FDA Drafts Guidance on Restricted Delivery Systems for Liquid Drugs
In an effort to reduce the incidence of accidental drug ingestion by children, the US Food and Drug Administration (FDA) on Tuesday issued draft guidance detailing considerations for when drugmakers should employ restricted delivery systems for oral liquid drugs.Despite advancements in other forms of child-resistant packaging, such as blister packaging and safety caps, FDA says that accidental ingestion of oral liquid drugs accounts for nearly 10,000 emergency department visits annually by children under six.
Specifically, the 10-page draft guidance provides recommendations for when restricted delivery systems should be considered, as well as human factors and design considerations and directions for use for products that feature restricted delivery systems. The guidance also describes two types of flow restrictors that could be used based on product characteristics, closed flow and open flow restrictors.
Closed flow restrictors are meant to limit access to a single-unit volume using a self-closing valve, whereas open flow restrictors allow for a “continuous, controlled volume.”
According to FDA, the target for restricted delivery systems should be to “reduce the amount of liquid that flows from a bottle in a 5-minute period based on the toxic dose of the drug product to a 2 year-old child.” More specifically, FDA says companies should use the 50th percentile weight for toxic dose calculations according to the Center for Disease Control and Prevention’s growth charts.
FDA says that drugmakers should consider closed flow restrictors for narrow therapeutic index drugs and drugs “with significant toxicities at doses that are close to the therapeutic dose,” such as acetaminophen.
The guidance features a flowchart to help drugmakers decide whether a restricted delivery system should be considered for their product.
The guidance also provides specific recommendations for products containing one or more of five active pharmaceutical ingredients: acetaminophen, dextromethorphan, diphenhydramine, ibuprofen and pseudoephedrine, which account for most emergency department visits for children involving over-the-counter (OTC) liquid medications. For each ingredient, FDA provides a maximum deliverable quantity within a 5-minute interval.
FDA