FDA issues final guidance on patient labeling for drugs and biologics

The US Food and Drug Administration (FDA) issued a final guidance for industry on July 15, 2022, entitled, “Instructions for Use – Patient Labeling for Human Prescription Drug and Biological Products – Content and Format.” This guidance is the final version of a draft guidance that FDA issued on June 30, 2019 for public comment.

Because Instructions for Use (IFUs) for patients typically are developed for medications which may be complicated to administer or use, FDA’s final guidance provides recommendations to maximize the clear presentation of IFU instructions and enhance patient understanding.  FDA’s recommendations focus on the content and organization of IFU information in order to best ensure a drug’s safe and effective use.

Changes from draft to final guidance

Though FDA’s changes to the draft guidance are relatively minor, the final guidance provides important insight into the Agency’s decision-making.

Most notably, the final guidance more thoroughly considers the role of the human factors engineering process in an IFU’s development. FDA adds: “The need for an IFU may be informed by following a human factors (HF) engineering process, which includes conducting comprehensive use-related risk analyses (URRA). The inclusion of an IFU document as a part of prescription drug labeling may be implemented as a mitigation for use-related risks. A comprehensive URRA helps to determine if an IFU is warranted.”

Though the draft guidance recognized that data from HF studies could be used to inform the development and design of the IFU, the final guidance amplifies the importance of this data to “inform the development and design of the IFU, including the content to be included under the headings recommended in this guidance . . .” Of course, should data from HF studies warrant deviation from FDA’s recommendations, FDA advises to consult with the Agency “early in the development process.”

Summary of recommendations

Content

• Include pertinent information: The IFU should include pertinent information from the Prescribing Information (PI) that explains how to use the drug. This information will generally come from the Dosage and Administration, How Supplied/Storage and Handling and Patient Counseling Information sections of the PI.
• Use simple language: FDA suggests writing the IFU at or below the national reading level in nontechnical language, using active voice and command language. For example, a “transdermal system” should be referred to as a “patch,” and the command “Wash your hands” should be used instead of “You should wash your hands.” FDA also suggests avoiding abbreviations and trailing zeros in dosing information.
• Use headings: The IFU should organize information under headings and subheadings that clearly identify the focus of each topic and allow the patient to quickly locate important information. Headings and subheadings should group related tasks that accomplish a single objective.
• Order of presentation: FDA makes specific content recommendations and suggests that the content be presented in the following order: (1) title, (2) product title, (3) purpose statement, (4) visual of drug product, (5) important information for patients, (6) preparation instructions, (7) administration instructions, (8) storage instructions, (9) disposal instructions and (10) additional information.

Format

• Font and size: FDA recommends using a sans-serif font, such as Verdana or Arial, no smaller than 10 points (with a handful of exceptions where 8-point font is acceptable).
• Limit use of ALL CAPS: The title “INSTRUCTIONS FOR USE” should appear in all uppercase, but all other headings should appear in title case, and FDA discourages the use of uppercase in the body of the IFU.
• Limit bold, italics and underlining: Though certain types of information, like the product title, headings and step numbers, should appear in bold type, FDA discourages the use of bolding, italicizing and underlining in the body of the IFU. FDA suggests that such emphasis be limited to important phrases or concepts, like “For oral use only” and “Step 1.”
• Use continuous numbering: FDA recommends numbering step-by-step instructions and using continuous numbering throughout the document. There should only be one “Step 1.”
• Instruct action first: Action-oriented instructions should appear before any other information related to that step in the instructions. For example, the patient should be instructed to “Check the liquid by looking through the viewing window” before learning that “you may see air bubbles. This is normal.”
• Use of visuals: FDA recognizes that visuals can help patients understand instructions. Visuals should be large enough to allow patients to see the focal point and should be placed immediately adjacent to the related instructional step.
• Visual balance: The IFU should have a balance of text, visuals and white space. For example, white space can be used to emphasize important text and visuals.
• Use of color: The IFU should be presented in black type on a white background. Colored text and visuals may be useful but should maintain clarity and legibility when printed in black and white or grayscale.

Industry comments

There were several comments from stakeholders that FDA did not incorporate into the final guidance. Those comments related to human factors; when IFUs are needed; identification of product parts in drug-led, drug-device combination products; whether the IFU document is included as a package insert; and IFUs presented in formats other than a full-page booklet.

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