MERP Annual Review Exposes How Manufacturer Labeling/Quality Issues Impact Medication Safety

From July 1, 2023, through June 30, 2024, a total of 1,016 voluntarily submitted reports were sent to the ISMP National Medication Errors Reporting Program (ISMP MERP). Healthcare practitioners utilize ISMP MERP to inform others about medication safety issues they have experienced and to seek recommendations for needed improvements in product and practice safety. ISMP professional staff reviews every report submitted and utilizes them for their educational value. As necessary, regulators, standards organizations, and manufacturers are contacted, and reports are also considered for publication in the ISMP Medication Safety Alert! ISMP also operates a separate reporting program for vaccine-related issues and another for consumers to report events.

Almost half of the reports (47%) involved errors that reached patients. The remaining reports were classified as close calls (18%) (errors that happened but did not reach the patient) or hazardous conditions that warrant concern (35%). While the event location was not included in the majority of reports, 19% of reports were submitted by practitioners who work in inpatient settings and 12% from community pharmacies. Reports were also submitted from other settings (e.g., specialty pharmacies, physician offices, mail order pharmacies), but each of these represented 2% or less of the submitted reports. Errors occurred during all phases of the medication-use process but close to three-quarters happened during dispensing (37%), administration (21%), prescribing (8%), or procurement (8%). While the literature suggests administration and prescribing errors are most common, the high reporting of dispensing errors reflects the most common reporter type—pharmacy personnel. The medications most commonly involved included opioids (4.2%), antineoplastic agents (3.8%), insulin (3.4%), heparin (3.1%), antipsychotics (2.4%), and glucagon-like peptide-1 (GLP-1) agonists (2.2%). Reports were analyzed to identify potential contributing factors. The two most commonly reported factors were related to similar labels/packaging (16.6%) and manufacturer/labeler issues (13.3%).

Similar Labels/Packaging

Given that this issue continues to be a common theme in many of our newsletter articles, errors caused by look-alike packages and labels being the most common contributing factor is not surprising. For example, errors have been reported that involved mix-ups with MYXREDLIN (insulin human) 100 units/100 mL infusion bags and two other intravenous (IV) medication bags, ZOSYN (piperacillin and tazobactam) 4.5 g/100 mL (Figure 1) and CARDENE IV (ni CAR dipine) 40 mg/200 mL (Figure 2). All three products are manufactured by Baxter and have nearly identical packaging. In one case, the pharmacy dispensed a Myxredlin bag instead of the ordered Zosyn after the pharmacy technician inadvertently placed the Zosyn label on the Myxredlin bag. The nurse scanned the pharmacy-generated barcode on the Zosyn label, rather than the manufacturer barcode on the bag and administered the insulin infusion. The patient was found unresponsive, a hypoglycemic protocol was initiated, and they recovered. In another case, a nurse replaced an empty Cardene infusion bag with a bag obtained from the automated dispensing cabinet (ADC) and administered it without using barcode scanning. An hour later, she returned to the patient’s room, scanned the barcode on the infusing medication to document administration, and identified that the patient received approximately 40 mL of Myxredlin. During the ADC stocking process, a pharmacy technician had scanned the barcode on only one of the Cardene cartons (following the pharmacy’s process) and placed a similar-looking Myxredlin carton in the Cardene bin in error.

Figure 1. Similar-looking Zosyn (left) and Myxredlin (right) infusion bags. 

Figure 2. Similar-looking Cardene IV (left) and Myxredlin (right) infusion bags.

Highly stylized graphics and prominent corporate names and logos may overshadow essential information. In addition, similar vial cap and label colors may make different products look-alike, especially if they have similar names and dosages, are used in the same setting, and/or are stored near one another. Complicating the situation, humans tend to see what they expect to see, rather than what is actually there (confirmation bias).

While prospective analysis of the package and label is a must prior to market launch, often this review is conducted with flat two-dimensional proofs that may be larger than the size of the actual label/product. Thus, vulnerabilities that may lead to a mix-up with another product may not be noticed prior to US Food and Drug Administration (FDA) approval. For this reason, ISMP recommends that healthcare organizations establish a process to ensure that all new products are evaluated by practitioners who may use them, looking at the actual packages in their work environment before drugs are added to inventory. If look-alike problems are identified, the product should be purchased from a different manufacturer if possible, or steps to catch or avoid a mix-up should be implemented (e.g., barcode scanning, separate storage, warning labels) before the drug is dispensed or administered. For more information, see our article, Safety considerations during expedited product approval, published in the April 6, 2023, issue.

