Ashlee Mattingly, PharmD, BCPS, assistant professor in the Department of Pharmacy Practice and Science (PPS) at the University of Maryland School of Pharmacy, has been awarded a three-year, $2.2 million grant from the U.S. Food and Drug Administration (FDA) to investigate the use in clinical practice of drugs, including certain bulk drug substances (active ingredients) that have been nominated for use in compounding by outsourcing facilities. The research will assist the FDA in its efforts to develop a list of bulk drug substances that outsourcing facilities can use in compounding under the Federal Food, Drug, and Cosmetic Act.
“Compounded drugs serve an important role for patients whose medication needs cannot be met by an FDA-approved drug product, such as patients who have an allergy and need a medication to be made without a certain dye,” says Mattingly. “Our research will examine how drugs compounded with certain bulk drug substances have been used historically, as well as how they are currently used in clinical practice, which will help the FDA determine whether these substances should be included on its list of bulk drug substances that outsourcing facilities can use in compounding.”
Improving Drug Quality
In 2012, contaminated injectable drugs that a state-licensed compounding pharmacy shipped across the country caused an outbreak of fungal meningitis that led to more than 60 deaths and 750 cases of infection across the United States. In response to this outbreak, Congress enacted the Drug Quality and Security Act (DQSA), which amended the Federal Food, Drug, and Cosmetic Act to strengthen the FDA’s authority to regulate and monitor compounded drugs.
The legislation, among other things, established a new category of compounders known as outsourcing facilities, which are registered with the FDA and operate under the direct supervision of a licensed pharmacist. These facilities can only compound using bulk drug substances if the substance is used to compound a drug on the FDA’s drug shortage list, or appears on a list that will be developed by the FDA of bulk drug substances for which there is a clinical need.
Stephen Hoag, PhD, professor in the Department of Pharmaceutical Sciences (PSC) and director of the Applied Pharmaceutics Lab at the School of Pharmacy, who joins Mattingly as a collaborator on this project, explains, “It’s a difficult balancing act with which the FDA has been tasked. The FDA wants to make compounded medications available for the patients who need them, but it must also take certain precautions to help ensure that the medications are compounded properly, and not otherwise harmful to patients. We will help the FDA collect information that it will use to make informed decisions about which substances should be used in compounding, as well as which substances should not be used in compounding.”
Leveraging an Existing Partnership
This University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) grant is part of an ongoing partnership between the University of Maryland, Baltimore; the University of Maryland, College Park; and the FDA. M-CERSI focuses on modernizing and improving the ways drugs and medical devices are evaluated. James Polli, PhD, the Shangraw/Noxell Endowed Chair in Industrial Pharmacy and Pharmaceutics at the School of Pharmacy and co-principal investigator for M-CERSI, will partner with Mattingly and Hoag on this project.
“The goal of M-CERSI is to bring together researchers from across the University of Maryland to assist the FDA with a wide range of regulatory science issues,” says Polli. “We want FDA scientists to be best informed when making decisions that will affect patients, providers, researchers, and manufacturers across the country. Through our involvement in this project, we are helping to support FDA’s efforts in identifying bulk drug substances for which there is a clinical need.”
Reaching Out to the Experts
The project will include an in-depth review of clinical practice guidelines, published literature, and other relevant sources regarding the clinical use of drugs containing certain bulk drug substances. Some of the bulk drug substances that Mattingly and her team have been tasked with evaluating include alpha lipoic acid (a supplement often used by individuals with diabetes and peripheral neuropathy) and glycolic acid (a substance used to treat conditions affecting the skin, such as scarring and hyperpigmentation).
Mattingly and her team will also conduct outreach to medical specialty groups, medical experts, and specialists in the relevant fields to gain a better understanding of the medical conditions these substances are used to treat, how long these substances have been in use in the clinical setting, the patient populations in which the substances have been used, the extent of their use, and whether the substances are used to compound drugs that health care providers store in their offices in advance of identifying the individual patients that will receive the drugs, as was the case for the contaminated steroid injections linked to the fungal meningitis outbreak in 2012.
“We want to make sure FDA has all of the information it needs to develop the best, most thorough list of bulk drug substances for use in compounding,” says Mattingly.
Informing Best Practices
From 2014 to 2015, FDA sought nominations from relevant medical experts and existing outsourcing facilities for bulk drug substances to include on its list. More than 200 substances have been nominated to-date.
Mattingly and her team will work together, while leveraging their individual expertise in pharmacy practice and pharmaceutical sciences as well as their extensive outreach to medical experts, to understand use in clinical practice of more than 200 substances. Once the research is complete, the team will prepare a report summarizing its findings, which the FDA will use to help inform its decisions regarding each substance.
“This project is really about learning as much as we can about each substance that has been nominated for inclusion on FDA’s list of bulk drug substances for which there is a clinical need,” says Mattingly. “Our goal is to support FDA’s efforts to preserve access to compounded drug products that meet individual patients’ medical needs.”
For more information about this project, please visit pharmacy.umaryland.edu/compounding.