Examining FDA's New Patient Labeling Draft Guidance

In accordance with the increasing emphasis on human factors as it applies to medical products and their associated written materials, the FDA recently released the draft guidance document Instructions for Use – Patient Labeling for Human Prescription Drug and Biological Products and Drug-Device and Biologic-Device Combination Products – Content and Format. Instructions for use (IFU) are a critical element of the device user interface, and special considerations must be accounted for in their design.

The FDA has released previous guidance on patient labeling, but this new labeling guidance arrives following the release of several human factors- and usability-focused guidance documents in the past several years, and it includes a more updated perspective on the current thinking with regard to these topics. Though this guidance document is not explicitly identified as a human factors guidance, IFU design and human factors are closely linked, and labeling can be used both as a tool to support product usability and as a secondary control measure to mitigate risk. In this draft, the FDA provides recommendations that incorporate human factors principles to meet these needs.

There are a few important things to keep in mind when reading the guidance. One is the type of product labeling to which the guidance is intended to be applied. Because the guidance is specific to combination products and not intended to cover general medical devices, the agency can be more specific about the expected content of these IFUs (e.g., how drug-specific information is included).

Another key point is the application of this guidance to patient users, a population that has different requirements for written materials than a clinical audience. For a lay user with limited or no medical knowledge, written materials must be designed in a manner that is understandable, easy to navigate, and promotes safe and correct use. Though the guiding principles of good IFU design are universal, specifying the type of product and applicable end user population focuses the document on a unique set of needs.

The following sections examine the content of different portions of the guidance document in more detail.

General Design Recommendations

Before delving into specific recommendations for the content of patient-facing IFUs, some general design principles are discussed. Two key topics covered here are readability and design of section headings, both of which are critical in promoting understandability and navigability. Using users’ language within the text is particularly important and is a well-established human factors principle that should always be a key consideration for any written materials. The guidance also calls out consideration of a low literacy population, which fits with long-standing recommendations from organizations such as the National Institutes of Health and the American Medical Association that patient instructions be written at or below and sixth-grade reading level. 

When it comes to utilizing headings to organize information in the IFU, the agency recognizes that consistency is key. Using consistent formatting, typeface, and location, along with appropriate grouping of similar information, allows users to more easily identify the type of information they are looking for.

This is another example of how human factors principles have been imbedded in the guidance document, even without being explicitly described as such.

General IFU Content

At this point in the guidance, the agency begins describing the content they want to see, how it should be displayed, and the particular order in which it should be presented. The first few sections focus on drug-related information. The recommendations are very specific, including expectations for naming conventions, use of capitalization and bold typeface, justification within the margins, and exact wording of the purpose statement.

General product information is also described, including expectations for a visual depiction of the product and important information to know before use. The content then turns to instructional steps for preparation and administration of the drug product, followed by sections on storage and disposal. At a high level, this covers the basic information that most combination product IFUs would require. The recommendations wisely aim to minimize the amount of information at the beginning of the IFU, focusing mostly product details and important cautionary information before the instructional steps. Reducing this introductory material allows the reader to more easily locate the instructions. However, several questions arise as we start to look at the specific order and location of the content.

Order of Information

Knowing the agency’s exact expectations for content and display of information takes a lot of the guesswork out of IFU design — which can be especially helpful for companies new to the FDA’s human factors expectations — and the standardization of drug-specific content may be particularly useful. However, IFU design may sometimes require a more analytical lens, rather than applying catch-all solutions. This can be especially applicable to devices that are unique and complex.

Some initial examples can be found in Section III.B.4 and III.B.5 of the draft guidance, after the product information and purpose statement. Section III.B.4 discusses the inclusion of a visual representation of the product, which makes sense at a high level. Illustrations can enhance understanding and allow the user to ensure they have all appropriate components in undamaged condition.

However, the FDA goes into more detail by recommending that oral drug products include a visual depiction of the product in a manipulated state, using the example of opening and sprinkling a capsule. Though it is important for lay users to understand how they are to administer a drug product, locating this information at this specific point in the IFU may have unintended consequences. By showing a user how to manipulate the product at the beginning of the IFU, readers could be influenced to prematurely begin administration before they have fully read the instructional materials. Thus, they may skip over the rest of the content with the expectation that they have already been given the information they need.

This trend continues with the discussion of “Important Information for Patients.” A section like this is common to combination product IFUs and typically contains general product warnings or cautionary information that a user may need to know (e.g., “For subcutaneous injection only;” “Take [Insert Drug Name] 1 hour before eating”) before proceeding to follow the stepwise instructions.

