Government and Industry Fail to Protect the Public When They Suggest “Carefully Following Instructions” Is Enough to Prevent Vaccine Errors

It’s difficult to say this, but we were truly disappointed in our colleagues at the Centers for Disease Control and Prevention (CDC) and the US Food and Drug Administration (FDA) after reading about a recent analysis that representatives from these agencies conducted on errors associated with administering just one component of the two-component vaccine, MENVEO (meningococcal groups A/C/Y, W-135 diphtheria conjugate vaccine).¹  We greatly respect the important work carried out by the CDC and FDA. However, the recommendations in the article seemed to take a giant step backwards to an earlier time when healthcare providers tried unsuccessfully to manage and improve patient safety simply by exhorting staff to be careful and to follow the rules. In the report, the central message to those who administer Menveo was that, “By carefully following instructions included with the vaccine, administration errors with Menveo and similarly packaged vaccines can be prevented.”¹ The article was clearly missing an understanding of why such errors occur and robust system strategies that would actually prevent ongoing errors with Menveo, or PENTACEL (diphtheria and tetanus toxoids, acellular pertussis, poliovirus, Haemophilus b conjugate), which was also mentioned in the article. Vaccines with diluents also present similar problems (e.g., diluent given instead of mixing with the vaccine first).

Menveo and Errors

Menveo is a two-component vaccine supplied by GlaxoSmithKline (previously Novartis) in two vials, one containing MenA lyophilized (freeze-dried) powder and the other containing MenCYW-135 liquid. The contents of the two vials must be mixed prior to intramuscular (IM) administration of the resulting solution. However, sometimes the liquid component of the vaccine has been administered alone, without the lyophilized component—an ongoing error that ISMP first published in 2014.² The vaccine comes in a carton containing five doses (10 vials total). A warning, “NEITHER MenCYW-135 NOR MenA COMPONENT TO BE USED ALONE,” is only visible on the back panel of the carton, despite plenty of “white” space elsewhere. The vial labels also contain language noting their proper use, but one’s vision is not immediately drawn to the warnings to combine these products, because it is presented in the same color font as the vaccine names (Figure 1). Even though the vials are slightly different sizes and have different cap colors, similarity in label style and color, and the small font size increase the risk of mistaking either vial as the complete vaccine. Also, both vials list the root Men—one MenCYW-135 and the other MenA—which could be mistaken to simply mean that either vial contains the Meningitis vaccine by those who do not know it is a two-component vaccine.

Several errors reported to ISMP also suggest that practitioners may mistakenly believe the “liquid” component of the vaccine is just a standard diluent.² As such, some errors involved administration of only the MenA powder after it was reconstituted with a “generic” diluent (e.g., normal saline) or diluent supplied with another vaccine (e.g., varicella; measles, mumps, and rubella). Some reported errors also involved accidentally diluting the MenA powder with another liquid vaccine, believing the liquid vaccine was a standard diluent. In addition, some of the errors in which the liquid MenCYW-135 component was given alone were reported as administration of just a “diluent,” without recognition that the “liquid” component is part of the vaccine.

All of these errors are serious because they leave people exposed to a potentially deadly disease—meningococcal meningitis, meningococcemia, or a related meningococcal disease. Furthermore, if an error goes unrecognized, which is certainly possible with these types of errors, individuals who have not received a proper dose will not know they are unprotected.

Although errors can be made by anyone preparing and administering vaccines, it should be noted that, in the US, unlicensed medical assistants who may not have the training or knowledge to recognize and address these challenges are often administering vaccines. About 40% of inpatient and outpatient vaccine errors reported to the ISMP National Vaccine Errors Reporting Program (VERP) involve unlicensed medical assistants who may be unfamiliar with the vaccine.

MMWR Article

Although ISMP has been writing about this type of error since 2014, the CDC-FDA analysis of Menveo errors and subsequent publication in the February 19, 2016, Morbidity and Mortality Weekly Report (MMWR)¹ was prompted by a question posed to the CDC by a practitioner who wanted to know if it was safe to administer a properly prepared vaccine dose of Menveo immediately after an error had been made by administering just the powder component alone. This led the CDC to search the national Vaccine Adverse Event Reporting System (VAERS) database for reports of Menveo errors from March 1, 2010, through September 22, 2015. The agency identified 390 reports where only one component of the vaccine was administered to a total of 407 patients. Most patients (66%) received only the MenCYW-135 liquid component, although some (34%) received only the MenA lyophilized component, reconstituted with sterile water, saline, a different liquid vaccine (e.g., hepatitis B vaccine), or an unspecified diluent. The data also identified disproportional reporting of errors associated with Menveo, two times more often when compared to other vaccines.

