US FDA Eyes New Investigational Drug Label Requirements That Bring International Harmonization - Pink Sheet

Sarah Karlin-Smith for Pink Sheet

The US Food and Drug Administration is considering new regulatory action to create more consistency in the labeling of investigational drugs to help reduce medication errors and protect patients as well as the integrity of the clinical trial results.

The agency is looking at recommending a harmonized global approach to the issue.

Recent studies that have pointed to missing or confusing information on investigational drug labels as a contributing factor for medication errors have recommended global harmonization of the labels, said Gerald Dal Pan, director of the Office of Surveillance and Epidemiology in FDA’s Center for Drug Evaluation and Research at an 18-19 May agency meeting held with the Reagan-Udall Foundation for the FDA on the topic.

“A creation of minimum best practices for investigational drug labels, aimed at reducing medication errors,” might be able to address the varied requirements for medication error reporting and investigational drug labeling among different regulators, added Lubna Merchant, Deputy Director of the Office of Medication Error Prevention and Risk Mitigation in CDER.

“This would certainly benefit our patients, but can also benefit the pharmaceutical industry by decreasing the regulatory burden on manufacturers that produce drugs for the global market.”

One avenue for new FDA recommendations could potentially come in upcoming guidance for sponsors and investigators on responsibilities for IND safety reporting, which is due out this year per FDA’s 2021 unified agenda, the agency indicated at the meeting. 

The potential changes and the FDA/Reagan-Udall meeting were partially motivated by concerns and pressure raised by clinical sites about problematic labeling and in some cases completely missing labeling or “naked containers.” The sites argue they bear the brunt of the work that comes from navigating inconsistent product labels.

The clinical sites said common problems include missing information, labels with too much extraneous information that make it difficult to find key information, illegible font sizes, and protocol and investigator brochures that don’t align with the naming information on the label.

Other issued raises by sites include the “license-plate naming,” of products with a combination of letters and numbers that change over the course of a study or are too similar to other study drugs. Drugs that change hands from one sponsor to another during development often experience labeling issues, the sites said. Another problem is that labels are often formatted with keys or legends that lack clear explanations for pharmacists.

Richard Needleman of Fox Chase Cancer Center presented slides with standardization recommendations from sites for oral and vial labels including information on font size and presentation, minimum required information and technology elements like barcode requirements.

While the agency has detailed requirements for approved product labels, there are much more minimal standards for investigational products. Those requirements are that labels of an investigational drug must include specific language indicating the product’s investigational status, the label must not contain any false or misleading statements and it must not contain any messaging indicating the drug is safe and effective for the use it is being investigated.

At the Reagan-Udall meeting, the agency acknowledged its division of medication error prevention and analysis (DMEPA) also does not currently review content of labels for investigational drugs.

Another gap in regulations is that medication errors that do not result in an adverse event may be reported to FDA in inconsistent ways.

While FDA does see some adverse event reports due to medication errors in trials, the agency knows from postmarket experience that these errors “often go unreported, said Jo Wyeth, postmarket safety program lead in CDER. “The reports that we receive are often just the tip of the iceberg," Wyeth said.