FDA Takes Steps to Advance Goals of Compounding Program

SEPTEMBER 09, 2018
The FDA is taking new steps to better ensure the quality of compounded drugs, while also preserving patient access to these medications. In a prepared statement, FDA Commissioner Scott Gottlieb said the agency’s compounding program, which includes implementation and provisions of the law, is a priority.

In a revised draft memorandum of understanding (MOU), the FDA is making changes to its 2018 Compounding Policy Priorities Plan. The MOU addresses investigations of complaints related to compounded drug products distributed outside the state, distribution of inordinate amounts of compounded drug products interstate, and submission and disclosure of information.

“The goal of the MOU is to collaborate with the states so that, working together, we can have the greatest public health impact while also maximizing our resources,” said Gottlieb, in a prepared statement. “Toward these goals, the revised draft MOU addresses patient access concerns previously raised by stakeholders, while retaining critical safety provisions.”

In addition, the FDA is working on new policies addressing insanitary conditions at compounding facilities and a risk-based approach to current good manufacturing practice (CGMP) requirements for outsourcing facilities.

“If a compounder distributes drugs to multiple states, it can be very 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,” said Gottlieb, in the prepared statement. “These risks were illustrated by the 2012 nationwide fungal meningitis outbreak. This tragic outbreak led to more than 750 cases of illness and the deaths of 64 individuals. They had used a compounded drug for injection that was supposed to be sterile but had become contaminated before distribution to patients and providers.”

Following that incident, the FDA issued a draft MOU to implement a key public health protection in section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Section 503A directs the FDA to develop an MOU for use by the states to address certain interstate distributions of compounded drugs by traditional compounders. These traditional compounders are, among others, pharmacies that operate under section 503A. The MOU also covers states’ investigations of complaints associated with compounded drugs distributed out of their state.

“We’ve taken steps with this revised MOU to address concerns that pharmacies raised with respect to previous drafts of the MOU, while making sure that we achieve appropriate safeguards for patients,” Gottlieb added.
Under the 2015 draft MOU, the states were expected to take action against a traditional compounder that distributed inordinate amounts of its compounded drugs interstate that were equal or greater to 30 percent of all drug products dispensed or distributed by the compounder. Under the revised draft MOU, states would agree to identify compounders that distribute more than 50% of their total prescription orders for compounded drugs interstate.

The revision also seeks to have states report certain information to the FDA about those compounders. This includes information about the volume of compounded drugs distributed interstate and the number of states in which the compounder is licensed.

“Our hope is that this information will assist both the FDA and the states in developing risk-based oversight priorities to have the greatest public health impact,” Gottlieb said, in the statement.
In addition, the revised draft MOU includes increased flexibilities concerning the mechanism for states to gather information on inordinate amounts, and the document removes a previous draft provision requiring the state to take action when a compounder distributes inordinate amounts of compounded drugs interstate. Under the new approach, Gottieb said, the state could consider whether to take action according to a more flexible, risk-based approach. The FDA intends to use this information to prioritize its inspections of compounders based on risk.

Section 503A limits distribution of compounded drugs outside the state by a pharmacist, pharmacy, or physician located in a state that has not entered into the MOU to 5% of its total prescription orders dispensed or distributed by the compounder. The MOU and the statutory 5% limit do not apply to drugs compounded by outsourcing facilities under section 503B of the Food, Drug, and Cosmetic Act, and they do not apply to drugs that are compounded for animals.

“When finalized, the revised MOU will provide clarity on state investigations of complaints associated with compounded drug products that have been distributed out of state. States that enter into the MOU will investigate complaints and advise the FDA when they receive reports of serious adverse drug experiences or serious product quality issues, like drug contamination,” said Gottlieb, in the statement. “We anticipate the MOU will help to facilitate increased collaboration between the FDA and the states that sign it. Working together, we can help promote safe compounding practices and better address emerging public health concerns that may affect patients.”

According to the FDA, the agency expects that the states will continue to have day-to-day oversight over traditional compounding pharmacies and physicians located in their state. Officials also said information that the FDA obtains from the states will enable the agency to focus inspection and enforcement resources pertaining to traditional compounders based on risk.
“Looking ahead, we intend to take several more actions in relation to compounding in the coming months. Our goal is to achieve an effective approach that promotes safe, appropriate compounding practices,” said Gottlieb, in the statement.

An issue of concern to FDA officials is identifying insanitary conditions during inspections of compounders. The agency plans to issue a revised draft guidance this fall that will address and describe insanitary conditions that the FDA has identified during inspections. These conditions include mold growth and animal hair in areas where sterile drugs are produced.
In addition, the FDA intends to issue a revised draft guidance, for public comment, describing its policies concerning CGMP requirements for outsourcing facilities. A goal of this guidance, which is expected to be issued in the coming months, is to make it more feasible for compounders to become and operate as outsourcing facilities.


Statement from FDA commissioner Scott Gottlieb, M.D., on new steps to help ensure the quality of and preserve access to compounded drugs by pursuing closer collaboration with states [news release]. Silver Spring, MD; September 7, 2018: FDA website. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm619796.htm. Accessed September 7, 2018.