By Dieanira Erudaitius, Ph.D, Scientist
This month, July 2019, the United States Food and Drug Administration (FDA) released a new draft guidance to meet Prescription Drug User Fee Act (PDUFA) VI performance goals for patient‑oriented labeling. This draft guidance provides recommendations on the content and format development for Instructions for Use (IFU) documents submitted under a new drug application (NDA) or a biologics license application (BLA).[] The recommendations in this guidance do not apply to labeling for stand-alone medical devices,[1, , ] devices regulated under a BLA, or to labeling intended for healthcare providers.
What is an IFU and who reads it?
An IFU is a document that clearly describes to the patient the proper use of a complicated drug product. A drug product can be a drug, biologic, drug‑device, or biologic‑device combination. A complicated drug product can be products having difficult dosing regimens, misleading dosage forms (i.e., capsule must be sprinkled over food not swallowed), special preparation instructions (i.e., thaw 30 minutes before administering), etc.
Because the targeted audience is the patient, the FDA recommends it be written in a patient‑friendly manner that is easily understood. To develop successful patient-facing documents at all literacy levels, the FDA suggests:
- Avoid using technical language and abbreviations
- Clearly state the actions a patient should take when using the product
- Write in active voice and command language
- Begin sentences or phrases with an action verb whenever possible (e.g., “Mix vial well” rather than “you should mix the vial well”)
- Write the dose designations (amount and volumetric units) clearly by expressing doses in whole numbers to avoid any confusion (e.g., 5 mg instead of 5.0 mg)
Applicants submitting an IFU
Applicants submit the IFU, along with the currently approved prescribing information (PI), to the FDA for review. The FDA will compare the IFU and the PI for scientific accuracy and consistency. The sections of the PI most often included in the IFU are the DOSAGE AND ADMINISTRATION, HOW SUPPLIED/STORAGE AND HANDLING, and PATIENT COUNSELING INFORMATION. The IFU submitted for FDA review must be a true representation of the content and format (same layout, color, etc.) that patients will read.
What is in the guidance?
The guidance gives examples and suggestions on the type of content to include in the IFU. The IFU should contain pertinent information on how the patient properly prepares, administers, handles, stores, and disposes the drug. Typically, this information comes from the PI; however, additional details to ensure safe and effective use of the drug by patients is also recommended to be included. For example, a section may be added to explain the route of administration for drugs where the dosage form may lead to confusion (e.g., oral tablet must dissolve in the mouth instead of being swallowed) or perhaps the drug has a difficult dosing regimen that needs describing. The guidance also discusses formatting tips and tricks for appropriate bolding techniques, utilizing white space and color to enhance document readability, etc.
The IFU must be written clearly to avoid medication errors or improper use of the drug product. IFU documents are required for drug products with complicated or detailed patient‑use instructions. To ensure appropriate use of the drug product, the IFU must be clearly and informatively written to enhance the patients’ understanding and ensure patient safety and drug efficacy.
[] “Instructions for Use – Patient Labeling for Human Prescription Drug and Biological Products and Drug‑Device and Biologic‑Device Combination Products — Content and Format” FDA Draft Guidance for Industry. July 2019.
[] FDA Title 21 Code of Federal Regulations part 801. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=801
[] FDA Title 21 Code of Federal Regulations part 809. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=809
[] TANZEUM prescribing information, medication guide, and instructions for use label. Accessed on: 22 July 2019.
[] Instructions for Use SPRAVATO. Accessed on: 22 July 2019.
[] Instructions for Use TALTZ. Accessed on: 22 July 2019.
[] Instructions for Use PROCRIT. Accessed on: 22 July 2019.
[] Instructions for Use Repatha. Accessed on: 22 July 2019.