'Creation engineering': The art and science of naming drugs

CNN)Yearly lists of the "most popular baby names" show how tastes change over time. While Jennifer, Heather, Michael and Jason may have been favorites in decades past, today's top contenders include Emma, Olivia, Liam and Noah.

The same applies to pharmaceutical drug names.

the cholesterol-lowering medication Crestor was the most-prescribed branded drug in the US in 2014-2015 with 21.014.669 prescriptions.

"Aspirin," for instance, was a name with legs in the early 20th century. Bayer branded its pain medication with this simple moniker in 1899 and sold it around the world for years. By the end of the century, though, drugs were named with a "blockbuster" edge and struck very different chords. The late 1990s was the era of Celebrex and Viagra as well as the now-infamous OxyContin.

More recently, drugs have reached for even more exotic sounds. Within the past few years, the US Food and Drug Administration has approved Farydak for treating multiple myeloma, Avycaz for abdominal infections, Vraylar for schizophrenia, Idelvion for hemophilia, Luzu for athlete's foot and Byvalson for high blood pressure.

Saying these names aloud, some may hear a strange and lovely music, while others may imagine aliens arriving from distant planets. Similarly, naming a drug is a complicated process.

The power of three

A branded prescription drug is actually known by three names.

The pharmaceutical company gives a new drug a chemical name based on a set of rules established by the International Union of Pure and Applied Chemistry.

For any drug that will be marketed in the United States, the next step is obtaining a name from United States Adopted Name Council. It assigns the active ingredient of the drug a generic name, which must be cleared and reviewed by the International Nonproprietary Name program run by the World Health Organization.

"This step assures that there is one non-proprietary (generic) name throughout the world for the drug," explained Stephanie C. Shubat, director of the Adopted Name Council.

With the generic name settled, a pharmaceutical company proposes a brand name to the FDA, to mark the product as its own.

For example, an antidepressant is known in the lab by its chemical name: N-methyl-3-phenyl-3-[4-(trifluoromethyl) phenoxy]propan-1-amine. The generic name assigned to this complex chemical is fluoxetine. To the rest of us, the drug is commonly known as Prozac.

"Prozac is what I call the Big Bang of pharmaceutical naming. It came out of nowhere, it means absolutely nothing, and it really just said, 'Wow, OK, this is blockbuster naming in the drug world,' " said Scott Piergrossi, vice president of creative development at the Brand Institute, which names, tests, markets or otherwise works on about 75% of FDA-approved names each year and about two-thirds of the global names.

David Wood, a pioneer in the field of branding and founder of Wood Worldwide, named Prozac in the early 1990s, before he sold his shop to InterbrandHealth. Today, Prozac even appears in the Oxford English Dictionary. According to R. John Fidelino, executive creative director at Interbrand, it was the first drug name that took both a condition and its treatment "out of the shadows."

Prioritizing safety

Though each step of the naming process presents hurdles, approval for a brand name is the most difficult to clear. "The FDA's Division of Medication Error Prevention and Analysis is responsible for proprietary name review prior to approval," explained Lyndsay Meyer, a spokeswoman for the agency, noting that this division can "require the company to select another name, for safety reasons, as part of the approval process."

Two departments within the FDA -- the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research -- scrutinize each proposed name and then reject about 20% and 35% of the names, respectively.

If reviewing names seems an unnecessary form of regulation, consider that the Institute of Medicine estimates that more than 1.5 million Americans are sickened, injured or killed each year by errors in prescribing, dispensing and taking medications. Meanwhile, a study published this year in the British Medical Journal found that 251,000 people die each year in the United States from medical error or medical care gone wrong, including drug name and dosage mixups.

Medical error is the third leading cause of death in the US, after heart disease and cancer, say the study authors, making the goal of everyone in this industry to avoid what they call LASAs: lookalikes, sound-alikes.

