Oral solid medication appearance should play a greater role in medication error prevention
From the July 28, 2011 issue
Generic products are widely dispensed in US hospitals and ambulatory pharmacies as a cost-effective substitute for brand-name medications. According to the Generic Pharmaceutical Association, generic medications are dispensed for 69% of all ambulatory prescription medications but account for only 16% of the total costs of all dispensed prescription drugs.(1) While generic medications have been approved by the US Food and Drug Administration (FDA) as bioequivalent to their associated brand-name medications, oral generic medications often look substantially different than their brand-name counterparts and other generic versions of the same medications. Thus, consumers can receive different looking tablets or capsules every time they refill their prescription if generic products are dispensed. For example, PROZAC (FLUoxetine) has ten different generic bioequivalent products, but each is different in appearance.(2) Generic manufacturers design their product’s appearance, making no effort to ensure it looks like other generics or the brand-name product, primarily to avoid litigation with brand-name manufacturers that claim intellectual rights to the appearance of their products.(3)
Risks when generics don’t look like the brand
Patients and many healthcare practitioners have learned to rely on the color, size, and shape of oral solid medications as one—but hopefully not the only—way to ensure the right medication has been dispensed, taken, or administered. When a generic drug is different in appearance from the brand product or other generic products, patients and healthcare practitioners can become confused. Historically, medication appearance was considered a passive control feature inherent in the medication- use system that helps control risk by alerting a patient or healthcare practitioner to an incorrect medication or dose. Thus, ISMP has encouraged patients and staff to avoid taking or administering medications that look different than expected without first verifying that the medication is correct. But today, with such wide variation in a single medication’s appearance, and with constant interchanging of products due to drug shortages, both patients and healthcare professionals have learned to attribute the differences in medication appearance to the purchase of the drug from a different manufacturer, rather than taking the time to investigate whether an error has been made. Thus, medication appearance no longer serves as an effective passive control feature in healthcare.
Why generics look different than the brand
According to Greene(2) and Engelberg,(3) the physical aspects of a medication (called trade dress), including size, shape, color, texture, aroma, and flavor, are considered intellectual property under trademark law. Court decisions have supported protection against copying the appearance of a medication on the theory that such action would reduce the practice of passing off counterfeit drugs as real brand products, prevent the substitution of a drug that was similar but not identical to another drug, and allow the appearance of a medication to serve as a branding function to identify the drug’s manufacturer.
In the 1960s and 1970s, the use of generic drugs rose quickly.(3) State laws mandating generic substitutions were passed; FDA published its first Orange Book listing all FDA-approved bioequivalent medications; and an Abbreviated New Drug Application for generic products was enacted based on bioequivalence to the brand product.(2) Since then, legal opinions on the issue of trade dress rights have changed.
In 1995, the Supreme Court ruled that a product’s appearance cannot be protected unless it can be proven that, in the mind of consumers, it is needed to identify the source of the product, not the product itself.(2,4) The Court also confirmed that a product’s appearance cannot be protected if it serves a functional purpose, such as identifying the type of medication in addition to its source.(2,4) More recently, the Third Circuit Court of Appeals handed down a decision regarding generic dextroamphetamine and amphetamine that upheld the generic manufacturer’s right to produce a generic bioequivalent of the brand drug ADDERALL using the same color, size, and shape of the various doses of the brand product.(5) The court agreed that the color, size, and shape of the doses help children adhere to the treatment regimen, making the overall appearance of the drug functional. These and other judicial precedents have significantly restricted brand manufacturers’ protection of the products’ trade dress, and the current practices of mandatory generic substitutions make it highly unlikely to assert such protections.(3)
Why generics should look like the brand
Today, a compelling argument can be made that the practice of making generic drugs look different than brand drugs carries a substantial risk. Medication errors have resulted from confusion regarding the appearance of medications, including incorrect assumptions regarding the identity of medications when their appearance has changed. The risk of error worsens for healthcare practitioners who routinely encounter medications that look different due to purchase from a different manufacturer—a common problem during the drug shortage crisis we currently face. The risk of error worsens for patients with complex medication regimens, health literacy issues, and for elderly patients who take multiple medications.(2) It is easy to see how healthcare practitioners and patients have become complacent regarding differences in the expected appearance of a medication, thus making them vulnerable to wrong drug or wrong dose errors.
