Two regulatory experts said in an editorial that suffixes for biosimilars can support adverse event reporting and build provider and patient confidence in biosimilars.
An editorial on the suffix naming convention for biosimilars makes the case for differentiation through product names as a means of tracking adverse events (AE) associated with each product and thereby “enhancing provider and patient confidence in and uptake of biosimilars.”
Biosimilars are approved for marketing if they have no “clinically meaningful” differences from reference products. “However, ambiguity in product-specific identification that hinders the ability to accurately trace AEs to the correct product may result in negative perceptions of biosimilars or an entire product class,” wrote the authors, John B Jordan and Leah Christl. Until a year ago, Christl was the FDA's associate director for Therapeutic Biologics and director of Therapeutic Biologics and biosimilar staff. She is currently Amgen’s executive director for global regulatory and research and development policy.
To illustrate how AEs may show little differentiation between biosimilars, the authors provided an infliximab example. Two infliximab biosimilars are approved and 2 are currently on the market. Using the FDA’s AE reporting system, Jordan and Christl counted the number of AE reports for infliximab products with distinguishable nonproprietary names.
They noted that 431 (87%) of the 494 spontaneous AE reports submitted from 2017 to 2018 included the brand name, and the remaining 63 (13%) used only the nonproprietary name. These 63 included 39 events (9%) for the originator product (Remicade; no suffix), 21 (5%) for infliximab-dyyb, and 3 (0.7%) for infliximab-abda. “This distribution of AEs was similar to the market share for the biosimilars at the time (5% and 0.3%, respectively),” the authors concluded.
The FDA’s Biosimilar Action Plan (BAP) is intended to improve patient and physician confidence in biosimilars by improving scientific and regulatory clarity and developing audience-appropriate educational materials to increase understanding of biosimilars, but with respect to pharmacovigilance and accurate product identification, the educational materials should include information about AEs and the “appropriate use of distinguishable suffixes in AE reporting,” the authors wrote.
The BAP was released in 2018. It provides information regarding what actions the FDA should or should not take in order to encourage innovation and competition among biologics and promote biosimilar development. “A balance between innovation and patient access should be maintained with patients ultimately benefitting from the potential for more treatment options and lower cost of biologics,” the BAP notes.
Amgen has a portfolio of 10 biosimilars, 4 of which are FDA-approved, and 2 are on the market. It also has an infliximab biosimilar, infliximab-axxq (Avsola), that was approved December 6, 2019, and has yet to launch.
“Improving understanding of the importance of distinguishable names and supporting FDA guidance on nonproprietary names for biologics through education also will advance pharmacovigilance and thereby enhance patient and physician confidence in and uptake of biosimilars,” the authors wrote.
Nonproprietary suffixes are required for all newly approved originator biologics, biosimilars, and interchangeable products. However, they do not apply to biologics that were approved before the BAP was introduced.
Distinguishable nonproprietary names are expected to minimize prescriber errors and mitigate the risks of prescription substitutions involving drugs not designated as interchangeable. They are also important for evaluating a biologic product’s risk profile since a biologic’s quality can be sensitive to changes in manufacturing or handling.
“Therefore, postmarketing safety surveillance is important for comprehensively evaluating the risk profile of a product during its life cycle...because the misattribution of [AEs] to the incorrect product could result in delayed identification of product-specific risks and overly broad regulatory action,” they wrote.
“Ambiguity in product-specific identification that hinders the ability to accurately trace AEs to the correct product may result in negative perceptions of biosimilars or an entire product class,” they added.
Pharmacovigilance, aided by suffixes, is essential for facilitating accurate safety records and supporting targeted regulatory action. It’s also important in making sure a manufacturer is held accountable for their products’ quality, safety, and efficacy, they wrote.
Some stakeholders have argued that suffix requirements could result in a competitive disadvantage by implying biosimilars with suffixes are inferior to or different from reference products. The same claim of potential unfairness has been applied to the waiver allowing previously approved biosimilars to continue without suffixes.
Jordan and Christl argued against this by using an example from the launch of the biosimilar filgrastim-sndz (Zarxio), which gained 24% of the market share for filgrastim in the United States within 4 months after it became available “and surpassed its reference product in terms of market share [at roughly 30 months], even though the reference product does not have a suffix.”
According to a 2019 survey, 84.6% of physicians support the use of suffixes and 82.1% support the use of them for interchangeable products.
Former FDA Commissioner, Scott Gottlieb, MD,had predicted that “as more biological products are introduced to the market with distinguishable suffixes, patient and providers increasingly will understand that the suffixes reflect a consistent naming convention and are not an indicator of product quality.”
The authors recommended that the FDA develop educational tools on the process for AE reporting and the appropriate use of distinguishable suffixes in reporting. They also suggest that educational programs should be extended to patients, nurses, pharmacists, and payers in addition to clinicians.
“It is important that materials be tailored to the intended audience; however, care should be taken to ensure that concepts are not simplified to the point of being inaccurate,” experts warned.
Jordan JB, Christl L. FDA Biosimilar Action Plan: could improving pharmacovigilance of biologics improve patient and physician confidence in biosimilars? Expert opinion on drug safety [published online March 2, 2020]. Taylor & Francis Online. doi: 10.1080/14740338.2020.1733966.