With seven biosimilars currently on the market and 18 biosimilars approved by the FDA as of April 2019, one question is sparking a lot of debate: What should the scientific, or nonproprietary, names of these products be?
There are two schools of thought on this. One says that a molecule that is highly similar to its reference biologic medicine should have the same nonproprietary name as the originator. The other says that for safety reasons it’s important to have distinct names for all biologics so we can more easily tell one from another. The naming decision extends far beyond marketing and directly affects how pharmacies fulfill prescriptions for these drugs and how they will be monitored once they’re on the market.
All biologics — biosimilars included — are complex medicines with complex manufacturing processes and distinct regulatory considerations that set them apart from small molecule therapies. In that world, generic drugs share the same nonproprietary names as their brand-name reference drugs because they share identical active ingredients. For example, all generic versions of Tylenol (acetaminophen) are known as acetaminophen.
Biological products, by comparison, are much more complex. In terms of the active pharmaceutical substance, biosimilars are “highly similar” to their reference products and not the “same” as them. So giving biologics distinguishable nonproprietary names is consistent with the fact that no two versions of a biologic are identical.
Acknowledging this, the FDA decided to take a different approach to naming biologics, given that the introduction of biosimilars increased the potential of having multiple versions of a biological drug from different manufacturers on the market at the same time (a reference product and one or more biosimilars). In January 2017, it released its guidance on nonproprietary naming of biological products, proposing that all biological products — reference products and biosimilars alike — receive unique nonproprietary names. Each product gets a “core” name followed by a unique but meaningless four-letter suffix.
Here’s an example provided by the FDA for a hypothetical biologic called replicamab. Under the FDA’s system, it might assign the original product a suffix such as “-cznm,” resulting in replicamab-cznm. The first biosimilar to that molecule might then be called replicamab-hjxf, and so on, such that every new biosimilar of replicamab on the market has a name that is both related to the original product but is also unique.
The FDA issued updated draft guidance last month stipulating that unique four-letter suffixes will be applied prospectively to all new originator and biosimilar products, as well as interchangeable biosimilar products, but not to biologics that are already being marketed without suffixes.
Some critics of the updated naming policy claim that exempting older approved products gives an advantage to pre-existing reference products because those products lack suffixes, creating a misperception about biosimilars for those products. In reality, that does not seem to be the case. In fact, a filgrastim biosimilar with a four-letter suffix, filgrastim-sndz, has taken the majority market share away from the originator product, filgrastim, and has nearly mirrored the uptake that has been observed in Europe. This suggests that these suffixes have not affected product perception or uptake.
I should note that these older originator products were approved years ago, well before discussions on distinguishable nonproprietary names were necessary. As more new originator and biosimilar products are approved and assigned names with suffixes, the fact that these older products do not have a unique suffix will become less of an issue.
Since 2017, the FDA has been consistent in assigning distinguishable suffixes to 22 newly approved originator biological products and 18 biosimilars.
I and my colleagues at Amgen (AMGN), which makes both originator biologics and biosimilars, believe that this naming policy is a well-informed and science-based approach that puts patient care first.
According to former FDA Commissioner Scott Gottlieb, the primary goals of using distinguishable nonproprietary names are to improve pharmacovigilance and to minimize inadvertent substitution by pharmacists. Distinguishable names can help physicians, pharmacists, and patients identify the specific biological product intended for and administered to patients. Such a naming system can help adverse events be identified more readily and attributed to the specific product involved. It can also help manufacturers and the FDA identify potential new safety signals.
Europe, Australia, and now Canada have taken a different approach by choosing not to adopt a policy that incorporates distinguishable suffixes. The European Union allows biologics to share nonproprietary names, and passed legislation in 2012 requiring the use of brand names rather than nonproprietary names in pharmacovigilance reporting. But according to adverse event data available in the public EudraVigilance database, nearly 26% of adverse event reports in 2017 for infliximab products, for example, did not include a brand name identifier. That percentage was even higher in 2018. This suggests that it is hard to change physician behavior, and that the European approach might not be as robust as initially thought. It could also mean that if a problem occurs with a single product, it might take longer to identify exactly which product is responsible.
In addition to improving pharmacovigilance, distinguishable nonproprietary names also have the potential to help minimize the risk of prescribing or dispensing errors. Unlike in Europe, where pharmacy substitution of biosimilars in most member states is generally not encouraged, pharmacy-level substitution is expected in the U.S. when the FDA has designated a biosimilar as “interchangeable” with its reference product.
As this landscape evolves, and interchangeable products enter the market, it will underscore the importance in the U.S. of building the capability for accurate traceability and intentional pharmacy substitution. Appropriate systems need to be in place to support this. Pharmacy laws in 47 states and Puerto Rico currently permit or require pharmacists to substitute interchangeable biosimilar products for the reference product without consulting the prescriber.
Since no interchangeable biosimilars are currently approved and marketed, the ability to distinguish one biological product from another may not seem as important now. But the day is coming when there will be multiple non-interchangeable and interchangeable biosimilars on the market that share the same reference product. The system will have to adapt to the availability of so many biosimilar — but in some cases non-interchangeable — products while maintaining product-specific traceability and minimizing the risk of inadvertent pharmacy substitution.
With the framework of the Biologics Price Competition and Innovation Act, which outlined approval standards for biosimilars and interchangeable biosimilars, and with states adopting pharmacy laws that allow the substitution of interchangeable biosimilars, physicians and pharmacists must have ways to know which products can and cannot be substituted at the pharmacy. The presence of a unique product identifier, such as a suffix, coupled with other measures (such as use of the FDA’s Purple Book) can help with this, an idea that two-thirds of pharmacists agreed with in a survey conducted by the Alliance for Safe Biologic Medicines in 2015.
Amgen is affected by the FDA’s naming policy, as it has three originator products for which the FDA already has licensed biosimilars and also has a portfolio of 10 biosimilar products, two currently approved in the U.S. and others in development. We do not see the suffix as a disadvantage to our biosimilars. Instead, we see it as a vital tool that serves both our originator products and our biosimilars. It helps hold manufacturers accountable for their products, can improve pharmacovigilance capabilities, helps ensure that patients get the medicines their doctors intended, and promotes rapid identification of specific products and targeted regulatory action when necessary.
Although the benefits of distinguishable nonproprietary names may not be immediately evident, it’s important to look to the long-term potential of this approach as more biologics, biosimilars, and interchangeable biosimilar products enter the marketplace. Amgen is committed to the belief that distinguishable nonproprietary names for biological products are an additional practical way to bolster pharmacovigilance.
It is time to put this long-standing issue to bed. We should now leverage this naming system as a tool to foster transparency, accountability, and safety, providing additional confidence in biosimilars and the ever-growing biologics marketplace.
Brad Jordan, Ph.D., is director of global regulatory and R&D policy at Amgen, Inc.