Dosing devices and liquid medicine labels

Researchers looking at the 200 top-selling children's liquid medicines sold over the counter in the US, in the 52 weeks ending October 30, 2009, covered 99 percent of that market. Measuring devices came with 148 of them. In 146 of those 148, the markings on the cup, dropper or syringe did not line up with the dosing directions on the label, the team reported in JAMA in December 2010, as summarized by the federal patient safety network PSNet⁶.

Some devices were missing a marking the directions called for. Far more, 120 of the 148, carried extra markings the label never mentioned. Ninety-seven products used an abbreviation for milliliter other than "mL."

FDA published a draft guidance on the problem that November, days after the study's sample period closed, and finalized it in May 2011. Since then, the push among standards bodies and medical groups has moved past matching markings toward a single unit, the milliliter. This explainer covers what FDA recommends, what the law actually requires, how the milliliter-only standard spread, and what the research measured. It is about labels and devices, and it gives no dosing information.

What FDA recommended in 2011

FDA announced the final guidance on dosage delivery devices¹ for orally ingested over-the-counter liquids in the Federal Register on May 5, 2011³, after a November 2009 draft⁴. The notice said FDA had found that many products came with devices bearing markings "inconsistent with the labeled dosage directions," superfluous markings, or missing ones, and that it was acting because of reports of accidental overdoses.

In the guidance document², FDA makes these recommendations to manufacturers, packers and distributors:

• Include a dosage delivery device with every orally ingested OTC liquid.
• Mark the device in the same units of liquid measure the directions use, with the same abbreviations, and define abbreviations such as "tsp" and "mL."
• Use leading zeros ("0.4," never ".4") and drop trailing zeros ("4," never "4.0") to avoid tenfold errors.
• Leave off extraneous or unnecessary markings.
• Tie the device to the product, either with a label statement or by attaching it.
• Keep the device from being much larger than the largest labeled dose, and make sure it can clearly measure the smallest.
• Keep markings visible when liquid is in the device.

FDA also suggested companies run usability studies. A footnote says the guidance does not address whether devices accurately deliver the dose, and that FDA might later issue guidance on factors such as age, weight and viscosity.

What the law actually requires

Guidance is advice. The document says so, noting that "should" in an agency guidance "means that something is suggested or recommended, but not required." The enforceable part comes from the Food, Drug, and Cosmetic Act.

Under 21 U.S.C. 321(m)¹³, labeling includes written, printed or graphic matter on a product's containers or "accompanying such article." FDA treats the markings on a cup or syringe packed with a medicine as labeling. Under 21 U.S.C. 352¹⁴, a drug is misbranded if its labeling is false or misleading, or if it lacks adequate directions for use. In the guidance, FDA says a device with markings that conflict with the directions makes the product misbranded under both provisions. The directions themselves sit in the Drug Facts panel required by 21 CFR 201.66¹⁵, which GxRadar walks through in how to read a Drug Facts label.

FDA had been using those powers for two decades before the guidance. Its own history, laid out in the 2011 document²:

Despite those efforts, FDA wrote in 2011, "an increasing number" of products were reaching shelves with incompatible devices.

How the milliliter-only standard spread

FDA's 2011 guidance accepted teaspoons as long as the device and label agreed. Professional and standards groups went further over the next decade, according to a 2021 white paper¹⁰ from the National Council for Prescription Drug Programs, the standards body for pharmacy claims and prescription labels.

According to the white paper, USP deleted its general chapter on the teaspoon in April 2010, removing it as an official alternative to metric units, and that a USP chapter update effective May 2019 removed the teaspoon as an official unit for drug packaging. In 2015, the federal health IT office's certification criteria for electronic health records limited e-prescribing of oral liquids to milliliters. NCPDP's own first version, in March 2014, recommended the milliliter as the universal unit on prescription container labels, along with leading zeros and devices whose markings match the label. Version 2.0, in March 2021, says e-prescribing software must not let prescribers override that to use household units. GxRadar's explainer on what USP means on a label covers the compendium's role.

The American Academy of Pediatrics issued a 2015 policy statement⁹ in Pediatrics backing milliliter-based dosing devices for children's liquid medicines. That June, the National Alert Network, drawing on the Institute for Safe Medication Practices' error reporting program, issued an alert on dosing cups¹¹ after a fatal event in which a nurse misread a fluid dram scale on a cup as milliliters. The alert called for cups with only a milliliter scale. CDC's PROTECT Initiative¹², a public-private partnership on children's medication overdoses, lists milliliter units on labels and dosing devices as one of its three focus areas.

What the research measured

Three widely cited studies, all led by the same pediatrics researcher, measured the problem from different angles.

In the 2016 experiment, a teaspoon-only label paired with a tool marked in both units produced more errors than milliliter-only labels and tools. The 2014 study found the gap widest among parents with low health literacy and those who did not speak English.

The acetaminophen concentration problem

Units were one source of confusion. Concentration was another. In a 2014 draft guidance⁵ on children's liquid acetaminophen, FDA said there had been many reports of overdose attributed to confusion between concentrated infant drops and the oral liquid sold for older children, which were sold at different strengths. The draft covered concentration, carton and container labels, packaging and the delivery devices sold with the products. GxRadar's account of the 2022 children's fever reducer shortage touches on the same product shelf.

Prescription liquids follow a separate track. Pharmacies print their own prescription labels, and the NCPDP recommendations are aimed at them. Questions about which device goes with a given medicine, or what a marking means, are ones a pharmacist can answer at pickup. Problems with a device or label can be reported to FDA, as GxRadar explains in its piece on MedWatch.

FDA's page for the 2011 guidance was last updated in October 2019. Its docket, FDA-2009-D-0322, still takes comments, as FDA allows for any guidance at any time.