To their credit, the authors note that some errors with Menveo were detected by routine processes as part of quality assurance, and they refer readers to other strategies available from the CDC to prevent vaccine administration errors.³ Yet, it is disappointing that these strategies address all vaccines together and do not speak to the particular problem of two-component vaccines. While there is clearly good information about vaccine safety in this CDC reference,³ it is also frustrating that the strategies begin with a recommendation to basically adhere to the five rights of medication administration and to provide staff training and education. We expected more from the CDC and FDA, who respectively, help shape public policy and regulate the labeling and packaging of vaccine products. We hope the agencies intend to do more than what is stated in the article.      

Error-reduction Strategies

Of course, staff education about two-component vaccines and working carefully are fundamental error-prevention strategies. But there are other high-leverage strategies that practitioners can utilize to reduce the risk of errors with two-component vaccines. Moreover, ISMP believes vaccine manufacturers must be required by FDA to improve vaccine labeling and packaging to reduce the risk of errors with two-component vaccines. This is a longstanding system problem, and the interim measures taken to date are not keeping patients or the public safe. 

Recommendations for Manufacturers and FDA

• The labeling on two-component vaccine containers (including those with associated diluents) must clearly distinguish each container, yet connect the two products so their contents are administered together. This is no easy task, but it is one that manufacturers should undertake. Suggestions for consideration include:
• Label the vials as “Vial 1 of 2” and “Vial 2 of 2,” or use a similar scheme to distinguish, yet link, the 2 vials whose contents must be administered together.
• Package two-component vaccines in redesigned vials that accommodate larger labels to reduce label crowding and increase the font size of important text.
• Provide clear directions for use and warnings to administer the contents of both vials together on the front label of the carton, each vial, and on the vial cap.
• Make any warnings stand out on the label by employing text in colors that differ from the standard text on the label.
• Conduct usability testing with vaccine users to test labels, packages, and preparation processes for safety, clarity, and effectiveness. Look for ways that the vial labels can be misunderstood and whether anticipated changes might improve understanding. Design labels to reduce the risk of either vial being mistaken as the complete vaccine alone.
• When product stability and storage allow, employ integrated packaging that forces or facilitates proper mixing of the two components prior to administration. For example, package the vaccines in dual-chamber vials similar to SOLU-MEDROL (methylPREDNISolone) (Figure 2), or in syringes similar to a European vaccine product, VIATIM (hepatitis A, typhoid polysaccharide vaccine) (Figure 3). Having a single expiration date for both products is an additional advantage.
• Ensure there are unique NDC numbers and barcodes on each vaccine component.
• Include 2D barcodes on all vaccine products (although not required by FDA presently). The government should incentivize access to barcode scanning systems for vaccine administration similar to what was done for electronic health records.

Recommendations for Healthcare Practitioners

• Circle or highlight critical information on vaccine containers or use flag-type labels without obscuring label information. Clearly label or distinguish each component if the manufacturer’s label could mislead staff into believing either is the vaccine itself.
• Establish a process to keep two-component vaccines together if storage requirements do not differ. Dispense the products together in a bag with an auxiliary label to remind staff to use both vials.
• Where technology is utilized, require barcode scanning of both components of two-component vaccines prior to mixing and administration. Barcode scanning of both components prior to vaccine administration could help catch an error if only one vial is being inadvertently used.
• Document the NDC number, lot number, and expiration date of each vial in the vaccination record or log before administration to confirm appropriate selection or preparation of both components of two-component vaccines. (With electronic inpatient records, prompts should require documentation of both components of two-component vaccines.) Documenting actual administration of the vaccine should always occur after it is administered.
• Be sure staff understand the differences between two-component vaccines and vaccines packaged with specific diluents.

References

1. Su JR, Miller ER, Duffy J, Baer BM, Cano MV. Notes from the field: administration error involving a meningococcal conjugate vaccine—United States, March 1, 2010–September 22, 2015. MMWR. 2016;65:161–2.
2. ISMP. Administering just the diluent or one of two vaccine components leaves patients unprotected. ISMP Medication Safety Alert! 2014;19(10):1-4.
3. Vaccine administration. Chapter 6. In: Hamborsky J, Kroger A, Wolfe S, eds. Epidemiology and prevention of vaccine-preventable diseases. 13th ed. Washington DC: Public Health Foundation; 2015.