Nancy J. Globus, PharmD, is Vice President of Regulatory Affairs for the Accreditation Council for Medical Affairs, based in Oradell, New Jersey. Nancy focuses on helping the industry build error prevention into products by evaluating proposed names and labels prior to regulatory approval. In her 20-year medication safety career, she has reviewed thousands of names for submission to FDA, European Medicines Agency, and Health Canada. In addition to medication safety, she is passionate about patient advocacy and community pharmacy. You can find her at www.medicalaffairsspecialist.org/approve or on Twitter @MedSafetyGal.
Have you ever wondered what is behind the seemingly random letter strings attached to the nonproprietary names (also known as “proper names”) of these biosimilars? The short answer is that they are used to distinguish a biosimilar product from the original biologic product. But it hasn’t always been this way.
In the past 5 years that have marked the brave new world of biosimilar products, the nomenclature of these products has shifted and evolved. Before we get into the nuts and bolts of the 4-letter suffixes, it is worthwhile to understand the reasoning behind using nomenclature to distinguish clinically similar biologic products from one another. A biosimilar product is not necessarily interchangeable with the reference product. Although the clinical effects may be the same, ancillary effects such as immunogenicity may not be. So, unlike multisource, small-molecule generic equivalents that are interchangeable, biologic products have differences in their manufacturing and stability, based on having been derived from living cells. To avoid medication selection errors while maintaining the ability to track the potential for differences in the adverse event profile, the “core name” plus “distinguishing suffix” were born.
The first biosimilar approved by the FDA via the 351(k) regulatory pathway was the filgrastim product Zarxio, licensed to Sandoz in March 2015. When the product was approved, the suffix “-sndz” was added to the nonproprietary core name “filgrastim” as a “placeholder”—not because there was an intention to change it, but because the guidance on the best way to distinguish a biosimilar product from the originator product was still being considered. A review of publicly available approval documents revealed that, although other 4-letter distinguishing suffixes were considered, the choice of “-sndz” and its derivation from the license holder’s name was deemed to not conflict with anything in Section 351 of the Public Health Service Act that allowed for this approval pathway or United States Adopted Name (USAN) guiding principles. The entire name “filgrastim-sndz” was still considered nonproprietary in nature.
By the time the next biosimilar product was approved by the FDA in April 2016, things had changed a bit. That product was Inflectra, the first biosimilar of Remicade, and it was assigned the proper name infliximab-dyyb. The FDA released a draft guidance entitled “Nonproprietary Naming of Biological Products” the previous August, so the “current thinking” was in circulation and available for public comment. That guidance stated that the proposed suffix should:
The proposed suffix should not:
When that guidance was finalized in January 2017, several other characteristics and refinements were added to the list of requirements for suffixes, as written below.
The proposed suffix should:
The proposed suffix should not:
These additional requirements are designed to prevent the addition of the suffix from causing unnecessary confusion that could lead to a medication error—such as the suffix being confused with another drug name, an unintended route of administration, or dosing interval. These characteristics also prevent new suffixes like “-sndz” from being used for future products. Likewise, suffixes with only 2 distinct letters—such as “-szzs,” the suffix attached to the etanercept product Erelzi, approved in August 2016—will be avoided in the future as well.
Initially, the suffix guidelines described here also applied to already marketed products—a move that sparked much controversy. The decision to apply suffixes retrospectively to so-called legacy products was reversed in March 2019, owing to the potential for increased confusion, product misrepresentation, and cost to the health care system—the very issues the naming policy was attempting to avoid. The 2019 guidance update upheld that suffixes would be applied to new originator biologics.
By contrast, the view in Europe is different. After several years of similar regulatory unrest regarding the nonproprietary naming of biosimilar products, the World Health Organization, which assigns nonproprietary names to drug products, decided to abandon its proposal for attaching 2-letter “biologic qualifiers” to the nonproprietary names. The European Medicines Agency (EMA) published a lengthy document in October 2019 outlining the role and regulation of biosimilars in the European Union. In this document, the EMA stated that products will be tracked for pharmacovigilance purposes by the tradename and a specific batch number. Specifically, “medicines have to be distinguished by the tradename and batch number and this is particularly important in cases where more than 1 medicine with the same [international nonproprietary name] exists on the market. This ensures that, in line with EU requirements for [adverse drug reaction] reporting, the medicine can be correctly identified if any product-specific safety (or immunogenicity) concern arises.”
Although these differences in nonproprietary naming do not necessarily fit with a goal of international harmonization of regulatory policy, they do provide a framework for preventing product selection and other medication errors, while allowing product identification for post-marketing surveillance. The FDA’s current thinking and application of the guidance were discussed at length in a recent FDA-sponsored conference that discussed medication error prevention and pharmacovigilance. To date, 28 biosimilar products bearing a 4-letter suffix have been approved by the FDA.