In the world of pharmaceutical names, the trademark has always been the star, and every other word has played a supporting role. But recent developments at FDA-and the industry's response to those developments-have set the stage for a new approach to nomenclature.

In July 2001, when Texas Biotechnology and its marketing partner GlaxoSmithKline failed to persuade FDA to accept a proposed trademark for argatroban, a new anticoagulant, the companies gave up their equity interests in a trademark and brought the product to market without a brand name. That may be the first time a major pharma company has gambled away all future brand equity in exchange for an immediate product launch.

FDA continues to raise the bar for what is an acceptable trademark, particularly in light of concerns about medication errors arising from confusion over similar names. Companies are under great financial pressure to bring their products to market as quickly as possible, and the uncertainty of timely FDA approval of trademarks--as was the case with argatroban--may become an incentive to launch a product under its generic name for immediate revenues and patient benefits.

Applications for US Adopted Names are subjected to a rigorous approval proccss.

Why Generics?The length and complexity of most chemical names make them unwieldy and impractical to use in the healthcare system. But the intellectual property protections and restrictions associated with trademarks place too many limitations on how the scientific community and healthcare practitioners can use them to communicate scientific findings. (See "On the Branded Side," page 76.) Those factors have resulted in the need for generic names for pharmaceuticals.

Generic names are part of the public domain and may be used without restrictions in commerce and literature, thereby permitting easy communication among scientists, health practitioners, laypersons, and investigators. Their creation and approval are controlled by national and international organizations and regulatory agencies. In the United States, the US Adopted Names (USAN) Council is the FDA-sanctioned group responsible for developing and adopting generic names for pharmaceuticals. Based in Chicago, the USAN Council works in conjunction with the International Nonproprietary Name (INN) Committee of the World Health Organization (WHO) and other national nomenclature groups to standardize drug names.

The US Pharmacopoeia (USP), which is the official dictionary of public standards for drugs in the United States, contains monographs describing how pharmaceutical substances and products should be tested to assure their quality. The USP Nomenclature and Labeling Committee uses each pharmaceutical substance's generic name in conjunction with other approved modifiers to describe any pharmaceutical containing that chemical. Any question about the purity, strength, or quality of a pharmaceutical listed with USP relies on its standards as a basis for legal or regulatory action. If the drug falls short of USP standards, it is deemed misbranded or adulterated and may be recalled.

Usually, the company that plans to market the drug takes the lead in developing the generic name. The USAN Council mandates that a compound enter clinical trials before the company can submit a generic name application for review. That stipulation prevents clogging the system with names for "dead" compounds that never reach the marketing stage. Typically, a company's initial contact with the USAN Council takes place after FDA has assigned the compound an investigational new drug (IND) application number for human trials.

Rules, Rules, RulesMost executives are surprised to learn that they cannot use certain letters in a generic name. The letters "h," "y," and "k" are on the "do not use" list. And "f" and "t" are preferred to "ph" and "th." (See "The ABCs of Generics.") The rationale behind those restrictions involves language patterns in certain countries.

For example, the letter "h" is pronounced in English but is silent in Spanish and French and does not exist in Italian. So the generic name "histidine" is pronounced "istidina" in Spanish and "istidine" in French. Those differences may result in uncertainty about whether they represent the same or different drugs. Because the USAN Council strives to select names that will be recognized universally, the council has established nomenclature rules to deal with such potentially confusing situations. So, unlike trademarks, generic names rarely differ from nation to nation.

The WHO INN Committee as well as the USAN Council and its sister agencies in other countries subscribe to the distinctive stem concept: generic names need a unique semantic stem that helps healthcare professionals distinguish between classes of compounds with different chemical or pharmacological profiles. That is accomplished by using the same stem in all generic names for compounds that share certain chemical, pharmacologic, or therapeutic features.

A widely known stem is "pril" for the angiotensin converting enzyme (ACE) inhibitor group of compounds, which includes captopril, enalapril, and lisinopril. "Vastatin" is another well known stem that is used for cholesterol-lowering compounds-lovastatin, simvastatin, and atorvastatin are examples.

The Name GameEach applicant's first goal is to convince the USAN Council that the name it proposes does not conflict with existing generic names or trademarks. (See "Approval Path," page 78.) If the initial candidate fails to meet its guidelines, the council will select and recommend altern-atives. The submitting company may then suggest other choices it feels are more suitable. The negotiation process continues until the council and the company arrives at a mutually acceptable generic name. An independent USAN review board settles disputes.

All new proposed name candidates are published in the Pharmaceutical Research and Manufacturers of America (PhRMA) Trademark Bulletin and USP's Pharmacopoeial Forum, which serve as public notice that the USAN Council is reviewing the listed names. Their publication is also meant to elicit comments or objections from the pharma industry and the scientific community. The USAN Council also forwards the names to the WHO INN Committee secretariat and to key liaison representatives in other countries for additional trademark and linguistic review.

With the sponsor's permission, after a name has been negotiated in the United States, the USAN Council makes a formal submission to the WHO INN Committee, which reviews the name for 20-24 weeks. Once that committee approves the name, it notifies the USAN Council, and the moniker is formally adopted as the generic name. The company may use the name once it has received the USAN Council's letter of adoption. On average, the entire process, from the time the company submits the proposal until the name becomes official, takes about one year.

The new generic name is then published in the Journal of Clinical Pharmacology and Therapeutics' "New Names" column, in USP's Dispensing Information Update and Pharmacopeial Forum, and in the USP Dictionary of USAN and International Drug Names. There is also a wealth of useful information, including new generic names adopted and approved for publication, under the "USAN" section of the American Medical Association's website (www.ama-assn.org).

Regulatory and Legal UseA pharmaceutical's generic name is its legal designation used on all official and legal documents. The Code of Federal Regulations (CFR) states that the trademark and generic name will always be listed together on a product label. To make generic names obvious and easy to read, they must be just as prominent as the trademark and printed in letters that are at least half as large.

No statutes require a trademark, and companies can gain FDA approval without one. But there is no legal way to market without a generic name. The two names' order of appearance is not mandated, although the trademark usually comes first. In the United States, most off-patent products have no trademark and are labeled with only the generic name, which may also be the only name that appears in countries that lack an effective trademark system or a closed national formulary of medications.

Pharmaceutical naming processes are complex and time consuming. Coordinating the organizational, regulatory, and administrative procedures for generic names and their trademarks with the investigational new drug and new drug application phases of development is a difficult task. Negotiations for a generic name can be as delicate as any trademark registration, and, when it's all over, the company doesn't even own the rights to it.