Drug names are the product of complex, multiparty negotiations in which the needs and desires of various stakeholders (patients, pharmaceutical firms, physicians, pharmacists, other health care professionals, and US and international regulators) must be balanced.
Since the 1960s, the United States Adopted Names Program has been assigning generic (nonproprietary) names to all active drug ingredients sold in the United States. Pharmaceutical names are assigned according to a scheme in which specific syllables in the drug name (called stems) convey information about the chemical structure, action, or indication of the drug. The name also includes a prefix that is distinct from other drug names and that is euphonious, memorable, and acceptable to the sponsoring pharmaceutical firm.
Overview of Generic Naming
The assignment of generic names to pharmaceuticals in development is an important prerequisite to marketing a drug. The United States Adopted Names (USAN) Program, which assigns generic (nonproprietary) names to all active drug ingredients in the United States, is the result of a long-time partnership between the American Medical Association (AMA), the United States Pharmacopeial Convention (USP), and the American Pharmacists Association (APhA). These 3 organizations are the sponsoring partners and receive support from the US Food and Drug Administration (FDA).
In the United States, the FDA recognizes the USAN as the legal name for the active drug ingredient, and the USAN appears in the titles of monographs published by the USP that define the standards, properties, and characteristics of marketed drugs. With few exceptions (eg, prophylactic vaccines and mixtures not named by the USAN Council), a drug cannot be marketed in the United States without a USAN. Consequently, the USAN assignment is a necessary step in drug development before a drug can be brought to the US market, and assignment of a USAN is required for a new drug before patients can have access to it.
Outside the United States, the World Health Organization (WHO) publishes recommended International Nonproprietary Names (INN) for active drug ingredients, but the INN is not a substitute for a USAN. The USAN and the INN programs work together to ensure that generic names are the same inside and outside the United States. Consequently, the generic names inside and outside the United States differ only rarely, and these differences can potentially be very important.
An example of a drug with 2 names is the substance known as acetaminophen inside the United States and as paracetamol internationally, although these 2 names represent the same substance.
Firms usually begin the process of obtaining a nonproprietary name by filing a submission with the USAN Program or the WHO when a drug is in phase I or phase II clinical trials. Most prefer to complete generic name assignments by the time they are ready to publish papers about the drug so that they can use the name instead of a manufacturer code in publications. The USAN must be assigned before conducting pre-marketing labeling negotiations with the FDA.
The USAN Council is committed to patient safety, facilitating communication among health care professionals and patients, and access to prescription medications. The USAN Council is, therefore, aware of the importance of coining names that will not be confused with other drug names, compromise patient safety, or mislead health care professionals and patients about the action or use of a new drug substance. The USAN Council is also mindful of concerns that high drug costs can limit patients’ access to them and, accordingly, must weigh this possibility against the possibility that pharmaceutical companies may choose not to develop drugs that they believe will not be profitable when they make their nomenclature decisions. Because the USAN name includes information about a drug’s structure, action, or planned use, the name can potentially affect how a drug is perceived by physicians, pharmacists, pharmacy benefits managers, or the investment community. These perceptions can affect drug pricing and which drugs companies choose to advance in clinical trials.
Over 10 000 drugs have received nonproprietary names since the WHO, AMA, USP, and APhA began assigning names to drugs, and they are listed in online databases such as the USP Dictionary of USAN and International Drug Names. In 2018, the USAN program named 198 substances. The number of USAN adoptions fluctuates from year to year but has grown steadily over the past 20 years.
Developing new drugs for common conditions for which drugs already exist poses challenges. Pharmaceutical companies are for-profit entities that seek to maximize returns and minimize potential risks, and developing new drugs is a high-risk enterprise. Although there has been some debate about the exact cost of developing a drug, the most widely disseminated recent estimate is that it costs about $2.6 billion to bring a drug to market. Although failure rates vary according to the therapeutic class, most drugs that enter clinical trials fail. Thus developing new drugs that target existing mechanisms and are differentiated from existing products in a clinically meaningful way can be challenging. Consequently, pharmaceutical companies might find it more financially viable to develop drugs when there is less competition from low-cost therapies.
What Names Mean
In naming drugs, the most important considerations are avoiding drug names that are too similar to existing names—and therefore might compromise patient safety—and making sure the drug name communicates accurate information about the action or use of the substance. Over time, the USAN and INN nomenclature scheme has developed into a system for classifying new pharmaceuticals.