The FDA also recommends using this “Important Information for Patients” section to highlight information that is critical for proper administration and use of the product. While it is extremely important to highlight any safety-critical information in the IFU, spotlighting safety-critical tasks at the beginning of the IFU rather than within (or in addition to) the instructional steps again poses the problem of potentially giving patients information at the wrong time. Like the previous example of showing a manipulated drug product at the beginning of the IFU, providing patients with information that appears to correlate to instructional steps but is out of context with the full instructions can promote premature use and induce use error.

Finally, the guidance provides a suggested order of sections for storage and disposal, both located after the injection instructions. Though some IFUs may benefit from displaying storage instructions near the end of the document, this may not work as well for single-use products. Given that understanding of proper storage of a single-use product is important for the user to understand before product administration, the “Important Information for Patients” section might be a more appropriate location. The guidance then presents disposal instructions after the storage section, though it may actually be better to place them directly after the drug administration steps to ensure timely and safe disposal practices for single-use products.

Considering the variety of combination products on the market and their varying needs, the FDA may receive comments from industry requesting relaxed requirements that allow for more IFU customization.

Formatting

After the content recommendations, the guidance returns to discussion of formatting. Most of the recommendations found here are consistent with good human factors design. For example, Section IV.A.1 emphasizes clearly distinguishable and appropriately sized fonts, which make IFUs easier for users to read. This is another point in which the application of this guidance to patient users is particularly important, as combination product IFUs intended for users with visual impairments or of advanced age should consider these limitations in their design.

Other topics covered in the formatting section include use of white space and color; thoughtful applications of bolding, italics, and underlined text; and formatting and wording choice for instructional steps.

Use of a standard format, while often advisable, is another area in which the recommended approach in the guidance may not be ideal in all circumstances. As with order of instructions, there may be good reason to stray from the suggested format. For example, the guidance recommends bold typeface for both headings and step numbers. Following this guidance, an IFU could be developed that uses the exact same formatting for headings and instructional steps. However, for products with multiple headings that include instructions, it is advisable to implement an additional design element, such as a larger font size or underlined text for headings, to distinguish between different types of information. The change in formatting would make heading text more salient, improving a user’s ability to quickly identify the major IFU sections.

What’s Missing

The guidance document covers IFU design expectations that generally adhere to human factors principles and provides very detailed recommendations for IFU content. As practitioners from the combination product and IFU development industries examine the draft and provide feedback to the agency, we might see requests for more information or clarification on certain topics, which may include:

• Document scope: The document’s introduction states that an IFU is developed for drug products that have complicated or detailed patient-use instructions. This may be an important point to clarify, in order to understand instances in which these recommendations may not apply. The guidance uses examples of products the industry might consider simple (e.g., prefilled syringe), so there could be some confusion around what products might require “complicated” or “detailed” instructions. Additionally, more guidance may be needed for products with a large number of instructional steps or multiple end user groups. 
• Discussion of human factors evaluation methods: Though the guidance recognizes that human factors studies should inform IFU development, this is only mentioned via a footnote that refers the reader to a different guidance document. A robust human factors process is critical in developing an IFU that promotes safe and effective use, and in some cases, data gathered from usability studies may contradict some of the guidance’s recommendations. The agency could address this by incorporating discussion of evaluation methods throughout the document or in a separate section.
• IFU form factor: Though content and formatting recommendations are very specific in the guidance, the overall form factor of the IFU is not emphasized. Paper size, foldability, division of the document into rows or columns, and overall layout constraints can have a substantial impact on usability. Though product developers may not want to be artificially restricted by too many formatting constraints, it may be beneficial to establish if any specific formats or layouts are not recommended.

Conclusion

This draft guidance provides industry with a good starting place for the basic principles of patient-use IFU design. Recommendations focus on creating readable, understandable documents that aim to help patients use products safely and correctly. Some areas, such as order of information display, may require further scrutiny to determine if recommendations are optimal. As the comment period closes (September 2, 2019), we can expect that the FDA will have robust feedback to incorporate into the final draft, which could include more leeway regarding specific design elements and recognition that additional customization may be required based on product needs.

About The Author

Natalie Abts is the head of human factors engineering at Genentech, where she manages a team of engineers conducting human factors assessments for drug delivery devices. Before joining Genentech, Abts worked as a consultant providing advisement on human factors considerations for medical products. She has specialized experience in planning and executing both formative stage usability evaluations and validation studies for medical devices and combination products on the FDA approval pathway. Abts holds a master’s degree in industrial engineering, with a focus on human factors and ergonomics, from the University of Wisconsin, where she was mentored by Ben-Tzion Karsh.