"Name safety is now the number one priority, and predicting name approvability is now the name of the game," said Arlene Teck, creative director at Ixxéo Healthcare, a name engineering agency. "The FDA wants to protect any American, traveling anywhere, from any kind of harm that could come from confusing one drug with any other drug or even a local food supplement."

The possibility of drug name confusion keeps regulators up at night. Because they can nix any proposed name, the FDA, the European Medicines Agency and HealthCanada exert the strongest influence on drug names, according to Teck. In fact, she says, we are living in "the regulated age of drug naming."

And for those who believe that computerized prescriptions will reduce mistakes caused by illegible handwriting, a white paper (PDF) commissioned by the FDA found that lookalikes still cause mistakes when prescribers accidentally choose a similar drug name from a drop-down menu.

Global influences

The FDA has a whole host of reasons why it might require a different name than the one selected by a company. For instance, the use of certain word "stems" are officially protected by the International Nonproprietary Names program. Word stems are groups of letters, usually just two -- "os," for instance, or "aj" -- that cannot appear within brand names, explains Teck, as it might cause confusion with a generic name.

The FDA also rejects names that seem too fanciful or overstate a drug's effectiveness and puts the kibosh on names that might stigmatize a patient (or condition).

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"If you are wanting to do metaphors that are life-affirming, and you want to think of things like trees or flowers or something strong like metal, you cannot do that, because it might suggest an ingredient," Teck noted.

The global nature of the pharmaceutical industry presents additional challenges. A name may be approved by the FDA and then rejected by European or Canadian authorities.

"To anticipate both the FDA and European Medicines Agency regulatory outcome, that's really the number one mission of any team or any agency," said Denis Ezingeard, Teck's naming partner and CEO of Geneva-based Ixxéo.If you fail, says Ezingeard, "you're down to square one."

Even once a product is commercially launched, the FDA retains the authority to request a name change. In fact, the agency may request a name change if doctors report confusion and medical errors even after a drug can be found on the shelf at your local pharmacy.

Naming drugs, says Ezingeard, is all about avoiding regulatory pitfalls and has become "less and less" about creation. After all, recovery from rejection, which could take a long time when coordinating the process across different countries, is costly and difficult.

Because of the many rules and regulations, pharmaceutical naming has become highly specialized work that is mostly farmed out to highly specialized creative agencies.

The creative process

Having developed strange and elaborate defenses to avert the disaster of rejection, namers resemble emus, those awkward birds that run instead of fly.

Most agencies begin the process by playing the numbers game. For any assignment, the Ixxéo team creates between 2,000 and 5,000 names. "That makes pharmaceutical naming different from consumer branding, where the constraints are not as stringent and where you can turn a much lower wheel of names," said Ezingeard, who refers to himself as "Dr. Destructo."

His job on the team is name elimination, because his primary concern is to "get out of the way" as many names as possible "that are by their nature" a possible liability. In the end, 10 are selected as "promising" from the original 2,000 or 3,000, and from there, the final selection of one name begins. The Brand Institute then typically submits two names at once to regulatory agencies, according to Piergrossi.

"But there are layers of contingency names in place, especially with Big Pharma planning years in advance," he said, adding, "we are well-versed in what's required by the regulators."

Another way the Brand Institute's subsidiary, the Drug Safety Institute, avoids rejection is by assessing name candidates using a methodology similar to those used by regulatory authorities.

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For example, FDA examiners are known to look at handwritten samples of a drug name and listen as a variety of people (each with different accents) pronounce the name. They also check for illegal stems, similarity to the names of discontinued products, and common medical or coined abbreviations tucked within the name. Meanwhile, examiners analyze for possible promotional claims and references to active or inert ingredients within the sound of the proposed name.

Ixxéo has developed its own "regulatory engineering model" that mirrors the "complex and evolving set of parameters" used by regulatory authorities.

"It's the very model the FDA could have built, but they didn't do it," Ezingeard said.