Many of the oldest drugs were named by shortening the systematic chemical name for the compound. However, the AMA-USP Nomenclature Committee quickly realized that a different way of naming drugs was needed and published a list of guiding principles to systematize nomenclature and move away from names derived from the chemical name of a substance. At that time, the AMA-USP Nomenclature Committee recognized 3 difficulties with chemically derived names: (1) the use of chemical syllables led to “complex, unmanageable” names for large classes of chemically related drugs; (2) common, chemically derived syllables (eg, di-, chlor-, meth-) were so overused that names were becoming less distinctive; and (3) some chemical compounds were so complex that the names derived from the proper chemical name were not meaningful to physicians.
Consequently, most USAN now include a stem. A stem consists of syllables—usually at the end of the name—that denote a chemical structure, indication, or action at a specific receptor. For example, in the name imatinib, the -tinib stem refers to the drug’s action as a tyrosine kinase (TYK) inhibitor. Occasionally, a sub-stem is used to further classify a drug. Thus, -citinib refers to drugs inhibiting a specific family of TYK inhibitors, the Janus kinases. There are currently over 600 stems and sub-stems that have been defined for classes of drugs.
A 1- or 2-syllable prefix at the beginning of each name differentiates each drug from other members of the same class. The most important concern in choosing a prefix is patient safety—specifically, reducing the risk of medication errors, which are a common and long-standing problem in medical practice. For this reason, the USAN Council avoids prefixes that will create new names that are too similar either to other drugs in the same stem class or to names in other stem classes that might look or sound similar to the new name. This means comparing drug names against lists of names for existing drugs.
The USAN Program carefully screens prefixes using searches of databases of existing drug names, and Phonetic and Orthographic Computer Analysis (POCA) software. The USAN Program, as much as possible, also avoids creating new drug names that begin and end with letters shared with existing generic or trade names for drugs or that have been found to have strong conflicts with other names in the POCA analysis. An analysis of trade-name pairs prone to look alike-sound alike medication errors found that these pairs often had shared strings of 3 or more letters in the prefix and POCA scores that indicated a conflict.
Balancing the Needs of Firms and Patients
As with any complex multiparty negotiation, there can be disagreements. The USAN Council’s focus on patient safety, access to new drugs, and communicating necessary information about drugs through the generic name is sometimes in conflict with the desires of pharmaceutical companies to create either a certain message about their drugs through the generic name or a positive image for their substances. While this desire on the part of companies is understandable, the USAN Council prioritizes patient safety and access to affordable drugs.
The class to which a drug is assigned can indirectly affect a company’s decisions about whether or not to continue developing it. Sometimes there are financial benefits if a drug is assigned to a specific drug class, and assignment to an undesirable drug class (often one in which there have been safety problems) might adversely affect drug development. Because pharmaceutical firms are in business to generate profits for their investors, they tend to develop more drugs in classes that they believe are commercially viable.
The USAN can also affect how a drug is perceived by payers or pharmacy benefits managers, who may be reluctant to list a “me-too” drug in their formulary but may accept an expensive drug if it is a first-in-class therapy because it is perceived as offering added value that justifies a higher price. For a small biotech firm, a first-in-class drug may be perceived as more valuable by investors or by larger, more established pharmaceutical firms looking to acquire the rights to develop and market new drugs. Firms might therefore request assignment of a new stem to indicate a drug is first in class. First-in-class drugs can achieve a larger market share, but the second or third member of a class can be a successful product if it improves on the first product in a clinically significant way.
The USAN Council must therefore be mindful of how firms’ desires for a drug to be named a specific way might affect access to medications and how much those medications cost. Assignment of a new stem is rare, occurring only after the council determines that a drug is truly novel and does not fit into any existing group. Unnecessary assignment of a new stem could lead insurers and patients to pay more for drugs similar to older, less-expensive products, indirectly affecting patients’ access to drugs. Similarly, an unfavorable nomenclature decision for the firm, if it contributes to a company’s decision to discontinue a developmental drug, might affect patient access.
Safe use of medications
For decades, assignment of a USAN has been a key step in the development and marketing of a new active pharmaceutical ingredient, because a substance cannot be marketed in the United States without a name. The primary goals of the USAN Council are to facilitate the safe use of medications by assigning names that are unlikely to result in medical errors and to ensure that drug names are reflective of what physicians, pharmacists, and patients need to know about each substance. The USAN can affect how payers, health care professionals, patients, and the investment community perceive a drug—and therefore patients’ access to drugs.
written by Gail B. Karet, PhD and previously published on https://journalofethics.ama-assn.org/