By Timothy S. Lesar, PharmD
Director of Clinical Pharmacy Services
Albany Medical Center

It has now been more than 10 years since the Institute of Medicine (IOM) released its report, "To Err is Human: Building a Safer Health System," which promoted the goal of a 50% reduction in medical errors by 2005. In November 2001, an article was published in the American Journal of Health-System Pharmacy titled "Naming, Labeling, and Packaging of Pharmaceuticals." The article describes the failure of pharmaceutical manufacturers to use proper safety design in naming, labeling, and packaging, and discusses the many reasons for this failure-none of which were deemed insurmountable.¹ Three years later, in November 2004, ISMP, which had strongly advocated improved safety of pharmaceutical naming, labeling, and packaging well before the first IOM report, published the article, "FDA and the Pharmaceutical Industry Must be More Responsive for a Safer Healthcare System."² This particular article, while noting that hospitals had taken significant steps to reduce errors due to confusing and look-alike pharmaceutical names and packages, discussed the lack of progress in improving the overall safety design aspects of pharmaceutical packaging and labeling. In 2006, the IOM³ called for the development of a comprehensive guidance document on labeling and packaging of pharmaceuticals.

Further to this, in 2007⁴ the International Network of Safe Medication Practice Centres (INSMPC) presented guidelines for safe pharmaceutical packaging, and in May 2009, the Consumers Union (publishers of Consumer Reports) cited the problem of poor pharmaceutical labeling and packaging, and called upon regulatory agencies and manufacturers to apply safety design to products.⁵ Clearly there have been many calls for improvements over the past decade, yet it is apparent that we still do not have significantly safer pharmaceutical products.

Pharmaceutical Products and Error

Providing safe pharmaceutical care is a primary goal of the practice of pharmacy, and those who work in pharmacy are fully aware of the many opportunities for error. Every pharmacy strives to design medication storage and workflow processes to reduce the incidence of error. Many of these safety measures-such as staff training, safe purchasing practices, stock separation, labeling, warning alerts, limitations on access, use of bar coding, and double checks-are designed to reduce complications resulting from "human error." Human errors usually occur when a mistake is made in the execution of a correct plan.⁶ An example of such an error would be the selection of a 40 mEq potassium chloride minibag instead of a similar looking 10 mEq potassium chloride minibag. Despite efforts to reduce risk to patients, whether through technology or practices, errors still occur. The ISMP routinely reports on continuing problems with similar looking products or confusing labels as causes of error in their Medication Safety Alert! newsletters.

When errors do occur, patient harm is more likely to result from errors in the use of injectable medications. Errors with injectables are not uncommon and occur in all steps of the medication administration process.⁷ These errors are often the result of misidentification of a product or misinterpretation of labels. This is not surprising given the large number of look-alike/sound-alike drugs (both brand and generic) available in a limited number of similar physically-shaped dosage forms (e.g., ampoules, vials, smalland large-volume bags) with contents expressed in variable ways (e.g., total contents, concentration, percentage), and in various formats (information in different places on the label).

As injectables are either prepared and labeled by the manufacturer or the pharmacy, the ISMP has developed guidelines for pharmacies to use when labeling prepared products. Pharmaceuticals in original packaging are used in the pharmacy to produce pharmacy-prepared dosage forms, or are dispensed and distributed in that original packaging for use by other caregivers. The design of packaging and labels can both contribute to safe use, and contribute to errors. Thus, as stated above, designing pharmaceutical naming, packaging, and labeling for safety is critical for patient safety and has been requested for many years by many professional organizations.^7-9

Efforts to improve the process of naming medications is part of the FDA's safety efforts¹⁰; however, medication names are only one component of the pharmaceutical package that can contribute to error. Other potentially problematic components include label size, readability, formatting, and/or clutter, extraneous information, colors, logos, abbreviations, and expressions. In recognition of the role of labeling and packaging in patient safety, many pharmaceutical manufacturers have made changes in an attempt to reduce error risk. These efforts have included changing (and hopefully improving) label formatting, de-cluttering, the use of graphic design, and use of novel packaging. These changes are intended to improve recognition and interpretation of important label information, improve differentiation between products, and to create physical "barriers" (e.g., overwraps on vials). Unfortunately, it is not clear whether these efforts will reduce errors, and if they do reduce errors, will the improvement occur in all environments the product is used and in all steps of the medication use system? Certain changes may be helpful in one environment, but may actually increase harm in another. Pharmaceutical products with robust safety design and testing will more likely result in safe use throughout the medication use system.⁹

Safe Design for Pharmaceuticals

While commonly applied outside the pharmaceutical market, there is expanding application of safety design and safety testing with pharmaceuticals-both in naming and in label and package design. There are now a number of recommendations for label and package design and testing based on currently available information.^{9, 11-13} However, these recommendations are not regulatory requirements or professional standards in the US, nor are they widely applied in a systematic way. Much more needs to be learned about what "safe design" principles are for medications. While considerable money is spent evaluating the clinical safety of medications, little is spent studying what constitutes a safe pharmaceutical product.

