More Can Be Done to Alleviate Errors Associated with Pharmaceutical Product Labeling and Packaging
Visual similarities and confusing or absent presentation of important information on medication container labels, carton labels, and product packaging have frequently contributed to medication errors in the US. In the 1990s, early in the management of the former USP-ISMP Medication Errors Reporting Program (USP-ISMP MERP), up to a third of the reports and fatalities voluntarily submitted to the program cited labeling and packaging as contributing to the medication error.1 Today, labeling- and packaging-related events continue to be one of the most frequent types of voluntary reports submitted to the ISMP National Medication Errors Reporting Program (ISMP MERP). These labeling- and packaging-related event reports continue despite significant advances in medical technology that could detect or prevent such errors (e.g., barcode scanning, clinical decision support [e.g., interactive warnings or cautionary statements that might be missed or absent on the label]); federal regulations related to the labeling and packaging of prescription drugs, biologics, and over-the-counter (OTC) products; US Food and Drug Administration (FDA) labeling and packaging Guidance for Industry documents; and USP standards associated with medication labeling and packaging. This is not surprising given that more than 20,000 prescription drugs and 300,000 OTC products, including thousands of generic products, are on the market today.2,3
Sources of Labeling- and Packaging-Related Errors
Common contributing factors identified in labeling- and packaging-related error reports submitted to ISMP are listed in Table 1. Most of these reports are associated with the immediate container label or carton label, rather than the official product labeling (i.e., package insert, patient package insert, Medication Guide) or packaging (e.g., container in which the medication is provided). The following are just a few examples of the many ways that labeling and packaging can contribute to a medication error: 1) packaging and/or labeling different medications or strengths of the same medication in a similar fashion; 2) labels with company names, logos, corporate dress (aspects of a product’s packaging and labeling that distinguish it from the competition), or colors that are more prominent than the essential drug information; 3) error-prone abbreviations, dose designations, symbols, or other unsafe ways of expressing the name, concentration, dosage, quantity, or strength of the medication on labels; and 4) an error-prone design of labels from a human factors standpoint. Many of the contributing factors in Table 1 have been previously described in this newsletter.
Table 1. Common Factors Associated with Labeling and Packaging Concerns (as reported to the ISMP MERP)
|Aspect of Product Labeling/Packaging||Examples of Error-Prone Conditions|
|Dose, Strength, and/or Amount in Container||
|Expiration Dates/Lot Numbers||
|Abbreviations and Symbols||
Labeling and Packaging Safety Evaluations
One of the guiding principles associated with the FDA premarket regulatory review and subsequent drug approval is that the product’s labeling and packaging should not mislead practitioners and consumers or be confused with any other medicinal product on the market. To that end, in November 2020, the American Society of Health-System Pharmacists (ASHP) House of Delegates adopted a policy to urge manufacturers, drug packagers and repackagers, outsourcing pharmacies, and the FDA to involve patients and practicing pharmacists, nurses, and physicians in decisions about drug labeling and packaging (and names) to help eliminate labeling and packaging characteristics that contribute to medication errors.4
Over the past two decades, the premarket safety evaluation of proposed labeling and packaging has grown somewhat but not as fast in contrast to trademark testing of brand names. Today, before seeking FDA approval of a new drug or changing the labeling or packaging, some pharmaceutical companies voluntarily use external companies to evaluate potential risks associated with proposed labeling and packaging. The Medication Safety Board (MSB), a wholly owned for-profit subsidiary of ISMP, is one of the independent companies that conducts these evaluations. Given ISMP’s vast experience in analyzing medication errors, MSB offers a unique perspective as well as a variety of consulting services to support the pharmaceutical industry in designing safe labeling and packaging that minimizes the potential for medication errors. A strict editorial wall between MSB and the editors of this newsletter publication is maintained to avoid any conflict of interest.
Label evaluation and design work may include the immediate container label and the label on the outer or secondary packaging and can range from a single label to labels for an entire product line. A network of practicing healthcare providers who prescribe, dispense, and/or administer medications must be utilized, as needed, to help safety experts evaluate and identify any error-prone aspects of proposed labeling and packaging. Additional services such as conducting risk assessments using failure mode and effects analysis (FMEA), human factors testing in collaboration with human factors experts, and professional focus groups/advisory boards must also be utilized when applicable. Recommendations regarding the presentation of important and required labeling information and/or the packaging of the drug can then be made. Remediation of labeling and packaging issues identified during postmarket surveillance is also a service that must be provided.
It is important to remember that external evaluation of labeling and packaging is voluntary and that pharmaceutical companies are NOT required by regulation to test or evaluate, particularly with patients and practicing clinicians, their proposed labeling and packaging for error-prone aspects prior to seeking FDA approval. Thus, many pharmaceutical and biotech companies, including generic manufacturers, packagers/repackagers, and outsourcing pharmacies, have not adopted this practice. However, FDA encourages companies to evaluate their proposed labeling (and naming), including packaging and design, for error-prone aspects, and it should be noted that the FDA Division of Medication Error Prevention and Analysis (DMEPA) evaluates the labeling and packaging of products submitted for approval. DMEPA conducts this independent evaluation of the labeling and packaging, even if the company conducts its own safety evaluation of the product labeling and packaging and submits the supporting documentation to FDA.
Managing the risks associated with similar or confusing drug labeling and packaging is an industry-wide obligation. Healthcare professionals can certainly implement some risk-mitigation strategies that address certain contributing factors associated with error-prone product labeling and packaging, such as purchasing products from different manufacturers to help differentiate products or affixing auxiliary warning labels to products. However, this can be likened to putting a Band-Aid on a gaping wound. A safer and more robust preventative solution begins with pharmaceutical companies that evaluate their proposed product labeling and packaging, utilizing patients and practitioners as needed, before product launch; with a standards organization (USP) that continues to require safe labeling and packaging practices; and with a regulatory organization (FDA) that enforces adherence to the standards and also utilizes patients and practitioners as needed in the review of labeling and packaging before approval.
ISMP believes FDA should work with industry leaders to develop a more robust, standard, and proactive evaluation process for labeling and packaging to be employed during product development and prior to product launch or a label change. The evaluation should employ consistent and standardized methods to determine the safety and acceptability of the proposed label and packaging. ISMP also recommends that ALL pharmaceutical companies, packagers and repackagers, and outsourcing pharmacies proactively use an independent source or internal process to evaluate proposed labeling and packaging for safety concerns, involving consumers and practicing healthcare clinicians as needed. This is critical to identify and remedy any potential issues that may lead to serious errors. This proactive approach can reduce labeling and packaging similarities or confusion that may cause serious errors, and it could save the pharmaceutical company from the additional expense of revising error-prone label and packaging after launch.
Furthermore, FDA and USP should require that companies develop a risk management program that includes the timely evaluation and correction of an error-prone label or package if postmarketing surveillance (including error reports) shows harmful or potentially harmful confusion or error risk with an existing label or package. Better premarket evaluation of labels and packaging, using patients and practicing clinicians, along with postmarketing monitoring and remediation of serious or potentially serious confusion occurs, should reduce the risk of labeling- and packaging-related medication errors.
- Berman A. Reducing medication errors through naming, labeling, and packaging. J Med Syst. 2004;28(1):9-29.
- US Food and Drug Administration (FDA). Fact sheet: FDA at a glance. November 18, 2020.
- FDA. Drug applications for over-the-counter (OTC) drugs. March 31, 2020.
- American Society of Health-System Pharmacists (ASHP). Professional policies approved by the 2020 ASHP November virtual House of Delegates. Am J Health-Syst Pharm. 2021;78(7):646-7.