How should you name a new drug product? That question is the subject of a new draft guidance by the US Food and Drug Administration (FDA), which hopes to help industry in selecting a proprietary name that can clear the agency's various regulatory hurdles.
The proprietary name for a drug is its "brand" name. For example, the erectile dysfunction drug sildenafil is marketed by Pfizer under the brand name "Viagra." In many cases, the brand name is easier to understand and recall for both consumers and healthcare providers alike.
However, because brand names are generally shorter than the established non-proprietary name for a drug, the potential for confusion can exist. A May 2013 article in the New England Journal of Medicine noted that many drugs approved in the last few years have started with the letters ”X” and “Z,” potentially confusing patients. To name a few from the last few years: Xofigo, Xtandi, Xarelto, Xalkori, Xgeva, Zaltrap, Zytiga, Zelboraf, Zioptan, and Zometa.
FDA regulators try to reduce the potential for confusion by approving final trade names submitted by companies, assessing them for similarity to other names. For example, if a company requested a proprietary name of "Simplus," but a similar drug was named "Simplos," regulators would almost certainly reject it based on the potential for mix-ups and errors.
For more about that process, read the RAPS Fundamentals book excerpt on Prescription Drug Product Submissions here.
Now FDA is out with a new draft guidance intended to establish how companies can navigate the drug naming process more easily.
As FDA explains at the outset of the draft guidance, its prime concern is that an individual drug is clearly identifiable by a single drug name without the possibility of confusion. Regulators cite a 1999 report by the Institute of Medicine (IOM) which estimates that 7,000 deaths each year are attributable to medication errors.
A subsequent 2006 report by IOM identified eight problems are contributing to medication errors, including that the names of drug products can sound or look the same, causing consumers to take the incorrect product. EU regulators have estimated that the medication-error rate in primary care is as high as 9.1% in some cases, though some of that is due to a medicine's physical attributes, and not its name.
In 2007, as part of the FDA Amendments Act (FDAAA), FDA unveiled an initiative aimed at reducing instances of so-called "look-alike sound-alike" (LASA) drugs, taken to mean drug products with names that either look similar to one another (Simplos/Simples) or sound similar to one another (Sohydroxy/Zohydroxee). This new guidance is a continuation of that initiative, FDA explains in the document.
The draft guidance is extensive at nearly 37 pages and covering a wide range of possible cases and evaluation methods, including computer-driven methods like the Phonetic Orthographic Computer Analysis (POCA).
Some key points to consider from the guidance:
- Avoid proprietary names which have "obvious similarities in spelling and pronunciation" to other, already-marketed drugs. Sponsors should screen for these similarities in early-stage assessments.
- Proprietary names should not incorporate medical abbreviations, as this could "inadvertently be a source for error." Consult the Joint Commission's "Do Not Use List" or the ISMP's "List of Error-Prone Abbreviations, Symbols and Dose Designations" for more information.
- The name should not reference the drug's inactive ingredient in such a way as to infer that it has a value greater than it provides.
- The name should "not include or suggest the name of one or more, but not all, of its active ingredients," as this can mislead the user into thinking the drug only has one of the drug ingredients in it.
- Names should not incorporate US Adopted Name (USAN) stems, as those designate a pharmacological or chemical trait of a drug, and are not unique (and can therefore lead to confusion).
- Proprietary names or the same root proprietary name should not be shared among products, even if owned by the same company, if they don't contain at least one common active ingredient contained in the original marketed product.
- Discontinued names should not be reused.
FDA also includes an extensive list of naming elements that might be considered "misleading or error prone," but not automatically so. Some selected highlights:
- Names shouldn't incorporate product-specific attributes, such as manufacturing characteristics, dosage form, or route of administration. Future changes to the product may complicate naming consistency, causing errors, FDA said. However, it is occasionally acceptable.
- Names incorporating dosing intervals are discouraged, even when accurate. However, it may be acceptable to include dose timing in conjunction with the name, such as "Drug 24 Hour." Drug24H wouldn't be acceptable, however.
- Modifiers, such as "XR" or "ER" should be used accurately, purposefully, in accordance with similar modifiers in the marketplace, and in such a way as to minimize risks to consumers. Number should not be used as modifiers. Device-related modifiers ("Pen," "Diskus") may be used. Descriptive modifiers, such as "Children's" may also be used, but only if the drug is limited to that population of use alone.
- Brand name extensions are evaluated on a case-by-case basis, but the products must share an active ingredient, be differentiated in labeling, and use different modifiers.
- Sponsors should be careful when assigning different proprietary names to similar active ingredients, as the potential for an overdose exists. FDA evaluates these on a case-by-case basis.
- Symbols should not be used in a name.
- The sponsor's name should not be incorporated into the proprietary name.
- Partial Rx-to-OTC switches may involve new names for the OTC product to avoid confusion.
- Proprietary names should take into account the use of medicines in foreign countries, where proprietary names differ.
- FDA also subjects proprietary names to reviews to ensure the name does not misbrand the drug (e.g. don't name your drug "Cancercure") or have prefixes that might indicate the drug is more effective than it is (e.g. "Bestbuprophen").
FDA also recommends sponsors conduct simulation studies using real-world environments, such as a name being written (perhaps in messy handwriting) on a prescription pad or ordered over the telephone. A "well-designed parallel group observational study" of healthcare professionals will suffice, FDA wrote. A minimum of 20 scenarios should be assessed. Examples of these scenarios are provided in the guidance.
Finally, FDA evaluates names using its POCA system, which provides a computational analysis of drug name similarity. Sponsors should do this prior to submission as well, FDA recommended. The POCA will score drug names as follows:
- Highly Similar Pair: combined match percentage score ≥70%.
- Moderately Similar Pair: combined match percentage score ≥50% to ≤ 69%.
- Low Similarity: combined match percentage score ≤49%.
Drug names which are highly similar are unlikely to obtain approval, while those with low levels of similarity are "generally acceptable." Moderate levels of similarity will subject a drug name to further review "to determine whether sufficient differences exist to prevent confusion."
Comments on the guidance will be accepted by FDA for the next 60 days.
Guidance for Industry: Best Practices in Developing Proprietary Names for DrugsFederal Register Notice