Manufacturer-Related Issues

Perhaps the most disturbing finding was that 43.2% of the events involved manufacturer-related issues: 13.3% were related to manufacturer/labeler issues; 7.5% involved manufacturer product quality issues; 6.7% involved confusing/incomplete information (label/labeling); 5.2% involved poor label design (label misleading or difficult to read); 4.2% involved poor packaging design; 3.3% involved a dispensing device issue; and 3% involved poor product design (e.g., vial, syringe, bag). These obstacles often set up practitioners for errors. For example, practitioners may be forced to employ workarounds such as when a barcode is hidden or damaged, is difficult to scan (e.g., white print on clear bag), or is missing. Unsafe practices include administering a medication even though the barcode will not scan, scanning after the medication has been administered, or scanning barcodes from sources other than the medication itself (i.e., proxy scanning), such as scanning a barcode that is not affixed to the product actually being administered.

In one case, a hospital reported that they received three 500 mL bags of 20% OSMITROL (mannitol) injection by Baxter that did not have barcodes (Figure 3).

Figure 3. This infusion bag of 20% Osmitrol (mannitol) injection 500 mL does not have a barcode.

Multiple hospitals have reported the inability to scan a medication barcode due to an overwrap seam centered over the barcode on an infusion bag (Figure 4). The overwrap obscures the white ink barcode on the heparin sodium 25,000 units/250 mL infusion bag made by B. Braun. Since removing the bag from the overwrap shortens the beyond-use date of the product, many hospitals store it in the overwrap until right before use. The reporting hospitals are concerned that without being able to scan the barcode when dispensing or restocking ADCs, this situation increases the potential for errors with this high-alert medication.

Figure 4. The barcode that identifies B. Braun's heparin 25,000 units/250 mL is under a crimpled seam on the clear overwrap, making it impossible to scan the barcode without first removing the bag.

In another case involving heparin, a hospital reported that the label on a Pfizer heparin 25,000 units/250 mL infusion bag was missing the medication name and concentration (Figure 5).

Figure 5. A heparin 25,000 units/250 mL bag (Pfizer) was missing the medication name and concentration (left), which is typically displayed on the top of the heparin bag in red font (right). 

In another case, an organization reported that they received a carton of succinylcholine 200 mg/10 mL vials made by Meitheal, but 4 of the 25 vials did not have medication labels (Figure 6). The only indication of the vial contents was the cap which states, "WARNING: PARALYZING AGENT." The reporting organization was concerned that this high-alert neuromuscular blocking agent could be mistaken as a diluent vial or another medication.

Figure 6. A practitioner found that 4 of the 25 vials in a carton of Meitheal's succinylcholine were unlabeled. 

Call to Action

ISMP’s subsidiary, Med Safety Board (MSB), has issued a white paper calling for pharmaceutical manufacturers to ensure injectable medication labels are well-differentiated to minimize mix-ups and prevent patient harm. The white paper includes key labeling attributes that manufacturers should consider when designing labels and healthcare organizations should consider when purchasing or adding products to their formulary or changing to another manufacturer of a formulary drug because of a shortage.

The FDA barcode rule (21 CFR 201.25) requires most prescription drugs to have a linear barcode on the label that contains, at a minimum, the drug’s national drug code (NDC) number. The linear barcode must appear on the label as defined by section 201(k) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) meaning that FDA intends for the linear barcode to be on the outside container/wrapper, as well as on the immediate container, unless the barcode is readily visible and machine-readable through the outside container/wrapper. The linear barcode must also be surrounded by sufficient blank space so it can be scanned correctly. However, we continue to receive reports where drug manufacturers failed to meet this basic requirement.

We urge the FDA and manufacturers to act and take steps to ensure better differentiation of similar-looking packaging and labeling. Manufacturers must address quality-related issues that often lead to the inability of practitioners to scan medication barcodes. The errors reported often involve high-alert medications that have the potential to harm patients.

Conclusion

The ISMP MERP provides a rich resource for learning and educating about medication errors. Your willingness to voluntarily report medication errors and hazards to ISMP and to proactively use the information we publish in the newsletter to prevent similar errors and hazards, motivates and inspires us as, together, we can continue to learn about the causes of medication errors and how to prevent them. We extend our sincere thanks to those who have submitted reports to the ISMP MERP and we encourage all of our readers to continue these efforts.