"The letters h, j, k, and w are off-limits because they lead to pronunciation problems in other languages."

From Chemical and Engineering News:

It isn’t every day that a molecular moniker is on the docket at Illinois’ Cook County Circuit Court. But then, the 2002 case of cis-8-methyl-N-vanillyl-6-nonenamide was most unusual.

The trouble wasn’t with the compound’s International Union of Pure & Applied Chemistry-approved name. It was that cis-8-methyl-N-vanillyl-6-nonenamide also happens to be a medication. Drug molecules get an additional, simpler name called a nonproprietary name or generic name. Winston Pharmaceuticals, a company that develops products based on cis-8-methyl-N-vanillyl-6-nonenamide, sought to change that molecule’s generic name, which an independent body had chosen in-line with decades of drug-naming conventions. If the case went Winston’s way, more than a name on a box would have been at stake.

Drug naming rarely involves drama. But this example illuminates a little-talked-about layer in drug development, one that affects doctors, pharmacists, and patients.

Unlike IUPAC-sanctioned chemical names, generic names usually describe a drug’s physiological function rather than its chemical structure. Today’s regimented generic-naming process got its start in the 1960s, a time when drugs had grown complex in structure and IUPAC names had grown to unwieldy lengths. In 1961, the American Medical Association, the U.S. Pharmacopeial Convention, and the American Pharmacists Association created the U.S. Adopted Names (USAN) Council to select concise generic names. The Food & Drug Administration joined the effort in 1967.

Today, the USAN Council names the active ingredients in drugs, biologics, vaccines, and even contact lenses and sunscreens. The council recommends names to the World Health Organization’s (WHO) International Nonproprietary Names (INN) program, which ultimately chooses a single name for each new drug that’s acceptable worldwide. For drugmakers, obtaining a generic name is a required part of bringing new products to market. Choosing a brand, or trade, name is an entirely separate process.

USAN Council members believe it’s important to develop drug names that are free for anyone to use, says Ruta Freimanis, who served as associate executive secretary and then as executive secretary of the USAN Council between 1978 and 2000. Brand names might be handy at first, “but eventually drugs do go off patent,” she says. A generic name “can go in the literature, on package labels, or even in educational materials” without copyright issues related to brand names, she explains.

The naming process itself “is an evolving type of science,” says Stephanie C. Shubat, the current director and secretary to the USAN Council. Generic names have evolved from being truncated versions of chemical terminology to being largely independent of it, she explains.

A list of naming rules, some of them quirky, has evolved as well. The letters h, j, k, and w are off-limits because they lead to pronunciation problems in other languages. Drugmakers can suggest names to the USAN Council, but any name with an implication that a drug is better, newer, or more effective than the competition heads straight for the reject pile, Shubat says. When a prospective name reaches the WHO stage, international connotations come into play. A name that sounds perfectly fine in English might have bad or even obscene connotations elsewhere. No one wants to sell the Chevy Nova of the drug world.

The crux of the generic-naming system is a collection of short name fragments called stems. Each stem has a meaning connected to a particular drug class or mode of action. The official list of USAN and INN stems and substems has grown and changed over time as companies come up with new classes of drugs, Shubat explains.

Understanding drug names through stems is a lot like learning English vocabulary by studying Greek and Latin roots. Learn what the stems mean, and you’re most of the way to figuring out what a drug does. Take top-selling drug Nexium, which has a generic name of esomeprazole. The stem in that name is -prazole, which means the drug is a benzimidazole antiulcer agent. The drug’s es- prefix describes the nature of the drug’s chirality—esomeprazole is dextrorotatory and contains a chiral center in the S configuration.

A prefix, in fact, was a player in the Winston case. The generic name Winston wanted to change, zucapsaicin, contains the prefix “zu,” which comes from German chemical nomenclature and indicates a cis isomer. Zucapsaicin is the cis isomer of capsaicin, a compound in chili peppers. The molecule targets a specific ion channel and can be used to treat pain, inflammation, or itch, says Joel E. Bernstein, a physician and Winston’s chief executive officer. Winston requested a name change from zucapsaicin to civamide, which according to the company was commonly used in hospitals and pharmacies.

It’s possible to change generic names, but only on rare occasions, and usually only for safety reasons. In 2009, for instance, the entire family of botulinum toxin drugs, which includes the popular cosmetic Botox, got a generic-name makeover in light of reports of serious side effects and deaths from dosage mix-ups.

Winston did not win its court case. A 2004 petition to FDA to change the name didn’t work out either. The name zucapsaicin was found to be in-line with established naming precedents. As for name confusion among physicians and pharmacists, the USAN Council concluded Winston was partly to blame.

The name zucapsaicin had been on the books since 1994. The council negotiated the name with a company called GenDerm, which owned the rights to the drug at the time. Civamide was a generic name GenDerm suggested. After that name was rejected, GenDerm continued to use the name civamide in the literature and its documentation. Winston continued the practice when it acquired the rights to the drug in 1999.

Most of the documents Winston cited to support its claim are dated after 1994, wrote then-USAN program director Sophia V. Fuerst in a letter to Winston. It’s both Winston and GenDerm’s “use of the name civamide after the name zucapsaicin was adopted that has caused the confusion,” she wrote.

Bernstein disputes that idea. Still, he says, “we weren’t able to get USAN to change their mind, nor FDA, so we have zucapsaicin.”

Most of the time, a simple back-and-forth between a company and the USAN Council is enough to settle any name disputes, says John E. Kasik, professor emeritus at the University of Iowa Carver College of Medicine and a longtime member of USAN’s review board, which settles naming spats. In fact, the review board has only had to step in to resolve five disputes throughout its decades-long existence.

Sometimes small disagreements occur when a manufacturer asks for a new stem to be created, Shubat says. It’s the council’s job to keep naming as streamlined as possible, which means being conservative when it comes to adding new stems, she explains.

“Manufacturers have to supply concrete arguments as to what differentiates their compound to qualify for a new stem,” Freimanis says. Drugs within the same category are different, she says, “otherwise manufacturers wouldn’t be selling them.”

Once the council builds in stems, prefixes, and other conventions, “a lot of times a name is three-quarters predetermined,” Shubat says. Once in a while, though, companies get to do something special with the syllable or two they supply. Onyx Pharmaceuticals’ experimental multiple myeloma treatment carfilzomib is named after molecular biologist Philip Whitcome and his wife, Carla, who both succumbed to cancer. (The ph in Philip was changed to an f to make the name compatible with multiple languages.) Philip Whitcome was a founder of the company Proteolix, which first developed carfilzomib, says Onyx spokeswoman Lori Melançon. With the name, the company “wanted to celebrate both Phil and Carla’s legacy,” she says.

Bristol-Myers Squibb’s experimental hepatitis C drug asunaprevir gets part of its name from Li-Qiang Sun, the chemist who first made it, says Joel C. Barrish, BMS’s vice president of medicinal chemistry.

And dasatinib, a chronic myelogenous leukemia medication BMS markets under the brand name Sprycel, is named for research fellow Jagabandhu Das. Das, or Jag, as he’s known around the labs, didn’t discover dasatinib. “What Jag did was challenge dogma,” Barrish explains. On two separate occasions, Das’s discoveries pulled his teammates out of medicinal chemistry ruts.

Long after a drug’s patent expires, “it’s the generic name that will always be remembered,” Barrish says. “Being able to recognize Jag that way for his accomplishments made the whole team feel good.”