In September 2007, the reauthorization of the Prescription Drug User Fee Act (PDUFA IV) was signed into law, broadening and strengthening FDA’s drug safety program. Along with PDUFA’s reauthorization came a number of performance goals related to the implementation of user fees. FDA stated that these fees would be used to reduce medication errors, and as one of its goals FDA agreed to implement measures to reduce medication errors related to product and packaging design.
In early April 2016, FDA published a guidance document entitled “Safety Considerations for Product Design to Minimize Medication Errors,” which is focused on completing FDA’s goal. The guidance provides very broad recommendations concerning product design safety, and applies to IND sponsors; NDA, BLA, and ANDA applicants; manufacturers of prescription drugs being marketed without an approved application; and manufacturers of over-the-counter (OTC) monograph drugs. Although the guidance touches on a range of topics, FDA places an emphasis on a number of early stage product design considerations that could minimize medication errors.
A drug’s user interface includes “all components of a product with which a user interacts (e.g., sees and touches), such as labels and packaging, and the container/closure system interacts, such as controls and displays.” According to the guidance, a product’s design and user interface typically involve the following elements:
- Active ingredient
- Strength
- Dosage form
- Product appearance
- Size
- Shape
- Palatability
- Storage and handling
- Indication
- Type of container/closure used to package the product
- The label affixed to the container/closure
- Secondary packaging such as outer carton or overwraps into which the container/closure is placed
- The labeling information describing the dose, preparation, and administration that accompanies the drug product
Locating necessary product information is essential to a product’s safe and effective use. Accordingly, how this information is located and interpreted by the end user is critical. The labeling, packaging, and terminology that is used by a manufacturer have a great influence on the use of a medication, and any weaknesses or failure in the design of these elements can lead to harmful medication errors. Accordingly, FDA states that “the goal is to design a drug product that enables safe and correct use and eliminates or reduces design elements which could cause use related hazards."
It is important for a product designer to understand how the product is used, including who the product will be used/handled by; the product’s chronicity and environments of use; and how the end users will interact with the product and its container closure, container label, and accompanying labeling. To ensure the product is used safely, these factors should be considered at various points throughout the product’s development before the design is finalized.
End Users & Environments of Use
In its guidance, FDA notes that “considering the end users and environments of use during drug development can allow identification of hazards that could lead to medication error during actual use.”
End users “include anyone involved in routine procurement, stocking, storage, and administration of the drug product, such as the patient or patient’s caregiver, the prescribing physician, nurse, pharmacist, or pharmacy technician, among others.” It is essential that these individuals are able to perform critical tasks appropriately in order to ensure the product is used safely and correctly. As such, products should be designed to make it as easy as possible for end users to perform these critical tasks without making unintentional errors and without being exposed to unnecessary safety hazards.
FDA states that sponsors and applicants “should not expect that the end users or the environments of use will change to fit the use of the drug product,” and it is important that the product’s design and user interface fit the end users’ needs within the typical environments of use. Furthermore, depending on the specific medication and indication, a product may have more than one environment of use, and states that the following are most common for drug products:
- Hospitals
- Long-term care facilities
- Physician offices
- Dialysis centers
- Other free-standing outpatient care centers
- Retail pharmacies
- Retail outlets for OTC drugs
- Specialty pharmacies
- Emergency transport
- Patient homes
FDA states that “environments of use may also contain a variety of sub-environments. For example, a hospital environment of use can include the pharmacy, operating room, emergency department, patient unit, critical care facilities, and outpatient clinic. To the extent possible, consider how the use of the product may differ in varying typical environments of use for the product under development.” In addition, FDA provides a list of questions that should be considered with respect to both end users and environments of use. For a full list of FDA’s questions, view the Agency’s full guidance document.
Drug Product-User Interface
“The most effective strategies to address use-related medication errors focus on improvements to the design of the drug product-user interface. A well-designed user interface facilitates correct actions and prevents or discourages actions that could result in medication error.” FDA notes that safety by design should be considered at all steps in the development process, and places a special emphasis on the following steps:
- When making decisions on what the finished dosage form of the drug will be.
- What physical characteristics it will have.
- What type of container closure will be used for marketing.
Evaluating the impact that each design choice and modification may have on the end user is essential. In the early stages of product development, the product’s clinical safety and efficacy should be the main focus. Additionally, FDA states that “many decisions regarding the design of a drug product are driven by clinical studies and manufacturing constraints to ensure that the drug product is safe and effective and meets CGMP quality standards. However, certain product modifications based on manufacturing constraints or clinical issues may inadvertently create the opportunity for medication error when the finished dosage form of the drug product is finalized.”
User interaction data gathered during clinical trials may not be sufficient to properly evaluate whether a drug can be used safely and correctly. Rather, “stimulated use studies with representative users from the intended end-user population may be more suitable for this purpose.”
A proactive risk assessment should begin with an evaluation of problems that similar products have experienced in the past, specifically looking into why and how they have occurred. This will help applicants and sponsors to eliminate any error-prone features as early as possible, thus eliminating the risk of the same type of medication error occurring.
The guidance also provides a number of examples of known problems and medication errors resulting from the design of the product and container closure systems. The examples included could have been avoided if the sponsor had conducted a risk assessment and made appropriate changes, as necessary. For additional information on the specific examples provided or the Agency’s recommendations in general, view FDA’s full guidance document.
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