FDA’s compounded drug list balances patient access and patient safety

The FDA recently took an important step to support access to compounded drugs for patients who need them, with its first additions to its list of bulk drug substances that outsourcing facilities may use.

Compounded drugs can play an important role when a patient’s medical needs cannot be met by an FDA-approved drug. But they also bring risk because they are not subject to the same level of oversight.

After an extensive evaluation, the agency added four substances to its 503B Bulks List, which is comprised of active pharmaceutical ingredients for which the FDA has determined there is a clinical need for use in compounding by outsourcing facilities: diphenylcyclopropenone, glycolic acid, squaric acid dibutyl ester and trichloroacetic acid, all in topical formulations.  

This marks a significant milestone in the agency’s work to protect patient safety following the 2012 outbreak of fungal meningitis linked to contaminated compounded drugs that were distributed to patients across the country.

In response to that tragic outbreak, in which 64 people died and more than 750 people were sickened, Congress in 2013 passed the Drug Quality and Security Act (DQSA). The legislation affirmed the need for enhanced federal controls on drug compounding; the importance of collaboration between federal and state authorities to advance safer drug compounding practices; and the need for a legal framework to investigate and hold accountable compounders that threaten public health. Outsourcing facilities must meet more stringent quality standards than entities that compound drug products under section 503A of the Federal Food, Drug, and Cosmetic Act. In addition, the act allowed outsourcing facilities to distribute compounded drugs to healthcare practitioners for office stock, to hold in their offices in advance of patient need.

While compounded drugs are not FDA-approved, outsourcing facilities must maintain critical quality conditions, such as compliance with current manufacturing practice requirements. Outsourcing facilities are also inspected by the FDA on a risk-based schedule to ensure their compliance with the law, and they must submit adverse event and other reports about products they have compounded, among other requirements. 

The FDA’s dedicated clinicians and researchers have implemented a careful and deliberative process to consider whether a bulk drug substance should be included in the 503B Bulks List. This process is also informed by external research partners, feedback from industry stakeholders, and other public commenters. As development of the 503B Bulks List progresses, nominations of bulk drug substances that are adequately supported will continue to undergo the thorough FDA vetting necessary to protect patients while meeting patient needs.

The integrity of the drug approval process remains a priority as the nation builds a stronger drug supply chain. The FDA will continue in its efforts to improve quality and safety in the drug compounding industry.

Donald D. Ashley is director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research.