The US Food and Drug Administration (FDA) has released a new draft guidance for industry recommending changes to the way companies place safety information on container labels and cartons, saying the changes are intended to reduce the number of medication errors.

Background

A 2006 report by the US' Institute of Medicine (IOM), a government think tank of sorts focused on healthcare, found that a major source of medication errors could be attributed to product labeling.

Eight problems were specifically identified in the IOM report are being contributing factors:

• The names of drug products can sound or look the same, causing consumers to consume the incorrect product.
• The same drug may have several formulations, which means consumers might take the wrong dose or be prescribed the incorrect product.
• Abbreviations on the product labeling might be used to represent several similar concepts.
• Symbols, derivatives and abbreviations could be confused.
• Labels are difficult to read because they are cluttered, use small fonts and illegible text.
• Company logos are too prominent and distract from more important information.
• Warnings and reminders are not properly or adequately emphasized.
• Terminology is not adequately standardized.

FDA has made strides in the last 15 years to correct some of these deficiencies, including recommending or requiring new drugs to use standardized formats, minimum requirements for labeling text, and regulating the use of similar-sounding names.

But more work remains to be done, FDA notes. IOM's report found that thousands of deaths are caused each year by medication errors-as many as 33% of all medication errors and 30% of all fatalities.

Such errors can be "magnified" in sub-populations, IOM observed. For example, if a label does not clearly have information pertaining to safe prescribing practices for children, that could result in a child receiving a higher- or lower-than-recommended dose of a given medication, injuring or even killing the patient. This is a particularly prescient concern given that many medications are approved based on safety and efficacy data in adults, and many companies only conduct pediatric studies after initial market approval. Other subpopulations of note include those over the age of 80, patients with existing kidney problems, and patients with multiple comorbidities.

New Guidance

So what's left to be done? Plenty, FDA concedes. In 2007, the FDA Amendments Act (FDAAA) gave the agency new authority to reduce errors by regulating the use of proprietary names, label abbreviations, acronyms, dose designations, and error-prone labeling and packaging designs-in other words, all of the problems identified by IOM.

A 2010 public hearing was intended to study various approaches to these concerns, and now FDA is out with a new draft guidance document, Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors, intended to make changes to labeling for all prescription drug and biological products approved under a new drug application (NDA), biologics licensing application (BLA) or abbreviated new drug applications (ANDA).

That guidance drills down into a subset of IOM's concerns; namely, the poor design of labels and labeling that can obscure or distract from important safety information.

FDA said this typically happens in one of seven ways:

• Key information is missing, poorly worded or not prominent.
• Key information is presented on another surface place of the container or requires rotating the package to view.
• Different dose forms of the drug look the same (e.g. color, size, images, etc).
• Labels and labeling are cluttered with unnecessary images, text or graphics, obscuring key information.
• Abbreviations and symbols are used when the original word would be better.
• The text is too small, poorly contrasted against the background, uses an illegible font or is otherwise designed poorly.
• Overlapping text is printed on a clear container such that the near side is illegible due to the far side text remaining visible.

FDA's new draft guidance goes on to make numerous recommendations regarding ways in which manufacturers and packaging entities can best mitigate these concerns.

Mitigating Errors: Practical Concerns

For example, FDA advises companies to utilize the principal display panel (PDP)-the panel most likely to be displayed to the end user-to display the proprietary name, the proper name, the product strength, the route of administration and any warnings or cautionary statements.

The guidance also establishes recommendations regarding the container label size, minimum standards for font size and style (12-point sans serif-type font such as Arial), the use of high-contrast backgrounds, and un-crowded text information that avoids the use of logos, bars, stripes, watermark graphics, lines or symbols.

Logos should be small and unobtrusive, FDA advises. In addition, abbreviations should not be used so as to avoid confusion. FDA noted that µg-the symbol for microgram-can often be mistaken for milligram for consumers, raising the potential of a massive overdose. Other abbreviations, such as IU, a measurement, have been mistaken for IV, a route of administration.

In other areas, companies need to be cognizant of the visual representation of their products. The use of two similar packages-for the sake of example, green, the same size and shape, and bearing the same graphics-could cause consumers or healthcare providers to accidentally prescribe the incorrect one to patients. As such, changes should be made-and in particular to the color-to distinguish various strengths and dose forms of a particular medication.

The guidance goes on to note a host of other issues, such as specific format recommendations for displaying the branded and generic name of a product, expiration dates, national drug code numbers, scheduling letters and product strength.

FDA notes that this is the second guidance document published since the passage of FDAAA on this particular topic, and that the agency is planning a third guidance on the use of proprietary names at an unknown point in the future. The first guidance pertained to container closure systems.

FDA: Guidance for Industry (Draft): Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors

Federal Register