Thomas F. Lavery IV
Should biosimilars have the same nonproprietary name as their reference products?
There is an ongoing debate over whether biosimilars and interchangeable biologics should share the same nonproprietary name as their reference biologics. As patents covering biologics expire, companies other than the original manufacturers will seek to market their own versions of the originators’ biologics as biosimilars, “bio-betters,” or interchangeable biologics. The commercial opportunities for these follow-on products are potentially enormous: It is predicted that by 2016 eight of the top 10 bestselling drug products will be biologics, and biologics with combined revenues of $79 billion are expected to go off-patent by 2018.1
As a counterweight to the potential commercial upside, companies wishing to market follow-on biologics face a number of significant challenges and barriers. First, the FDA’s approval standards are rigorous: A biosimilar must be “highly similar” to the reference product and there must be “no clinically meaningful differences” between the biosimilar and the reference product. Interchangeable biologics must meet an even higher standard.2 Second, biosimilar manufacturers are confronted with a patchwork of varying state laws governing the requirements for substituting a biosimilar for a prescribed reference product. Even the seemingly simple question of how to name a biosimilar remains unanswered and has become another source of difficulty and dispute.
Because no law dictates how biosimilars should be named, numerous stakeholders, including pharmaceutical companies such as Janssen, Novartis, Amgen, Genentech, and Momenta, as well as nonprofit associations such as the Pharmaceutical Research and Manufacturers of America, the Generic Pharmaceutical Association, and the Biotechnology Industry Organization, have submitted citizen petitions or responses to citizen petitions, requesting that the FDA either (1) allow biosimilars to share the same nonproprietary name as their reference products, or (2) require biosimilars to have distinct nonproprietary names. The arguments on each side of the debate have focused primarily on two issues: pharmacovigilance and patient safety.
Pharmacovigilance refers to procedures for monitoring the safety of drugs to detect, assess, and prevent adverse effects or other safety-related issues. Some stakeholders assert that allowing a biosimilar to have the same nonproprietary name as its reference product would impair pharmacovigilance. Their reasoning can be summarized as follows:
- If adverse events were to identify a biologic solely by nonproprietary name, the shared names would complicate, if not prevent, tracing the adverse report to a specific product.
- If a patient is switched from the reference biologic to a biosimilar without knowledge of a physician, the physician may not know the particular product administered and may thus submit an adverse event report that incorrectly identifies the product administered to the patient.
- Shared names may lead to more patients being switched from one product to another; this switching would further complicate efforts to determine the product responsible for an adverse event.
Other stakeholders take the opposite view, contending that requiring distinct names for biosimilars is unnecessary for—and may impair—pharmacovigilance, arguing that:
- In Europe, where biosimilars have been in the market since 2006, no tracking issues have arisen from biosimilars sharing nonproprietary names.
- Requiring unique nonproprietary names would segregate the safety data for brand and biosimilar products, making it more difficult to detect rare adverse event signals across classes of products.
- A well-established process exists to track quality and adverse events that does not rely primarily on nonproprietary names, but instead uses a product’s brand name, manufacturer, lot number, and National Drug Code (NDC). The NDC reflects the manufacturer of the product; the active ingredient and its strength, dosage form, and formulation; and the package size.3 The NDC is unique to the product and manufacturing batch, and can be used to track biosimilars.
- Brand products are sold interchangeably and have the same name despite product “drift” that occurs over time. The FDA has authorized originator manufacturers to modify a biologic’s manufacturing process and market a biologic that has minor changes and differences that are not clinically meaningful—without requiring a change in nonproprietary name. The originator must demonstrate that the post-change biologic is “comparable” to the pre-change version. The standards for comparability and biosimilarity are largely the same. Some stakeholders have thus asserted that biosimilars, as highly similar to their reference products, should share nonproprietary names just as biologics maintain their nonproprietary names after manufacturing changes.
- Competing brand products in the same class of biologics share a nonproprietary name. The FDA routinely allows originator biologic products in the same class to have the same nonproprietary name, even though they were approved under different applications, manufactured by different companies, and manufactured using different methods. For example, Bayer’s Kogenate® FS, Genetics Institute’s ReFacto®, and Baxter’s Recombinate® are all recombinant factor VIII treatments made by different manufacturers but share the same nonproprietary name—“antihemophilic factor (recombinant).”
Some stakeholders have asserted that shared names could undermine patient safety, pointing out that:
- Shared names could lead to greater switching among products. For example, if a physician typically prescribes medications by nonproprietary name and does so for a biologic, the patient may inadvertently be switched to a different product. This switching could increase the risk to patients if the FDA has not deemed the new product interchangeable with the old product.
- Shared names could lead to inadvertent switching to a product that has not been approved for the indication for which the patient seeks treatment. For example, the FDA may approve a biosimilar for only a subset of the uses for which the reference product is approved.
Other stakeholders have taken the opposite view, offering several arguments in support of the proposition that requiring biosimilars to have unique nonproprietary names would jeopardize patient safety:
- Requiring different nonproprietary names could inaccurately suggest that a biosimilar has meaningful clinical differences as compared to its reference product, even though the FDA has determined that the biosimilar and its reference product are “highly similar.” The resulting clinical confusion may lead to prescribing errors, compromise patient access to follow-on biologics, cause patients to potentially go untreated, or disaggregate adverse event data for the products, thereby hindering rapid identification of class effects and rare safety signals.
- Just as requiring a biosimilar to have a different nonproprietary name could suggest that it has meaningful clinical differences, this requirement could lead prescribers to infer that two originator biologics that share the same nonproprietary name are interchangeable and produce the same clinical outcome. A prescriber may thus switch a patient from one originator biologic to another originator biologic with the same nonproprietary name, even though the FDA may not have deemed them interchangeable.
Biosimilars present an opportunity to provide greater access to biologic therapy and to control healthcare costs. Whether companies will pursue biosimilars and thus provide biosimilars to patients may depend in part on whether the FDA allows follow-on biologics to have the same nonproprietary name as the reference product or requires unique nonproprietary names for each product. The numerous citizens’ petitions and responses reflect the importance of this issue to the industry. It seems likely that the FDA will need to address this issue before it approves the first follow-on biologic, which some predict could be as early as 2015. How the FDA settles this naming contest will likely affect investment in and access to follow-on biologics.