Where We Are Now

The critical need to improve the safety of pharmaceutical labeling and package design has long been recognized, and now appears to be somewhat better appreciated, prompting a broad-based call for changes from numerous concerned groups. Knowledge of safety design and testing as it applies to pharmaceutical labeling and packaging is limited, but growing. Improvements in product recognition, interpretation, ease of use, and incorporation of error prevention elements are all important, and recognition that design principles used outside of the health care industry are applicable to pharmaceuticals is a key first step.

Some pharmaceutical manufacturers have undertaken independent efforts to improve the safety design of their products. These changes are a positive sign that safety considerations are playing a greater role in packaging design and in the potential marketing advantages of such products. While there has been modest progress toward the development of regulatory requirements for pharmaceutical labeling or packaging, the FDA just recently announced a public meeting on the topic titled "Developing Guidance on Naming, Labeling, and Packaging Practices to Reduce Medication Errors; Public Workshop; Request for Comments." (For more information on this meeting go to http://edocket.access.gpo.gov/2010/2010-8233.htm). This is an encouraging development in moving forward with this difficult but important task.

Major change in pharmaceutical package safety in the very near term is unlikely, leaving the practices of product users as the critical safety net for our patients. Good internal error reporting is key to safety in any organization. Care providers should review their medication-use system and implement improvements based on internal and external reports of errors and recommended practices that reduce potential for errors. New or changed products should be reviewed for potential errors before being brought into an organization, and necessary safeguards should be implemented, particularly for injectables.¹⁴ Technologies particularly helpful in assuring proper product identification and selection, such as bar coding, should be extended across the care continuum whenever feasible.^14-15 Continually improving and increasing the use of safety strategies, both technology based and workflow based, within your care setting is necessary, independent of any improvements in pharmaceutical product design.

Conclusion

Poorly designed pharmaceutical products continue to contribute to the problem of medication errors. This is of particular concern with injectable medications due to the higher risk for patient harm and various methods of use. Comprehensive improvement in pharmaceutical product design will likely require FDA regulation, changes in USP standards, and collaboration between manufactures, caregivers, and professional organizations. I urge you to follow the FDA's efforts in this area in 2010, and contribute your thoughts and ideas. While improved pharmaceutical packaging and labeling is necessary, no pharmaceutical product can be made error-proof, and additional safety strategies will continue to be critical to minimizing risk to patients.

References

1. Kenagy JW, Stein GC. Naming, labeling, and packaging of pharmaceuticals. Am J Health Syst Pharm. 2001;58:2033-2044.
2. Institute for Safe Medication Practices. FDA and the pharmaceutical industry must be more responsive for a safer healthcare system. ISMP Medication Safety Alert! November 4, 2004.
3. Aspden P, Wolcott J, Bootman JL, Cronenwett LR. Preventing Medication Errors. Washington, DC: National Academy Press; 2006.
4. International Network of Safe Medication Practices Centres. Unit dose packaging of pharmaceutical packages. October 2007. Available at http://www.intmedsafe.net/INSMP-unitDosePackaging.pdf
5. Jewell K, McGiffert L. To err is human-to delay is deadly. Safe Patient Project. May 2009. Available at http://www.safepatientproject.org/safepatientproject.org/pdf/safepatientproject.org-ToDelayIsDeadly.pdf
6. Cohen MR. The role of drug packaging and labeling in medication errors. In Cohen MR, ed. Medication Errors. Washington, DC: American Pharmacists Association; 2007:111-152.
7. McDowell SE, Mt-Isa S, Ashby D, Ferner RE. Where errors occur in the preparation and administration of intravenous medicines: a systematic review and Bayesian analysis. Qual Saf Health Care. 2010. Published online.
8. Cohen MR, Olson BL, Pangilinan JM. Drug mix-ups threaten patient safety. http://rxrama.com/news20080507.html (last accessed March 24, 2010).
9. Berman A. Reducing medication errors through naming, labeling, and packaging. J Med Syst. 2004;28(1):9-29

10. National Health Service. Design for patient safety: A guide to labeling and packaging of injectable medications. http://www.npsa.nhs.uk/nrls/improvingpatientsafety/design/injectable-medicines (last accessed January 21, 2010).

11. Food and Drug Administration. PDUFA pilot project: Proprietary name review. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072229.pdf (last accessed March 24, 2010).

12. Canadian Standards Association. Labelling of drug ampoules, vials, and prefilled syringes. (Vol. CAN/CSA?Z264.2?99). Ontario, Canada: CSA, 1999.

13. Medicines and Healthcare Products Regulatory Agency (MHRA). MHRA Guidance Note No. 25. Best practice guidance on labelling and packaging of medicines. June 2003. available at: http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON007554&RevisionSelectionMethod=Latest&noSaveAs=0&Rendition=WEB

14. Phillips J, Beam S, Brinker A, et al. Retrospective analysis of mortalities associated with medication errors. Am J Health-Syst Pharm. 2001;58(19):1835-1841.

15. Poon EG, Cina JL, Churchill W, et al. Medication dispensing errors and potential adverse drug events before and after implementing bar code technology in the pharmacy. Ann Intern Med. 2006;145(6):426-434.