Beyond the rules

Like poets who write Elizabethan sonnets rather than free verse, pharmaceutical namers must make difficult decisions based on arcane rules, but their work is still a form of artistry.

Teck says Ezingeard, an engineer and polymath, developed Ixxéo's elaborate naming process when he was studying Darwinian evolution. "Creation engineering," as Teck refers to the drug-naming process, is based on evolutionary science as well as art history and merges creation with the screening process.

In practice, this means swapping names back and forth between Teck, Ezingeard and Ignasi Fontvila, a colleague in Barcelona. Together, they craft names blended from English, French, German, Spanish and Catalan linguistics and based on four distinct dimensions: visual distinctiveness, melodic contrast, verbal velocity -- how it sounds when spoken within a sentence -- and language neutrality, which is the ability to work across many different languages.

Teck and Fontvila then develop a final list of name candidates and tweak each other's to ensure a higher chance of approval.

Teck is legendary in the industry for naming Viagra while at Wood Worldwide in 1992. To name Pfizer's blockbuster, she ran a focus group with urologists who treated erectile dysfunction. At the conclusion of the session, Teck asked one of the doctors what it felt like for men when the condition went away.

The doctor said, "Visualize a strong stream." Melting the words "vigorous" and "Niagara," Teck came up with "Viagra."

Neo-linguistics

Now an entry in the Oxford English Dictionary, Viagra is an example of how a name can "fundamentally create, not just change, conversation," Interbrand's Fidelino said.

"Prior to Viagra, impotence was a psychological disorder that went to the core of how men defined themselves," he said. "By creating a brand that is named in a way that allows people to discuss it, and creating language or using language to describe the condition in a way that makes it easier for people to engage in conversation, you had more people seeking treatment and also improving sexual health and relationships around the world."

Later, Interbrand was tasked with creating a moniker for what's now known as Cialis, a second-to-market impotence drug. But naming a drug that is not first to market is difficult because "the name of the game is being unprecedented ... being the breakthrough," Fidelino said.

He explains that the goal was to find a sound that fit with Cialis' improvements over its predecessor, the macho-sounding Viagra.

Cialis' treatment window is longer than that of Viagra -- it works throughout the day -- so if an opportunity arises, a man can spontaneously respond. This unique attribute and improvement over Viagra required "new messages and a new framing," said Fidelino, who says naming drugs is about naming "the invisible, the intangible."

The resulting approach for Cialis was more about relationships and less about sex. "A different type of emotion is conveyed by Cialis," rhapsodized Fidelino, noting that it's a "tonally softer" name and more elegant.

Of the many names created by the Brand Institute, Piergrossi says he is proudest of Latisse, the eyelash growth drug from Allergan. This name was crafted by merging two words: "lash" and "Matisse," the French painter and sculptor. Latisse is marketed directly to consumers, so the name must appeal to those who will use the product.

From prescription to OTC

Names intended for doctors are often a play on words or technologies familiar to them or suggestive of a drug's mechanism of action. For instance, the hepatitis B and C drug Pegasys, adds Michael Dijkstra Taurel of the Amsterdam based Pharmanaming.com, is based on a pharmaceutical technology known as pegalation. But as more prescription drugs are transfered into OTC drugs and keep their original brand name, it is important that when coming up with the name to also see the patient as a target group.

Zantac for instance is both available as prescription and over the counter. So if you find yourself wondering if you can purchase Zantac over the counter, or if you will need a prescription, you are not alone. The fact is, these acid-reflux medications come in both OTC and prescription forms depending on the severity the nature of the ailment. Zantac 75, and Zantac 150, for example, are both relatively weak variants of the drug and can be purchased over the counter; these would be used to extinguish a small brush fire in your gut. Zantac 300 contains twice the active ingredient as the 150 option, and is a prescription drug; best reserved for when you feel that raging inferno which threatens to burn a hole right through the lining in your stomach.