On September 27, 2007, the Prescription Drug User Fee Act (PDUFA IV) reauthorization and expansion was signed into law, significantly strengthening FDA’s drug safety program. As part of the reauthorization, FDA committed to a number of performance goals, which included its obligation to “implement measures to reduce medication errors related to look-alike and sound-alike proprietary names, unclear label abbreviations, acronyms, dose designations, and error-prone labeling and packaging designs.”
FDA to Publish Guidance Series
In an effort to achieve its PDUFA IV performance goals, FDA is developing a series of three planned guidances aimed at minimizing the risks that contribute to medication errors. The three guidances will focus on the following topics:
- “Minimizing risks associated with the design of the drug product and its container closure system.”
- “Minimizing risks associated with the design of drug product container labels and carton labeling.”
- “Minimizing risks when developing and selecting proposed proprietary names.”
First Guidance in Series of Three
On April 11, 2016, FDA published the first guidance in this series. The guidance, entitled “Safety Considerations for Product Design to Minimize Medication Errors,” offers broad recommendations regarding the development of drug and biologic products, and applies to:
- Sponsors of investigational new drugs (INDs)
- Applicants of:
- Manufacturers of:
- Prescription drugs marketed without an approved application
- Over-the-counter (OTC) monograph drugs
In its guidance, FDA provides “a set of principles for using a systems approach to minimize medication errors relating to product design and container closure design and thus enhance patient safety.” Furthermore, FDA states that its recommendations “are intended to provide best practices on how to improve the drug product and container closure design for all prescription and nonprescription drugs and biologic products regulated by the Center for Drug Evaluation and Research (CDER).”
Proactive Risk Assessments
Many medication errors can be avoided by simply looking at past errors and learning from the mistakes through the conduct of a proactive risk assessment before marketing a drug. Although the guidance does not describe how to conduct, document, or submit these assessments, nor does it detail how they will be evaluated if conducted and submitted, FDA does provide valuable information regarding proactive risk assessments.
The guidance states that proactive risk assessments “should be employed from the earliest stages of product design to help manufacturers anticipate potential use-related medication errors, identify the need for iterative design modifications, and ensure that such modifications do not introduce unintended consequences.” Ideally, assessments that use an analytical approach should occur as early in the product design development process as possible. FDA notes that sponsors and applicants can reduce post approval safety issues by considering the needs of end users, environments of use, and contexts of use when developing and designing a drug product.
FDA recommends that applicants and sponsors use failure mode and effects analysis (FMEA) and simulated use testing (i.e., human factors or user testing) “to identify medication error concerns relating to product design and the container closure.”
Failure Mode & Effect Analysis
“FMEA is a systematic evaluation of the proposed product within the medication use system and provides an understanding of the relative impact of different types of system failures that may affect use-related medication error and prioritization of risk.” In addition, FMEA provides a multidisciplinary review that considers everyone in the medication use process, and includes:
- “Analyzing all steps involved in user interactions with the drug product within the anticipated environments of use.
- Identifying potential use-related medication errors and system failures that could occur at each step of the medication use process.
- Estimating the probability of occurrence of identified potential medication errors and system failures.
- Assessing potential effects and the severity of consequences of identified potential medication errors and system failures.”
The recommended steps for conducting use-related medication error FMEA can be found in the Handbook of Human Factors and Ergonomics in Health Care and Patient Safety.
Stimulated Use Testing
“Simulated use testing involves systematic collection of data from representative end users’ realistic use of early, interim, or final product designs, including product labels and labeling.” The test assesses the product’s actual use and expands on the results of other analytical approaches, such as FMEA. As such, the results of stimulated use tests should be used to update the FMEA to include additional use-related risks that were not previously anticipated. Applicants and sponsors should use stimulated use testing when determining whether the product design enables or hinders end users from safely and correctly performing the product’s critical tasks.
In addition to right before a product is submitted for approval, FDA states that risk assessments “should also be conducted before any subsequent product modifications such as additions to a product line (e.g., adding an extended release formulation), changes to a currently marketed product (e.g., new strength, new dosage form, new packaging configuration, new indication, new delivery system).”
Early Stage Product Design Considerations
In its guidance, FDA provides a number of recommendations concerning what should be considered during the early stages of drug product design in order to minimize medication errors.
Interested in learning more? Part two, entitled “Minimizing Medication Errors Related to Product Design, Part Two: FDA’s Early Stage Product Design Considerations,” has everything you need to know about early stage product design considerations.
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