During transition periods when brand products lose market exclusivity, inconsistency in appearance between brand and generic products can reduce patient adherence.(3) Also, studies have shown that the placebo effect of medications is reduced if product appearance, external packaging, and perceived value are not as expected, particularly for medications used to treat conditions such as depression, anxiety, insomnia, impotence, and other diseases that have a psychosomatic element.(3) By not allowing generic medications to look like brand medications, the effectiveness of some generic drugs may be reduced.(3)
ISMP is taking a formal stand on the need to eliminate any remaining barriers to a standardized appearance of bioequivalent brand and generic medications. Just this Monday evening, in an ABC News special on generic medications (Prescription Drug Prices Drop, on World News with Diane Sawyer at: http://abcnews.go.com/WN/), concern was expressed that, with all the generics on the market, many look similar to one another because they are just basic white tablets. According to the news report, consumers are asking for generic medications that look more distinctive—certainly, looking like the brand product would help achieve this goal. While we support the right of pharmaceutical companies to recover their large investments in the research and development of new drugs via time-limited exclusivity of the product on the market, we must take the position that, at the end of that exclusive period, generic manufacturers should be required to manufacture products that are both bio-equivalent and appearance-equivalent—meaning the same size, shape, and color, but not the same imprint—to the brand products. We hope key stakeholders in the federal and state government, healthcare industry, and pharmaceutical industry will join in this effort.
ISMP is also taking a formal stand on the use of a standard, universal imprint system for identification of oral solid prescription medications. Currently, each manufacturer—both brand and generic—assigns its own identifying codes and symbols to its products. Standardization of the imprint system for identifying solid dosage forms has been widely advocated by many organizations, including the American Medical Association and the World Health Organization.(6,7) One study found that physicians and pharmacists incorrectly identified three common oral medications more than a third of the time, even when using resources such as the Physicians’ Desk Reference, IDENTIDEX, Drug Facts and Comparisons, and other reliable resources.(6) More than 90% of study participants favored a universal imprint coding system for oral dosage forms. As noted by a longtime proponent of such standardization, Gordon Schiff, MD, “There is one piece of real estate that should be off limits for marketing—the surface of the pill itself.”(7) However, pharmaceutical manufacturers have suggested that the costs associated with retooling the manufacturing process would be high.
We call upon FDA to lead the way on both of these initiatives. We firmly believe that instituting a standardized appearance for bioequivalent drugs and a standard universal imprint system will enhance medication safety and product identification, increase patient adherence to medication regimens, and thus improve the overall efficacy of medication therapy.
1) Generic Pharmaceutical Association. Facts at a glance. www.gphaonline.org/about-gpha/about-generics/facts. Accessed July 25, 2011.
2) Greene JA, Kesselheim AS. Why do the same drugs look different? Pills, trade dress, and public health. N Engl J Med. 2011;365(1):83-89.
3) Engelberg AB. The case for standardizing the appearance of bioequivalent medications. J Manag Care Pharm. 2011;17(4):321-23.
4) United States Supreme Court. Qualitex Co. v. Jacobson Products Co., Inc. No. 93-1577; 514 US. 159, 162-63. http://supreme.justia.com/us/514/159/case.html. Accessed July 25, 2011.
5) Shire US Inc. v. Barr Laboratories, Inc. No. 02-3647 (3rd Circuit, 2003). http://caselaw.findlaw.com/us-3rd-circuit/1047171.html. Accessed July 25, 2011.
6) Schiff GD, Seijeoung K, Seger AC, Bult J, Bates DW. Ability of practitioners to identify solid oral dosage tablets. Am J Health-Syst Pharm. 2006;63:838-43.
7) Schiff G. Standardized pill imprint codes: a pharma fantasy. J Med Syst. 2004;28(1):1-7.