports of adverse events associated with their products and for providing adverse event reports to the agency.  Furthermore, we continue to work with our state regulatory partners to finalize a standard memorandum of understanding under which states would agree to, among other things, investigate complaints of adverse events associated with certain compounded drugs from pharmacies operating under section 503A and report serious adverse events and serious product quality issues to the agency. States that sign the memorandum of understanding with the FDA will agree to investigate and share their findings. Collaboration with states has the potential to help prevent serious and widespread problems by helping to better identify adverse events and product quality issues across the country. For example, if a compounder distributes drugs to multiple states, it can be difficult to gather information about possible adverse events associated with those drugs, connect them to the compounder and undertake coordinated action to address a potentially serious public health problem. Collaboration with our state partners would be crucial in such an instance. While adverse event reports have some limitations, this information is one of the best safety tools we have at our disposal. The FDA is dedicated to increasing public awareness about drug safety issues and we're continuing our efforts to improve reporting for all types of drugs, including compounded medicines. We anticipate finalizing our MOU with the states later this year.

To further enhance our understanding of the safety of compounded hormones, the FDA has contracted with the National Academy of Sciences, Engineering, and Medicine (NASEM) to conduct a study on the risks associated with compounded hormone products. Our collaboration with NASEM will also continue to examine the clinical utility of treating patients with compounded products and the available evidence of the safety and effectiveness of multi-ingredient compounded topical pain creams. The FDA plans to share updates about this study with the public as information is available.

We'll continue to work to ensure patients have appropriate access to compounded medications. However, we must also ensure that all steps are taken to help reduce risks to patients. Patient health and safety is the FDA's highest priority.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Media Inquiries: Jeremy Kahn, 301-796-8671; jeremy.kahn@fda.hhs.gov 
Consumer Inquiries: 888-INFO-FDA

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SOURCE U.S. Food and Drug Administration