How To Choose A Proprietary Rx Drug Name
Executive Summary
US FDA final guidance describes possible study design to test whether selected names may misbrand a drug. Agency also okays use of two-letter USAN stems in product names and clarifies use of modifiers.
The US Food and Drug Administration has given sponsors further advice on how they can test the acceptability of proposed proprietary names for prescription drug products to prevent medication errors.
The agency’s final guidance, Best Practices in Developing Proprietary Names for Human Prescription Drug Products, describes how drug makers can minimize proprietary name-related medication errors and avoid adoption of proprietary names that are false or misleading, and thus misbrand the drug in violation of the federal Food, Drug, and Cosmetic Act and its implementing regulations.
The document is similar to draft guidance released in May 2014 but includes several revisions, including the addition of a potential way to test a name to ensure it does not misbrand the drug. FDA has also split the draft document, which covered all drugs, into a final guidance for Rx drugs and a draft guidance for nonprescription drugs.
FDA issued both documents in December. FDA Principal Deputy Commissioner Amy Abernethy said in a release that the guidances “will assist developers in choosing names that minimize the risk that end users receive the wrong product, which could be harmful to their health.”
The draft guidance recommended that drug sponsors conduct simulation studies with health care professionals and consumers to evaluate the safety of a proposed proprietary name and described how to design such studies. (Also see "Draft Guidance On Developing Drug Names Calls For Simulation Studies" - Pink Sheet, 2 Jun, 2014.)
The final guidance streamlines the name simulation study section and includes an appendix with information on possible study methodology that sponsors may consider to test proposed names for misbranding concerns.
It suggests a crossover design in which the proposed proprietary name is evaluated in the context of both a neutral control name and an extreme control name. The study participants would be split into two groups, which would both evaluate the proposed proprietary name but in a different order from each other.
The guidance includes examples of questions to pose to study participants, including what, if anything, the product name suggests about the product and which of a list of conditions the drug treats. Participants could also be asked, based on the name of the product, how effective or ineffective and how safe or unsafe they would say it is.
The guidance also includes an appendix describing research methodology considerations for conducting name simulation studies. The studies test how subjects respond to a proposed proprietary name by asking them to use the name in use conditions that simulate the real world. The guidance recommends that all study participants be actively participating health care professionals and that sponsors test a number or prescribing conditions.
Two-Letter Stems Now Allowed
FDA also changed its position on the use of United States Adopted Name (USAN) stems in product names. The agency will no longer object to the use of two-letter USAN stems in names for products that do not share any association with the stem in question.
USAN stems are intended to indicate a pharmacological or chemical trait of a drug, and a single stem may be applicable to multiple drug products. The agency continues to recommend that sponsors avoid proprietary names that incorporate USAN stems in the position that USAN designates for the stem in a nonproprietary or established name. It says that when used inconsistently with the intended USAN meaning, using stems in this position may imply that a product has a pharmacological or chemical trait that it does not.
However, FDA said it is less concerned about USAN stems that consist of two letters in proprietary names and would generally not object to their use.
“The two-letter stems are often not distinct enough to be recognized as USAN stems. Also, some two-letter stems are outdated and have not been used by the USAN Council for years,” the guidance states.
It notes that there are currently five stems that consist of two letters as identified by the USAN Council. They include -ac: anti-inflammatory agents (acetic acid derivatives); -aj: antiarrhythmics (ajmaline derivatives); and -ef: Fc fusion protein.
Acceptable Modifiers
The final guidance also provides clarification on the use of medical abbreviations, modifiers and computational methods. Modifiers generally consist of one or more letters, symbols, numbers and/or words that appear at the beginning or end of the root proprietary name.
FDA encourages sponsors that choose to use modifiers to select those with an established meaning that has not been a sources of confusion. An appendix has been added to the guidance that lists examples of previously used modifiers that have not been a source of confusion along with their commonly understood meanings. The modifiers include XR and ER (extended-release product); DS (double strength); Depot (depot injection) and ODT (orally disintegrating tablets).
FDA generally recommends that sponsors avoid the use of numbers and symbols within a proprietary name. The guidance notes that there may be a few instances where the use of modifiers minimizes the risk of errors and promotes appropriate use of the products, such as proprietary names of oral contraceptives with numerical modifiers that help differentiate among various dosage strengths of the products.
The agency also added definitions in the glossary, including definitions of active ingredient, active moiety, adverse reaction, family trade name, medication error and serious adverse event.
Proprietary Names To Avoid
The final guidance retains the appendices in the draft that provide checklists of highly similar and moderately similar name pairs and name pairs with low similarity. The highly similar name pair checklist asks if product names begin with a different first letter, if the lengths of the names are dissimilar when scripted or printed, and if the infixes and suffixes of the names appear dissimilar when scripted.
As in the draft guidance, the final document advises against proprietary names that are similar in spelling or pronunciation to existing proprietary names, established (or proper) names, or names of ingredients of other products. It also recommends that proprietary names not incorporate any reference to an inert of inactive ingredient.
In addition, the guidance advises sponsors not to use brand name extensions to introduce a new product, noting that in some cases, using the same proprietary name that is already associated with another marketed product has led to the use of a product for the wrong indication, in the wrong patient population, at the wrong dose, or in a contraindicated manner.
The agency also recommends that sponsors refrain from using the proprietary name of a product that is no longer marketed to name a different drug product. It also advises that they avoid incorporating product specific attributes, such as manufacturing characteristics (e.g., “NameLyophilized”), dosage form (e.g., “Nametabs”) or route of administration (e.g., “Nameoral”), as part of the proposed root proprietary name. And it discourages sponsors from incorporating symbols, dose designations, and medical abbreviations commonly used for prescription communication in the proposed proprietary name.
FDA makes similar recommendations for the naming of over-the-counter drugs in its draft guidance on developing proprietary names for nonprescription drugs. (Also see "US FDA: User-Error Risks Grow When OTC Brands Extend With Different Ingredients, Indications" - HBW Insight, 9 Dec, 2020.)
FDA Okays More Brand Names
FDA developed the guidance to help sponsors develop brand names that do not lead to medication errors. In 1999, the Institute of Medicine released a report that found medication errors account for an estimated 7,000 deaths annually in the United States. It recommended that FDA encourage pharmaceutical companies to test proposed proprietary names to identify and avoid potential sound-alike and look-alike confusion with existing drug names.
In 2003, FDA held two public meetings to discuss the methods used for proprietary name evaluation and in 2007, committed to certain performance goals, including implementing evaluation measures to help reduce medication errors related to look-alike and sound-alike proprietary names in the reauthorization of the Prescription Drug User Fee Act (PDUFA IV).
FDA had historically rejected about a third of proprietary names proposed by drug sponsors, a rate that grew to 36% in fiscal year 2004. (Also see "The Name of the Game: Adjusting to a Tougher FDA Brand Name Review Process" - Pink Sheet, 1 Dec, 2006.)
But in fiscal year 2015, following issuance of the draft guidance, the agency was approving 86% of proprietary names submitted by sponsors of new drugs and biologics. (Also see "Brand Name Review By FDA: Predictability Returns To Process" - Pink Sheet, 18 Apr, 2016.)