Trade dress is the concept that underlies labelling and packaging issues for the pharmaceutical industry. Trade dress refers to how the drug package actually looks. The imperatives of trade dress are an important part of the culture of each company.

The dominant message is, ‘Don’t change anything that works.’ The more successful the company, the more resistant it is to changing trade dress.

Options for trade dressing
 The concept of trade dress originated when human factors issues were not a major concern and the primary concerns were marketing and image. Criteria for trade dress are that the package must ‘look good’ - clean, neat and tidy; it should project an image of quality; it should be identifiable from a distance as a quality product; it should allow a salesperson to easily scan a pharmacy’s shelves to see how many of a company’s products are there and how they compare with other companies’ products; and it should differentiate a product from that of its generic competitor, if there is one.

Just as having only 26 letters in the alphabet complicates naming issues, so too are labelling and packaging issues complicated by the basic requirements of the market. It is difficult to enact any broad changes. Packages must fit on shelves, and space on labels is limited. The more companies move to small, single-use packages, the more difficult the differentiation problem becomes.

Colour-coding seems like one solution to product differentiation issues and has been used successfully in a few instances. For example, ophthalmic solutions are colour-codedd, and colourcoding has been used for anesthetics. But even advocates of human factors evaluation believe that colour-coding is of limited usefulness. For example, colour is not a fixed property. Perceptions of red vary among individuals. Colours fade with time and the type of packaging. The number of obviously different colours is limited, creating opportunities for confusion. USP, which would have to specify all the colour options and maintain the system, is against the use of colour for these reasons, and pharmaceutical companies dislike the idea intensely.

Barcoding is seen by most as an important error prevention tool. But technology companies capable of creating a barcoding system for drug products are reluctant to do so unless they can see a market for it.

The regulatory initiatives
 ASHP has been vocal in calling for change in the drug-naming process, particularly by asking FDA to develop better controls over naming and packaging. In written comments to FDA in 1998, ASHP noted that FDA was well aware of the problems inherent in sound-alike and lookalike drug names and packaging; the agency had noted those problems and proposed solutions at a meeting between the Center for Drug Evaluation and Research and representatives of health professional organizations in 1996. In 2000, with FDA maintaining that it was still considering options, ASHP stated that it was ‘time to stop considering options and take substantive action.’

At a 1999 conference entitled ‘Postmarketing Surveillance: Considerations for Policy-makers’ that was co-sponsored by the General Accounting Office and the Drug Information Association, Henri R. Manasse, Jr. of ASHP stated that patients were being harmed as a result of FDA’s delays and the lack of a coordinated effort among the various stakeholders to solve the problems of poor product package design and nomenclature.

Said Manasse: ‘One solution is to require real life submissions from the pharmaceutical industry - final product labels and actual market packaging - prior to drug approval.’ Manasse also asked FDA to require failure-mode and effects analysis as part of the NDA safety summary.

Pharmaceutical packaging : Typical solutions
An example of the difficulty of resolving labelling and packaging problems is provided by the attempt to decrease patient deaths caused by accidental injection of concentrated potassium chloride solution. Concentrated potassium chloride solution can, of course, be fatal if injected intravenously.

Potassium is an essential part of the body’s chemistry, and many treatments deplete potassium. Therefore, potassium supplements are commonly used. For sick, unstable patients with low potassium levels, potassium is often given slowly in a diluted solution (potassium chloride diluted in a large fluid volume).

Many patients have been killed by inadvertent I.V. injection of concentrated potassium chloride. The nurses knew that concentrated potassium chloride was dangerous but thought they were injecting something else.

The apparent answer was to create a unique ‘signal’ for nurses directly on the bottle of potassium chloride so that they would be reminded of the potential problem every time they used one of these containers. After a great deal of discussion, it was decided that the signal would be a black cap on the container. It would be impossible to open the container without seeing the black cap. Abbott Laboratories manufactured 80 per cent  of the concentrated  potassium chloride used for injection. Initially, Abbott wanted to use red because that was technically easier to accomplish, but after long discussion black won out. The results:

In 1991, Abbott and everyone else changed the mcaps on potassium chloride bottles to black.

• The cost to Abbott was between $500,000 and $1 million.
• Black was no longer
• available for other packaging uses.
• There was no change in the number of deaths from potassium chloride poisoning.

What happened? In nurses’ minds, potassium is associated with the diuretic furosemide. Many patients receiving furosemide also receive diluted injectable potassium chloride because furosemide depletes the body of potassium. Therefore nurses – good, well trained, but harried nurses - have sometimes picked up potassium chloride instead of furosemide, and patients have died.

A well-thought-out attempt to implement a simple technical fix backfired because the problem was different than it initially appeared. The problem was not that nurses mistook the potassium chloride bottle for something else. They grabbed exactly what they intended. It was the mental connection that was the flaw.

Ultimately, hospitals took concentrated potassium chloride, black cap and all, off the nursing floors. This unsophisticated fix appears to work. Deaths from inadvertent injection of potassium chloride declined from 12 in 1997 to one  each in 1998 and 1999.

Experiences like that with potassium chloride illustrate why pharmaceutical companies have been reluctant to change the brand name, label, or package of a medication once it is in the market, even when a potential problem has been demonstrated. Expensive solutions may not be the answer.

When a serious hazard does lead a company to make a change, it typically takes about six months to make the change and another year for the old product to ‘clear the shelves.’ When written by hand (as most prescriptions are), ‘Norvasc’ may look like ‘Navane.’ In 1998, ISMP received reports of this mix-up. Both ISMP and FDA recommended to Norvasc’s manufacturer that it change the last letter of ‘Norvasc’ to k.

Another example of company resistance to changes in drug names or packaging involves lidocaine, which formerly was supplied by five companies in ready-to use syringes in two strengths: 2% (100 mg) for I.V. infusion and 2 g for mixing I.V. solutions. Each syringe had a red ‘2’ prominently on its label. Errors occurred when some physicians used the 2-g syringe instead of the 2% (100-mg) syringe. Injecting this volume of lidocaine could result in death or serious injury.

ISMP issued the first warning about this in 1984. An FDA advisory board subsequently reviewed the situation but made no recommendations. By 1992, there were reports of 70 deaths or brain damage. ISMP’s Cohen described the problem on the NBC news show ‘Dateline.’ The companies continued to market both products until they were easily confused. The products have since been withdrawn from the market.

ISMP is not the only organization that has led the way to greater safety. USP was instrumental in changing the labelling for two anticancer drugs, vincristine and vinblastine, whose names were easily confused. The product labels were changed to highlight the differing syllables with all-capital letters: vinCRIstine and vinBLAstine.

In some cases, pharmaceutical companies have taken the lead in changing labelling that could lead to errors. For example, Bristol- Myers Squibb faced a problem with cisplatin labelling and packaging and took an active role in solving it. There is no easy way to make changes in pre-existing names, packages,and labels, and when change happens, it is almost always the result of several parties efforts.